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Bibliography on: Invasive Ductal Carcinoma

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 20 Jul 2024 at 01:49 Created: 

Invasive Ductal Carcinoma

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.

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

Citations The Papers (from PubMed®)

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RevDate: 2024-07-19

Shenkman G, Shrira A, Kornadt AE, et al (2024)

Cultural Differences in Daily Coupling of Subjective Views of Aging and Negative Affect.

The journals of gerontology. Series B, Psychological sciences and social sciences pii:7717117 [Epub ahead of print].

OBJECTIVES: The established link between subjective views of aging (VoA) and well-being shows variations across different cultures. Although VoA show daily fluctuations, little is known about cultural differences in such fluctuations and the daily coupling of VoA and well-being. We compared Israeli Arabs to Israeli Jews in the daily coupling of VoA and negative affect (NA).

METHODS: Community-dwelling older adults (N=76, Mage=66.71) completed measures of subjective age, subjective accelerated aging, ageist attitudes, and NA over 14 consecutive days.

RESULTS: Respondents reported higher daily NA when they felt older, reported to be aging faster, or had more ageist attitudes. The daily coupling between subjective age/subjective accelerated aging and NA was stronger among Israeli Arabs compared to Israeli Jews. There was no such interaction with ageist attitudes.

DISCUSSION: It is important to adopt a cultural perspective when investigating daily fluctuations in VoA and their correlates. In applied contexts, this might help to identify cultural groups that are particularly sensitive to the effects of VoA.

RevDate: 2024-07-18

Boudagh G, Kieft A, Choudhury MSR, et al (2024)

Invasive Ductal Breast Carcinoma Metastasis to the Uterine Cervix Presenting As Heavy Vaginal Bleeding: A Case Report and a Literature Review.

Cureus, 16(6):e62523.

Breast carcinoma metastasis to the uterine cervix is a rare occurrence with diagnostic intricacies. We present a case of a 38-year-old woman diagnosed with bilateral stages IIIA and IIIB invasive ductal carcinoma of the breast who developed heavy vaginal bleeding post-treatment, revealing metastatic involvement of the cervix, confirmed by CT imaging and pathological examination, as the presenting sign of widely metastatic disease. This case underscores the importance of a thorough review of systems and physical exams as well as considering uncommon metastatic sites in breast cancer patients.

RevDate: 2024-07-16

Cha E, Oluyemi ET, Ambinder EB, et al (2024)

Clinical Outcomes of Benign Concordant MRI-Guided Breast Biopsies.

Clinical breast cancer pii:S1526-8209(24)00175-7 [Epub ahead of print].

INTRODUCTION: MRI-guided biopsy is the standard of care for breast imaging findings seen only by MRI. Although a non-zero false-negative rate of MRI-guided breast biopsy has been reported by multiple studies, there are varied practice patterns for imaging follow-up after a benign concordant MRI guided biopsy. This study assessed the outcomes of benign concordant MRI-guided biopsies at a single institution.

PATIENTS AND METHODS: This IRB-approved, retrospective study included patients with MRI-guided biopsies of breast lesions from November 1, 2014, to August 31, 2020. Only image-concordant breast lesions with benign histopathology and those follow up with MRI imaging or excision were included in the study.

RESULTS: Out of 275 lesions in 216 patients that met the inclusion criteria, 274 lesions were followed with MRI (range, 5-79 months; average, 25.5 months) and showed benign or stable features upon follow-up. One out of 275 lesions (0.4%), a 6 mm focal nonmass enhancement, was ultimately found to represent malignancy after initial MRI-guided biopsy yielded fibrocystic changes. The lesion was stable at a 6-month follow-up MRI but increased in size at 18 months. Repeat biopsy by ultrasound guidance yielded invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS).

CONCLUSION: Breast MRI-guided biopsy has a low false-negative rate. Our single malignancy from a total of 275 lesions gives a false negative rate of 0.4%. This data also supports a longer follow-up interval than the commonly performed 6-month follow-up, in order to assess for interval change.

RevDate: 2024-07-16
CmpDate: 2024-07-16

Zin I, China A, Khan K, et al (2024)

AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.

Proceedings of the National Academy of Sciences of the United States of America, 121(30):e2303642121.

Glutamyl-prolyl-tRNA synthetase (EPRS1) is a bifunctional aminoacyl-tRNA-synthetase (aaRS) essential for decoding the genetic code. EPRS1 resides, with seven other aaRSs and three noncatalytic proteins, in the cytoplasmic multi-tRNA synthetase complex (MSC). Multiple MSC-resident aaRSs, including EPRS1, exhibit stimulus-dependent release from the MSC to perform noncanonical activities distinct from their primary function in protein synthesis. Here, we show EPRS1 is present in both cytoplasm and nucleus of breast cancer cells with constitutively low phosphatase and tensin homolog (PTEN) expression. EPRS1 is primarily cytosolic in PTEN-expressing cells, but chemical or genetic inhibition of PTEN, or chemical or stress-mediated activation of its target, AKT, induces EPRS1 nuclear localization. Likewise, preferential nuclear localization of EPRS1 was observed in invasive ductal carcinoma that were also P-Ser[473]-AKT[+]. EPRS1 nuclear transport requires a nuclear localization signal (NLS) within the linker region that joins the catalytic glutamyl-tRNA synthetase and prolyl-tRNA synthetase domains. Nuclear EPRS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1), a DNA-damage sensor that directs poly(ADP-ribosyl)ation (PARylation) of proteins. EPRS1 is a critical regulator of PARP1 activity as shown by markedly reduced ADP-ribosylation in EPRS1 knockdown cells. Moreover, EPRS1 and PARP1 knockdown comparably alter the expression of multiple tumor-related genes, inhibit DNA-damage repair, reduce tumor cell survival, and diminish tumor sphere formation by breast cancer cells. EPRS1-mediated regulation of PARP1 activity provides a mechanistic link between PTEN loss in breast cancer cells, PARP1 activation, and cell survival and tumor growth. Targeting the noncanonical activity of EPRS1, without inhibiting canonical tRNA ligase activity, provides a therapeutic approach potentially supplementing existing PARP1 inhibitors.

RevDate: 2024-07-16
CmpDate: 2024-07-16

Ghai S, Klotz L, Pond GR, et al (2024)

Comparison of Multiparametric MRI-targeted and Systematic Biopsies for Detection of Cribriform and Intraductal Carcinoma Prostate Cancer.

Radiology, 312(1):e231948.

Background Intraductal carcinoma (IDC) and invasive cribriform (Cr) subtypes of prostate cancer (PCa) are an indication of aggressiveness, but the evidence regarding whether MRI can be used to detect Cr/IDC-pattern PCa is contradictory. Purpose To compare the detection of Cr/IDC-pattern PCa at multiparametric MRI (mpMRI)-targeted biopsy versus systematic biopsy in biopsy-naive men at risk for PCa. Materials and Methods This study was a secondary analysis of a prospective randomized controlled trial that recruited participants with a clinical suspicion of PCa between April 2017 and November 2019 at five centers. Participants were randomized 1:1 to either the MRI arm or the systematic biopsy arm. Targeted biopsy was performed in participants with a Prostate Imaging Reporting and Data System score of at least 3. MRI features were recorded, and biopsy slides and prostatectomy specimens were reviewed for the presence or absence of Cr/IDC histologic patterns. Comparison of Cr/IDC patterns was performed using generalized linear mixed modeling. Results A total of 453 participants were enrolled, with 226 in the systematic biopsy arm (median age, 65 years [IQR, 59-70 years]; 196 biopsies available for assessment) and 227 in the mpMRI-targeted biopsy arm (median age, 67 years [IQR, 60-72 years]; 132 biopsies available for assessment). Identification of Cr/IDC PCa was lower in the systematic biopsy arm compared with the mpMRI arm (31 of 196 biopsies [16%] vs 33 of 132 biopsies [25%]; P = .01). No evidence of a difference in mean cancer core length (CCL) (11.3 mm ± 4.4 vs 9.7 mm ± 4.5; P = .09), apparent diffusion coefficient (685 µm[2]/sec ± 178 vs 746 µm[2]/sec ± 245; P = .52), or dynamic contrast-enhanced positivity (27 [82%] vs 37 [90%]; P = .33) for clinically significant PCa (csPCa) was observed between participants with or without Cr/IDC disease in the MRI arm. Cr/IDC-positive histologic patterns overall had a higher mean CCL compared with Cr/IDC-negative csPCa (11.1 mm ± 4.4 vs 9.2 mm ± 4.1; P = .009). Conclusion MRI-targeted biopsy showed increased detection of Cr/IDC histologic patterns compared with systematic biopsy. Clinical trial registration no. NCT02936258 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Scialpi and Martorana in this issue.

RevDate: 2024-07-16

Akbari ME, Akbari A, S Ebrahimian (2024)

Pathological characteristics predicting sentinel lymph node metastasis in early breast cancer patients.

Caspian journal of internal medicine, 15(3):472-477.

BACKGROUND: In this study, we aimed to identify the predicting pathological factors affecting sentinel lymph node biopsy (SLNB) in patients with clinically node-negative breast cancer.

METHODS: Our single institution retrospective study was conducted at the Cancer Research Center of Shahid Beheshti University of Medical Sciences from 2018 to 2021. Data were imported into and analyzed using SPSS Version 28 for Windows (IBM Corp., Armonk, NY, USA).

RESULTS: Of the 76 patients who underwent SLNB, 43 (56.6%) had negative SLNB and 33 (43.4%) had positive SLNB which led to axillary lymph node dissection (ALND). The relationship between hormone receptor status (ER/PR/Her2), pathology type (IDC, ILC, DCIS, LCIS), tumor size, and Ki67 expression was assessed. According to the results, axillary lymph node involvement can be predicted based on the scores and results of the three variables: IDC tumor type, lympho vascular invasion (LVI), and Ki67 expression. The positive relationship between IDC tumor type and LVI with SLNB indicates that with positive IDC tumor type and LVI, there is a higher probability of positive axillary lymph nodes (3.88 times higher probability for IDC tumor type and 6.75 times higher probability for the LVI factor). However, when the Ki67 expression is lower, the probability of positive axillary lymph nodes is higher (3.58 times higher probability).

CONCLUSION: IDC tumor type, LVI, and lower Ki67 expression are independent predictive factors of positive SLNB.

RevDate: 2024-07-15

Jiang H, Cartwright S, Wagner DG, et al (2024)

Pathologic Complete Response to Neoadjuvant Chemotherapy and Pembrolizumab in Postpartum High-Risk Basal-Type Breast Cancer.

Cureus, 16(6):e62338.

Neoadjuvant chemoimmunotherapy with pembrolizumab now defines the standard of care for early high-risk triple-negative breast cancer (TNBC). However, the role of pembrolizumab in neoadjuvant therapy (NAT) for estrogen receptor-positive (ER+) breast cancer remains uncertain. A 39-year-old G2P2 female discovered a palpable mass in the right breast while breastfeeding her 7-month-old child, leading to the diagnosis of a high-grade ER+ (80% moderate staining), human epidermal growth factor receptor 2-negative (ErbB2-) invasive ductal carcinoma with axillary nodal involvement. Gene expression profiling with the MammaPrint 70-gene signature and BluePrint 80-gene signature revealed a tumor with high-risk, basal-type biology. The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. Within six weeks, the patient exhibited a remarkable response, with no palpable mass or lymph node, and post-treatment examinations confirmed a complete clinical and radiologic response. The patient underwent lumpectomy and sentinel lymph node biopsy, revealing a pathological complete response with minimal ductal carcinoma in situ and negative axillary nodes. Adjuvant radiation therapy was administered, and the patient completed adjuvant pembrolizumab, currently showing no evidence of recurrence. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.

RevDate: 2024-07-15

Duan W, Wu Z, Zhu H, et al (2024)

Deep learning modeling using mammography images for predicting estrogen receptor status in breast cancer.

American journal of translational research, 16(6):2411-2422.

BACKGROUND: The estrogen receptor (ER) serves as a pivotal indicator for assessing endocrine therapy efficacy and breast cancer prognosis. Invasive biopsy is a conventional approach for appraising ER expression levels, but it bears disadvantages due to tumor heterogeneity. To address the issue, a deep learning model leveraging mammography images was developed in this study for accurate evaluation of ER status in patients with breast cancer.

OBJECTIVES: To predict the ER status in breast cancer patients with a newly developed deep learning model leveraging mammography images.

MATERIALS AND METHODS: Datasets comprising preoperative mammography images, ER expression levels, and clinical data spanning from October 2016 to October 2021 were retrospectively collected from 358 patients diagnosed with invasive ductal carcinoma. Following collection, these datasets were divided into a training dataset (n = 257) and a testing dataset (n = 101). Subsequently, a deep learning prediction model, referred to as IP-SE-DResNet model, was developed utilizing two deep residual networks along with the Squeeze-and-Excitation attention mechanism. This model was tailored to forecast the ER status in breast cancer patients utilizing mammography images from both craniocaudal view and mediolateral oblique view. Performance measurements including prediction accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curves (AUCs) were employed to assess the effectiveness of the model.

RESULTS: In the training dataset, the AUCs for the IP-SE-DResNet model utilizing mammography images from the craniocaudal view, mediolateral oblique view, and the combined images from both views, were 0.849 (95% CIs: 0.809-0.868), 0.858 (95% CIs: 0.813-0.872), and 0.895 (95% CIs: 0.866-0.913), respectively. Correspondingly, the AUCs for these three image categories in the testing dataset were 0.835 (95% CIs: 0.790-0.887), 0.746 (95% CIs: 0.793-0.889), and 0.886 (95% CIs: 0.809-0.934), respectively. A comprehensive comparison between performance measurements underscored a substantial enhancement achieved by the proposed IP-SE-DResNet model in contrast to a traditional radiomics model employing the naive Bayesian classifier. For the latter, the AUCs stood at only 0.614 (95% CIs: 0.594-0.638) in the training dataset and 0.613 (95% CIs: 0.587-0.654) in the testing dataset, both utilizing a combination of mammography images from the craniocaudal and mediolateral oblique views.

CONCLUSIONS: The proposed IP-SE-DResNet model presents a potent and non-invasive approach for predicting ER status in breast cancer patients, potentially enhancing the efficiency and diagnostic precision of radiologists.

RevDate: 2024-07-15

Olbromski M, Mrozowska M, Piotrowska A, et al (2024)

Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.

American journal of cancer research, 14(6):3036-3058.

Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents.

RevDate: 2024-07-15

Taitelbaum-Swead R, BM Ben-David (2024)

The Role of Early Intact Auditory Experience on the Perception of Spoken Emotions, Comparing Prelingual to Postlingual Cochlear Implant Users.

Ear and hearing [Epub ahead of print].

OBJECTIVES: Cochlear implants (CI) are remarkably effective, but have limitations regarding the transformation of the spectro-temporal fine structures of speech. This may impair processing of spoken emotions, which involves the identification and integration of semantic and prosodic cues. Our previous study found spoken-emotions-processing differences between CI users with postlingual deafness (postlingual CI) and normal hearing (NH) matched controls (age range, 19 to 65 years). Postlingual CI users over-relied on semantic information in incongruent trials (prosody and semantics present different emotions), but rated congruent trials (same emotion) similarly to controls. Postlingual CI's intact early auditory experience may explain this pattern of results. The present study examined whether CI users without intact early auditory experience (prelingual CI) would generally perform worse on spoken emotion processing than NH and postlingual CI users, and whether CI use would affect prosodic processing in both CI groups. First, we compared prelingual CI users with their NH controls. Second, we compared the results of the present study to our previous study (Taitlebaum-Swead et al. 2022; postlingual CI).

DESIGN: Fifteen prelingual CI users and 15 NH controls (age range, 18 to 31 years) listened to spoken sentences composed of different combinations (congruent and incongruent) of three discrete emotions (anger, happiness, sadness) and neutrality (performance baseline), presented in prosodic and semantic channels (Test for Rating of Emotions in Speech paradigm). Listeners were asked to rate (six-point scale) the extent to which each of the predefined emotions was conveyed by the sentence as a whole (integration of prosody and semantics), or to focus only on one channel (rating the target emotion [RTE]) and ignore the other (selective attention). In addition, all participants performed standard tests of speech perception. Performance on the Test for Rating of Emotions in Speech was compared with the previous study (postlingual CI).

RESULTS: When asked to focus on one channel, semantics or prosody, both CI groups showed a decrease in prosodic RTE (compared with controls), but only the prelingual CI group showed a decrease in semantic RTE. When the task called for channel integration, both groups of CI users used semantic emotional information to a greater extent than their NH controls. Both groups of CI users rated sentences that did not present the target emotion higher than their NH controls, indicating some degree of confusion. However, only the prelingual CI group rated congruent sentences lower than their NH controls, suggesting reduced accumulation of information across channels. For prelingual CI users, individual differences in identification of monosyllabic words were significantly related to semantic identification and semantic-prosodic integration.

CONCLUSIONS: Taken together with our previous study, we found that the degradation of acoustic information by the CI impairs the processing of prosodic emotions, in both CI user groups. This distortion appears to lead CI users to over-rely on the semantic information when asked to integrate across channels. Early intact auditory exposure among CI users was found to be necessary for the effective identification of semantic emotions, as well as the accumulation of emotional information across the two channels. Results suggest that interventions for spoken-emotion processing should not ignore the onset of hearing loss.

RevDate: 2024-07-12
CmpDate: 2024-07-12

Nascimento KCG, São Marcos BF, Fontes PHB, et al (2024)

HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Cells, 13(13): pii:cells13131132.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

RevDate: 2024-07-12
CmpDate: 2024-07-12

Jamjoum G, Arab FS, Tayeb R, et al (2024)

Cutaneous Metastasis in Breast Cancer: A Case Report.

The American journal of case reports, 25:e943999 pii:943999.

BACKGROUND Breast cancer (BC) is the most common malignant disease in females and one of the leading causes of death worldwide. Its treatment plan includes a long-term follow-up and close surveillance, as recurrence is a well-acknowledged concern. BC can recur either locally or as a metastasis, and skin metastasis is a common complication in advanced breast cancer patients. It can present as a skin nodule, plaque, or erythematous lesion, and can be difficult to distinguish from benign skin conditions. The risk of skin metastasis is higher in patients with inflammatory BC. Treatment of such a complex condition is even more challenging, with poor prognosis. Here, we report a case of a 42-year-old woman with stage 4 luminal A BC who had soft tissue recurrence. CASE REPORT A 42-year-old woman with a history of left-sided BC diagnosed and treated 10 years ago presented with multiple soft tissue masses mimicking abscesses at the right lower middle of the back, bilateral thighs, and back of the neck, in the last 6 months, the largest measuring 8×10 cm. The masses were found to be metastatic BC that had spread to the skin and lungs. Because it was invasive ductal carcinoma with positive ER and PR receptors, she was started on hormonal treatment and chemotherapy. CONCLUSIONS This case report highlights the importance of follow-up in patients with a history of BC, as the cancer can recur and spread many years after treatment.

RevDate: 2024-07-11
CmpDate: 2024-07-11

Wang X, Qi L, Chen M, et al (2024)

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

World journal of urology, 42(1):404.

BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions.

PATIENTS AND METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues.

RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively).

CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

RevDate: 2024-07-11

Kim KE, Lee HW, SU Bae (2024)

Rectal metastasis arising from breast cancer: a case report.

Korean journal of clinical oncology, 20(1):41-45.

Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.

RevDate: 2024-07-10

Long M, Calude A, J Burnette (2024)

"This was never about a virus": Perceptions of Vaccination Hazards and Pandemic Risk in #Covid19NZ Tweets.

The Journal of medical humanities [Epub ahead of print].

In this paper, we draw on qualitative methods from the medical humanities and quantitative approaches from corpus linguistics to assess the different mappings of pandemic risks by Twitter (X) users employing the #Covid19nz hashtag. We look specifically at their responses to government measures around vaccines between August and November 2021. Risk, we reveal, was a major discursive thread in tweets during this period, but within our tweets, it was the vaccine rather than the virus around which hazard perception and response were grouped. We find that the discursive stance of those opposed to the vaccine evoked entangled medical and political hazards, untrustworthy experts, obscure information, restrictions on sovereignty, threats to children, and uncertain future dangers, all of which positioned them within what Ulrich Beck termed the world risk society. We also found that these narratives of risk manifested in specific Twitter styles, which employed a consistently larger number of hashtags. The lack of conjunctions between the hashtags, we argue, encouraged a disordered reading of doubt and precaution, as the hashtags presented triggering phrases whose interconnections were hinted at rather than specified. By contrast, those who tweeted in support of government measures were rhetorically led by solutions rather than risks, with one exception: their perception of those who were vaccine opposed. We use scholarship on risk and precautionary logic to map out the contrasting positions in tweets addressing Aotearoa New Zealand's pandemic experience during the closing months of 2021.

RevDate: 2024-07-10
CmpDate: 2024-07-10

Uppal R, Saeed U, Uppal MR, et al (2024)

SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.

Brazilian journal of biology = Revista brasleira de biologia, 84:e271452 pii:S1519-69842024000101178.

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.

RevDate: 2024-07-10

Aldarayseh M, Sodhi SS, Musleh G, et al (2024)

Unforeseen Complications of Pembrolizumab in Breast Reconstruction Post-Mastectomy.

European journal of case reports in internal medicine, 11(7):004675.

UNLABELLED: A 53-year-old post-menopausal Indian female presented with invasive ductal carcinoma, treated with neoadjuvant chemotherapy and pembrolizumab due to a PD-L1 combined positive score of 5. Following a right mastectomy and axillary dissection, she received a breast expander and AlloDerm™ graft. After resuming pembrolizumab and paclitaxel postoperatively, she developed severe breast redness and high-grade fever, necessitating expander removal due to suspected pembrolizumab-induced complications. This case underscores the unique and severe adverse effects of pembrolizumab on breast reconstruction, highlighting the need for careful monitoring and management in patients undergoing similar treatments.

LEARNING POINTS: Among patients with early triple-negative breast cancer, the combination of pembrolizumab with neoadjuvant chemotherapy enhances outcomes compared to chemotherapy alone.Early recognition is essential for managing pembrolizumab-induced complications, as demonstrated by the need for expander removal and debridement in this case.The unique adverse effects observed in this case underscore the importance of tailoring cancer treatment plans to individual patients, taking into account the potential risks associated with immunotherapy in the context of reconstructive surgery.

RevDate: 2024-07-10

Balbino M, Montatore M, Masino F, et al (2024)

Cat scratch disease unveils hidden breast carcinoma: A diagnostic twist.

Radiology case reports, 19(9):3770-3775.

Cat scratch disease is a rare condition that can present with different clinical manifestations, including axillary lymphadenopathy. Here, we report the case of a 45-year-old female who presented with axillary lymphadenopathy attributable to a process of differential diagnosis to cat scratch disease. During the thorough investigation of her condition, a routine mammogram was performed, due to the unilateral axillary lymphadenopathy, revealing the presence of previously undiagnosed breast carcinoma in situ; in fact, a DCIS (invasive ductal carcinoma with spread to the ipsilateral axillary nodes) was incidentally found. This case highlights the importance of comprehensive differential diagnosis and a multidisciplinary approach in managing patients with atypical presentations of common diseases, given that other alarming but unrelated findings are visible.

RevDate: 2024-07-09

Hofmann LC, Strauss S, Shpigel M, et al (2024)

The green seaweed Ulva: tomorrow's "wheat of the sea" in foods, feeds, nutrition, and biomaterials.

Critical reviews in food science and nutrition [Epub ahead of print].

Ulva, a genus of green macroalgae commonly known as sea lettuce, has long been recognized for its nutritional benefits for food and feed. As the demand for sustainable food and feed sources continues to grow, so does the interest in alternative, plant-based protein sources. With its abundance along coastal waters and high protein content, Ulva spp. have emerged as promising candidates. While the use of Ulva in food and feed has its challenges, the utilization of Ulva in other industries, including in biomaterials, biostimulants, and biorefineries, has been growing. This review aims to provide a comprehensive overview of the current status, challenges and opportunities associated with using Ulva in food, feed, and beyond. Drawing on the expertise of leading researchers and industry professionals, it explores the latest knowledge on Ulva's nutritional value, processing methods, and potential benefits for human nutrition, aquaculture feeds, terrestrial feeds, biomaterials, biostimulants and biorefineries. In addition, it examines the economic feasibility of incorporating Ulva into aquafeed. Through its comprehensive and insightful analysis, including a critical review of the challenges and future research needs, this review will be a valuable resource for anyone interested in sustainable aquaculture and Ulva's role in food, feed, biomaterials, biostimulants and beyond.

RevDate: 2024-07-08

Thakur AS, Srivatava V, Park HKB, et al (2024)

Calligraphic interdigitated capacitive sensors for green electronics.

Scientific reports, 14(1):15685.

This study presents a novel approach to fabricating interdigitated capacitive (IDC) touch sensors using graphite-based pencils on a wood substrate. The sensors were designed to detect touches and pressure variations, offering a cost-effective and environmentally friendly solution for sensor fabrication. The fabrication process involved abrasion of graphite pencils on a wooden substrate to create conductive traces, followed by the integration of interdigitated electrode structures. Capacitance variations resulting from touch interactions were investigated to calibrate sensor responses for tailored tasks. The sensitivity of the sensor was found to be 1.2 pF/kPa, highlighting its responsiveness to pressure variations. Additionally, the sensors were interfaced with an Arduino Uno microcontroller board to demonstrate practical applications, such as replicating arrow key functionality. Additionally, the sensors exhibit sensitivity to environmental factors, with the relative change in capacitance increasing from 0.1 to 0.65 as relative humidity ranges from 30 to 90%. Furthermore, variations in temperature from 30 to 60ºC result in a relative change in capacitance increasing to approximately 0.5. The results indicate the feasibility and versatility of using wood-based substrates and graphite-based pencils for fabricating IDC touch sensors, offering promising prospects for sustainable and accessible sensor technology.

RevDate: 2024-07-08

Huang Y, Dai D, Zhu L, et al (2024)

Novel associations between MTDH gene polymorphisms and invasive ductal breast cancer: a case-control study.

Discover oncology, 15(1):273.

OBJECTIVE: To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC).

PATIENTS AND METHODS: A case-control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case-control study and a multinomial logistic regression model.

RESULTS: Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk.

CONCLUSION: In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.

RevDate: 2024-07-08

Kwon Y, Gottmann P, Wang S, et al (2024)

Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease.

Journal of hepatology pii:S0168-8278(24)02347-X [Epub ahead of print].

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its limited treatment options warrant novel pre-clinical models for target selection and drug validation. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide treatment strategies for MASLD.

METHODS: Cryopreserved primary human hepatocytes from five donors varying in sex and ethnicity were cultured with free fatty acids (FFA) in 3D collagen sandwich for 7 days and the development of MASLD was followed by assessing classical hepatocellular functions. As proof of concept, the effects of the drug Firsocostat (GS-0976) on in vitro MASLD phenotypes were evaluated.

RESULTS: Incubation with FFA induced steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and alterations in prominent human gene signatures similar to patients with MASLD, indicating the recapitulation of human MASLD in this system. As the application of Firsocostat rescued clinically observed fatty liver disease pathologies, it highlights the ability of the in vitro system to test drug efficacy and potentially characterize their mode of action.

CONCLUSIONS: Altogether, our human MASLD in vitro model system could guide the development and validation of novel targets and drugs for the treatment of MASLD.

IMPACT AND IMPLICATIONS: Due to low drug efficacy and high toxicity, a clinical treatment option for MASLD is limited. To facilitate earlier stop-go decisions in drug development, we have established a primary human steatotic hepatocyte in vitro model. As the model recapitulates clinically relevant MASLD characteristics at high phenotypic resolution, it can serve as a pre-screening platform and guide target identification and validation in MASLD therapy.

RevDate: 2024-07-08

Batra H, Bose PSC, Ding Y, et al (2024)

MYB expression by immunohistochemistry is highly specific and sensitive for detection of solid variant of adenoid cystic carcinoma of the breast among all triple-negative breast cancers.

Histopathology [Epub ahead of print].

BACKGROUND: Adenoid cystic carcinoma is a rare subtype of triple-negative breast carcinoma. These low-grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple-negative breast carcinomas. Solid-variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple-negative breast cancers. Breast adenoid cystic carcinoma exhibits MYB protein overexpression, which can be detected by immunohistochemistry (IHC).

AIM: We compared the IHC expression of MYB in solid-variant adenoid cystic carcinoma with that in other triple-negative breast cancers.

METHODS: We conducted IHC staining of 210 samples of triple-negative breast cancers, including solid-variant adenoid cystic carcinoma (n = 17), metaplastic breast carcinoma (n = 44), basaloid triple-negative breast cancer (n = 21), and other triple-negative invasive ductal carcinoma (n = 128). We classified nuclear staining of MYB as diffuse/strong (3+), focal moderate (2+), focal weak (1+), or none (0).

RESULTS: All 17 solid/basaloid adenoid cystic carcinoma cases exhibited 3+ MYB expression. Of the 21 solid/basaloid triple-negative breast cancers, one (5%) had 2+ expression, seven (33%) 1+ expression, and 13 (62%) 0 expression. Of the 44 metaplastic carcinoma cases, 39 cases (89%) had no (0) staining, and the other five cases had focal weak (1+) or moderate (2+) staining. Among the 128 triple-negative invasive ductal carcinoma cases, 92 cases (72%) had no (0) staining, 36 cases (28%) exhibited focal weak (1+) or moderate (2+) staining.

CONCLUSIONS: Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple-negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy.

RevDate: 2024-07-05
CmpDate: 2024-07-05

Zhang Z, Huang C, Wu J, et al (2024)

TICRR as a potential prognostic biomarker for lung adenocarcinoma: A comprehensive analysis using TCGA database.

Medicine, 103(27):e38660.

To investigate the role of TopBP1-interacting checkpoint and replication regulator (TICRR) in the tumorigenesis and prognosis of lung adenocarcinoma (LUAD) patients. Wilcoxon signed-rank test and logistic regression were utilized to analyze the relationship between clinical characteristics and TICRR expression in LUAD from TCGA dataset. Kaplan-Meier plots and Cox regressions were used to assess the impact of TICRR impact on prognosis. ROC curves and nomograms were generated to further evaluate the relationship between TICRR expression and the risk of LUAD. Gene set enrichment analysis (GSEA) was conducted on TCGA dataset, and ssGSEA was employed to investigate the association between TICRR and immune infiltrates. The results showed that high TICRR expression was significantly associated with various clinical factors including gender, age, pathological stage, T stage, N stage, M stage, outcome of primary therapy and smoking status. ROC curves also demonstrated that TICRR was a promising biomarker for molecular pathology diagnosis in LUAD patients (AUC = 0.952). Further analysis using gene ontology (GO) term enrichment and GSEA revealed an abnormal correlation between TICRR expression and cell division. Interestingly, ssGSEA analysis showed that TICRR expression correlated with multiple immune cell types, such as Th2 cell, TFH cell, mast cell, iDC, eosinophils, and dendritic cell. Lastly, the KM-plotters indicated that LUAD patients with high TICRR expression obtained worse life expectancy (P < .001). TICRR has proven to be a valuable tool in predicting disease progression and prognosis in patients with LUAD, thereby establishing itself as a fitting biomarker for forecasting overall survival (OS) of LUAD patients.

RevDate: 2024-07-05

Zaldarriaga JMH, Aw AMN, Vega GP, et al (2024)

Breast Cancer in a Filipino Male: A Case Report and Brief Literature Review.

Acta medica Philippina, 58(3):70-75 pii:AMP-58-3-6742.

This is a case report of a 76-year-old Filipino male who presented with a six-year history of a steadily growing left breast mass. The mass was eventually diagnosed to be Invasive Ductal Carcinoma, Anatomic and Prognostic Stage IIIB (T4b cN0 M0), Grade 3, Luminal A. Subsequently, the patient underwent neoadjuvant chemotherapy of doxorubicin/cyclophosphamide and paclitaxel, followed by modified radical mastectomy with axillary lymph node dissection, concluded by post-mastectomy radiation therapy. The patient had complete clinical response to this trimodality therapy. The rarity of this case is juxtaposed and integrated with the present literature on male breast cancer.

RevDate: 2024-07-04

Yan X, Yang L, Ye X, et al (2024)

Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.

Injury pii:S0020-1383(24)00412-1 [Epub ahead of print].

The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.

RevDate: 2024-07-04

Moore KA, Ostrowsky JT, Mehr AJ, et al (2024)

Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

The Lancet. Infectious diseases pii:S1473-3099(24)00229-9 [Epub ahead of print].

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

RevDate: 2024-07-04

Magnoni F, Bianchi B, Pagan E, et al (2024)

Long-term outcome of invasive pure micropapillary breast cancer compared with invasive mixed micropapillary and invasive ductal breast cancer: a matched retrospective study.

Breast cancer research and treatment [Epub ahead of print].

PURPOSE: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients.

METHODS: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype.

RESULTS: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07).

CONCLUSION: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment.

RevDate: 2024-07-02
CmpDate: 2024-07-02

Wu F, Andaleeb U, I Ahmed (2024)

Extramammary breast cancer of the vulva.

BMJ case reports, 17(7): pii:17/7/e259567.

A woman in her 70s was seen in the gynaecology outpatient clinic with a swelling on the right side of the vulva. Surgical excision of the lesion revealed unexpectedly an extensive ductal carcinoma in situ with a focus of a grade 2 invasive ductal carcinoma arising in extramammary breast tissue of the vulva. Postoperative staging studies showed normal breasts, with no evidence of disease elsewhere. The patient underwent a wider excision of the right vulva and sentinel node biopsy of the right inguinal region, which revealed no further disease. The patient is currently taking adjuvant hormonal therapy and has remained disease free at 2-year follow-up. This case underscores the importance of considering rare presentations of vulvar malignancies and the necessity for a multidisciplinary approach in managing such cases.

RevDate: 2024-07-02

Setyawan G, Sejati PA, Ogawa R, et al (2024)

Detection of Invasive Ductal Carcinoma in Quadrant Breast Areas by Electrical Impedance Tomography Implemented with Gaussian relaxation-time Distribution (EIT-GRTD).

Biomedical physics & engineering express [Epub ahead of print].

Invasive ductal carcinoma (IDC) in breast specimens has been detected in the quadrant breast area: (I) upper outer, (II) upper inner, (III) lower inner, and (IV) lower outer areas by electrical impedance tomography implemented with Gaussian relaxation time distribution (EIT-GRTD). The EIT-GRTD consists of two steps which are 1) the optimum frequencyf[opt]selection and 2) the time constant enhancement of breast imaging reconstruction.f[opt]is characterized by a peak in the majority measurement pair of the relaxation time distribution function γ, which indicates the presence of IDC. γ represents the inverse of conductivity and indicates the response of breast tissues to electrical currents across varying frequencies based on the Voigt circuit model. The EIT-GRTD is quantitatively evaluated by multi-physics simulations using a hemisphere container of mimic breast, consisting of IDC and adipose tissues as normal breast tissue under one condition with known IDC in quadrant breast area II. The simulation results show that EIT-GRTD is able to detect the IDC in four layers atf[opt]=30,170 Hz. EIT-GRTD is applied in the real breast by employed six mastectomy specimens from IDC patients. The placement of the mastectomy specimens in a hemisphere container is an important factor in the success of quadrant breast area reconstruction. In order to perform the evaluation, EIT-GRTD reconstruction images are compared to the CT scan images. The experimental results demonstrate that EIS-GRTD exhibits proficiency in the detection of the IDC in quadrant breast areas while compared qualitatively to CT scan images.

RevDate: 2024-07-02

Majeed AI, Zinan S, R Faryal (2024)

Unraveling the Role of BRCA1 variants in Dysregulation of Transcriptional and Post-Transcriptional Mechanisms in Breast Cancer.

Pakistan journal of medical sciences, 40(6):1093-1098.

OBJECTIVE: To screen BRCA1 gene variants and predict potential role of the identified variants in breast cancer.

METHOD: This case-control study included two hundred and fifty breast cancer patients and equal healthy individuals from the Federal Breast Cancer Screening Centre, Pakistan Institute of Medical Sciences, Islamabad from March 2021- January 2023. Demographic data was collected through questionnaires and clinical data was assessed using mammograms, ultrasound, histopathology and immunohistochemistry reports. Polymerase chain reaction and Sanger sequencing approach were used to detect variants in BRCA1 gene. In-silico analyses were carried out to predict mutation effect, miRNA binding site alterations and change in mRNA structure and stability.

RESULTS: Invasive ductal carcinoma was the most prevalent type of breast cancer. Old age [OR: 2.8149 (1.5995 to 4.9538) p value = 0.0003] and family history [OR: 4.3186 (1.7336 to 10.7581) p value = 0.001] were significant breast cancer risk. Six variants were identified. Two novel missense variants, Chr17:43082553A>T and Chr17:43093710A>T were predicted deleterious as these disrupted interaction with PALB2 and importin alpha's NLS2 site, respectively. In silico analysis predicted the loss of hsa-miR-1179 binding site due to variant Chr17:43093220T>C. Moreover, four variants were predicted to affect the mRNA structure and stability.

CONCLUSION: Two novel variants were predicted to be pathogenic. In-silico analysis predicted the loss of miRNA binding site along with change in mRNA secondary structure plus stability, possible mechanisms for oncogenesis. Further, expressional studies are required to confirm BRCA1 gene dysregulation in breast cancer due to these variants.

RevDate: 2024-07-02
CmpDate: 2024-07-02

Nisar MI, Kabole I, Khanam R, et al (2024)

Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.

BMC pregnancy and childbirth, 24(1):451.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.

METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group.

RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.

CONCLUSION: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.

RevDate: 2024-07-01

Kim JM, EY Cho (2024)

Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer.

Journal of breast cancer, 27(3):201-214.

PURPOSE: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods.

METHODS: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established.

RESULTS: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%.

CONCLUSION: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.

RevDate: 2024-07-01

Alan Selçuk N, Akçay K, Beydağı G, et al (2024)

Revision of the Histopathological Examination Following [68]Ga-DOTA-FAPI-04 PET/CT of a Breast Tumor Diagnosed as Invasive Ductal Carcinomatosis.

Molecular imaging and radionuclide therapy, 33(2):134-137.

Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.

RevDate: 2024-07-01
CmpDate: 2024-07-01

Dhone K, G Aurangabadkar (2024)

Invasive ductal carcinoma of the breast presenting as a cauliflower-like growth.

The Pan African medical journal, 48:4 pii:PAMJ-48-4.

RevDate: 2024-06-30

Bogaard M, Strømme JM, Kidd SG, et al (2024)

GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer.

Neoplasia (New York, N.Y.), 55:101023 pii:S1476-5586(24)00065-4 [Epub ahead of print].

Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.

RevDate: 2024-06-29

González-López MM, Esquinas-López C, Romero-García M, et al (2024)

Intensity of Interprofessional Collaboration and related factors in Intensive Care Units. A descriptive cross-sectional study with an analytical approach.

Enfermeria intensiva pii:S2529-9840(23)00068-X [Epub ahead of print].

OBJECTIVE: To determine the Intensity of Collaboration between the intensive care professionals of a third level hospital.

METHOD: Descriptive cross-sectional study with an analytical approach.

SETTING: 6 intensive care units of a third level hospital.

SAMPLE: nurses and doctors. Consecutive type non-probabilistic sampling.

DATA COLLECTION: sociodemographic, economic, motivation and professional satisfaction variables, and the intensity of collaboration using the "Scale of Intensity of Interprofessional Collaboration in Health."

RESULTS: A total of 102 health professionals (91 nurses and 11 doctors) were included. The mean overall Intensity of Collaboration (IoC) was moderate. Men showed higher scores in all factors (p<.05). The IoC global score was higher in the group of professionals with ≤10 years of experience (p=.043) and those who were highly satisfied with the profession (p=.037). Physicians presented higher scores in the global IdC (p=.037) and in the Collaboration mean (p=.020) independently in the multivariate models. A negative linear relationship (rho: -0,202, p=.042) was observed between age and the overall IoC score. Professionals aged ≤30years reported a higher perception of Shared Activities (p=.031). Negative linear relationships were observed between years of experience and total IoC score (rho: -0,202, p=.042) and patients' Perception score (rho: -0.241, p=0.015). The research activity also showed to be a variable related to a greater degree of Collaboration at a global level and in some of the factors (p<.05). The scale of IoC obtained a Cronbach's α of 0,9.

CONCLUSIONS: The intensity of interprofessional collaboration in ICUs is moderate. Professionals with experience of ≤10 years, a higher level of satisfaction and participation in research activities show a greater intensity of collaboration. Doctors perceive collaboration more intensely than nurses. All factors contribute equally to the internal consistency of the questionnaire.

RevDate: 2024-06-28
CmpDate: 2024-06-28

Pantazi V, Miklós V, Smith P, et al (2024)

Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors.

Scientific reports, 14(1):14912.

Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.

RevDate: 2024-06-28

Shrivastava N (2024)

A Retrospective Analysis of Breast Cancer Presentation Among Young and Older Women in an Indian Cohort of 70 Patients.

Cureus, 16(5):e61239.

Introduction In females, carcinoma of the breast is a common malignancy. Disease management can be challenging for the treating clinician if the condition is presented in a locally advanced stage. Clinical presentation of a disease in a defined area provides a comprehensive map to target the at-risk population efficiently and select the appropriate intervention accordingly. In this retrospective study, we analyzed different factors that can affect breast carcinoma outcomes by assessing patients for a specific period of one year. Methods This is a retrospective study of carcinoma of breast patients and was conducted between 2017 and 2018. Results We reported a 25.83% incidence of breast cancer during the study period. A painful breast lump was present in 54.2% of patients, axillary nodes were present in 50% of patients, ulcers were present in 10% of patients, and nipple discharge was present in 8.5% of patients. According to the side and quadrant of involvement, the right side was the most common site of involvement in 55.7% of patients, and the upper outer quadrant was the most common quadrant involved in 61.4% of patients. The most familiar stage of the presentation was stage II, presented in 45.7% of patients. The most common histology was infiltrating ductal carcinoma, presented in 85.7% of patients. Conclusions This retrospective cohort study shows that carcinoma of the breast is a predominant malignancy among middle-aged females in developing countries such as India. This predominance is due to unawareness regarding disease symptoms and the fear of diagnosed malignancy during the investigation of symptoms. Early detection by screening and intervention at an early stage is the core of treatment success in this malignant disease. However, it is still challenging to apply screening as a tool to pick up early malignant disease in developing countries like India.

RevDate: 2024-06-27
CmpDate: 2024-06-27

Kurokawa K, Yamada Y, Sakamoto S, et al (2024)

Implications of unconventional histological subtypes on magnetic resonance imaging and oncological outcomes in patients who have undergone radical prostatectomy.

Scientific reports, 14(1):14868.

The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22-0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P < 0.0001). Further, increased PI-RADS v2.1 score did not correlate with larger TV in UH (P = 0.991), whereas a significant difference in TV was observed in CH (P < 0.0001). The prognostic significance of UH tumor was independent of tumor localization, and shorter PFS was observed even in RM-negative cases, indicating an aggressive subtype with micro-metastatic potential. Furthermore, UH tumors are more likely to harbor a large TV despite PI-RADS v2.1 score ≤ 3. These findings will help optimal perioperative management for PCa with UH.

RevDate: 2024-06-27
CmpDate: 2024-06-27

Delfin L, Doff JJ, Gagan J, et al (2024)

Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.

Head and neck pathology, 18(1):58.

BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.

METHODS: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.

RESULTS: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.

CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.

RevDate: 2024-06-27
CmpDate: 2024-06-27

Yoo KC, Kim DH, Park S, et al (2024)

Gastric Metastasis Mimicking Early Gastric Cancer from Invasive Ductal Carcinoma of the Breast: Case Report and Literature Review.

Medicina (Kaunas, Lithuania), 60(6): pii:medicina60060980.

Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.

RevDate: 2024-06-27
CmpDate: 2024-06-27

Hulahan TS, Spruill L, Wallace EN, et al (2024)

Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.

International journal of molecular sciences, 25(12): pii:ijms25126748.

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.

RevDate: 2024-06-27
CmpDate: 2024-06-27

Markalunas EG, Arnold DH, Funkhouser AT, et al (2024)

Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.

Genes, 15(6): pii:genes15060818.

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.

RevDate: 2024-06-26

Baranová I, Samec M, Dvorská D, et al (2024)

Droplet digital PCR analysis of CDH13 methylation status in Slovak women with invasive ductal breast cancer.

Scientific reports, 14(1):14700.

Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR- versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.

RevDate: 2024-06-26
CmpDate: 2024-06-26

Sendag S, Koca D, Arslan T, et al (2024)

Oestrogen and progesterone concentrations in intrapartum cows with insufficient cervix dilation.

Reproduction in domestic animals = Zuchthygiene, 59(6):e14656.

The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important.

RevDate: 2024-06-26

Wang A, Quint E, Kukeev I, et al (2024)

Application of Intraoperative Radiotherapy in Early-Stage Breast Cancer Patients in a Clinical Setting.

International journal of breast cancer, 2024:5551907.

Background: Intraoperative radiation therapy (IORT) has gained popularity in recent years as an alternative to external beam whole breast radiation therapy (WBRT) for early-stage breast cancer. Here, we report 43-month recurrence and survival outcomes in a multiethnic cohort treated with IORT in a clinical context. Method: Two hundred and eleven patients with low-risk features were treated with IORT for early-stage breast cancer from 2014 to 2021. Selection criteria were based on Group Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines: preferably unifocal intraductal carcinoma (IDC), aged > 50, tumor size ≤ 2.0 cm, and without lymph node involvement. All patients received 20 Gy of radiation dose during the lumpectomy. Information on patient and tumor characteristics was collected. Results: The mean age of this cohort was 67.5 years; 95.2% of patients are Jewish, and the rest are Bedouins (4.7%). Most tumors were intraductal carcinoma (97.2%) and stage 1 (94.8%). The mean follow-up time was 43.4 months. Bedouins had larger tumor sizes (mean 1.21 vs. 1.13 cm) and were younger at diagnosis than Jewish patients (mean 65.4 vs. 67.6 years), although the differences are not significant. The overall recurrence rate was 1.4%. One case of local recurrence (0.5%) and two cases of metastasis (0.9%) were observed during the study period. One patient died from metastasis. Conclusion: Our findings suggest that IORT in selected low-risk patients can achieve an excellent prognosis with low rates of recurrence and metastasis.

RevDate: 2024-06-24

Zhou YT, Zhang PJ, Wang SP, et al (2024)

Biosafety assessments of hexafluoropropylene trimer derivative as a fluorinated cooling fluid for electronics.

Toxicological research, 40(3):431-440.

UNLABELLED: The Internet Data Center (IDC) is one of the most important infrastructures in the field of information technology. The cooling system for heat dissipation of IDC is indispensable due to it generates a large amount of heat during its calculation process, which may potentially harm its normal operation. Electronic fluorinated fluids have been widely used in cooling systems of IDC with stable physical and chemical properties. However, the biological toxicity of electronic fluorinated fluids has not been fully evaluated and there is a lack of unified safety standards, which may pose potential risks to the environment and human health. Here, hexafluoropropylene terpolymer (HFPT) as an example has been systematically studied, fully considering the application scenarios of data centers. Also, the emergency effects of fluorinated coolants in mammalian models from the perspectives of inhalation, skin contact, accidental entry into eyes, accidental ingestion, and chronic toxicity, are evaluated. Multiple in vivo experiments have proven that HFPT not only has stable physical and chemical properties, that can maintain the safe operation of IDC, but also has low physiological toxicity to mammals and can provide health benefits to data center staff and the assurance of surrounding environment. This study proves the good biological safety of electronic fluorinated fluids and provides a reference for environmental assessment and risk management of liquid cooling technology in IDC.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-024-00234-3.

RevDate: 2024-06-24

Mello RM, Ceballos DG, Sandate CR, et al (2024)

BMAL1-HIF2α heterodimers contribute to ccRCC.

bioRxiv : the preprint server for biology.

Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). Furthermore, the clock gene BMAL1 is higher in ccRCC than in healthy kidneys, unlike in other tumor types. BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 reprograms HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). We show that BMAL1-HIF2α is more sensitive than ARNT-HIF2α to suppression by PT2399, and increasing BMAL1 sensitizes 786O cells to growth inhibition by PT2399. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 contributes to HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.

RevDate: 2024-06-22

Berndt C, Alborzinia H, Amen VS, et al (2024)

Ferroptosis in health and disease.

Redox biology, 75:103211 pii:S2213-2317(24)00189-7 [Epub ahead of print].

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis.

RevDate: 2024-06-22

Shenkman G, Ifrah K, D Shmotkin (2024)

Evil-related threats and mental health concomitants among offspring of Holocaust survivors gay men.

Aging & mental health [Epub ahead of print].

OBJECTIVES: In view of the accumulated stress associated with the combination of intergenerational trauma and minority stress, we aimed to examine whether offspring of Holocaust survivors (OHS) reported stronger evil-related threats compared to non-OHS individuals and whether OHS gay men experienced stronger threats. We also examined whether sexual orientation moderated the hypothesized indirect effect of Holocaust background on mental health through evil-related threats.

METHOD: Participants were 346 middle-aged and older Israeli men (mean age = 60.56, SD = 8.42, range 50-86). Among them, 173 identified as gay men, and 81 identified as OHS. Participants completed measures of evil-related threats, depression, and life satisfaction.

RESULTS: Analysis of covariance revealed that OHS men reported stronger evil-related threats compared to non-OHS men. Yet, an interaction between Holocaust background and sexual orientation indicated that OHS gay men reported stronger evil-related threats compared to non-OHS gay men, while no such difference existed among heterosexual counterparts. Conditional indirect effect analysis showed a significant indirect effect, in which Holocaust background related to higher depressive symptoms and lower life satisfaction through evil-related threats among gay men, but not among heterosexual men.

CONCLUSION: This study sheds light on the particular experience of evil-related threats, focusing on older OHS gay men and the mental health vulnerability associated with it. In applied contexts, this might help identify a sexual minority group that is particularly sensitive to adverse mental health and offer it supporting interventions.

RevDate: 2024-06-21

von Rauchhaupt E, Rodemer C, Kliemank E, et al (2024)

Glucose Load Following Prolonged Fasting Increases Oxidative Stress-Linked Response in Individuals With Diabetic Complications.

Diabetes care pii:156887 [Epub ahead of print].

OBJECTIVE: Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D.

RESEARCH DESIGN AND METHODS: Glucose-tolerant individuals (CON, n = 10), T2D individuals with (T2D+, n = 10) and without diabetes complications (T2D-, n = 10) underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet. Peripheral blood mononuclear cells' (PBMC) resistance to ex vivo dicarbonyl methylglyoxal (MG) exposure after glucose load was assessed. Markers of dicarbonyl detoxification, oxidative stress, and mitochondrial biogenesis were analyzed by quantitative PCR, with mitochondrial complex protein expression assessed by western blotting.

RESULTS: T2D+ exhibited decreased PBMC resistance against MG, while T2D- resistance remained unchanged, and CON improved postglucose load and fasting (-19.0% vs.-1.7% vs. 12.6%; all P = 0.017). T2D+ showed increased expression in dicarbonyl detoxification (mRNA glyoxalase-1, all P = 0.039), oxidative stress (mRNA glutathione-disulfide-reductase, all P = 0.006), and mitochondrial complex V protein (all P = 0.004) compared with T2D- and CON postglucose load and fasting. Citrate synthase activity remained unchanged, indicating no change in mitochondrial number. Mitochondrial biogenesis increased in T2D- compared with CON postglucose load and fasting (mRNA HspA9, P = 0.032). T2D-, compared with CON, exhibited increased oxidative stress postfasting, but not postglucose load, with increased mRNA expression in antioxidant defenses (mRNA forkhead box O4, P = 0.036, and glutathione-peroxidase-2, P = 0.034), and compared with T2D+ (glutathione-peroxidase-2, P = 0.04).

CONCLUSIONS: These findings suggest increased susceptibility to glucose-induced oxidative stress in individuals with diabetes complications after prolonged fasting and might help in diet interventions for diabetes management.

RevDate: 2024-06-20

Mayfield JD, Ataya D, Abdalah M, et al (2024)

Presurgical Upgrade Prediction of DCIS to Invasive Ductal Carcinoma Using Time-dependent Deep Learning Models with DCE MRI.

Radiology. Artificial intelligence [Epub ahead of print].

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To determine whether time-dependent deep learning models can outperform single timepoint models in predicting preoperative upgrade of ductal carcinoma in situ (DCIS) to invasive malignancy on dynamic contrastenhanced (DCE) breast MRI without lesion segmentation prerequisite. Materials and Methods In this exploratory study, 154 cases of biopsy-proven DCIS (25 upgraded at surgery and 129 not upgraded) were selected consecutively from a retrospective cohort of preoperative DCE MRI in women with an average age of 58.6 years at time of diagnosis from 2012 to 2022. Binary classification was implemented with convolutional neural network-long short-term memory (CNN-LSTM) architectures benchmarked against traditional CNNs without manual segmentation of the lesions. Combinatorial performance analysis of ResNet50 versus VGG16-based models was performed with each contrast phase. Binary classification area under the receiver operating characteristic curve (AUC) was reported. Results VGG16-based models consistently provided better hold-out test AUCs than ResNet50 in CNN and CNNLSTM studies (multiphase test AUC: 0.67 versus 0.59, respectively, for CNN models; P = .04 and 0.73 versus 0.62 for CNN-LSTM models; P = .008). The time-dependent model (CNN-LSTM) provided a better multiphase test AUC over single-timepoint (CNN) models (0.73 versus 0.67, P = .04). Conclusion Compared with single-timepoint architectures, sequential deep learning algorithms using preoperative DCE MRI improved prediction of DCIS lesions upgraded to invasive malignancy without the need for lesion segmentation. ©RSNA, 2024.

RevDate: 2024-06-19

Corso G, Fusco N, Guerini-Rocco E, et al (2024)

Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.

Seminars in oncology pii:S0093-7754(24)00038-1 [Epub ahead of print].

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.

RevDate: 2024-06-19

Zhang Z, Lan H, S Zhao (2024)

Analysis of the Value of Quantitative Features in Multimodal MRI Images to Construct a Radio-Omics Model for Breast Cancer Diagnosis.

Breast cancer (Dove Medical Press), 16:305-318.

OBJECTIVE: To analyze the diagnostic value of quantitative features in multimodal magnetic resonance imaging (MRI) images to construct a radio-omics model for breast cancer.

METHODS: Ninety-five patients with breast-related diseases from January 2020 to January 2021 were grouped into the benign group (n=57) and malignant group (n=38) according to the pathological findings. All cases were randomized as the training group (n=66) and validation group (n=29) in a 7:3 ratio based on the examination time. All subjects were examined by T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE), and apparent diffusion coefficient (ADC) multimodality MRI. The MRI findings were analyzed against pathological findings. A diagnostic breast cancer radiomics model was constructed. The diagnostic efficacy of the model in the validation group was analyzed, and the diagnostic efficacy was analyzed via the ROC curve.

RESULTS: Fibroadenoma accounted for 49.12% of benign breast diseases, and invasive ductal carcinoma accounted for 73.68% of malignant breast diseases. The sensitivity of T1WI, T2WI, DWI, ADC, and DCE in diagnosing breast cancer was 61.14%, 66.67%, 73.30%, 78.95%, and 85.96%, using the four-fold table method. The area under the curves (AUCs) of T1WI, T2WI, DWI, ADC, and DCE for diagnosing breast cancer were 0.715, 0.769, 0.785, 0.835, and 0.792, respectively. The AUCs of plain scan, diffuse, enhanced, plain scan + diffuse, plain scan + enhanced, enhanced + diffuse, and plain scan + enhanced + diffuse for diagnosing breast cancer were 0.746, 0.798, 0.816, 0.839, 0.890, 0.906, and 0.927, respectively.

CONCLUSION: The construction of a radio-omics model by quantitative features in multimodal MRI images was valuable in the diagnosis of breast cancer. The value of radio-omics models such as plain scan + enhanced + diffuse was higher than the other models in diagnosing breast cancer and could be widely applied in clinical practice.

RevDate: 2024-06-19

Ramamoorthy P, Ramakantha Reddy BR, Askar SS, et al (2024)

Histopathology-based breast cancer prediction using deep learning methods for healthcare applications.

Frontiers in oncology, 14:1300997.

Breast cancer (BC) is the leading cause of female cancer mortality and is a type of cancer that is a major threat to women's health. Deep learning methods have been used extensively in many medical domains recently, especially in detection and classification applications. Studying histological images for the automatic diagnosis of BC is important for patients and their prognosis. Owing to the complication and variety of histology images, manual examination can be difficult and susceptible to errors and thus needs the services of experienced pathologists. Therefore, publicly accessible datasets called BreakHis and invasive ductal carcinoma (IDC) are used in this study to analyze histopathological images of BC. Next, using super-resolution generative adversarial networks (SRGANs), which create high-resolution images from low-quality images, the gathered images from BreakHis and IDC are pre-processed to provide useful results in the prediction stage. The components of conventional generative adversarial network (GAN) loss functions and effective sub-pixel nets were combined to create the concept of SRGAN. Next, the high-quality images are sent to the data augmentation stage, where new data points are created by making small adjustments to the dataset using rotation, random cropping, mirroring, and color-shifting. Next, patch-based feature extraction using Inception V3 and Resnet-50 (PFE-INC-RES) is employed to extract the features from the augmentation. After the features have been extracted, the next step involves processing them and applying transductive long short-term memory (TLSTM) to improve classification accuracy by decreasing the number of false positives. The results of suggested PFE-INC-RES is evaluated using existing methods on the BreakHis dataset, with respect to accuracy (99.84%), specificity (99.71%), sensitivity (99.78%), and F1-score (99.80%), while the suggested PFE-INC-RES performed better in the IDC dataset based on F1-score (99.08%), accuracy (99.79%), specificity (98.97%), and sensitivity (99.17%).

RevDate: 2024-06-19

Cicciarelli F, Guiducci E, Galati F, et al (2024)

Digital Mammography (DM) vs. Dynamic Contrast Enhancement-Magnetic Resonance Imaging (DCE-MRI) in Microcalcifications Assessment: A Radiological-Pathological Comparison.

Diagnostics (Basel, Switzerland), 14(11):.

The aim of this study was to compare the characteristics of breast microcalcification on digital mammography (DM) with the histological and molecular subtypes of breast cancer and to identify the predictive value of DM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing microcalcifications for radiologic-pathologic correlation. We relied on our prospectively maintained database of suspicious microcalcifications on DM, from which data were retrospectively collected between January 2020 and April 2023. We enrolled 158 patients, all of whom were subjected to biopsy. Additionally, 63 patients underwent breast DCE-MRI. Microcalcifications with a linear branched morphology were correlated with malignancies (p < 0.001), among which an association was highlighted between triple negatives (TNs) and segmental distribution (p < 0.001). Amorphous calcifications were correlated with atypical ductal hyperplasia (ADH) (p = 0.013), coarse heterogeneous (p < 0.001), and fine-pleomorphic (p = 0.008) with atypical lobular hyperplasia (ALH) and fine pleomorphic (p = 0.009) with flat epithelial atypia (FEA). Regarding DCE-MRI, no statistical significance was observed between non-mass lesions and ductal carcinoma in situ (DCIS). Concerning mass lesions, three were identified as DCIS and five as invasive ductal carcinoma (IDC). In conclusion, microcalcifications assessed in DM exhibit promising predictive characteristics concerning breast lesion subtypes, leading to a reduction in diagnostic times and further examination costs, thereby enhancing the clinical management of patients.

RevDate: 2024-06-18
CmpDate: 2024-06-18

Su HZ, Hong LC, Su YM, et al (2024)

A Nomogram Based on Conventional Ultrasound Radiomics for Differentiating Between Radial Scar and Invasive Ductal Carcinoma of the Breast.

Ultrasound quarterly, 40(3): pii:00013644-202409000-00002.

We aimed to develop and validate a nomogram based on conventional ultrasound (CUS) radiomics model to differentiate radial scar (RS) from invasive ductal carcinoma (IDC) of the breast. In total, 208 patients with histopathologically diagnosed RS or IDC of the breast were enrolled. They were randomly divided in a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Overall, 1316 radiomics features were extracted from CUS images. Then a radiomics score was constructed by filtering unstable features and using the maximum relevance minimum redundancy algorithm and the least absolute shrinkage and selection operator logistic regression algorithm. Two models were developed using data from the training cohort: one using clinical and CUS characteristics (Clin + CUS model) and one using clinical information, CUS characteristics, and the radiomics score (radiomics model). The usefulness of nomogram was assessed based on their differentiating ability and clinical utility. Nine features from CUS images were used to build the radiomics score. The radiomics nomogram showed a favorable predictive value for differentiating RS from IDC, with areas under the curve of 0.953 and 0.922 for the training and validation cohorts, respectively. Decision curve analysis indicated that this model outperformed the Clin + CUS model and the radiomics score in terms of clinical usefulness. The results of this study may provide a novel method for noninvasively distinguish RS from IDC.

RevDate: 2024-06-19

Nemerovsky L, Ghetler Y, Wiser A, et al (2024)

Two types of cleavage, from zygote to three cells, result in different clinical outcomes and should be treated differently.

Frontiers in cell and developmental biology, 12:1398684.

RESEARCH QUESTION: What is the utilization rate of embryos that exert inadequate zygote cleavage into three daughter cells?

DESIGN: This study used a retrospective dataset from a single IVF Unit. A total of 3,060 embryos from 1,811 fresh IVF cycles were analyzed. The cleavage pattern, morphokinetics, and outcome were recorded. Only 2pn embryos, fertilized by ejaculated sperm, and cultured in a time-lapse system for at least 5 days were included. We generated three study groups according to the embryo's cleavage pattern: (I) Control, normal cleavage (n = 551); (II) fast cleavage, zygote to three cells within 5 h (n = 1,587); and (III) instant direct tripolar cleavage (IDC) from zygote to three cells (n = 922).

RESULTS: The rate of usable fast cleavage blastocysts was 108/1,587 (6.81%) and usable control blastocysts was 180/551 (32.67%). The time of PN fading and from fading to first cleavage differed significantly between the three groups. Although the pregnancy rate of control and fast cleavage blastocysts were comparable (40.35% and 42.55%, respectively), the amount of instant direct cleavage embryos that reached blastocyst stage was neglectable (only four embryos out of 922 analyzed IDC embryos) and unsuitable for statistical comparison of pregnancy rates.

CONCLUSION: Our results indicate the need to culture instant direct cleavage embryos for 5 days, up to the blastocyst stage, and avoid transfer of embryos that are fated to arrest even when their morphological grade on day 3 is acceptable, whereas fast cleavage embryos could be transferred on day 3 when there is no alternative.

RevDate: 2024-06-17

Ibrahim EH, Ali TA, Sharbatti S, et al (2024)

Histopathological Profile of Different Breast Lesions: A Single-Center Observational Study.

Cureus, 16(5):e60408.

OBJECTIVE: To describe the histopathological pattern of different breast lesions among tissue specimens sent to our laboratory.

METHOD: A record-based study using a retrospective review of 255 histologically diagnosed breast biopsy reports in the histopathology department of authors from December 2016 to November 2021 was conducted. The specimens were collected from core biopsy, lumpectomy, and mastectomy. All data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) version 28 (IBM SPSS Statistics, Armonk, NY). Then, the findings were presented using text, tables, and charts.

RESULT: A total of 255 breast lesions were analyzed in this study. Most of the cases were benign (58.8%), followed by inflammatory lesions (21.6%), and malignant (19.6%). Fibroadenoma was the most prevalent benign lesion (36.7%), and most of the patients (70.9%) were in the age group of 20-39 years old. The most common inflammatory lesion was granulomatous mastitis (56.4%), and most of the cases were diagnosed in the age group of 30-39 years old. Invasive ductal carcinoma (IDC) was the most encountered histological type of carcinoma (62%). Of the malignant cases, 52% were diagnosed before the age of 50 years. Among these 50 cases, grade 2 was the most prevalent one (46%).

CONCLUSION: Benign breast lesions are more common than malignant breast lesions, and fibroadenoma is the most common benign subtype. Granulomatous mastitis is the most prevalent inflammatory breast lesion. About two-thirds of malignant cases are non-Arab. Invasive ductal carcinoma with no special type (NST) is the most common malignant subtype.

RevDate: 2024-06-17

Vasudevan S, Kannan K, Raghavan AV, et al (2024)

Analyzing Tumor Budding Scores in Invasive Breast Carcinoma: A Tertiary Care Center Study in South India.

Journal of pharmacy & bioallied sciences, 16(Suppl 2):S1850-S1853.

INTRODUCTION AND AIM: Tumor budding is a distinctive phenomenon which involves the presence of small clusters or individual cancer cells at the invasive front of tumors. Tumor budding has garnered attention due to its potential implications for prognosis, treatment strategies, and our understanding of cancer progression. Our aim is to study the distribution of tumor buds and its scoring in patients with infiltrating breast carcinoma and to associate with other histopathological parameters like the size of the tumor, its grade, lymphovascular invasion, and lymph node metastasis.

MATERIALS AND METHODS: This was a study analyzing the data of 70 resected specimens of primary breast carcinomas and providing a descriptive overview. Tumor budding was recognized, counted, and graded in hematoxylin and eosin slides. The cases were classified as low (0-4), intermediate (5-9), and high (≥10 buds) based on the count of tumor buds. Tumor budding has significant correlation with tumor grade and tumor size.

RESULTS: Of the 70 cases, 60 cases (85.71%) were diagnosed as invasive ductal carcinoma NOS. The majority [38 (54.28%)] of the cases showed an intermediate tumor budding score of 5-9/10 HPF.

CONCLUSION: Evaluation of tumor budding allows pathologists and oncologists to gather valuable information about the tumor's biological aggressiveness and potential for metastasis. It also helps in better risk stratification of patients, enabling a more personalized and tailored approach to treatment planning. In conclusion, assessing tumor budding in breast carcinoma holds significant clinical importance in the management and prognosis of this disease.

RevDate: 2024-06-17

Rotstein MS, Zimmerman-Brenner S, Davidovitch S, et al (2024)

Gamified Closed-Loop Intervention Enhances Tic Suppression in Children: A Randomized Trial.

Movement disorders : official journal of the Movement Disorder Society [Epub ahead of print].

BACKGROUND: Gamification of behavioral intervention for tic disorders (TDs) potentially enhances compliance and offers key clinical advantages. By delivering immediate positive feedback upon tic-suppression, games may counteract negative reinforcement, which presumably contribute to tic consolidation by relieving uncomfortable premonitory urges.

OBJECTIVES: We developed a gamified protocol (XTics), which leverages this potential by combining gamified tic-triggering with immediate feedback, and evaluated its clinical value in enhancing tic suppression.

METHODS: XTics encompasses two conditions: Immediate and Contingent Reward (ICR), where game progression is contingent upon successful tic suppression, and Delayed Reward (DR), where game events' outcomes are random. Employing a randomized crossover design, 35 participants (aged 7-15 years) underwent daily gaming sessions over a week per condition. Improvements in our primary measures, including the inter-tic interval (ITI) and tic severity assessment by blinded evaluators (Yale Global Tic Severity-Total Tic Score [YGTSS-TTS], Rush), and parents (Parent Tic Questionnaire [PTQ]), were compared between ICR and DR, and assessed across conditions for the 4-week protocol.

RESULTS: No participant voluntarily left the study before completing its two-phase protocol. As expected, ITI showed significantly larger improvement (Z = 4.19, P = 2.85 × 10-5) after ICR (1442 ± 2250%) versus DR (242 ± 493%) training, increasing at a higher pace (t(67) = 3.15, P = 0.0025). Similarly, Rush tic severity scores reduced more post-ICR versus DR (t(47) = 3.47, P = 0.002). We observed a clinically significant reduction of 25.69 ± 23.39% in YGTSS-TTS following a f4-week protocol including both conditions. Parent-reported tic severity decreased by 42.99 ± 31.69% from baseline to 3 months post-treatment.

CONCLUSIONS: The combination of gamified tic-triggering with immediate and contingent rewards demonstrates a promising approach for enhancing treatment efficacy in TDs, boosting traditional therapeutic methods. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

RevDate: 2024-06-14

Alabedi HH, Ahmed IK, ASM Jamil (2024)

Incidence of local breast cancer recurrence with delayed radiation therapy.

Breast cancer research and treatment [Epub ahead of print].

BACKGROUND: The purpose of this research was to examine the probability of ipsilateral breast cancer recurrence in individuals whose RT was delayed after the first chemotherapy and surgery.

PURPOSE: To analyze the effect of delaying RT for breast cancer patients (by more than 6 weeks after treatment).

METHODOLOGY: A retrospective analysis comprised 136 female breast cancer patients treated at the Baghdad Centre for Radiation Oncology and Nuclear Medicine from 2021 to May 2022. External beam radiation was started more than 6 weeks after chemotherapy was finished for all patients who also had surgery. Clinical examination and ultrasound were part of the follow-up process.

RESULTS: Patients' ages varied from 28 to 71, and the majority (83%) had a mastectomy. The majority of cases (95.5%) were diagnosed as invasive ductal carcinoma on histopathology, with 49.6% being at stage 2 and 42.6% being at stage 3. Seventy-six percent of patients tested positive for hormones. Although 10 patients (7.35%) acquired distant metastases within 5 years, only 2 (1.47%) had local recurrence because of the delay in RT. Specifically, 91.1% had complete local control with no evidence of disease spread.

CONCLUSION: Delaying RT by more than 6 weeks in patients with breast cancer did not substantially affect local control, according to the results of a new research, the first of its type in Iraq.

RevDate: 2024-06-12

Andrianto A, Sudiana IK, DGA Suprabawati (2024)

α-Smooth Muscle Actin as Predictors of Early Recurrence in Early-Stage Ductal Type Breast Cancer After Mastectomy and Chemotherapy.

Iranian journal of pathology, 19(1):67-74.

BACKGROUND & OBJECTIVE: Breast cancer recurrence after surgery was a sign that the progress of the disease was continuing. Early detection of breast cancer patients who are at risk requires development of a marker. Alfa smooth muscle actin (α-SMA) plays a role in the local recurrence process of invasive ductal carcinoma (IDC). Currently, existing tumor markers are used to predict the prognosis of breast cancer in general, not the early stages. Therefore, it was thought that finding α-SMA expression might predict early recurrence in early-stage IDC more accurately than others. This study investigated the potential role of α-SMA expression as a predictor of early recurrence in early-stage IDC and its relationship to clinicopathological factors.

METHODS: The study design was cross-sectional, with data obtained from the medical records of Dr. Koesnadi, General Hospital, Bondowoso, Indonesia. Bivariate and multivariate analysis was performed to analyze data.

RESULTS: We included 50 subjects divided into the local recurrence group (n=25) and the non-local recurrence group (n=25). We found a statistically significant correlation between the incidence of local recurrence in early-stage IDC and the high expression of α-SMA (odd ratio [OR]=23.22, 95% confidence interval [CI]=5.101-105.7, P=0.001). Clinicopathological variables and α-SMA expression did not have a significant correlation.

CONCLUSION: In early-stage IDC, α-SMA expression had the potential to predict and could be an independent prognostic factor for early recurrence.

RevDate: 2024-06-12

Qamar MA, Rehman A, HUR Toor (2024)

Multidisciplinary management of necrotizing fasciitis as a postoperative complication after mastectomy in an adult male in a low- and middle-income country.

Journal of surgical case reports, 2024(6):rjae412.

Necrotizing fasciitis, a rare, potentially life-threatening infection, often necessitates urgent medical intervention and surgical excision of the affected tissue. We present a 55-year-old male patient with a progressively enlarging lump in the left breast that was diagnosed as a breast carcinoma. Post-modified radical mastectomy, histopathological examination revealed Grade II invasive ductal carcinoma with neuroendocrine features. Due to financial constraints, the patient missed post-operative follow-ups and did not complete the prescribed radiotherapy sessions. Three months later, the patient returned with fever, swelling alongside sharp pain in the left arm and oozing blood. A clinical diagnosis of necrotizing fasciitis was made, leading to urgent surgical debridement. While the wound progressively healed, a contracture developed restricting elbow movement. An Orthopedic Review and Bone scintigraphy revealed metastasis of breast carcinoma to the sternum. This case report highlights the multi-disciplinary management required in such financially constrained rare cases in low- and middle-income countries.

RevDate: 2024-06-11

Shetty ND, Dhande R, Parihar P, et al (2024)

Magnetic Resonance Imaging of Radiation-Induced Brachial Plexopathy.

Cureus, 16(5):e60067.

This report illustrates the case of a 37-year-old woman following chemoradiotherapy for invasive ductal carcinoma of the right breast. The patient underwent surgery and received a radiation dose of 50 gray to the chest wall and 45 gray to the regional lymph nodes in 25 total fractions. She developed motor and sensory weakness in the right upper limb eight years after treatment. Brachial plexus neuropathy in cancer patients may result from either trauma to the plexus during surgery, the spread of cancer, or radiation therapy, and distinguishing between them may be difficult. The case highlights the importance of recognizing the signs, symptoms, and possible differential diagnosis of radiation-induced brachial plexopathy in cancer patients post-radiation therapy. It emphasizes the role of magnetic resonance imaging in the careful assessment and diagnosis of such a case.

RevDate: 2024-06-08

Cheng L, Wang J, L Tang (2024)

Analysis of prognostic factors and construction of prognostic models for invasive lobular carcinoma of the breast.

Biomolecules & biomedicine [Epub ahead of print].

Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most cases of breast cancer. However, there is ongoing debate about any potential variations in overall survival (OS) between ILC and IDC. This study aimed to compare survival between IDC and ILC, identify prognostic factors for ILC patients, and construct a nomogram for predicting OS rates. This retrospective cohort analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Database. Patients diagnosed with ILC and IDC between 2000 and 2019 were enrolled. To minimize baseline differences in clinicopathological characteristics and survival outcomes, a propensity score matching (PSM) method was used. Data from the multivariate Cox regression analyses were used to construct a predictive nomogram for OS at 1, 3, and 5 years, incorporating all independent prognostic factors. Following the PSM procedure, patients with ILC exhibited a better prognosis compared to those with IDC. TNM stage, age >70, radiotherapy, surgery, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HR-/HER2+) subtype were identified as independent factors for OS in ILC patients. Surgery and radiotherapy effectively reduced the risk of death, while chemotherapy did not demonstrate the same benefit. This model could support clinicians in evaluating the prognosis of ILC for decision-making and patient counseling.

RevDate: 2024-06-07
CmpDate: 2024-06-07

Hunt KN, Conners AL, Gray L, et al (2024)

Molecular Breast Imaging Biopsy with a Dual-Detector System.

Radiology. Imaging cancer, 6(4):e230186.

Purpose To develop a molecular breast imaging (MBI)-guided biopsy system using dual-detector MBI and to perform initial testing in participants. Materials and Methods The Stereo Navigator MBI Accessory biopsy system comprises a lower detector, upper fenestrated compression paddle, and upper detector. The upper detector retracts, allowing craniocaudal, oblique, or medial or lateral biopsy approaches. The compression paddle allows insertion of a needle guide and needle. Lesion depth is calculated by triangulation of lesion location on the upper detector at 0° and 15° and relative lesion activity on upper and lower detectors. In a prospective study (July 2022-June 2023), participants with Breast Imaging Reporting and Data System category 2, 3, 4, or 5 breast lesions underwent MBI-guided biopsy. After injection of 740 MBq technetium 99m sestamibi, craniocaudal and mediolateral oblique MBI (2-minute acquisition per view) confirmed lesion visualization. A region of interest over the lesion permitted depth calculation in the system software. Upper detector retraction allowed biopsy device placement. Specimen images were obtained on the retracted upper detector, confirming sampling of the target. Results Of 21 participants enrolled (mean age, 50.6 years ± 10.1 [SD]; 21 [100%] women), 17 underwent MBI-guided biopsy with concordant pathology. No lesion was observed at the time of biopsy in four participants. Average lesion size was 17 mm (range, 6-38 mm). Average procedure time, including preprocedure imaging, was 55 minutes ± 13 (range, 38-90 minutes). Pathology results included invasive ductal carcinoma (n = 1), fibroadenoma (n = 4), pseudoangiomatous stromal hyperplasia (n = 6), and fibrocystic changes (n = 6). Conclusion MBI-guided biopsy using a dual-head system with retractable upper detector head was feasible, well tolerated, and efficient. Keywords: Breast Biopsy, Molecular Breast Imaging, Image-guided Biopsy, Molecular Breast Imaging-guided Biopsy, Breast Cancer Clinical trial registration no. NCT06058650 © RSNA, 2024.

RevDate: 2024-06-05

Pickett MR, Chen YI, Kamra M, et al (2024)

Assessing the impact of extracellular matrix fiber orientation on breast cancer cellular metabolism.

Cancer cell international, 24(1):199.

The extracellular matrix (ECM) is a dynamic and complex microenvironment that modulates cell behavior and cell fate. Changes in ECM composition and architecture have been correlated with development, differentiation, and disease progression in various pathologies, including breast cancer [1]. Studies have shown that aligned fibers drive a pro-metastatic microenvironment, promoting the transformation of mammary epithelial cells into invasive ductal carcinoma via the epithelial-to-mesenchymal transition (EMT) [2]. The impact of ECM orientation on breast cancer metabolism, however, is largely unknown. Here, we employ two non-invasive imaging techniques, fluorescence-lifetime imaging microscopy (FLIM) and intensity-based multiphoton microscopy, to assess the metabolic states of cancer cells cultured on ECM-mimicking nanofibers in a random and aligned orientation. By tracking the changes in the intrinsic fluorescence of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, as well as expression levels of metastatic markers, we reveal how ECM fiber orientation alters cancer metabolism and EMT progression. Our study indicates that aligned cellular microenvironments play a key role in promoting metastatic phenotypes of breast cancer as evidenced by a more glycolytic metabolic signature on nanofiber scaffolds of aligned orientation compared to scaffolds of random orientation. This finding is particularly relevant for subsets of breast cancer marked by high levels of collagen remodeling (e.g. pregnancy associated breast cancer), and may serve as a platform for predicting clinical outcomes within these subsets [3-6].

RevDate: 2024-06-05

Sun T, Golestani R, Zhan H, et al (2024)

Clinicopathologic Characteristics of MYC Copy Number Amplification in Breast Cancer.

International journal of surgical pathology [Epub ahead of print].

Introduction. MYC overexpression is a known phenomenon in breast cancer. This study investigates the correlation of MYC gene copy number amplification and MYC protein overexpression with coexisting genetic abnormalities and associated clinicopathologic features in breast cancer patients. Methods. The study analyzed data from 81 patients with localized or metastatic breast cancers using targeted next-generation sequencing and MYC immunohistochemical studies, along with pathological and clinical data. Results. Applying the criteria of MYC/chromosome 8 ratio ≥5, MYC copy number amplified tumors (n = 11, 14%) were associated with invasive ductal carcinoma (91% vs 68%, P = .048), poorly differentiated (grade 3, 64% vs 30%, P = .032), mitotically active (Nottingham mitotic score 3, 71% vs 20%, P = .004), estrogen receptor (ER)-negative (45% vs 12%, P = .008), and triple-negative (56% vs 12%, P = .013) compared to MYC non-amplified tumors. Among MYC-amplified breast cancer patients, those with triple-negative status showed significantly shorter disease-free survival time than non-triple negative MYC-amplified patients (median survival month: 25.5 vs 127.6, P = .049). MYC amplification is significantly associated with TP53 mutation (P = .007). The majority (10 of 11; 91%) of MYC-amplified tumors showed positive c-MYC immunostaining. Conclusion. Breast cancers with MYC copy number amplication display distinct clinicopathologic characteristics indicative of more aggressive behavior.

RevDate: 2024-06-05

Wang Y, Li G, Chen B, et al (2024)

Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner.

Cardiovascular research pii:7688406 [Epub ahead of print].

AIMS: Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signaling in atherosclerosis.

METHODS AND RESULTS: Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1 deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences in proliferation were dependent on estrogen receptor (ER)α-estradiol signaling. Kinase activity profiling identified a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further revealed chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism and inflammatory markers, suggesting a possible implication of CB1-dependent regulation in human pathophysiology.

CONCLUSION: Impaired macrophage CB1 signaling is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming in male mice. The importance of macrophage CB1 signaling appears to be sex-dependent.

RevDate: 2024-06-05

Voloch L, Icht M, Ben-David BM, et al (2024)

Seven Days of Voice Rest Post-phonosurgery Is Not Better than 3 days: A Prospective Randomized Short-term Outcome Study.

The Laryngoscope [Epub ahead of print].

OBJECTIVE: The aim of the study is to compare the short-term effect of 7 versus 3 days of voice rest (VR) on objective vocal (acoustic) parameters following phonosurgery.

METHODS: A prospective randomized study conducted at a tertiary referral medical center. Patients with vocal fold nodules, polyps, or cysts and scheduled for phonosurgery were recruited from the Voice Clinic. They were randomized into groups of 7- or 3-day postoperative VR periods and their voices were recorded preoperatively and at 4-week postoperatively. A mixed linear model statistical analysis (MLMSA) was used to compare pre- and postoperative jitter, shimmer, harmonic-to-noise ratio, and maximum phonation time between the two groups.

RESULTS: Sixty-five patients were recruited, but only 34 fully complied with the study protocol, and their data were included in the final analysis (19 males, 20 females; mean age: 40.6 years; 17 patients in the 7-day VR group and 16 in the 3-day VR group). The groups were comparable in age, sex, and type of vocal lesion distribution. The preoperative MLMSA showed no significant group differences in the tested vocal parameters. Both groups exhibited significant (p < 0.05) and comparable improvement in all vocal parameters at postoperative week 4.

CONCLUSIONS: A VR duration of 7 days showed no greater benefit on the examined vocal parameters than the 3-day protocol 4-week postoperatively. Our results suggest that a 3-day VR regimen can be followed by patients who undergo phonosurgery without compromising the vocal results. Larger-scale and longer-duration studies are needed to confirm our findings.

LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.

RevDate: 2024-06-05

Wang WE, Ho CC, CH Chang (2024)

Taxane-Induced Cutaneous Toxic Effects.

JAMA dermatology pii:2819236 [Epub ahead of print].

RevDate: 2024-06-04

Wang L, Vasudevaraja V, Tran I, et al (2024)

Novel Androgen Receptor Splice Variant 7 in Gynecologic Tumors.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists pii:00004347-990000000-00164 [Epub ahead of print].

Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma.

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

Wearn A, Tremblay SA, Tardif CL, et al (2024)

Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.

Nature communications, 15(1):4706.

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

RevDate: 2024-06-03

Morla-Barcelo PM, Laguna-Macarrilla D, Cordoba O, et al (2024)

Unraveling malignant phenotype of peritumoral tissue: transcriptomic insights into early-stage breast cancer.

Breast cancer research : BCR, 26(1):89.

BACKGROUND: Early-stage invasive ductal carcinoma displays high survival rates due to early detection and treatments. However, there is still a chance of relapse of 3-15% after treatment. The aim of this study was to uncover the distinctive transcriptomic characteristics and monitoring prognosis potential of peritumoral tissue in early-stage cases.

METHODS: RNA was isolated from tumoral, peritumoral, and non-tumoral breast tissue from surgical resection of 10 luminal early-stage invasive ductal carcinoma patients. Transcriptome expression profiling for differentially expressed genes (DEGs) identification was carried out through microarray analysis. Gene Ontology and KEGG pathways enrichment analysis were explored for functional characterization of identified DEGs. Protein-Protein Interactions (PPI) networks analysis was performed to identify hub nodes of peritumoral tissue alterations and correlated with Overall Survival and Relapse Free Survival.

RESULTS: DEGs closely related with cell migration, extracellular matrix organization, and cell cycle were upregulated in peritumoral tissue compared to non-tumoral. Analyzing PPI networks, we observed that the proximity to tumor leads to the alteration of gene modules involved in cell proliferation and differentiation signaling pathways. In fact, in the peritumoral area were identified the top ten upregulated hub nodes including CDK1, ESR1, NOP58, PCNA, EZH2, PPP1CA, BUB1, TGFBR1, CXCR4, and CCND1. A signature performed by four of these hub nodes (CDK1, PCNA, EZH2, and BUB1) was associated with relapse events in untreated luminal breast cancer patients.

CONCLUSIONS: In conclusion, our study characterizes in depth breast peritumoral tissue providing clues on the changes that tumor signaling could cause in patients with early-stage breast cancer. We propose that the use of a four gene signature could help to predict local relapse. Overall, our results highlight the value of peritumoral tissue as a potential source of new biomarkers for early detection of relapse and improvement in invasive ductal carcinoma patient's prognosis.

RevDate: 2024-06-03

Sitharthan D, P Sved (2024)

A rare case of fatal rectal perforation and sepsis following traumatic urinary catheterization.

Urology case reports, 54:102706.

This case report details a fatal rectal perforation and sepsis in a comorbid 96-year-old male after traumatic urinary catheterization, highlighting the risks of IDC management in elderly patients with complex health backgrounds. Despite maximal medical therapy, including escalated antibiotics and ICU care, the patient died from septic shock linked to improper catheter insertion by a non-specialist nurse in the community. This case emphasizes the urgent need for better catheterization practices, specialized nursing education, and clear guidelines to prevent such outcomes.

RevDate: 2024-05-31

LaRota-Aguilera MJ, Zapata-Caldas E, Buitrago-Bermúdez O, et al (2024)

New criteria for sustainable land use planning of metropolitan green infrastructures in the tropical Andes.

Landscape ecology, 39(6):112.

CONTEXT: Urbanization is rapidly increasing worldwide, with about 60% of the global population currently residing in cities and expected to reach 68% by 2050. In Latin America's tropical Andes region, managing these changes poses challenges, including biodiversity loss and vulnerability to climate change.

OBJECTIVES: This study assesses urban growth and agricultural intensification impacts on the ecological functionality of metropolitan green infrastructures and their capacity to provide ecosystem services using a landscape sustainability and sociometabolic approach. Specifically, it aims to identify landscape configurations promoting socio-ecological sustainability amidst rapid urbanization.

METHODS: A landscape-metabolic model (IDC) was applied to evaluate the interactions between land use changes and ecosystem functions in the metropolitan region of Cali.

RESULTS: Agricultural intensification and industrialization, coupled with uncontrolled urban growth, have significantly transformed the landscape, posing threats to its sustainability. The prevailing biocultural landscapes hold a substantial potential to provide essential ecosystem services to the metropolis. The IDC offers an approach that utilizes a land cover map and agricultural production/metabolism data to calculate an indicator closely related to ecosystem services and multifunctionality.

CONCLUSIONS: The IDC model stands out for efficiently capturing landscape dynamics, providing insights into landscape configuration and social metabolism without extensive resource requirements. This research highlights the importance of adopting a landscape-metabolic and green infrastructure framework to guide territorial policies in the tropical Andes and similar regions. It stresses the need for informed land use planning to address challenges and leverage opportunities presented by biocultural landscapes for regional sustainability amidst rapid urbanization and agricultural expansion.

RevDate: 2024-05-30

Roca Navarro MJ, Oliver Goldaracena JM, Garrido Alonso D, et al (2024)

Pre-surgical cryoablation in ≤ 2 cm ER + /HER2-tumors. Prognostic factors for the presence of residual invasive carcinoma.

Breast cancer research and treatment [Epub ahead of print].

BACKGROUND: Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery.

PURPOSE: To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes.

MATERIALS AND METHODS: This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing-thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables.

RESULTS: Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications.

CONCLUSIONS: Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients.

RevDate: 2024-05-28

Burns N, A Bourke (2024)

Recurrence in lobular carcinoma of the breast: A 14-year review.

Journal of medical imaging and radiation oncology [Epub ahead of print].

INTRODUCTION: The two most common types of breast cancer are invasive or infiltrating ductal carcinoma (IDC) and invasive or infiltrating lobular carcinoma (ILC) (Pestalozzi et al., J. Clin. Oncol., 26, 2008, 3006). Between 5% and 15% of invasive breast carcinomas are lobular carcinomas (Pestalozzi et al., J. Clin. Oncol., 26, 2008, 3006; Dossus and Benusiglio, Breast Cancer Res., 17, 2015, 37; Braunstein et al., Breast Cancer Res. Treat., 149, 2015, 555). The paucity of data relating to recurrence rates of lobular cancers prompted this study.

METHODS: A retrospective cohort study of all cases of lobular breast carcinoma reported to the Western Australia Cancer Registry with the clinical and pathological details between 2000 and 2014.

RESULTS: Overall, 2463 subjects with a total of 2526 events of invasive lobular carcinoma of the breast. 11/2463 (0.45%) subjects met criteria for local recurrence of invasive lobular breast cancer, with an incidence of 1 in 224.

CONCLUSION: There are clinical implications for the management and follow-up for patients with a diagnosis of lobular cancer of the breast. Due to the low recurrence rate, now, the standard practice in our institution does not offer magnetic resonance imaging (MRI) as part of the follow-up for ILC patients. Other centres should establish local recurrence rates to aid development of appropriate management protocols.

RevDate: 2024-05-28

Peng L, Ma M, Zhao D, et al (2024)

Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma.

Frontiers in oncology, 14:1291034.

BACKGROUND: Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion.

METHODS: We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis.

RESULTS: A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5 cm (36.5%) and >5 cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients.

CONCLUSIONS: Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.

RevDate: 2024-05-25

Voß F, Zweck E, Ipek R, et al (2024)

Myocardial Mitochondrial Function Is Impaired in Cardiac Light-Chain Amyloidosis Compared to Transthyretin Amyloidosis.

RevDate: 2024-05-27

Makhlouf S, Atallah NM, Polotto S, et al (2024)

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype.

Cancers, 16(10):.

BACKGROUND: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes.

METHODS: A large (n = 7140) well-characterised and histologically reviewed BC cohort with treatment and long-term follow-up data was investigated. The cohort was classified based on the WHO classification of tumours into main histological subtypes, including ILC and IDC-NST. ILCs were further classified into variants. Clinicopathological parameters and patient outcomes in terms of BC-specific survival (BCSS) and disease-free survival (DFS) were evaluated.

RESULTS: ILC constituted 11% of the cohort. The most common non-classic ILC variants were pleomorphic (pILC) and solid (sILC), constituting 19% of ILC. Compared to classic and related variants (alveolar, trabecular, papillary, and tubulolobular; cILC), pILC and sILC variants were associated with aggressive tumour characteristics. The histologic grade of ILC was an important prognostic variable. The survival patterns identified an aggressive ILC subtype encompassing pILC and high-grade sILC. These tumours, which comprised 14% of the cases, were associated with clinicopathological characteristics of poor prognosis and had high BC-specific death and recurrence rates compared not only to cILC (p < 0.001) but also to IDC-NST (p = 0.02) patients. Contrasting this, cILC patients had significantly longer BCSS and DFS than IDC-NST patients in the first 10 to 15 years of follow-up. Adjuvant chemotherapy did not improve the outcome of patients with aggressive ILC subtypes.

CONCLUSIONS: pILC and high-grade sILC variants comprise an aggressive ILC subtype associated with poor prognostic characteristics and a poor response to chemotherapy. These results warrant confirmation in randomised clinical trials.

RevDate: 2024-05-24

Ben-David BM, Chebat DR, M Icht (2024)

"Love looks not with the eyes": supranormal processing of emotional speech in individuals with late-blindness versus preserved processing in individuals with congenital-blindness.

Cognition & emotion [Epub ahead of print].

Processing of emotional speech in the absence of visual information relies on two auditory channels: semantics and prosody. No study to date has investigated how blindness impacts this process. Two theories, Perceptual Deficit, and Sensory Compensation, yiled different expectations about the role of visual experience (or its lack thereof) in processing emotional speech. To test the effect of vision and early visual experience on processing of emotional speech, we compared individuals with congenital blindness (CB, n = 17), individuals with late blindness (LB, n = 15), and sighted controls (SC, n = 21) on identification and selective-attention of semantic and prosodic spoken-emotions. Results showed that individuals with blindness performed at least as well as SC, supporting Sensory Compensation and the role of cortical reorganisation. Individuals with LB outperformed individuals with CB, in accordance with Perceptual Deficit, supporting the role of early visual experience. The LB advantage was moderated by executive functions (working-memory). Namely, the advantage was erased for individuals with CB who showed higher levels of executive functions. Results suggest that vision is not necessary for processing of emotional speech, but early visual experience could improve it. The findings support a combination of the two aforementioned theories and reject a dichotomous view of deficiencies/enhancements of blindness.

RevDate: 2024-05-25

Ahmad H, Ali A, Khalil AT, et al (2024)

Clinico-genomic findings, molecular docking, and mutational spectrum in an understudied population with breast cancer patients from KP, Pakistan.

Frontiers in genetics, 15:1383284.

In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATM p. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants.

RevDate: 2024-05-21

Wang S, Zhang Q, Zhang T, et al (2024)

Invasive papillary carcinoma of the breast: A case report.

Oncology letters, 28(1):300.

Invasive papillary carcinoma (IPC) of the breast is a rare form of cancer. The current report documents a case of IPC characterized by a large tumor size and skin involvement. Surgical exploration revealed no evidence of axillary lymph node metastasis in breast cancer. Due to financial constraints, the patient opted solely for anastrozole endocrine therapy at a dosage of 1 mg/day for a period of 5 years post-surgery, foregoing other treatments such as radiotherapy and chemotherapy. Since discharge, 2.5 years have passed, during which the patient has been followed up via phone every 3 months, showing a good prognosis. A literature review indicated that IPC is prevalent amongst the elderly population and can be misdiagnosed due to its morphological, cytomorphological and immunophenotypic overlap with other types of papillary neoplasms. This tumor exhibits a more favorable prognosis compared with IDC, primarily attributed to its advantageous gene and molecular expression patterns, coupled with its decreased invasiveness. Despite limited evidence-based research on the treatment of IPC, the present case report, albeit with limitations, underscores the importance of avoiding over-treatment and suggests the feasibility of combining surgery with endocrine therapy for IPC.

RevDate: 2024-05-20

Dor YI, Algom D, Shakuf V, et al (2024)

Age-related differences in processing of emotions in speech disappear with babble noise in the background.

Cognition & emotion [Epub ahead of print].

Older adults process emotional speech differently than young adults, relying less on prosody (tone) relative to semantics (words). This study aimed to elucidate the mechanisms underlying these age-related differences via an emotional speech-in-noise test. A sample of 51 young and 47 older adults rated spoken sentences with emotional content on both prosody and semantics, presented on the background of wideband speech-spectrum noise (sensory interference) or on the background of multi-talker babble (sensory/cognitive interference). The presence of wideband noise eliminated age-related differences in semantics but not in prosody when processing emotional speech. Conversely, the presence of babble resulted in the elimination of age-related differences across all measures. The results suggest that both sensory and cognitive-linguistic factors contribute to age-related changes in emotional speech processing. Because real world conditions typically involve noisy background, our results highlight the importance of testing under such conditions.

RevDate: 2024-05-17

Langer HT, Rohm M, Goncalves MD, et al (2024)

AMPK as a mediator of tissue preservation: time for a shift in dogma?.

Nature reviews. Endocrinology [Epub ahead of print].

Ground-breaking discoveries have established 5'-AMP-activated protein kinase (AMPK) as a central sensor of metabolic stress in cells and tissues. AMPK is activated through cellular starvation, exercise and drugs by either directly or indirectly affecting the intracellular AMP (or ADP) to ATP ratio. In turn, AMPK regulates multiple processes of cell metabolism, such as the maintenance of cellular ATP levels, via the regulation of fatty acid oxidation, glucose uptake, glycolysis, autophagy, mitochondrial biogenesis and degradation, and insulin sensitivity. Moreover, AMPK inhibits anabolic processes, such as lipogenesis and protein synthesis. These findings support the notion that AMPK is a crucial regulator of cell catabolism. However, studies have revealed that AMPK's role in cell homeostasis might not be as unidirectional as originally thought. This Review explores emerging evidence for AMPK as a promoter of cell survival and an enhancer of anabolic capacity in skeletal muscle and adipose tissue during catabolic crises. We discuss AMPK-activating interventions for tissue preservation during tissue wasting in cancer-associated cachexia and explore the clinical potential of AMPK activation in wasting conditions. Overall, we provide arguments that call for a shift in the current dogma of AMPK as a mere regulator of cell catabolism, concluding that AMPK has an unexpected role in tissue preservation.

RevDate: 2024-05-18

Ma S, Li Y, Yin J, et al (2024)

Prospective study of AI-assisted prediction of breast malignancies in physical health examinations: role of off-the-shelf AI software and comparison to radiologist performance.

Frontiers in oncology, 14:1374278.

OBJECTIVE: In physical health examinations, breast sonography is a commonly used imaging method, but it can lead to repeated exams and unnecessary biopsy due to discrepancies among radiologists and health centers. This study explores the role of off-the-shelf artificial intelligence (AI) software in assisting radiologists to classify incidentally found breast masses in two health centers.

METHODS: Female patients undergoing breast ultrasound examinations with incidentally discovered breast masses were categorized according to the 5[th] edition of the Breast Imaging Reporting and Data System (BI-RADS), with categories 3 to 5 included in this study. The examinations were conducted at two municipal health centers from May 2021 to May 2023.The final pathological results from surgical resection or biopsy served as the gold standard for comparison. Ultrasonographic images were obtained in longitudinal and transverse sections, and two junior radiologists and one senior radiologist independently assessed the images without knowing the pathological findings. The BI-RADS classification was adjusted following AI assistance, and diagnostic performance was compared using receiver operating characteristic curves.

RESULTS: A total of 196 patients with 202 breast masses were included in the study, with pathological results confirming 107 benign and 95 malignant masses. The receiver operating characteristic curve showed that experienced breast radiologists had higher diagnostic performance in BI-RADS classification than junior radiologists, similar to AI classification (AUC = 0.936, 0.806, 0.896, and 0.950, p < 0.05). The AI software improved the accuracy, sensitivity, and negative predictive value of the adjusted BI-RADS classification for the junior radiologists' group (p< 0.05), while no difference was observed in the senior radiologist group. Furthermore, AI increased the negative predictive value for BI-RADS 4a masses and the positive predictive value for 4b masses among radiologists (p < 0.05). AI enhances the sensitivity of invasive breast cancer detection more effectively than ductal carcinoma in situ and rare subtypes of breast cancer.

CONCLUSIONS: The AI software enhances diagnostic efficiency for breast masses, reducing the performance gap between junior and senior radiologists, particularly for BI-RADS 4a and 4b masses. This improvement reduces unnecessary repeat examinations and biopsies, optimizing medical resource utilization and enhancing overall diagnostic effectiveness.

RevDate: 2024-05-16

Shaw AK, Khurana D, S Soni (2024)

Assessment of thermal damage for plasmonic photothermal therapy of subsurface tumors.

Physical and engineering sciences in medicine [Epub ahead of print].

Plasmonic photothermal therapy (PPTT) involves the use of nanoparticles and near-infrared radiation to attain a temperature above 50 °C within the tumor for its thermal damage. PPTT is largely explored for superficial tumors, and its potential to treat deeper subsurface tumors is dealt feebly, requiring the assessment of thermal damage for such tumors. In this paper, the extent of thermal damage is numerically analyzed for PPTT of invasive ductal carcinoma (IDC) situated at 3-9 mm depths. The developed numerical model is validated with suitable tissue-tumor mimicking phantoms. Tumor (IDC) embedded with gold nanorods (GNRs) is subjected to broadband near-infrared radiation. The effect of various GNRs concentrations and their spatial distributions [viz. uniform distribution, intravenous delivery (peripheral distribution) and intratumoral delivery (localized distribution)] are investigated for thermal damage for subsurface tumors situated at various depths. Results show that lower GNRs concentrations lead to more uniform internal heat generation, eventually resulting in uniform temperature rise. Also, the peripheral distribution of nanoparticles provides a more uniform spatial temperature rise within the tumor. Overall, it is concluded that PPTT has potential to induce thermal damage for subsurface tumors, at depths of upto 9 mm, by proper choice of nanoparticle distribution, dose/concentration and irradiation parameters based on the tumor location. Moreover, intravenous administration of nanoparticles seems a good choice for shallower tumors, while for deeper tumors, uniform distribution is required to attain the necessary thermal damage. In the future, the algorithm may be extended further, involving 3D patient-specific tumors and through mice model-based experiments.

RevDate: 2024-05-17

Lv Y, Zhang H, Zhao Y, et al (2024)

A case report of low-dose apatinib in the treatment of advanced triple-negative breast cancer.

Translational breast cancer research : a journal focusing on translational research in breast cancer, 5:8.

BACKGROUND: The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means.

CASE DESCRIPTION: A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months.

CONCLUSIONS: Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.

RevDate: 2024-05-17

Luo T, Zhu K, Zhong X, et al (2023)

CDK4/6 inhibitors for primary endocrine resistant HR-positive/HER2-negative metastatic breast cancer: a case report.

Translational breast cancer research : a journal focusing on translational research in breast cancer, 4:33.

BACKGROUND: We report a case of hormone receptor (HR) positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer with multiple liver metastases who achieved good clinical benefit across cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy. Prior to this, the patient underwent neoadjuvant therapy and surgery as well as adjuvant endocrine therapy. We present and discuss three important treatment decision nodes associated with it.

CASE DESCRIPTION: A 60-year-old woman was diagnosed with invasive ductal carcinoma of the left breast (cT4bN2M0, stage IIIB, Luminal B HER2-negative type) at the West China Hospital of Sichuan University in 2020, and received neoadjuvant chemotherapy and modified radical mastectomy of the left breast from 2020 to 2021. Postoperative radiotherapy was performed in the left chest wall and left upper and lower clavicular region. Adjuvant therapy is anastrozole endocrine therapy. Multiple liver metastases developed in 2022. The pathological molecular typing of liver metastases was confirmed to be consistent with the primary lesion. In the context of primary endocrine resistance, the first-line treatment of choice was fulvestrant in combination with a targeted CDK4/6 inhibitor (abemaciclib). This combination regimen made the liver metastases visibly shrunk, leading to partial response (PR) and has achieved a progression-free survival of 12 months. And there were no serious drug-related adverse events during first-line treatment.

CONCLUSIONS: CDK4/6 inhibitor is a promising antineoplastic agent for HR positive, HER2 negative breast cancer patients. With the development of research, the application scope of CDK4/6 inhibitors is gradually expanding, and the precision treatment of breast cancer requires more rational drug selection and combination.

RevDate: 2024-05-16
CmpDate: 2024-05-16

Shirazi B, Niaz M, MA Khan (2024)

The characteristics and risk factors of breast cancer patients trend distinctive regional differences: a cross-sectional study.

JPMA. The Journal of the Pakistan Medical Association, 74(4):672-676.

OBJECTIVE: To determine the characteristics and risk factors of breast cancer patients in a tertiary care setting.

METHODS: The retrospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, and comprised data of all patients diagnosed with breast cancer from March 2017 to December 2021. Demographic characteristics, clinical presentation, stage of the disease and histopathological characteristics were noted. Data related to all the variables was not available in all cases. Data was analysed using SPSS 23.

RESULTS: Of the 690 patients, 683(99%) were females and 7(1%) were males. The mean age at presentation was 49.3±13.5 years, while the mean duration of symptoms was 10.24±17.64) months. Most of the females were married 642(93%) and multiparous 484(70.9%), while 293(42.5%) had breastfed their children for >1 year, and 412(59.7%) had no history of contraception use. The most common stage at presentation was stage II (48.6%), and most patients had grade II 395(57.2%) invasive ductal carcinoma, with Luminal A molecular subtype noted in 287(41.6%) cases.

CONCLUSIONS: The characteristics of breast cancer in the sample had certain distinctions compared to other populations. It is important to integrate all datasets and develop guidelines appropriate to Pakistani population.

RevDate: 2024-05-27

Stindt KR, MN McClean (2024)

Tuning interdomain conjugation to enable in situ population modification in yeasts.

mSystems [Epub ahead of print].

The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to the widespread use of IDC is its limited efficiency. In this work, we manipulated metabolic and physical interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture and model how these tunable controls can predictably yield a range of IDC outcomes. Furthermore, we demonstrate that these controls can be utilized to irreversibly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.IMPORTANCEFungi are important but often unaddressed members of most natural and synthetic microbial communities. This work highlights opportunities for modifying yeast microbiome populations through bacterial conjugation. While conjugation has been recognized for its capacity to deliver engineerable DNA to a range of cells, its dependence on cell contact has limited its efficiency. Here, we find "knobs" to control DNA transfer, by engineering the metabolic dependence between bacterial donors and yeast recipients and by changing their ability to physically adhere to each other. Importantly, we functionally validate these "knobs" by irreversibly altering yeast populations. We use these controls to "rescue" a failing yeast population, demonstrate the capacity of conjugated CRISPR/Cas9 to depress or collapse populations, and show that conjugation can be easily interrupted by disrupting cell-to-cell binding. These results offer building blocks toward in situ mycobiome editing, with significant implications for clinical treatments of fungal pathogens and other fungal system engineering.

RevDate: 2024-05-15

Rampal R, Jones S, Hogg W, et al (2024)

Evaluation of long-term outcome following therapeutic mammaplasty: the effect of wound complication on initiation of adjuvant therapy and subsequent oncological outcome.

Annals of the Royal College of Surgeons of England [Epub ahead of print].

INTRODUCTION: Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation.

METHODS: Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death.

RESULTS: In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis.

CONCLUSION: Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.

RevDate: 2024-05-24

Thiriveedhi VK, Krishnaswamy D, Clunie D, et al (2024)

Cloud-based large-scale curation of medical imaging data using AI segmentation.

Research square.

Rapid advances in medical imaging Artificial Intelligence (AI) offer unprecedented opportunities for automatic analysis and extraction of data from large imaging collections. Computational demands of such modern AI tools may be difficult to satisfy with the capabilities available on premises. Cloud computing offers the promise of economical access and extreme scalability. Few studies examine the price/performance tradeoffs of using the cloud, in particular for medical image analysis tasks. We investigate the use of cloud-provisioned compute resources for AI-based curation of the National Lung Screening Trial (NLST) Computed Tomography (CT) images available from the National Cancer Institute (NCI) Imaging Data Commons (IDC). We evaluated NCI Cancer Research Data Commons (CRDC) Cloud Resources - Terra (FireCloud) and Seven Bridges-Cancer Genomics Cloud (SB-CGC) platforms - to perform automatic image segmentation with TotalSegmentator and pyradiomics feature extraction for a large cohort containing >126,000 CT volumes from >26,000 patients. Utilizing >21,000 Virtual Machines (VMs) over the course of the computation we completed analysis in under 9 hours, as compared to the estimated 522 days that would be needed on a single workstation. The total cost of utilizing the cloud for this analysis was $1,011.05. Our contributions include: 1) an evaluation of the numerous tradeoffs towards optimizing the use of cloud resources for large-scale image analysis; 2) CloudSegmentator, an open source reproducible implementation of the developed workflows, which can be reused and extended; 3) practical recommendations for utilizing the cloud for large-scale medical image computing tasks. We also share the results of the analysis: the total of 9,565,554 segmentations of the anatomic structures and the accompanying radiomics features in IDC as of release v18.

RevDate: 2024-05-14

Tan RYC, Ong WS, Lee KH, et al (2024)

Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

Journal of the National Comprehensive Cancer Network : JNCCN [Epub ahead of print].

BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties.

METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC.

RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups.

CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

RevDate: 2024-05-15

Song L, Qiu Y, Huang W, et al (2024)

Untypical bilateral breast cancer with peritoneal fibrosis on [18]F-FDG PET/CT: case report and literature review.

Frontiers in medicine, 11:1353822.

BACKGROUND: Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using [18]F-FDG PET/CT, providing help for clinical diagnosis and treatment.

CASE REPORT: A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, [18]F-deoxyglucose positron emission tomography/computer tomography ([18]F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal [18]F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal [18]F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant [18]F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction.

CONCLUSION: In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.

RevDate: 2024-05-15

Ahuja S, G K, S Zaheer (2024)

Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.

Indian journal of surgical oncology, 15(2):236-240.

Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5 years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.

RevDate: 2024-05-14
CmpDate: 2024-05-13

Amado IR, Romaní-Pérez M, Fuciños P, et al (2024)

Editorial: Novel and emerging therapies for the treatment of obesity and related disorders.

Frontiers in endocrinology, 15:1371113.

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RJR Experience and Expertise

Researcher

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.

Educator

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.

Administrator

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.

Technologist

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.

Publisher

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.

Speaker

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.

Facilitator

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.

Designer

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

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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