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22 Apr 2024 at 01:46
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Bibliography on: Invasive Ductal Carcinoma (causes)


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RJR: Recommended Bibliography 22 Apr 2024 at 01:46 Created: 

Invasive Ductal Carcinoma (causes)

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

The causes of invasive ductal carcinoma have not been conclusively established. Researchers have determined that cancer can form when the cells in a milk-producing duct undergo changes that cause them to grow uncontrollably, divide very rapidly or remain viable longer than they should. The result is an accumulation of excess cells that can form a mass, or tumor, and potentially spread to nearby lymph nodes and distant areas of the body. The underlying reason for those cellular changes, however, remains unclear.

By evaluating the results of extensive studies, scientists have identified certain hormonal, environmental and lifestyle factors that are believed to influence a person's breast cancer risk, such as smoking, poor nutrition and prior radiation therapy administered to the chest area. Even so, it's important to keep in mind that some individuals who have no risk factors develop cancer, while others with one or more risk factors do not. Most likely, the precise cause is a complex interaction of many factors.

In rare cases, the causes of invasive ductal carcinoma have been traced to inherited attributes, such as mutations of the: (a) Breast cancer gene 1 (BRCA1), a tumor suppressor gene, (b) Breast cancer gene 2 (BRCA2), a tumor suppressor gene, or (c) ErbB2 gene, which produces the HER2 protein that promotes cellular proliferation.

Created with PubMed® Query: ( ("invasive ductal carcinoma" OR IDC) AND (cause OR caused OR etiology) ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2024-04-21

Satoh E, Innami Y, Uehira D, et al (2024)

[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].

Gan to kagaku ryoho. Cancer & chemotherapy, 51(4):427-429.

We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer(invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).

RevDate: 2024-04-19

Zhou H, Liu D, Chen L, et al (2024)

Metastasis to the bladder from primary breast cancer: A case report and literature review.

Oncology letters, 27(6):249.

Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.

RevDate: 2024-04-18
CmpDate: 2024-04-18

Mohammed BT, Uzodi N, Gotimukul A, et al (2024)

Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.

Current rheumatology reviews, 20(2):213-218.

BACKGROUND: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.

CASE PRESENTATION: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.

CONCLUSION: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.

RevDate: 2024-04-09
CmpDate: 2024-04-09

Ruan GJ, Zanwar S, Ravindran A, et al (2024)

Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.

American journal of hematology, 99(5):871-879.

Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.

RevDate: 2024-04-08
CmpDate: 2024-04-08

Rodriguez GF, Shah A, AD Maderal (2024)

Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer.

Breast disease, 43(1):61-64.

BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding.

OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma.

RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions.

CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.

RevDate: 2024-04-05

Sukhija S, Purohit P, Pareek P, et al (2024)

Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.

Indian journal of clinical biochemistry : IJCB, 39(2):214-220.

Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m[2]), Cyclophosphamide (600 mg/m[2]) with or without Taxane (75-175 mg/m[2]) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.

RevDate: 2024-04-05

Jamal O, Makhchoune M, Laidi A, et al (2024)

Rupture of a dermoid cyst in the subarachnoid space: a case report.

Annals of medicine and surgery (2012), 86(4):2366-2369.

INTRODUCTION AND IMPORTANCE: Intracranial dermoid cysts (IDC) are defined as rare, slow-growing cystic congenital neoplasms. Rupture of an intracranial dermoid cyst occurs rarely and most often spontaneously and results in potentially serious symptoms.

CASE PRESENTATION: A39-year-old female, with mechanical prosthetic heart valve presented with history of headache for 10 months and generalized tonicoclonic seizures. On the admission, the patient had a normal neurological and cranial nerve exam. The authors performed a computed tomography of the brain, The MRI could not be performed because of the presence of the prosthetic valve, revealed rupture of the dermoid cyst in the bilateral subarachnoid spaces. The patient underwent a large temporal craniotomy and the tumour was well exposed and completely removed without incident, the histopathological examination concludes to dermoid cyst, the patient recovered well from surgery.

CLINICAL DISCUSSION: Rupture is a very rare phenomenon. there are about 60 cases reported in the literature. the contents of the cyst disseminate into the subarachnoid and ventricular spaces in the event of rupture. A variety of clinical symptoms is usually caused. The mechanism of spontaneous rupture of the dermoid cyst is unclear. Among the proposed mechanisms is a rapid expansion of the cyst. Complete surgical resection of dermoid cysts is the only effective treatment for the prevention of recurrences and/or complications.

CONCLUSION: Rupture of an intracranial dermoid cyst is associated with significant morbidity and mortality, although it remains a rare phenomenon. Surgical excision should be considered as soon as the diagnosis is made in order to prevent more severe intracranial complication.

RevDate: 2024-04-05
CmpDate: 2024-04-05

Wang J, Li B, Luo M, et al (2024)

Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.

Signal transduction and targeted therapy, 9(1):83.

Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

RevDate: 2024-04-04

Maiti S, Nayak S, Hebbar KD, et al (2024)

Differentiation of invasive ductal and lobular carcinoma of the breast using MRI radiomic features: a pilot study.

F1000Research, 13:91.

BACKGROUND: Breast cancer (BC) is one of the main causes of cancer-related mortality among women. For clinical management to help patients survive longer and spend less time on treatment, early and precise cancer identification and differentiation of breast lesions are crucial. To investigate the accuracy of radiomic features (RF) extracted from dynamic contrast-enhanced Magnetic Resonance Imaging (DCE MRI) for differentiating invasive ductal carcinoma (IDC) from invasive lobular carcinoma (ILC).

METHODS: This is a retrospective study. The IDC of 30 and ILC of 28 patients from Dukes breast cancer MRI data set of The Cancer Imaging Archive (TCIA), were included. The RF categories such as shape based, Gray level dependence matrix (GLDM), Gray level co-occurrence matrix (GLCM), First order, Gray level run length matrix (GLRLM), Gray level size zone matrix (GLSZM), NGTDM (Neighbouring gray tone difference matrix) were extracted from the DCE-MRI sequence using a 3D slicer. The maximum relevance and minimum redundancy (mRMR) was applied using Google Colab for identifying the top fifteen relevant radiomic features. The Mann-Whitney U test was performed to identify significant RF for differentiating IDC and ILC. Receiver Operating Characteristic (ROC) curve analysis was performed to ascertain the accuracy of RF in distinguishing between IDC and ILC.

RESULTS: Ten DCE MRI-based RFs used in our study showed a significant difference (p <0.001) between IDC and ILC. We noticed that DCE RF, such as Gray level run length matrix (GLRLM) gray level variance (sensitivity (SN) 97.21%, specificity (SP) 96.2%, area under curve (AUC) 0.998), Gray level co-occurrence matrix (GLCM) difference average (SN 95.72%, SP 96.34%, AUC 0.983), GLCM interquartile range (SN 95.24%, SP 97.31%, AUC 0.968), had the strongest ability to differentiate IDC and ILC.

CONCLUSIONS: MRI-based RF derived from DCE sequences can be used in clinical settings to differentiate malignant lesions of the breast, such as IDC and ILC, without requiring intrusive procedures.

RevDate: 2024-04-01
CmpDate: 2024-04-01

Dogan I, Khanmammadov N, Ozkurt S, et al (2024)

Outcomes of the patients with metastatic male breast cancer.

Journal of cancer research and therapeutics, 20(1):98-102.

BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).

METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables.

RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC.

CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.

RevDate: 2024-03-30

Dreindl R, Bolsa-Ferruz M, Fayos-Sola R, et al (2024)

Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.

Journal of applied clinical medical physics [Epub ahead of print].

PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center.

METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined.

RESULTS: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated.

CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.

RevDate: 2024-03-28

Esmat E, Haidary AM, Saadaat R, et al (2024)

Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.

BMC cancer, 24(1):388.

BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.

METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.

RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.

CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

RevDate: 2024-03-26
CmpDate: 2024-03-26

Yanase Y, Bando H, Sato R, et al (2024)

Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.

Journal of medical case reports, 18(1):150.

BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.

CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine.

CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.

RevDate: 2024-03-25

Lopez-Vazquez P, Fernandez-Caggiano M, Barge-Caballero E, et al (2024)

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Frontiers in cardiovascular medicine, 11:1349417.

INTRODUCTION AND OBJECTIVES: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.

METHODS: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.

RESULTS: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.

CONCLUSION: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

RevDate: 2024-03-25

Seth A, EM Slama (2024)

Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.

The American surgeon [Epub ahead of print].

Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.

RevDate: 2024-03-25
CmpDate: 2024-03-25

Hu J, Chen X, Sun F, et al (2024)

Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.

Neoplasia (New York, N.Y.), 50:100983.

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

RevDate: 2024-03-25
CmpDate: 2024-03-25

Nakagawa S, Miyashita M, Maeda I, et al (2024)

Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.

Breast cancer research and treatment, 204(3):453-463.

BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.

METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.

RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.

CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.

RevDate: 2024-03-25
CmpDate: 2024-03-25

Chappidi MR, Sjöström M, Greenland NY, et al (2024)

Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.

European urology oncology, 7(2):222-230.

BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.

OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.

This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.

Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival.

RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity.

CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments.

PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.

RevDate: 2024-03-15

Heidari N, Abbasi-Kenarsari H, Niknam B, et al (2024)

Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.

Iranian journal of allergy, asthma, and immunology, 23(1):97-106.

Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.

RevDate: 2024-03-14

Shi Y, Wang H, Golijanin B, et al (2024)

Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.

Urologic oncology pii:S1078-1439(24)00053-X [Epub ahead of print].

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.

RevDate: 2024-03-11
CmpDate: 2024-03-11

Wang B, Fu Y, Chen M, et al (2024)

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.

Urologic oncology, 42(3):67.e9-67.e15.

OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer.

METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology.

RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis.

CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

RevDate: 2024-03-11
CmpDate: 2024-03-11

Miyajima K, Sato S, Uchida N, et al (2024)

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.

Clinical genitourinary cancer, 22(2):149-156.e1.

BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT).

METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P.

RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003).

CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

RevDate: 2024-03-10

Turhan Ş, Sultan DAO, Altuner EM, et al (2024)

Determination of radon concentrations and physicochemical parameters of non-alcoholic carbonated beverages consumed in Türkiye and assessment of radiological health risk.

International journal of environmental health research [Epub ahead of print].

The strategy for controlling the existence of radionuclides in drinking water depends upon an individual dose criterion (IDC) of 0.1 mSv/y, which represents a very low level of risk that is not expected to cause any identified adverse health effects. Radon gas, considered a carcinogenic radionuclide, can dissolve and accumulate in drinking water. Non-alcoholic carbonated beverages (NACBs), which mainly contain drinking water, phosphoric acid, citric acid, caffeine, and sugar, represent one of the most consumed groups worldwide and in Türkiye. In this study, the radon activity concentration and some physicochemical characteristics of 45 NACB samples from 24 most preferred commercial brands in Türkiye were determined to assess the radiological health risk associated with the ingestion of these samples. Radon activity concentrations measured in NACB samples using the AlphaGUARD radon analyzer ranged from 22.8 ± 0.7 to 54.9 ± 1.7 mBq/L. The pH, conductivity, total dissolved solids, and brix values in NACB samples ranged from 2.31 to 7.29, 401 to 3281 μSv/cm, 355 to 2453 mg/L, and 0.10 to 12.95%, respectively. Total (ingestion and inhalation) annual effective doses and the corresponding excess lifetime cancer risks estimated for adults to assess the radiological health risk are significantly below the IDC and advised safety limit (10[-3]), respectively.

RevDate: 2024-03-08
CmpDate: 2024-03-08

Saeed U, Uppal R, Khan AA, et al (2024)

Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.

Brazilian journal of biology = Revista brasleira de biologia, 84:e265550 pii:S1519-69842024000101101.

Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.

RevDate: 2024-03-06
CmpDate: 2024-03-06

Mouabbi JA, Qaio W, Shen Y, et al (2024)

Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.

The oncologist, 29(3):213-218.

BACKGROUND: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

MATERIALS AND METHODS: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.

RESULTS: CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001).

CONCLUSION: In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.

RevDate: 2024-03-04
CmpDate: 2024-03-04

Agaoglu NB, Unal B, Hayes CP, et al (2024)

Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.

Cancer medicine, 13(3):e6852.

OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).

METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated.

RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable = 32, VUS = 89) and 223 variants in the non-cancer cohort (actionable = 25, VUS = 188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p < 0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign.

CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.

RevDate: 2024-03-03

Chuang ML (2024)

Analyzing Key Elements of Breathing Patterns, Deriving Remaining Variables, and Identifying Cutoff Values in Individuals with Chronic Respiratory Disease and Healthy Subjects.

Respiratory physiology & neurobiology pii:S1569-9048(24)00035-1 [Epub ahead of print].

BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.

METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.

RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104L/min may differentiate ILD from control, while V̇E of 54L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99s, and IDC of.45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90).

CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.

RevDate: 2024-03-01

Samreen N, Moy L, CS Lee (2020)

Architectural Distortion on Digital Breast Tomosynthesis: Management Algorithm and Pathological Outcome.

Journal of breast imaging, 2(5):424-435.

Architectural distortion on digital breast tomosynthesis (DBT) can occur due to benign and malignant causes. With DBT, there is an increase in the detection of architectural distortion compared with 2D digital mammography, and the positive predictive value is high enough to justify tissue sampling when imaging findings are confirmed. Workup involves supplemental DBT views and ultrasound, with subsequent image-guided percutaneous biopsy using the modality on which it is best visualized. If architectural distortion is subtle and/or questionable on diagnostic imaging, MRI may be performed for problem solving, with subsequent biopsy of suspicious findings using MRI or DBT guidance, respectively. If no suspicious findings are noted on MRI, a six-month follow-up DBT may be performed. On pathology, malignant cases are noted in 6.8%-50.7% of the cases, most commonly due to invasive ductal carcinoma, followed by invasive lobular carcinoma. Radial scars are the most common benign cause, with stromal fibrosis and sclerosing adenosis being much less common. As there is an increase in the number of benign pathological outcomes for architectural distortion on DBT compared with 2D digital mammography, concordance should be based on the level of suspicion of imaging findings. As discordant cases have upgrade rates of up to 25%, surgical consultation is recommended for discordant radiologic-pathologic findings.

RevDate: 2024-02-26

Asad S, Khan SA, Khan FA, et al (2023)

Pattern Of Breast Cancer: Experience At Ayub Teaching Hospital, Abbottabad.

Journal of Ayub Medical College, Abbottabad : JAMC, 35(4):629-632.

BACKGROUND: Breast cancer is the most common malignancy found in females all over the world and the second leading cause of cancer death in European countries. The purpose of this study was to find out the pattern of disease presentation in our region where a proper tumour registry system is lacking.

METHODS: This descriptive study was carried out in the Department of Surgery, Ayub Teaching Hospital Abbottabad, from July 2021 to June 2022. All female patients with biopsy-proven breast cancer were included in the study: benign lumps, refused to enrol, and those who were lost to follow-up were excluded.

RESULTS: A total of 87 patients with carcinoma breast were included: 92 % (n=80) had invasive ductal carcinoma. Axillary lymph nodes were involved in 88.5% (n=77), 75.8% of the tumours, (n=66), were Grade 2, 34.5% (n=30) were in the 40-49 years age group, and 30 % (n=27) of the disease was categorized as Stage III or IV. In 55 % (n=48), the tumour was on the right side and in 39% (n=34), the upper outer quadrant was involved. Most of the patients, 90.8% (n=79), were married and had used contraceptive measures. Only 19.5% of patients (n=17), had a history of nipple discharge and 56% (n=49) had a positive family history: 71% (n=62) had nipple retraction, and 54% (n=47), proved to be ER PR positive.

CONCLUSIONS: Our patients presented late: axilla was commonly involved and a third had advanced disease. Screening and community awareness programs may help in early detection. Hormone use for contraception needs to be weighed carefully. Better data collection may help in designing screening and care programs.

RevDate: 2024-02-26

Bhunisha, Haider G, Shaikh Z, et al (2023)

Significance of ca15-3 in carcinoma of the breast with Visceral metastases.

Journal of Ayub Medical College, Abbottabad : JAMC, 35(Suppl 1)(4):S710-S714.

BACKGROUND: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi.

METHODS: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data.

RESULTS: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L).

CONCLUSION: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.

RevDate: 2024-02-26
CmpDate: 2024-02-26

Derakhshan F, Da Cruz Paula A, Selenica P, et al (2024)

Nonlobular Invasive Breast Carcinomas with Biallelic Pathogenic CDH1 Somatic Alterations: A Histologic, Immunophenotypic, and Genomic Characterization.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 37(2):100375.

CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.

RevDate: 2024-02-24

Khan MRR (2024)

Development of a Battery-Free, Chipless, and Highly Sensitive Radio Frequency Glucose Biosensor.

Micromachines, 15(2): pii:mi15020272.

In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms.

RevDate: 2024-02-23

Matsumoto T, Tanaka G, Mori S, et al (2024)

A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.

Clinical journal of gastroenterology [Epub ahead of print].

A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.

RevDate: 2024-02-23
CmpDate: 2024-02-23

Mahlow J, Barry M, Albertson DJ, et al (2024)

Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway.

Human pathology, 144:28-33.

Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.

RevDate: 2024-02-23
CmpDate: 2024-02-23

Soman PS, Hemalatha A, PN Sreeramulu (2023)

Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.

Journal of cancer research and therapeutics, 19(Suppl 2):S706-S711.

BACKGROUND: Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established.

AIMS AND OBJECTIVES: To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression.

MATERIALS AND METHODS: This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant.

RESULTS: Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available.

CONCLUSION: Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.

RevDate: 2024-02-22
CmpDate: 2024-02-22

Zhu S, Xu N, H Zeng (2024)

Molecular complexity of intraductal carcinoma of the prostate.

Cancer medicine, 13(2):e6939.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.

RevDate: 2024-02-21
CmpDate: 2024-02-21

Piracha ZZ, U Saeed (2023)

Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.

Journal of cancer research and therapeutics, 19(7):1870-1879.

BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.

METHODS: LRIG1 expression was determined in Erbb2 + cell lines by western blotting, and cell motility was examined by cell migration assay. The AKT/GSK3-β/β-catenin pathway was determined in the presence of LRIG1 and Erbb2 by using western blotting.

RESULTS: So far, no study has reported the expression of LRIG1 in benign forms of tumor such as fibroadenoma. The current study aims to analyze LRIG1 expression in fibroadenoma and invasive ductal carcinoma (IDC) tissues. In this study, we compared the LRIG1 expression with different clinicopathological parameters of patients having IDC or fibroadenoma. LRIG1 expression was low in Erbb2+ cell lines, and more cell motility was observed. The AKT/GSK3-β/β-catenin pathway was activated when LRIG1 was downregulated; consequently, Erbb2 was upregulated. Our results indicated that LRIG1 expression can be significantly correlated with age, Nottingham index, and Her2/neu status of cancer. The expression of LRIG1 in IDC and fibroadenoma were found to be significantly different.

CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.

RevDate: 2024-02-21
CmpDate: 2024-02-21

Huang T, Lu C, Zhang Y, et al (2023)

Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.

Annals of medicine, 55(2):2250987.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer.

METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS).

RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p < 0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p = 0.035).

CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.

RevDate: 2024-02-20
CmpDate: 2024-02-20

Liu XS, Chen YX, Wan HB, et al (2024)

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.

Scientific reports, 14(1):4042.

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.

RevDate: 2024-02-18

Gomez D, S Seneviratne (2024)

Invasive breast carcinoma with ipsilateral axillary squamous carcinoma of unknown primary: A case report.

INTRODUCTION & IMPORTANCE: Invasive ductal carcinoma is the commonest primary breast carcinoma to metastasize to the axillary nodes. Squamous carcinoma (SCC) of the breast is seen rarely as a primary breast malignancy. Breast SCC with coexistent invasive ductal/lobular carcinoma as a 'collision tumour' is rare.

CASE PRESENTATION: A 52-year-old Sri Lankan female presented with a right sided breast lump and ipsilateral cystic axillary mass. She was diagnosed with locally advanced invasive breast carcinoma and underwent neoadjuvant chemotherapy followed by mastectomy and axillary clearance where tumour infiltration of the brachial plexus was observed. Histology revealed two separate carcinomas; an invasive carcinoma of the breast and squamous carcinoma in the axilla. A squamous primary was not found despite evaluation. The patient developed recurrent axillary ulceration due to residual tumour and was transferred for oncological care.

CLINICAL DISCUSSION: This patient had a biopsy-proven invasive breast carcinoma with a cystic axillary mass with lymphadenopathy. This was concluded as locally advanced breast cancer. Pathological examination of the specimen indicated the presence of two separate malignancies of the breast and axilla. No evidence of squamous metaplasia or carcinoma of the breast was seen on histology, neither was a squamous primary identified on imaging or endoscopy. Neoadjuvant therapy may have caused resolution of the squamous component.

CONCLUSION: The presence of two separate cancers of varied histology in the breast and ipsilateral axilla in close proximity to each other is a rare phenomenon. Clinicians must be cautious not to misinterpret it as evidence of lymphatic spread.

RevDate: 2024-02-14
CmpDate: 2024-02-14

Santos MM, Baerga CG, Lamsal S, et al (2023)

Breast cancer in a Hispanic patient with Werner syndrome.

Journal of radiology case reports, 17(10):21-31.

Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.

RevDate: 2024-02-14
CmpDate: 2024-02-14

Ye C, Shi M, Xie D, et al (2024)

A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.

BMC musculoskeletal disorders, 25(1):118.

BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition.

CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion.

CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.

RevDate: 2024-02-05
CmpDate: 2024-02-05

Coria LM, Rodriguez JM, Demaria A, et al (2024)

A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.

Nature communications, 15(1):997.

In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.

RevDate: 2024-02-09
CmpDate: 2024-02-09

Verma VK, Beevi SS, Nair RA, et al (2024)

MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.

Cell communication and signaling : CCS, 22(1):100.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.

METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation.

RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity.

CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.

RevDate: 2024-02-09
CmpDate: 2024-02-09

Dimitrov G, Shousha S, P Troianova (2024)

CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.

Experimental and molecular pathology, 135:104885.

BACKGROUND: Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.

AIM: This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.

METHODS: We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.

RESULTS: Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p < 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p = 0.0003]. Concordance was observed between core biopsies and excised samples.

CONCLUSION: Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.

RevDate: 2024-02-08

Fang L, Simman R, Workman L, et al (2024)

Malignant wound aetiology, diagnosis and management: a case series and literature review.

Journal of wound care, 33(2):102-117.

OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy.

METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles.

RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC.

CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.

RevDate: 2024-02-06

Youh J, Yamaguchi Y, E Hiraguchi (2024)

Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.

Cureus, 16(1):e51641.

Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.

RevDate: 2024-02-05
CmpDate: 2024-02-05

Tsilingiris D, Schimpfle L, Κender Z, et al (2024)

Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.

Diabetes & vascular disease research, 21(1):14791641231223701.

PURPOSE: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).

METHODS: PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured.

RESULTS: PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5° for males and 5.2-5.8° for females were predictive of commonly used cutoffs. The combination of ΑCC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders.

CONCLUSIONS: PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.

RevDate: 2024-02-05
CmpDate: 2024-02-05

Aoyagi T, Namura M, Sakata H, et al (2023)

[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].

Gan to kagaku ryoho. Cancer & chemotherapy, 50(13):1462-1464.

The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.

RevDate: 2024-02-05
CmpDate: 2024-02-05

Takeda Y, Ohmura Y, Katsura Y, et al (2023)

[Robotic and Laparoscopic Pancreaticoduodenectomy for the Elderly Patients-A Single Institutional Experience].

Gan to kagaku ryoho. Cancer & chemotherapy, 50(13):1688-1690.

INTRODUCTION: Laparoscopic pancreaticoduodenectomy(LPD)has been covered by insurance since 2016 in Japan. Advance LPD and robotic pancreaticoduodenectomy(RPD)has been also covered by insurance since 2020 in Japan. The aim of this study was to analyze the perioperative results and outcomes of RPD and LPD for the elderly patients and to compare to the non-elderly patients.

PATIENTS AND METHOD: Between July 2020 and April 2023, 67 patients underwent RPD and between May 2012 and February 2021, 63 patients underwent LPD at Kansai Rosai Hospital. Sixty-seven RPD and 62 LPD patients without extended resection were divided into 2 groups those who were over 75 years old(R/LPD E)(n=55)and under 74 years old(R/LPD non-E)(n=74). Control patients who received open pancreaticoduodenectomy(OPD)without extended resection between April 2010 and April 2023 were also divided into 2 groups those who were over 75 years old(OPD E)(n =60)and under 74 years old(OPD non-E)(n=78). The patient age was 79.0 and 60.5 years, the male to female ratio was 35/20 and 45/29, disease ratio(invasive ductal carcinoma or not)was 7/48 and 9/65 in R/LPD E and R/LPD non-E groups, respectively. The patient age was 79.0 and 79.5 years, the male to female ratio was 35/20 and 31/29, disease ratio (invasive ductal carcinoma or not)was 7/48 and 30/30(p<0.0001)in R/LPD E and OPD E groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2001019).

RESULTS: The average operation time was 644.6 and 675.2 minutes, an estimated blood loss was 220.8 and 134.4 g, postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 28/25/21/0, delayed gastric emptying(ISGPS 2007, [-]/Grade A/B/C)was 48/0/4/3 and 61/2/6/5 and postoperative hospital stay was 27.9 and 25.9 and in R/LPD E and R/LPD non-E groups, respectively. No significant differences were noted between the groups, However, postoperative complication over Ⅲa Clavien-Dindo classification was 8(15.7%)and 3(4.4%)cases(p=0.0319)in R/LPD E and R/ LPD non-E groups. The average operation time was 644.6 and 492.1 minutes(p<0.0001), an estimated blood loss was 220.8 and 534.8 g(p=0.0004), postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 27/8/24/1(p=0.0442), postoperative hospital stay was 27.9 and 42.0(p=0.0490)in R/LPD E and OPD E groups, respectively.

CONCLUSION: The R/LPD was undergone in safety, even for the over 75 years old patients.

RevDate: 2024-01-31
CmpDate: 2024-01-31

Younas H, Shahid M, Khan Z, et al (2024)

Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.

Asian Pacific journal of cancer prevention : APJCP, 25(1):79-85 pii:90991.

The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.

RevDate: 2024-01-31
CmpDate: 2024-01-31

Maggi G, Giacobbe C, Vitale C, et al (2024)

Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.

Cognitive, affective & behavioral neuroscience, 24(1):156-170.

BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).

METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.

RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.

CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.

RevDate: 2024-01-29
CmpDate: 2024-01-29

Yang ZJ, Xin F, Chen ZJ, et al (2024)

Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer.

BMC cancer, 24(1):134.

BACKGROUND: Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.

METHODS: This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.

RESULTS: The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68-0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index < 30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.

CONCLUSIONS: Patients with ER-negative, PR-negative, HER2 3 + and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.

RevDate: 2024-01-29
CmpDate: 2024-01-29

Saad HA, Baz A, Riad M, et al (2024)

Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.

BMC immunology, 25(1):9.

BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.

METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.

RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.

CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.

RevDate: 2024-01-29
CmpDate: 2024-01-29

Avatefi M, HadavandSiri F, Nazari SSH, et al (2024)

Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.

Cancer reports (Hoboken, N.J.), 7(1):e1927.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem.

AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors.

METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC.

CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.

RevDate: 2024-01-25

Failayev H, Ganoth A, Y Tsfadia (2024)

Molecular insights on the coronavirus MERS-CoV interaction with the CD26 receptor.

Virus research pii:S0168-1702(24)00023-6 [Epub ahead of print].

The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.

RevDate: 2024-01-24

Dai Q, Feng K, Liu G, et al (2024)

Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.

Targeted oncology [Epub ahead of print].

BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.

OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups.

PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months.

RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.

CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.

RevDate: 2024-01-24
CmpDate: 2024-01-24

Schwartz CJ, Khorsandi N, Blanco A, et al (2024)

Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.

Breast cancer research and treatment, 204(1):171-179.

PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.

METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n = 23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).

RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45 years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER + (79% ER + HER2-, 16% ER + HER2 + , 5% ER-HER2 +), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n = 34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50 months).

CONCLUSION: Almost all CHEK2-associated BCs were ER + IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.

RevDate: 2024-01-24
CmpDate: 2024-01-24

Zhao YY, Ge HJ, Yang WT, et al (2024)

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

Breast cancer research and treatment, 203(3):543-551.

PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method.

RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients.

CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.

RevDate: 2024-01-23
CmpDate: 2024-01-23

Li QY, Guo Q, Luo WM, et al (2024)

Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.

Aging, 16(1):66-88.

OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis.

METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting.

RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC.

CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

RevDate: 2024-01-22

Wang Y, Zhang X, Yan Y, et al (2023)

GmABCG5, an ATP-binding cassette G transporter gene, is involved in the iron deficiency response in soybean.

Frontiers in plant science, 14:1289801.

Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant's tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.

RevDate: 2024-01-18
CmpDate: 2024-01-18

Ido M, Fujii K, Mishima H, et al (2024)

Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.

BMC cancer, 24(1):85.

AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.

PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.

RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.

CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.

RevDate: 2024-01-17
CmpDate: 2024-01-17

Zheng X, J Yin (2023)

Efficacy of texture analysis in determining the gene amplification status of HER2 2+ for invasive ductal carcinoma cases.

Minerva medica, 114(6):832-838.

BACKGROUND: Gene amplification of human epidermal growth factor receptor2 (HER2) 2+ is essential to be determined for treatment planning. A search of the PubMed database indicates that the correlation between texture features from dynamic contrast enhanced (DCE)-MRI and HER2 2+ status has not been investigated extensively in invasive ductal carcinoma cases.

METHODS: Seventy-one DCE-MRI cases of HER2 2+ status verified using fluorescence in-situ hybridization (FISH) were selected, including 36 positive and 35 negative cases. Overall, 279 texture features were derived from lesion regions of interest manually drawn onto the subtraction images between pre- and post-contrast agent. Fisher coefficient, mutual information, minimization of both classification error probability and average correlation coefficients as well as a combination of all three methods (MPF) were independently used to reduce the dimensionality of texture parameters. A popular machine learning algorithm, the Support Vector Machine, was further applied to determine HER2 2+ status. Receiver operating characteristic (ROC) analysis was conducted to evaluate the classification performance.

RESULTS: Diagnostic accuracy was optimal when the most significant discriminatory features were selected using MPF. The area under ROC curve reached 0.863 with corresponding accuracy, sensitivity and specificity rates of 81.80%, 85.71% and 77.78%, respectively.

CONCLUSIONS: Texture analysis based on breast MRI delivered consistently high performance with FISH detection and may serve as a useful supplementary tool for determining the gene amplification status of HER2 2+ for cases with invasive ductal carcinoma.

RevDate: 2024-01-09

Okano K, Miyai K, Mikoshi A, et al (2024)

Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.

International journal of urology : official journal of the Japanese Urological Association [Epub ahead of print].

OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer.

METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups.

RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup.

CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.

RevDate: 2024-01-03
CmpDate: 2024-01-03

Zhao J, Xu N, Zhu S, et al (2024)

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Cancer research, 84(1):154-167.

UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.

SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

RevDate: 2023-12-29

Shinohara T, Asoda T, Nakano Y, et al (2023)

Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.

The American journal of case reports, 24:e942208 pii:942208.

BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.

RevDate: 2023-12-22

Özden A, Dalgıç B, Demir M, et al (2023)

Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.

Journal of chemotherapy (Florence, Italy) [Epub ahead of print].

It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.

RevDate: 2023-12-20
CmpDate: 2023-12-20

Siregar KB, M Al Anas (2023)

Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.

Cancer treatment and research communications, 37:100764.

INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each.

METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories.

RESULTS: The average age was 44.28±9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively).

CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.

RevDate: 2023-12-17

Maman A, O Senol (2023)

Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.

Puerto Rico health sciences journal, 42(4):276-282.

OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery.

MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm.

RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient.

CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.

RevDate: 2023-12-16
CmpDate: 2023-12-16

Adedokun KA, Oluogun WA, Oyenike MA, et al (2023)

Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.

Sultan Qaboos University medical journal, 23(4):526-533.

OBJECTIVES: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.

METHODS: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.

RESULTS: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.

CONCLUSION: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.

RevDate: 2023-12-16
CmpDate: 2023-12-16

Tractenberg RE, Groah SL, Frost JK, et al (2023)

Urinary Symptoms Among People With Neurogenic Lower Urinary Tract Dysfunction (NLUTD) Vary by Bladder Management.

Topics in spinal cord injury rehabilitation, 29(3):31-43.

OBJECTIVES: To determine whether assessment and decision-making around urinary symptoms in people with neurogenic lower urinary tract dysfunction (NLUTD) should depend on bladder management.

METHODS: Three surveys of urinary symptoms associated with NLUTD (USQNBs) were designed specific to bladder management method for those who manage their bladders with indwelling catheter (IDC), intermittent catheter (IC), or voiding (V). Each was deployed one time to a national sample. Subject matter experts qualitatively assessed the wording of validated items to identify potential duplicates. Clustering by unsupervised structural learning was used to analyze duplicates. Each item was classified into mutually exclusive and exhaustive categories: clinically actionable ("fever"), bladder-specific ("suprapubic pain"), urine quality ("cloudy urine"), or constitutional ("leg pain").

RESULTS: A core of 10 "NLUTD urinary symptoms" contains three clinically actionable, bladder-specific, and urine quality items plus one constitutional item. There are 9 (IDC), 11 (IC), and 8 (V) items unique to these instruments. One decision-making protocol applies to all instruments.

CONCLUSION: Ten urinary symptoms in NLUTD are independent of bladder management, whereas a similar number depend on bladder management. We conclude that assessment of urinary symptoms for persons with NLUTD should be specific to bladder management method, like the USQNBs are.

RevDate: 2023-12-16
CmpDate: 2023-12-16

Martelli G, Barretta F, Vernieri C, et al (2023)

Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.

JAMA surgery, 158(12):1275-1284.

IMPORTANCE: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.

OBJECTIVE: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.

This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.

EXPOSURE: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not.

MAIN OUTCOMES AND MEASURES: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality.

RESULTS: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality.

CONCLUSIONS: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.

RevDate: 2023-12-09

Bernhardt M, G Kristiansen (2023)

Molecular Alterations in Intraductal Carcinoma of the Prostate.

Cancers, 15(23): pii:cancers15235512.

Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.

RevDate: 2023-12-06
CmpDate: 2023-12-06

Roberts AC, Lunt LG, Coogan AC, et al (2023)

The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.

The American surgeon, 89(11):4958-4960.

Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.

RevDate: 2023-12-05
CmpDate: 2023-12-05

Zhang W, Nowotny H, Theodoropoulou M, et al (2023)

E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.

Frontiers in endocrinology, 14:1249863.

PURPOSE: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.

METHODS: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47.

RESULTS: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission.

CONCLUSION: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia.

RevDate: 2023-12-05
CmpDate: 2023-12-05

Naeimzadeh Y, Ilbeigi S, Dastsooz H, et al (2023)

Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.

BioMed research international, 2023:8236853.

Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.

RevDate: 2023-12-04
CmpDate: 2023-12-04

Liao H, Wang H, Zheng R, et al (2024)

LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.

Cellular signalling, 113:110943.

Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.

RevDate: 2023-11-29

Günay S, Gökçek B, Kandemir Ö, et al (2023)

Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.

Turkish journal of surgery, 39(2):115-120.

OBJECTIVES: Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up.

MATERIAL AND METHODS: One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale).

RESULTS: Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96.

CONCLUSION: IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.

RevDate: 2023-11-29

Prabhu SD, Rai HS, Nayak R, et al (2023)

Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.

Cureus, 15(11):e48557.

BACKGROUND: Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells.

OBJECTIVE: To study the expression of p63 in various histological subtypes and grades of breast carcinomas.

METHODS: After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted.

RESULTS: In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells.

CONCLUSION: p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.

RevDate: 2023-11-29

Zhu XD, Yu JH, Ai FL, et al (2023)

Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.

World journal of oncology, 14(6):476-487.

BACKGROUND: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.

METHODS: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.

RESULTS: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.

CONCLUSIONS: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.

RevDate: 2023-11-28

Deguchi S, Iwakami A, Tujigiwa M, et al (2023)

Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.

Journal of pharmaceutical health care and sciences, 9(1):44.

BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).

METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.

RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.

CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.

RevDate: 2023-11-28
CmpDate: 2023-11-28

Jalilian E, Abolhasani-Zadeh F, Afgar A, et al (2023)

Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.

Scientific reports, 13(1):20770.

Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.

RevDate: 2023-11-27
CmpDate: 2023-11-27

Stead Z, Capuano R, Di Natale C, et al (2023)

The volatilome signatures of Plasmodium falciparum parasites during the intraerythrocytic development cycle in vitro under exposure to artemisinin drug.

Scientific reports, 13(1):20167.

Volatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.

RevDate: 2023-11-22

Wang H, Ma X, Li S, et al (2023)

SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.

Aging, 15: pii:205227 [Epub ahead of print].

BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.

METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.

RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.

CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.

RevDate: 2023-11-22
CmpDate: 2023-11-22

McMurtry V, Cleary AS, Ruano AL, et al (2023)

Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.

American journal of clinical oncology, 46(12):559-566.

OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.

METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).

RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2 cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.

CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.

RevDate: 2023-11-22
CmpDate: 2023-11-22

Li X, Stitt D, Lanzino G, et al (2023)

Teaching NeuroImage: Pachymeningitis and Aortitis as the Initial Presentation of Granulomatosis With Polyangiitis.

Neurology, 101(21):979-980.

RevDate: 2023-11-20
CmpDate: 2023-11-20

Ito T, Takahara T, Taniguchi N, et al (2023)

PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.

Pathology international, 73(11):542-548.

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.

RevDate: 2023-11-03

Maggi G, Giacobbe C, Iannotta F, et al (2023)

Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.

European journal of neurology [Epub ahead of print].

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms.

METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA.

RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations.

CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.

RevDate: 2023-11-06
CmpDate: 2023-11-06

Kalra R, Lim B, Ellis MJ, et al (2023)

The uncharted role of HER2 mutant alleles in breast cancer.

Oncotarget, 14:904-907.

Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.

RevDate: 2023-11-01

Shuman E, Goldenberg A, Saguy T, et al (2023)

When Are Social Protests Effective?.

Trends in cognitive sciences pii:S1364-6613(23)00261-9 [Epub ahead of print].

Around the world, people engage in social protests aimed at addressing major societal problems. Certain protests have led to significant progress, yet other protests have resulted in little demonstrable change. We introduce a framework for evaluating the effectiveness of social protest made up of three components: (i) what types of action are being considered; (ii) what target audience is being affected; and (iii) what outcomes are being evaluated? We then review relevant research to suggest how the framework can help synthesize conflicting findings in the literature. This synthesis points to two key conclusions: that nonviolent protests are effective at mobilizing sympathizers to support the cause, whereas more disruptive protests can motivate support for policy change among resistant individuals.

RevDate: 2023-11-13
CmpDate: 2023-11-03

Imamichi T, Chen Q, Sowrirajan B, et al (2023)

Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.

PloS one, 18(11):e0287829.

Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.

RevDate: 2023-10-27
CmpDate: 2023-10-27

Wang HY, Li SJ, Zhang AL, et al (2023)

[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].

Zhonghua yi xue za zhi, 103(40):3204-3210.

Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.

RevDate: 2023-10-26
CmpDate: 2023-10-26

Coskunpinar E, Tiryakioglu DZ, Abaci N, et al (2023)

Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.

Bratislavske lekarske listy, 124(11):814-820.

OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers.

BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors.

METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR.  Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing  IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power.

CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).

RevDate: 2023-10-24

Patel K, Rao DM, Sundersingh S, et al (2023)

MicroRNA Expression Profile in Early-Stage Breast Cancers.

MicroRNA (Shariqah, United Arab Emirates) pii:MIRNA-EPUB-135260 [Epub ahead of print].

BACKGROUND: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. We identified 76 miRNAs that were differentially expressed in DCIS and IDC.

METHODS: Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in early-stage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples.

RESULTS: Higher expression of miR-301a-3p is associated with poor overall survival in The Can-cer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.

CONCLUSION: We also analyzed competing endogenous networks associated with differentially expressed miRNAs and identified LRRC75A-AS1 and MAGI2-AS3 as lncRNAs that potentially play an important role in early-stage breast cancers.

RevDate: 2023-10-31

Khalid A, Mehmood A, Alabrah A, et al (2023)

Breast Cancer Detection and Prevention Using Machine Learning.

Diagnostics (Basel, Switzerland), 13(19):.

Breast cancer is a common cause of female mortality in developing countries. Early detection and treatment are crucial for successful outcomes. Breast cancer develops from breast cells and is considered a leading cause of death in women. This disease is classified into two subtypes: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The advancements in artificial intelligence (AI) and machine learning (ML) techniques have made it possible to develop more accurate and reliable models for diagnosing and treating this disease. From the literature, it is evident that the incorporation of MRI and convolutional neural networks (CNNs) is helpful in breast cancer detection and prevention. In addition, the detection strategies have shown promise in identifying cancerous cells. The CNN Improvements for Breast Cancer Classification (CNNI-BCC) model helps doctors spot breast cancer using a trained deep learning neural network system to categorize breast cancer subtypes. However, they require significant computing power for imaging methods and preprocessing. Therefore, in this research, we proposed an efficient deep learning model that is capable of recognizing breast cancer in computerized mammograms of varying densities. Our research relied on three distinct modules for feature selection: the removal of low-variance features, univariate feature selection, and recursive feature elimination. The craniocaudally and medial-lateral views of mammograms are incorporated. We tested it with a large dataset of 3002 merged pictures gathered from 1501 individuals who had digital mammography performed between February 2007 and May 2015. In this paper, we applied six different categorization models for the diagnosis of breast cancer, including the random forest (RF), decision tree (DT), k-nearest neighbors (KNN), logistic regression (LR), support vector classifier (SVC), and linear support vector classifier (linear SVC). The simulation results prove that our proposed model is highly efficient, as it requires less computational power and is highly accurate.

RevDate: 2023-11-06
CmpDate: 2023-11-02

Yang SY, Zhang J, Yang ZQ, et al (2023)

Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.

Science progress, 106(4):368504231201043.

The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.

RevDate: 2023-11-01
CmpDate: 2023-11-01

Dieu Vuong L, Q Ngoc Nguyen (2023)


Experimental oncology, 45(2):195-202.

BACKGROUND: Epigenetic alteration is one of the most common molecular changes identified in the progression of breast cancer (BC).

AIM: To study the frequency and relation between methylation of BRCA1, MLH1, MGMT, GSTP1, APC, RASSF1A, p16, WIF, and EGFR and the clinicopathological features in Vietnamese BC patients.

MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MS-PCR) and SPSS 20.0 software were utilized in order to identify methylated frequency as well as evaluate its relationship with the patient's clinical features.

RESULTS: In 162 BC cases, the methylation rates of the selected genes were 53.7%, 22.8%, 38.9%, 34.6%, 29.0%, 46.3%, 20.4%, 18.5%, and 28.4% respectively. In 32 cases of benign breast diseases (BBD) - 12.5%, 15.6%, 6.3%, 3.1%, 12.5%, 21.9%, 3.1%, 15.6% and 3.1%. BC samples displayed higher BRCA1, MGMT, GSTP1, APC, RASSF1A, WIF1, and p16 methylation levels than BBD samples (p < 0.001). Hypermethylation of BRCA1, GSTP1, and RASSF1A was predominant in the invasive ductal carcinoma, while hypermethylation of BRCA1, GSTP1, RASSF1A, WIF-1, and p16 was found to significantly correlate with lymph node metastasis (p < 0.05). Hypermethylation of BRCA1, MGMT, and GSTP1 was more common in stage III (p < 0.05) than in stages I/II, whereas MLH1 methylation was predominant in stage I and APC methylation was less common in stage III (p = 0.03). In addition, methylation of RASSF1A and EGFR was more frequent in younger patients (p < 0.01) than in elder patients.

CONCLUSION: These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.

RevDate: 2023-11-02
CmpDate: 2023-11-02

Takashima Y, Terasawa R, Hirata A, et al (2023)

[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].

Gan to kagaku ryoho. Cancer & chemotherapy, 50(9):1009-1011.

The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.

RevDate: 2023-10-03

Al-Refai R, Bendari A, Morrar D, et al (2023)

Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.

Diagnostics (Basel, Switzerland), 13(18):.

Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.

RevDate: 2023-11-15

Taylor J, Uhl L, Moll I, et al (2023)

Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.

Nature cancer [Epub ahead of print].

Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

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Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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