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29 Sep 2023 at 01:49
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 29 Sep 2023 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®)


RevDate: 2023-09-28

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

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

Diagnostics (Basel, Switzerland), 13(18): pii:diagnostics13182966.

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

RevDate: 2023-09-25

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

Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.

Nature cancer [Epub ahead of print].

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

RevDate: 2023-09-25

Choi JH, Yu J, Jung M, et al (2023)

Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.

Medicine, 102(38):e35267.

Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.

RevDate: 2023-09-25

Stindt KR, MN McClean (2023)

Tuning Interdomain Conjugation Toward in situ Population Modification in Yeast.

bioRxiv : the preprint server for biology pii:2023.09.12.557379.

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 widespread use of IDC is its limited efficiency. In this work, we utilize 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. Further, we demonstrate that these lessons can be utilized to lastingly 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.

RevDate: 2023-09-24

Pourriahi R, Omranipour R, Alipour S, et al (2023)

Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.

BMC women's health, 23(1):511.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran.

METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist.

RESULTS: A total of 1476 patients with a mean age of 48.03 (± 11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B.

CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.

RevDate: 2023-09-22

Peng L, He X, Peng X, et al (2023)

STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering.

Computers in biology and medicine, 166:107440 pii:S0010-4825(23)00905-8 [Epub ahead of print].

BACKGROUND: Spatial transcriptomics technologies fully utilize spatial location information, tissue morphological features, and transcriptional profiles. Integrating these data can greatly advance our understanding about cell biology in the morphological background.

METHODS: We developed an innovative spatial clustering method called STGNNks by combining graph neural network, denoising auto-encoder, and k-sums clustering. First, spatial resolved transcriptomics data are preprocessed and a hybrid adjacency matrix is constructed. Next, gene expressions and spatial context are integrated to learn spots' embedding features by a deep graph infomax-based graph convolutional network. Third, the learned features are mapped to a low-dimensional space through a zero-inflated negative binomial (ZINB)-based denoising auto-encoder. Fourth, a k-sums clustering algorithm is developed to identify spatial domains by combining k-means clustering and the ratio-cut clustering algorithms. Finally, it implements spatial trajectory inference, spatially variable gene identification, and differentially expressed gene detection based on the pseudo-space-time method on six 10x Genomics Visium datasets.

RESULTS: We compared our proposed STGNNks method with five other spatial clustering methods, CCST, Seurat, stLearn, Scanpy and SEDR. For the first time, four internal indicators in the area of machine learning, that is, silhouette coefficient, the Davies-Bouldin index, the Caliniski-Harabasz index, and the S_Dbw index, were used to measure the clustering performance of STGNNks with CCST, Seurat, stLearn, Scanpy and SEDR on five spatial transcriptomics datasets without labels (i.e., Adult Mouse Brain (FFPE), Adult Mouse Kidney (FFPE), Human Breast Cancer (Block A Section 2), Human Breast Cancer (FFPE), and Human Lymph Node). And two external indicators including adjusted Rand index (ARI) and normalized mutual information (NMI) were applied to evaluate the performance of the above six methods on Human Breast Cancer (Block A Section 1) with real labels. The comparison experiments elucidated that STGNNks obtained the smallest Davies-Bouldin and S_Dbw values and the largest Silhouette Coefficient, Caliniski-Harabasz, ARI and NMI, significantly outperforming the above five spatial transcriptomics analysis algorithms. Furthermore, we detected the top six spatially variable genes and the top five differentially expressed genes in each cluster on the above five unlabeled datasets. And the pseudo-space-time tree plot with hierarchical layout demonstrated a flow of Human Breast Cancer (Block A Section 1) progress in three clades branching from three invasive ductal carcinoma regions to multiple ductal carcinoma in situ sub-clusters.

CONCLUSION: We anticipate that STGNNks can efficiently improve spatial transcriptomics data analysis and further boost the diagnosis and therapy of related diseases. The codes are publicly available at https://github.com/plhhnu/STGNNks.

RevDate: 2023-09-22

Coffey K, Dixon LB, Sevilimedu V, et al (2023)

Short-term follow-up of contrast-enhanced mammography lesions after negative breast MRI in women with elevated breast cancer risk.

European journal of radiology, 168:111097 pii:S0720-048X(23)00411-4 [Epub ahead of print].

PURPOSE: To determine the outcome of enhancing lesions detected on contrast-enhanced mammography (CEM) that had no correlate on magnetic resonance imaging (MRI) and underwent short-term follow-up CEM.

METHODS: In this retrospective single-center study, we identified patients with elevated breast cancer risk who had a CEM between 2014 and 2021 showing indeterminate enhancement on recombined images (BI-RADS 0, 3, 4) that had no correlate on subsequent MRI (performed within one month), and therefore underwent short-term follow-up CEM (performed within eight months). Medical records and imaging studies were reviewed to collect data on patient and lesion characteristics, and outcomes. Cancer incidence with 95% confidence interval (CI) was calculated.

RESULTS: This study included 71 women (median age 49 years) with 81 enhancing CEM lesions who underwent short-term follow-up CEM (median 6.2 months) after MRI reported no correlate. Of 81 lesions (median size = 0.7 cm), 73 (90%) were non-mass enhancement and 8 (10%) were enhancing masses. No sonographic correlate was identified for 75 lesions that had a same-day targeted ultrasound. Two cancers (2.5%, 95% CI 0.3-8.6) were diagnosed during the short-term follow-up period, one at 6-months (invasive ductal carcinoma) and one at 12-months (ductal carcinoma in situ). The remaining 79 lesions were benign at 6-month follow-up CEM and at one-year mammographic follow-up.

CONCLUSIONS: Follow-up CEM of MRI-occult lesions is prudent and may be reasonable to perform at one-year given the low incidence of cancer detected at six-months (one of 81) in our small study sample.

RevDate: 2023-09-22

Sijnesael T, Richard F, Rätze MA, et al (2023)

Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.

The Journal of pathology [Epub ahead of print].

Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ER[POS] Her2[NEG] breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

RevDate: 2023-09-21

Deberti M, Goupille C, Arbion F, et al (2023)

Prognostic value of axillary lymph node metastases in invasive lobular breast carcinoma.

Journal of gynecology obstetrics and human reproduction pii:S2468-7847(23)00132-0 [Epub ahead of print].

BACKGROUND: Axillary lymph node involvement is a well-established prognostic factor for recurrence in breast cancer, specifically the number of nodes affected and the ratio of the number of affected nodes to the number of harvested nodes for non-specific invasive breast cancer (invasive ductal carcinoma). However, there is limited information on the impact of lymph node involvement in the case of invasive lobular carcinoma.

OBJECTIVES: our study aimed to evaluate the prognostic impact of lymph node involvement on overall survival and distant metastatic-free survival according to the number of nodes affected and the ratio of positive nodes (LNR) for patients managed for invasive lobular carcinoma.

METHODS: This is a monocentre, comparative, observational study of patients managed for invasive lobular carcinoma at the Gynaecology Department of the University Hospital Centre of Tours between January 1, 2007 and December 31, 2018. The LNR cut-off values used were: low risk if LNR ≤ 0.2; intermediate risk if LNR > 0.2 and ≤ 0.65, and high risk for LNR >0.659 RESULTS: Our study demonstrated a significant difference in overall survival and distant metastasis free survival (p < 0.0001). The 5-years Overall survival was 94% for N0 patients, 92.4% for low-risk patients, 85.6% for intermediate-risk patients and 58.5% for high-risk patients. The 5-year distant metastasis-free survival was 98.2% for N0 patients, 95.9% for low-risk patients, 80.1% for intermediate-risk patients, and 60.3% for high-risk patients. Multivariate analysis identified age, invasive lobular histologic type, presence of clinical inflammation, and intermediate and high risk classes of LNR ratio as independent factors affecting overall survival. For metastatic-free survival, the presence of clinical inflammation, the presence of LVSI and the low, intermediate, or high-risk classes of LNR ratio were identified as independent factors . However, age and invasive lobular histologic type did not appear to be independent factors affecting metastatic-free survival.

CONCLUSION: Our study highlights the significant prognostic impact of lymph node involvement in patients with invasive lobular carcinoma. The LNR ratio can be used as a reliable predictor of overall survival and metastatic-free survival in these patients.

RevDate: 2023-09-21

Okubo T, Minari Y, Y Ikura (2023)

Change in Main Histological Type of Invasive Breast Cancer From Ductal to Lobular Carcinoma by Neoadjuvant Chemotherapy.

Cureus, 15(8):e43816.

We present a case study of breast cancer initially diagnosed as invasive ductal carcinoma (IDC), which subsequently substituted into invasive lobular carcinoma (ILC) following neoadjuvant chemotherapy (NAC). A 61-year-old woman presented with a palpable breast lump, and histological examination through core needle biopsy (CNB) confirmed the presence of IDC. After a 6-month course of NAC, the patient achieved a clinically complete response (cCR) and underwent mastectomy. The surgical specimen showed no detectable tumor upon palpation, but microscopic analysis revealed a highly infiltrative growth of poorly-cohesive small atypical cells in the original tumor area. Immunohistochemical staining demonstrated that the tumor cells were negative for E-cadherin, leading to a diagnosis of ILC. To address the histological discrepancy before and after NAC, we re-evaluated the initial CNB using E-cadherin immunohistochemistry. While most tumor cells were E-cadherin positive, a small area displaying scirrhous subtype-like morphology exhibited E-cadherin negativity. Consequently, we revised the diagnosis to mixed IDC-ILC. The differential chemosensitivity between IDC and ILC may provide insight into this phenomenon.

RevDate: 2023-09-20

Ferreira CJDS, Caires IQS, Costa Neto WJBD, et al (2023)

Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma.

Revista da Associacao Medica Brasileira (1992), 69(9):e20221210 pii:S0104-42302023000900600.

OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data.

METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images.

RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%).

CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

RevDate: 2023-09-20

Rezaei A, Shayan N, Shirazinia S, et al (2023)

The Prognostic Significance of P16 Immunohistochemical Expression Pattern in Women with Invasive Ductal Breast Carcinoma.

Reports of biochemistry & molecular biology, 12(1):83-91.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The p16 protein is a cell cycle regulator and tumor suppressor implicated in several types of cancers. However, its relationship to breast cancer is still unknown. The present study aimed to assess the association of p16 protein expression with clinicopathological features in breast cancer.This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

METHODS: The study enrolled 100 patients with invasive ductal carcinoma. The samples were collected before any adjuvant chemotherapy, and p16 protein expression was determined using immunohistochemistry. Clinicopathological features were obtained from the patient's medical records.

RESULTS: Our findings demonstrated that p16 protein expression increased in estrogen receptor-positive tumor tissues (P< 0.01). However, no significant correlation was found between the p16 protein expression and the other clinicopathological features.

CONCLUSIONS: Our study demonstrated that p16 protein expression increased in ER-positive tumor tissue from patients with invasive ductal breast carcinoma. However, no correlation was found between the p16 protein expression and the other clinicopathological features.

RevDate: 2023-09-14

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

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

American journal of clinical oncology pii:00000421-990000000-00129 [Epub ahead of print].

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

METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).

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

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

RevDate: 2023-09-18

Neth BJ, Raghunathan A, Kizilbash SH, et al (2023)

Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.

Neurology, 101(12):e1256-e1271.

BACKGROUND AND OBJECTIVES: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood.

METHODS: We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses.

RESULTS: We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses.

DISCUSSION: We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).

RevDate: 2023-09-12

Lu D, Li F, Zhao C, et al (2023)

A Remineralizing and Antibacterial Coating for Arresting Caries.

Journal of dental research [Epub ahead of print].

Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.

RevDate: 2023-09-11

Onega T, Abraham L, Miglioretti DL, et al (2023)

Digital mammography and digital breast tomosynthesis for detecting invasive lobular and ductal carcinoma.

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

PURPOSE: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that can make early detection with mammography challenging. We compared imaging performance of digital breast tomosynthesis (DBT) to digital mammography (DM) for diagnoses of ILC, invasive ductal carcinoma (IDC), and invasive mixed carcinoma (IMC) in a screening population.

METHODS: We included screening exams (DM; n = 1,715,249 or DBT; n = 414,793) from 2011 to 2018 among 839,801 women in the Breast Cancer Surveillance Consortium. Examinations were followed for one year to ascertain incident ILC, IDC, or IMC. We measured cancer detection rate (CDR) and interval invasive cancer rate/1000 screening examinations for each histological subtype and stratified by breast density and modality. We calculated relative risk (RR) for DM vs. DBT using log-binomial models to adjust for the propensity of receiving DBT vs. DM.

RESULTS: Unadjusted CDR per 1000 mammograms of ILC overall was 0.33 (95%CI: 0.30-0.36) for DM; 0.45 (95%CI: 0.39-0.52) for DBT, and for women with dense breasts- 0.33 (95%CI: 0.29-0.37) for DM and 0.54 (95%CI: 0.43-0.66) for DBT. Similar results were noted for IDC and IMC. Adjusted models showed a significantly increased RR for cancer detection with DBT compared to DM among women with dense breasts for all three histologies (RR; 95%CI: ILC 1.53; 1.09-2.14, IDC 1.21; 1.02-1.44, IMC 1.76; 1.30-2.38), but no significant increase among women with non-dense breasts.

CONCLUSION: DBT was associated with higher CDR for ILC, IDC, and IMC for women with dense breasts. Early detection of ILC with DBT may improve outcomes for this distinct clinical entity.

RevDate: 2023-09-11

Bernardino RM, Sayyid RK, Lajkosz K, et al (2023)

Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer.

European urology focus pii:S2405-4569(23)00195-5 [Epub ahead of print].

BACKGROUND: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions.

OBJECTIVE: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples.

Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study.

We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC.

RESULTS AND LIMITATIONS: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36-49%) for detection of cribriform morphology and 44.1% (95% CI 36-52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47-58%). Among patients who underwent multiparametric magnetic resonance imaging-guided biopsies, the sensitivity was 54% (95% CI 39-68%) for detection of cribriform morphology and 37% (95% CI 19-58%) for detection of IDC.

CONCLUSIONS: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed.

PATIENT SUMMARY: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.

RevDate: 2023-09-11

Tanpure VR, Palagiri FB, Kolhe KK, et al (2023)

A Study to Assess Indian Patients' Expectations of Check-Up and Diagnosis or Discussion about Treatment at their Initial Orthodontic Visit.

Journal of pharmacy & bioallied sciences, 15(Suppl 2):S1253-S1256.

AIM: To access the patient's expectations of orthodontic treatment at the first visit.

MATERIALS AND METHODS: Three hundred new patients to the orthodontics department were included in the analysis. Their demographic details and their opinions on what they hoped to gain from orthodontic treatment were gleaned from their replies to a well-crafted questionnaire.

RESULTS: Most respondents were more concerned with the cosmetic results of orthodontic treatment than they were with the therapy's practical benefits. They hoped that after having their teeth straightened, they would feel more comfortable interacting with others and have a better overall appearance. In terms of improving one's job and making one's speaking simpler, the mean scores were the lowest. The female participants averaged higher marks than the male participants across all areas studied, with the greatest mark coming in the area of improved smiles.

CONCLUSION: An effective outcome from orthodontic therapy requires full patient participation. Before beginning treatment, it is important for the orthodontist and patient to have an agreement on the patient's reasonable expectations for the therapy's outcomes.

RevDate: 2023-09-11

Yang SY, Kang DS, CY Lee (2023)

Coloration on Bluish Alginate Films with Amorphous Heterogeneity Thereof.

Polymers, 15(17):.

Using sodium alginate (Alg) aqueous solution containing indigo carmine (IdC) at various concentrations we characterized the rippled surface pattern with micro-spacing on a flexible film as intriguing bluish Alg-IdC iridescence. The characterization was performed using Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, field emission scanning electron microscopy, atomic force microscopy, electron microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction analysis, and photoluminescence detection. The edge pattern on the film had a maximum depth of 825 nm, a peak-to-peak distance of 63.0 nm, and an average distance of 2.34 nm. The center of the pattern had a maximum depth of 343 nm and a peak-to-peak distance of 162 nm. The pattern spacing rippled irregularly, widening toward the center and narrowing toward the edges. The rippled nano-patterned areas effectively generated iridescence. The ultraviolet absorption spectra of the mixture in the 270 and 615 nm ranges were the same for both the iridescent and non-iridescent film surfaces. By adding Ag[+] ions to Alg-IdC, self-assembled microspheres were formed, and conductivity was improved. Cross-linked bluish materials were immediately formed by the addition of Ca[2+] ions, and the film was prepared by controlling their concentration. This flexible film can be used in applications such as eco-friendly camouflage, anti-counterfeiting, QR code materials for imaging/sensing, and smart hybrid displays.

RevDate: 2023-09-09

Timbres J, Kohut K, Caneppele M, et al (2023)

DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different?.

Cancers, 15(17): pii:cancers15174397.

Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35-60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT.

RevDate: 2023-09-08

Zhao F, Zhang T, Sun X, et al (2023)

A strategy for Cas13 miniaturization based on the structure and AlphaFold.

Nature communications, 14(1):5545.

The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2. In addition, we construct an RNA base editor, mini-Vx, and a single AAV (adeno-associated virus) carrying a mini-RfxCas13d and crRNA expression cassette, which individually shows efficient conversion rate and RNA-knockdown activity. In summary, these findings highlight a feasible strategy for generating downsized CRISPR/Cas13 systems based on structure predicted by AlphaFold2, enabling targeted degradation of RNAs and RNA editing for basic research and therapeutic applications.

RevDate: 2023-09-08

Moon SY, Lim KR, JS Son (2023)

The role of infectious disease consultations in the management of patients with fever in a long-term care facility.

PloS one, 18(9):e0291421 pii:PONE-D-23-09237.

BACKGROUND: Infectious disease (ID) clinicians can provide essential services for febrile patients in tertiary hospitals. The aim of this study was to evaluate the role of ID consultations (IDC) in managing hospitalized patients with infections in an oriental medical hospital (OMH), which serves as a long-term care facility. To our knowledge, this is the first study on the role of IDCs in managing patients in an OMH.

METHODS: This retrospective study was conducted in an OMH in Seoul, Korea, from June 2006 to June 2013.

RESULTS: Among the 465 cases of hospital-acquired fever, 141 (30.3%) were referred for ID. The most common cause of fever was infection in both groups. The peak body temperature of the patient was higher in IDC group (38.8±0.6°C vs. 38.6±0.5°C, p<0.001). Crude mortality at 30 days (14.6% vs. 7.8%, p = 0.043) and infection-attributable mortality (15.3% vs. 6.7%, p = 0.039) were higher in the No-IDC group. Multivariable analysis showed that infection as the focus of fever (adjusted Odd ratio [aOR] 3.49, 95% confidence interval (CI) 1.64-7.44), underlying cancer (aOR 10.32, 95% CI 4.34-24.51,), and multiorgan dysfunction syndrome (aOR 15.68, 95% CI 2.06-119.08) were associated with increased 30-day mortality. Multivariate analysis showed that in patients with infectious fever, appropriate antibiotic therapy (aOR 0.19, 95% CI 0.05-0.76) was the only factor associated with decreased infection-attributable mortality while underlying cancer (aOR 7.80, 95% CI 2.555-23.807) and severe sepsis or septic shock at the onset of fever (aOR 10.15, 95% CI 1.00-102.85) were associated with increased infection-attributable mortality.

CONCLUSION: Infection was the most common cause of fever in patients hospitalized for OMH. Infection as the focus of fever, underlying cancer, and MODS was associated with increased 30-day mortality in patients with nosocomial fever. Appropriate antibiotic therapy was associated with decreased infection-attributable mortality in patients with infectious fever.

RevDate: 2023-09-08

Goh SSN, Syn NLX, Lim CJE, et al (2023)

Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget's disease of the breast: systematic review and meta-analysis.

The British journal of surgery pii:7264735 [Epub ahead of print].

BACKGROUND: The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast.

METHODS: Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy.

RESULTS: Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20).

CONCLUSION: BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.

RevDate: 2023-09-08

Wang W, Ge J, Ma H, et al (2023)

Cladribine and cytarabine in children refractory high risk multisystem Langerhans cell histiocytosis.

Heliyon, 9(9):e19277 pii:S2405-8440(23)06485-X.

There is no uniform regimen for refractory Langerhans cell histiocytosis (LCH). We retrospectively described patients with refractory multisystem and risk organ involvement LCH treated with the low-dose (Ara-c, 100 mg/m[2]/d × 5day; 2-CDA, 5 mg/m[2]/d × 5day) chemotherapy (LDC) and the intermediate-dose (Ara-c, 500 mg/m[2]/d × 5day; 2-CDA, 9 mg/m[2]/d × 5day) chemotherapy (IDC). 26 patients and 10 patients receiving the LDC and IDC regimen from January 2013 to December 2016 were included in the study. The overall response rate exhibited no significant difference between the LDC and IDC groups after four courses (76.9% vs 90%, P = 0.375) and eight courses (80.8% vs 100%, P = 0.135) of treatment. No statistical differences in the overall survival rate were observed between the two groups, but 5-year event-free survival rate of patients in the IDC group was higher than that in the LDC group at the median follow-up of 6.16 and 5.07 years (88.9% vs 52.9%, P = 0.033). The patients in the IDC group had more severe myelosuppression than those in the LDC group (grade 3/4 myelosuppression, 80% vs 19.2%, P = 0.001). The intermediate-dose regimen of 2CDA and Ara-c had a higher event-free survival rate and a similar overall survival rate compared with the low-dose regimen.

RevDate: 2023-09-06

Mudeng V, Farid MN, Ayana G, et al (2023)

Domain and Histopathology Adaptations-Based Classification for Malignancy Grading System.

The American journal of pathology pii:S0002-9440(23)00312-7 [Epub ahead of print].

Through accurate proliferation rate quantification, an appropriate treatment for breast cancer may be devised. Pathologists use breast tissue biopsy glass slides stained with hematoxylin and eosin to obtain grading information. However, this manual evaluation may lead to high costs and ineffectiveness because diagnosis depends on the facility and the pathologists' insights and experiences. A convolutional neural network is considered feasible as a computer-based observer to improve clinicians' capacity in grading breast cancer. Therefore, this study propose a novel scheme for automatic breast cancer malignancy grading from invasive ductal carcinoma. The proposed classifiers implement multistage transfer learning incorporating domain and histopathological transformations. Domain adaptation using pre-trained models, such as InceptionResNetV2, InceptionV3, NASNet-Large, ResNet50, ResNet101, VGG19, and Xception, was applied to classify the 40× magnification BreaKHis dataset into eight classes. Then, the best models, in this study, InceptionV3 and Xception, which contain the domain and histopathology pre-trained weights, were used to categorize the Databiox database into grades 1, 2, or 3. To provide a comprehensive report, this study offers a patchless automated grading system for magnification-dependent and magnification-independent classifications. With an overall accuracy of 90.17%±3.08%-97.67%±1.09% and F1-score of 0.9013-0.9760 for magnification-dependent classification, the classifiers in this work achieved outstanding performance. The proposed approach could be used for breast cancer grading systems in clinical settings.

RevDate: 2023-09-06

Giroud M, Kotschi S, Kwon Y, et al (2023)

The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes.

EMBO reports [Epub ahead of print].

Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.

RevDate: 2023-09-05

Amiri A, Dietz C, Rapp A, et al (2023)

The cyto-linker and scaffolding protein "plectin" mis-localization leads to softening of cancer cells.

Nanoscale [Epub ahead of print].

Discovering tools to prevent cancer progression requires understanding the fundamental differences between normal and cancer cells. More than a decade ago, atomic force microscopy (AFM) revealed cancer cells' softer body compared to their healthy counterparts. Here, we investigated the mechanism underlying the softening of cancerous cells in comparison with their healthy counterparts based on AFM high resolution stiffness tomography and 3D confocal microscopy. We showed microtubules (MTs) network in invasive ductal carcinoma cell cytoskeleton is basally located and segmented for around 400 nm from the cell periphery. Additionally, the cytoskeleton scaffolding protein plectin exhibits a mis-localization from the cytoplasm to the surface of cells in the carcinoma which justifies the dissociation of the MT network from the cell's cortex. Furthermore, the assessment of MTs' persistence length using a worm-like-chain (WLC) model in high resolution AFM images showed lower persistence length of the single MTs in ductal carcinoma compared to that in the normal state. Overall, these tuned mechanics support the invasive cells to ascertain more flexibility under compressive forces in small deformations. These data provide new insights into the structural origins of cancer aids in progression.

RevDate: 2023-09-04

Aiello EN, D'Iorio A, Solca F, et al (2023)

Correction: Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.

RevDate: 2023-09-04

Haque E, Mushtaq AH, Alkhatib R, et al (2023)

An Unexpected Diagnosis of Second Primary Malignancy in a Breast Cancer Survivor: A Case Report.

Cureus, 15(8):e42819.

BACKGROUND: Breast cancer survival rates are increasing more than ever with the development of better diagnostic and therapeutic techniques. Survivors of breast cancer have an increased risk of developing second primary malignancies, which may be mistaken for breast cancer recurrence and lead to delayed diagnosis and poor prognosis.

CASE REPORT: We report a case of a 62-year-old female who presented with shortness of breath and bone pain. She had a history of left triple-positive invasive ductal carcinoma (T1N0M0) treated with bilateral skin-sparing mastectomy, adjuvant Taxotere, and trastuzumab-based therapy and then continued on trastuzumab and letrozole. She underwent imaging to explore the source of her symptoms at which new pulmonary nodules were discovered. During workup, she was found to have elevated tumor markers. They were initially suspected to be breast cancer recurrence metastases based on elevated tumor markers; however, further investigations confirmed that the nodules were a second primary lung adenocarcinoma with a different molecular profile. The patient had disease progression despite chemotherapy and eventually succumbed to her disease.

CONCLUSION: This case highlights the importance of considering second primary malignancies in breast cancer survivors and utilizing advanced diagnostic modalities to efficiently diagnose such cases.

RevDate: 2023-09-03

Park SY, Kim HJ, Lee J, et al (2023)

A Radiation Induced Low-Grade Myofibroblastic Sarcoma in the Retropectoral Area After Breast Conserving Surgery: A Case Report.

Journal of breast cancer, 26(4):397-402.

Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.

RevDate: 2023-08-31

Ramli Hamid MT, Loi KS, Chan WY, et al (2023)

Clinical usefulness of abbreviated mri protocol in breast cancer detection.

Current medical imaging pii:CMIR-EPUB-134129 [Epub ahead of print].

BACKGROUND: The use of breast MRI for screening has increased over the past decade, mostly in women with a high risk of breast cancer. Abbreviated breast MRI (AB-MR) is introduced to make MRI a more accessible screening modality. AB-MR decreases scanning and reporting time and the overall cost of MRI.

OBJECTIVE: This study aims to evaluate the diagnostic efficacy of abbreviated MRI protocol in detecting breast cancer in screening and diagnostic populations, using histopathology as the reference standard.

MATERIALS AND METHODS: This is a single-centre retrospective cross-sectional study of 134 patients with 198 histologically proven breast lesions who underwent full diagnostic protocol contrast-enhanced breast MRI (FDP-MR) at the University Malaya Medical Centre (UMMC) from 1st January 2018 to 31st December 2019. AB-MR was pre-determined and evaluated with regard to the potential to detect and exclude malignancy from 3 readers of varying radiological experiences. The sensitivity of both AB-MR and FDP-MR were compared using the McNemar test, where both protocols' diagnostic performances were assessed via the receiver operating characteristic (ROC) curve. Inter-observer agreement was analysed using Fleiss Kappa.

RESULT: There were 134 patients with 198 lesions. The average age was 50.9 years old (range 27 - 80). A total of 121 (90%) MRIs were performed for diagnostic purposes. Screening accounted for 9.4% of the cases, 55.6% (n=110) lesions were benign, and 44.4% (n=88) were malignant. The commonest benign and malignant lesions were fibrocystic change (27.3%) and invasive ductal carcinoma (78.4%). The mean sensitivity, specificity, positive predictive value, and negative predictive value for AB-MR were 0.96, 0.57, 0.68 and 0.94, respectively. Both AB-MR and FDP-MR showed excellent diagnostic performance with AUC of 0.88 and 0.96, respectively. The general inter-observer agreement of all three readers for AB-MR was substantial (k=0.69), with fair agreement demonstrated between AB-MR and FDP-MR (k=0.36).

CONCLUSION: The study shows no evidence that the diagnostic efficacy of AB-MR is inferior to FDP-MR. AB-MR, with high sensitivity, has proven its capability in cancer detection and exclusion, especially for biologically aggressive cancers.

RevDate: 2023-08-30

Miljanic M, Nwachukwu C, A Rahimi (2023)

Definitive ablative stereotactic partial breast irradiation in early stage inoperable breast cancer.

Journal of cancer research and clinical oncology [Epub ahead of print].

PURPOSE: This case series and literature review aims to investigate the efficacy and safety of definitive ablative radiation therapy as a treatment modality for non-operable patients with early stage breast cancer. We present two cases demonstrating the potential of this approach to achieve durable responses.

METHODS: We assessed the long-term response of two non-operable patients diagnosed with Stage II (cT2N0M) and Stage IA (T1bN0M0) invasive ductal carcinoma (IDC), who were deemed unfit for surgery due to significant co-morbid conditions. Definitive ablative radiation therapy was administered using stereotactic partial breast irradiation with ablative doses delivered in either a single fraction or two fractions. Serial imaging was conducted to assess treatment response and monitor adverse events.

RESULTS: Both patients exhibited notable treatment responses following definitive ablative radiation therapy. The first patient, an 84-year-old woman, experienced a 69% reduction in tumor size over a follow-up period exceeding 2 years. The second patient, an 87-year-old woman, achieved complete resolution of disease on imaging, with no signs of progression even 26 month post-treatment. Both patients tolerated the treatment well, without significant treatment-related adverse events.

CONCLUSIONS: Our case series suggests that definitive ablative radiation therapy may serve as a safe and effective treatment option for non-operable patients with early stage breast cancer. The observed durable treatment responses and minimal toxicity support the potential of this approach. Furthermore, a longer interval between ablative radiation therapy and surgery may enhance treatment response, potentially leading to increased complete pathologic response rates.

RevDate: 2023-08-31
CmpDate: 2022-10-26

Shoshani A, A Kor (2022)

The mental health effects of the COVID-19 pandemic on children and adolescents: Risk and protective factors.

Psychological trauma : theory, research, practice and policy, 14(8):1365-1373.

OBJECTIVE: The restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic have led to considerable social isolation, posing significant threats to mental health worldwide. The preventive lockdowns may be especially difficult for children and adolescents, who rely extensively on their daily routines and peer connections for stability and optimal development. However, there is a dearth of longitudinal research examining the mental health and daily life impact of the pandemic among children and adolescents. This study addresses this gap by examining the influence of the COVID-19 pandemic on children and adolescents' mental health and well-being, and potential risk and protective moderators of mental health change.

METHOD: In the present study, 1,537 Israeli children and adolescents (Mage = 13.97; 52% girls) completed a battery of questionnaires in September 2019; before the COVID-19 outbreak and immediately after an 8-week lockdown period when schools reopened in May 2020.

RESULTS: A repeated measures multivariant analysis of variance (MANOVA) revealed significantly greater anxiety, depression, and panic symptoms, increases in video game, Internet and TV screen time use, and decreases in positive emotions, life satisfaction, social media use, and peer support during the pandemic. Participants with higher baseline mental health symptoms showed greater symptoms after the lockdown period. Perceived social support and consistent daily routines were found to act as significant protective factors against symptomatology.

CONCLUSIONS: The results highlight the significant mental health consequences of the pandemic on children and adolescents, and substantiate the significant parents' and peers' roles in children's and adolescents' coping during this global pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

RevDate: 2023-08-28

Abbasi A, Ghaffarizadeh F, H Mojdeganlou (2023)

Prognostic Significance of Microvessel Density in Invasive Ductal Carcinoma of Breast.

International journal of hematology-oncology and stem cell research, 17(2):100-105.

Background: Breast cancer is the most common malignant tumor and cause of death in women. Factors that play role in tumor metastasis are lymph node involvement, lack of tumor differentiation and hormone receptor expression, high proliferation rate, and angiogenesis. In the present study, we tried to evaluate the microvessel density (MVD) using Immunohistochemistry for the CD34 marker to investigate the amount of angiogenesis in breast cancer and its relationship with other histopathological parameters and compare it with normal tissue. Materials and Methods: 58 paraffin-embedded samples of breast cancer were enrolled. All blocks were sectioned and stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and CD34 by immunohistochemistry (IHC) method. Results: The mean age of patients in this study was 49.6 ± 10.6 years. Statistically, there was a significant relationship between the grade of the tumor (P = 0.01), absence of expression of estrogen receptor (P = 0.008), and progesterone receptor (P = 0.003) with MVD. Conclusion: Due to the association between MVD, tumor grade, and absence of ER and PR expression, this valuable marker can play an important role in the prediction of prognosis in breast cancer patients and can lead to new-targeted therapy in the future.

RevDate: 2023-08-28

Barlier A, Romanet P, NS Pellegata (2023)

Editorial: New insights into multiple endocrine neoplasia type 1.

Frontiers in endocrinology, 14:1266148.

RevDate: 2023-08-28
CmpDate: 2023-08-28

Liu G, Kong X, Dai Q, et al (2023)

Clinical Features and Prognoses of Patients With Breast Cancer Who Underwent Surgery.

JAMA network open, 6(8):e2331078.

IMPORTANCE: Breast cancer (BC) remains a pervasive malignant neoplasm worldwide, with increasing incidence. However, there are a scarcity of studies examining the clinical characteristics and prognosis of Chinese patients with BC who have undergone surgery.

OBJECTIVE: To evaluate overall survival (OS) and disease-free survival (DFS) in patients with surgically treated BC in China, focusing on histopathology and surgical approach.

This cohort study included a retrospective review of the medical records of patients with unilateral BC who underwent surgery between January 2009 and September 2017, with a median follow-up time of 7.69 years. Clinical features were extracted from these records, and survival analysis was performed. Data analysis was conducted in March 2023.


RESULTS: The study included 14 782 patients (14 724 [99.6%] female patients; mean [SD] age, 51.6 [10.9] years). Invasive ductal carcinoma (IDC) was the most prevalent type, observed in 12 671 patients (85.6%). Stages 0, I, II, III, and IV accounted for 6.4% (919 patients), 32.0% (4579 patients), 40.5% (5791 patients), 20.2% (2896 patients), and 0.9% (126 patients) of cases, respectively. Hormone receptor (HR) positivity was observed in 10 241 patients (75.1%), and 3665 (29.1%) tested positive for ERBB2 (formerly HER2/neu). The HR-negative-ERBB2-negative, HR-negative-ERBB2-positive, HR-positive-ERBB2-negative, and HR-positive-ERBB2-positive subtypes constituted 13.3% (1666 patients), 12.7% (1595 patients), 57.8% (7251 patients), and 16.2% (2034 patients) of cases, respectively. Breast-conserving surgery (BCS) was performed in 2884 patients (19.5%). The 5-year and 10-year OS rates were 92.9% (13 689 of 14 732) and 87.4% (3287 of 3760), while the 5-year and 10-year DFS rates were 89.0% (12 916 of 14 512) and 82.9% (3078 of 3713), respectively. Multivariate analysis found that for patients with IDC, age, BCS, invasive tumor size, tumor grade, lymphovascular invasion (LVI), the number of lymph node metastases (LNMs), distant metastasis, Ki67, and HR status were associated with OS, whereas invasive tumor size, tumor grade, LVI, the number of LNMs, HR status, and ERBB2 status were associated with DFS. After propensity score matching, BCS was equivalent to mastectomy with respect to survival in patients with IDC.

CONCLUSIONS AND RELEVANCE: This cohort study of patients with BC who underwent surgery in China provides valuable insights into the histopathological characteristics and survival outcomes of this population. The diverse histopathological features emphasize the necessity for customized treatment strategies. The relatively low BCS rate in the study population suggests the need for heightened awareness and adoption of this approach, considering its potential advantages for survival.

RevDate: 2023-08-28

Goubar A, Martin FC, Sackley C, et al (2023)

Development and Validation of Multivariable Prediction Models for In-Hospital Death, 30-Day Death, and Change in Residence After Hip Fracture Surgery and the "Stratify-Hip" Algorithm.

The journals of gerontology. Series A, Biological sciences and medical sciences, 78(9):1659-1668.

BACKGROUND: To develop and validate the stratify-hip algorithm (multivariable prediction models to predict those at low, medium, and high risk across in-hospital death, 30-day death, and residence change after hip fracture).

METHODS: Multivariable Fine-Gray and logistic regression of audit data linked to hospital records for older adults surgically treated for hip fracture in England/Wales 2011-14 (development n = 170 411) and 2015-16 (external validation, n = 90 102). Outcomes included time to in-hospital death, death at 30 days, and time to residence change. Predictors included age, sex, pre-fracture mobility, dementia, and pre-fracture residence (not for residence change). Model assumptions, performance, and sensitivity to missingness were assessed. Models were incorporated into the stratify-hip algorithm assigning patients to overall low (low risk across outcomes), medium (low death risk, medium/high risk of residence change), or high (high risk of in-hospital death, high/medium risk of 30-day death) risk.

RESULTS: For complete-case analysis, 6 780 of 141 158 patients (4.8%) died in-hospital, 8 693 of 149 258 patients (5.8%) died by 30 days, and 4 461 of 119 420 patients (3.7%) had residence change. Models demonstrated acceptable calibration (observed:expected ratio 0.90, 0.99, and 0.94), and discrimination (area under curve 73.1, 71.1, and 71.5; Brier score 5.7, 5.3, and 5.6) for in-hospital death, 30-day death, and residence change, respectively. Overall, 31%, 28%, and 41% of patients were assigned to overall low, medium, and high risk. External validation and missing data analyses elicited similar findings. The algorithm is available at https://stratifyhip.co.uk.

CONCLUSIONS: The current study developed and validated the stratify-hip algorithm as a new tool to risk stratify patients after hip fracture.

RevDate: 2023-08-25

Dao E, Gohla G, Williams P, et al (2023)

Multivariate analysis of breast tissue using optical parameters extracted from a combined time-resolved fluorescence and diffuse reflectance system for tumor margin detection.

Journal of biomedical optics, 28(8):085001.

SIGNIFICANCE: Breast conservation therapy is the preferred technique for treating primary breast cancers. However, breast tumor margins are hard to determine as tumor borders are often ill-defined. As such, there exists a need for a clinically compatible tumor margin detection system.

AIM: A combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system has been developed to determine the optical properties of breast tissue. This study aims to improve tissue classification to aid in surgical decision making.

APPROACH: Normal and tumor breast tissue were collected from 80 patients with invasive ductal carcinoma and measured in the optical system. Optical parameters were extracted, and the tissue underwent histopathological examination. In total, 761 adipose, 77 fibroglandular, and 347 tumor spectra were analyzed. Principal component analysis and decision tree modeling were performed using only TRF optical parameters, only DR optical parameters, and using the combined datasets.

RESULTS: The classification modeling using TRF data alone resulted in a tumor margin detection sensitivity of 72.3% and specificity of 88.3%. Prediction modeling using DR data alone resulted in greater sensitivity and specificity of 80.4% and 94.0%, respectively. Combining both datasets resulted in the improved sensitivity and specificity of 85.6% and 95.3%, respectively. While both sensitivity and specificity improved with the combined modeling, further study of fibroglandular tissue could result in improved classification.

CONCLUSION: The combined TRF-DR system showed greater tissue classification capability than either technique alone. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection.

RevDate: 2023-08-23

Barker VR, Naffouje SA, Mallory MA, et al (2023)

Surgical Management of the Axilla in HR+/HER2- Breast Cancer in the Z1071 Era: A Propensity Score-Matched Analysis of the National Cancer Database.

Annals of surgical oncology [Epub ahead of print].

BACKGROUND: Axillary management varies between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) for patients with clinical N1 (cN1), hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)/neu-negative (HER2-), infiltrative ductal carcinoma (IDC) who achieve a complete clinical response (cCR) to neoadjuvant systemic therapy (NAST). This study sought to evaluate clinical practice patterns and survival outcomes of SLNB versus ALND in this patient subset.

METHODS: Patients with cN1, HR+/HER2-, unilateral IDC demonstrating a cCR to NAST were identified from the 2012-2017 National Cancer Database (NCDB) and stratified based on final axillary surgery management (SLNB vs ALND). After propensity score-matching, overall survival (OS) was compared using a Kaplan-Meier analysis, and significant OS predictors were identified using Cox regression.

RESULTS: Of the 1676 patients selected for this study, 593 (35.4%) underwent SLNB and 1083 (64.6%) underwent ALND. Use of SLNB increased by 28 % between 2012 and 2017. Among a total of 584 matched patients, 461 matched ypN0 patients, and 108 matched ypN+ patients, mean OS did not differ between SLNB and ALND (all patients [92.1 ± 0.8 vs 90.2 ± 1.0 months; p = 0.157], ypN0 patients [92.4 ± 0.8 vs 89.9 ± 0.9 months; p = 0.105], ypN+ patients [83.5 ± 2.3 vs 91.7 ± 2.7 months; p ± 0.963). Cox regression identified age, Charlson score, clinical T stage, and pathologic nodal status as significant predictors of OS.

CONCLUSION: The final surgical management strategy used for cN1, HR+/HER2- IDC patients who achieved a cCR to NAST did not have a significant impact on survival outcomes in this analysis. Potential opportunities for de-escalation of axillary management among this patient subset exist, and validation studies are needed.

RevDate: 2023-08-23

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

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

Pathology international [Epub ahead of print].

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

RevDate: 2023-08-22

Wang Y, Liang Y, Ye F, et al (2023)

Histologic heterogeneity predicts patient prognosis of HER2-positive metastatic breast cancer: A retrospective study based on SEER database.

Cancer medicine [Epub ahead of print].

BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the relationship between histology and prognosis among different distant metastasis sites (DMS). Our aims were to explore the prognostic value of histologic subtypes in different DMS and screen out specific subtypes with particular DMS that need more attention in HER2+ MBC.

METHODS: HER2+ MBC patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. Chi-squared tests were utilized to compare histologic subtypes in four DMS. The logistic regression analyses were used to control confounding factors. The log-rank tests were used to analyze the correlation of histologic subtype with disease-specific survival and overall survival. The survival data was analyzed using Kaplan-Meier methods.

RESULTS: A total of 1174 HER2+ MBC patients were involved. First, the distribution of histological subtypes varied across metastatic sites, and the proportions of metastatic sites in different histological subtypes were also different. Furthermore, different histological subtypes within specific DMS showed divergent prognoses, and the different outcomes were shown by distinct DMS for specific histological subtypes. Among them, lobular carcinoma (ILC) subtypes showed the worst prognosis in bone metastasis, and lung metastasis predicted the worst prognosis in infiltration duct and lobular carcinoma (IDC-ILC) subtypes. After further consideration of hormone receptor (HR) status, the IDC-ILC subtype with liver metastasis in HR+/HER2+ MBC patients and the ILC subtype with bone metastasis in HR-/HER2+ MBC patients proved to be noteworthy.

CONCLUSIONS: Histological subtypes are involved in determining the heterogeneity of HER2+ MBC patient prognosis, which is helpful to guide the prognosis prediction and monitoring of HER2+ breast cancer patients in clinics.

RevDate: 2023-08-21

Amritanand A, Arthur A, Horo S, et al (2023)

Comparative evaluation of diabetic retinopathy screening programs in regular ophthalmology clinics versus integrated diabetic clinics within rural health-care services.

Oman journal of ophthalmology, 16(2):237-243.

BACKGROUND: Robust integration of diabetic retinopathy (DR) screening within health systems is essential to prevent DR-related blindness. This, however, remains a challenge in the developing world. The aim of this study was to evaluate two models of DR screening programs within rural general health-care services.

MATERIALS AND METHODS: This was a retrospective observational study from two rural health centers. Demographic and clinical data of patients completing DR screening were analyzed. Patients were screened in regular ophthalmology clinics (ROC) or integrated diabetic clinics (IDC). Referral and treatment completion data were retrieved from the clinical charts at the base hospital.

RESULTS: A total of 2535 DR screenings were conducted for 2296 patients. The total population prevalence for any DR was 14.2% (95% confidence interval [CI]: 12.8%-15.6%) and vision-threatening DR (VTDR) was 4.7% (95% CI: 3.8%-5.6%). In the ROC and IDC groups, respectively, the prevalence of any DR was 20.4% and 8.2%, VTDR, 7.8% and 1.7%, and blindness, 1.4% and 0.4% (all P < 0.001). Referral completion rates were higher in the ROC group (44.8% vs. 25.2%, P < 0.001), while treatment completion in both was similar (69.6% vs. 70.6%). Referral and treatment completion rates for referable DR were 61.2% and 48.2%, and for VTDR, 62% and 38.8%, respectively. Only 11.45% of patients completed the repeat screening follow-up.

CONCLUSIONS: Patients attending IDCs had a significantly lower prevalence of any DR, VTDR, and blindness demonstrating the advantages of integrated diabetic care in a rural setting. However, referral uptake and DR treatment completion need strengthening.

RevDate: 2023-08-21

Ayandipo O, Ajagbe O, Afolabi A, et al (2023)

Venous Thromboembolism in Hospitalized Patients With Surgical Breast Cancer: Risks and Outcomes.

Cureus, 15(7):e42096.

Background The Caprini risk assessment model has been validated in breast cancer surgery patients. However, its utility in our population has not been described. This study evaluated the benefits and risks of the Caprini risk stratification tool and the incidence of venous thromboembolism (VTE) in the 30-day postoperative period among surgical female patients with breast cancer who were hospitalized during their treatment. Methodology This is a retrospective review of prospectively collected data of all surgical patients with histologically confirmed breast cancer who were hospitalized between January and December 2018. Caprini score, treatment information, and 30-day outcome of prophylaxis were collated and analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA). Results A total of 167 female patients with breast cancer aged 19 to 75 years were hospitalized during the study period. All patients had invasive ductal carcinoma, and the majority (76.6%) were premenopausal. Two fatal VTE events occurred during hospitalization, giving a 30-day incidence of 1.2%. There was no adverse event from chemoprophylaxis. Conclusions VTE is rare in hospitalized surgical patients with breast cancer undergoing routine pharmacologic and mechanical prophylaxis. The Caprini tool can identify extremely low-risk patients who require no prophylaxis.

RevDate: 2023-08-21

Liu G, Xing Z, Guo C, et al (2023)

Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.

Frontiers in oncology, 13:1217869.

OBJECTIVES: To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS).

MATERIALS AND METHODS: Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model.

RESULTS: We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients.

CONCLUSION: In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.

RevDate: 2023-08-21
CmpDate: 2023-08-21

Aftab A, Ahmad B, Bashir S, et al (2023)

Comparative study of microscale and macroscale technique for encapsulation of Calotropis gigantea extract in metal-conjugated nanomatrices for invasive ductal carcinoma.

Scientific reports, 13(1):13474.

The encapsulation of plant extract in nanomatrices has limitations due to its adhesion to walls, size control, high cost and long durations that results in low yield. Macroscale and microscale level techniques for development of micro/nanoparticles may impact the encapsulation of plant extract. This study aimed to evaluate the relative efficiency of microscale and macroscale techniques for encapsulation of plant extract, which is not compared yet. Keeping this in view, encapsulation of Calotropis gigantea leaves extract (CaG) was attained in silver-conjugated poliglusam nanomatrices (POL/Ag) to induce apoptosis in invasive ductal carcinoma (IDC) cells. The ethanolic CaG extract was prepared using percolation method and characterized by chemical tests for its active phytochemical compounds. The droplet-based microfluidic system was utilized as microscale encapsulation technique for CaG in nanomatrices at two different aqueous to oil flow rate ratios 1.0:1.5, and 1.0:3.0. Moreover, conventional batch system was utilized as macroscale encapsulation technique consisted of hot plate magnetic stirrer. The prepared nanomatrices were analysed for antioxidant activity using DPPH test and for cytotoxicity analysis using MCF-7 cells. The characteristic peaks of UV-Vis, FTIR and XRD spectrum confirmed the synthesis of CaG(POL/Ag) by both the encapsulation methods. However, microfluidic system was found to be more expedient because of attaining small and uniform sized silver nanoparticles (92 ± 19 nm) at high flow rate and achieving high encapsulation efficiency (80.25%) as compared to the conventional batch method (52.5%). CaG(POL/Ag) nanomatrices found to have significant antioxidant activity (p = 0.0014) against DPPH radical scavenging activity. The CaG(POL/Ag) of the smallest sized formulated by the microfluidic system has also shown the highest cytotoxicity (90%) as compared to batch method (70%) at 80 µg/mL. Our results indicate that the microscale technique using microfluidic system is a more efficient method to formulate size-controlled CaG(POL/Ag) nanomatrices and achieve high encapsulation of plant extract. Additionally, CaG(Pol/Ag) was found to be an efficient new combination for inducing potent (p < 0.0001) apoptosis in IDC cells. Therefore, CaG(Pol/Ag) can be further tested as an anti-cancer agent for in-vivo experiments.

RevDate: 2023-08-18

Hu J, Effiong K, Liu M, et al (2023)

Broad spectrum and species specificity of plant allelochemicals 1,2-benzenediol and 3-indoleacrylic acid against marine and freshwater harmful algae.

The Science of the total environment pii:S0048-9697(23)04981-1 [Epub ahead of print].

Allelochemicals derived from plants have shown great potential in mitigating harmful algal blooms (HABs), although different algal species can respond differently to these chemicals. Therefore, we first investigated the allelopathic effects of two newly identified plant-derived allelochemicals, 1,2-benzenediol (1,2-BD) and 3-indoleacrylic acid (3-IDC), on six algal species. Then we further evaluated the allelopathic responses of two bloom-forming species, Microcystis aeruginosa FACHB-905 and Heterosigma akashiwo to 1,2-BD. Results showed that 1,2-BD had a broader antialgal spectrum than 3-IDC. Allelopathic response analysis indicated that 1,2-BD consistently and stably inhibit the growth of M. aeruginosa FACHB-905, with inhibitory mechanism being disruption of photosynthetic activity, overwhelming of the antioxidant system and activation of programmed cell death (PCD). H. akashiwo displayed resistance to 1,2-BD during exposure, and the growth inhibition was mainly attributed to PCD. Therefore, the species-specific allelopathic responses provide new insights for controlling HABs using 1,2-BD and 3-IDC.

RevDate: 2023-08-18

Rosa C, Singh P, Chen P, et al (2023)

Cohesin contributes to transcriptional repression of stage-specific genes in the human malaria parasite.

EMBO reports [Epub ahead of print].

The complex life cycle of the human malaria parasite, Plasmodium falciparum, is driven by specific transcriptional programs, but it is unclear how most genes are activated or silenced at specific times. There is an association between transcription and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome-organizing proteins found in metazoans, it has all core components of the cohesin complex. To investigate the role of cohesin in P. falciparum, we functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown during early stages of the intraerythrocytic developmental cycle (IDC) upregulates a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq analyses reveal that during the IDC, SMC3 enrichment at the promoter regions of these genes inversely correlates with gene expression and chromatin accessibility. These data suggest that SMC3 binding contributes to the repression of specific genes until their appropriate time of expression, revealing a new mode of stage-specific gene repression in P. falciparum.

RevDate: 2023-08-14

Ishtiaq A, Nasrullah MA, Khan JS, et al (2023)

A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer.

Journal of cancer research and clinical oncology [Epub ahead of print].

BACKGROUND: Breast cancer is an abnormal division of breast cells. Bisphenol A (BPA), an environmental toxicant, is identified as an emerging risk factor for breast cancer development. However, to the best of our knowledge, no previous study has investigated the BPA levels in breast cancer patients in Pakistan. The present study sought to explore the role of BPA in tumor growth among the Pakistani population.

METHODS: The levels of BPA were analyzed in the serum samples of breast cancer patients and controls by using HPLC. To elucidate the role of BPA to initiate tumorigenic events in breast tissue different biochemical assays along with expression analysis of tumor markers were performed.

RESULTS: The level of BPA in the serum samples of breast cancer patients was significantly higher than control. Histological analysis of breast cancer tissue samples revealed distinct subtypes of tumor, such as ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). There was a significant increase in ROS level while a significant decrease in the levels of superoxide dismutase (SOD) and catalase (CAT) enzymes in malignant breast tissue samples as compared to control tissue samples. We found upregulated expression of p53, ZEB1 and WNT1 genes at mRNA level in malignant breast tissue samples by 17 folds, 328 folds and 35 folds, respectively. p53 protein expression in malignant breast tissue samples was also enhanced at the translational level.

CONCLUSION: Current findings suggest a relationship between BPA and the progression of breast cancer among the Pakistani population.

RevDate: 2023-08-14

Bencherifi Y, Watik F, Lyafi Y, et al (2023)

Mucinous carcinoma of the breast: Rare histological entity to know: About two cases and review of literature.

INTRODUCTION AND IMPORTANCE: Breast cancer is the first gynecological cancer in women, dominated by invasive ductal cancer . It is characterized by the presence of extracellular mucus, mucinous carcinoma represents one to 7 % of all invasive carcinomas and by a more favorable prognosis, Presentation of the case: We present two patients followed for an invasive mucinous carcinoma, CLINICAL DISCUSSION: Mucinous carcinoma of the breast is a rare entity. Therapeutic management does not differ from other histological types. It is based on surgery, chemotherapy and radiotherapy. Conservative treatment is recommended for T1, T2. Partial and accelerated irradiation of the breast is currently the most recommended after breast-conserving surgery.

CONCLUSION: Mucinous carcinoma is a rare histological entity with a favorable prognosis compared to other histological types. A benign-looking mass on imaging is not always reassuring, especially if it occurs in a woman over 60 years old. Since it can reveal colloid carcinoma.

RevDate: 2023-08-14

Mooshage CM, Tsilingiris D, Schimpfle L, et al (2023)

Insulin resistance is associated with the capillary permeability of thigh muscles in patients with type 2 diabetes.

The Journal of clinical endocrinology and metabolism pii:7242538 [Epub ahead of print].

OBJECTIVE: Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals. The aim of this study was to demonstrate the feasibility of a non-invasive assessment of human muscles' microcirculation via dynamic contrast-enhanced (DCE)-MRI of skeletal muscle in patients with type two diabetes (T2D).

METHODS: 56 participants (46 with T2D, 10 healthy controls, HC) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated.

RESULTS: In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; p = 0.042) while the homeostasis model assessment (HOMA)-index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; p = 0.011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, p = 0.018) and HOMA-index (r = -0.38, p = 0.020).

CONCLUSION: The results signify that skeletal muscle DCE MRI can be employed as a non-invasive technique for the assessment of muscles' microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regards to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.

RevDate: 2023-08-14

Alfaro AJ, Dittner C, Becker J, et al (2023)

Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism.

EMBO reports [Epub ahead of print].

Accumulation of excess nutrients hampers proper liver function and is linked to nonalcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the small ubiquitin-like modifier (SUMO) allows for a dynamic regulation of numerous processes including transcriptional reprogramming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 is highly SUMOylated on lysine 556 in the liver of ad libitum and refed mice, while this modification is abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation becomes less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet leads to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of "fasting-based" approaches for the preservation of metabolic health.

RevDate: 2023-08-10

Bai X, Fang C, Liu B, et al (2023)

Breast cancer metastases to the thyroid and stomach: A case report.

Oncology letters, 26(3):386.

The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.

RevDate: 2023-08-09

Doi K, Fujii T, Hanamoto M, et al (2023)

[A Case of BRCA2 Mutation-Positive Intraductal Carcinoma of the Prostate].

Hinyokika kiyo. Acta urologica Japonica, 69(7):189-192.

A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.

RevDate: 2023-08-09

Downes MR, Liu KN, Yu Y, et al (2023)

Addition of Cribriform and Intraductal Carcinoma Presence to Prostate Biopsy Reporting Strengthens Pretreatment Risk Stratification Using CAPRA and NCCN Tools.

Clinical genitourinary cancer pii:S1558-7673(23)00182-9 [Epub ahead of print].

BACKGROUND: Pretreatment stratification tools can help in clinical decision making in prostate cancer. To date, none incorporates well-established routinely reported adverse prognostic pathologic features such as intraductal carcinoma of prostate (IDC) or cribriform pattern 4 (CC).

OBJECTIVE: To assess the impact of addition of CC and/or IDC on the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) tools for predicting biochemical recurrence free survival (BCR-FS) and event-free survival (EFS) across multiple patient cohorts.

Matched prostate biopsies and radical prostatectomies from institutions in Toronto, Wisconsin and Rotterdam. The presence/absence of CC/IDC was recorded on all biopsies.

Relationship to outcome was assessed using Cox proportional hazard models, ANOVA and Harrell's concordance index.

RESULTS AND LIMITATIONS: We included 1326 patients (Toronto- 612, Wisconsin- 542, Rotterdam- 172) with median follow up of 4.2 years (IQR 2.9-6.4 years); 306 (23.1%) had CC/IDC on biopsy with 207 (20.9%) BCR and 154 (11.6%) events (metastases/death). Addition of CC/IDC improved stratification in CAPRA scores 3 to 5 for BCR-FS (c-index increase 0.633-0.658, P < .001) and scores 6-10 for EFS (c-index increase 0.653-0.697, P < .001). For NCCN, all risk groups apart from score 1 to 2 showed improvement in BCR-FS (c-index increase 0.599-0.636, P < 0.001) and EFS prediction (c-index increase 0.648-0.697, P < .001). Sub-analysis of grade group (GG) 2 biopsies showed similar findings. The retrospective nature and inclusion of cases only reported by genitourinary pathologists are study limitations.

CONCLUSIONS: The clinical benefit of the addition of CC/IDC to both CAPRA and NCCN pretreatment tools was validated in 3 cohorts, including the subset of biopsy GG2 prostate cancer patients.

PATIENT SUMMARY: Including additional pathologic features to existing pretreatment, clinical decision making tools improves the ability to predict prostate cancer recurrence, cancer spread and death of disease.

RevDate: 2023-08-09

Chen H, Li X, Li F, et al (2023)

Prediction of coexisting invasive carcinoma on ductal carcinoma in situ (DCIS) lesions by mass spectrometry imaging.

The Journal of pathology [Epub ahead of print].

Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.

RevDate: 2023-08-08

He Y, Cazoulat G, Wu C, et al (2023)

Quantifying the Effect of 4-Dimensional Computed Tomography-Based Deformable Dose Accumulation on Representing Radiation Damage for Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Standard-Fractionated Intensity-Modulated Radiation Therapy.

International journal of radiation oncology, biology, physics pii:S0360-3016(23)07648-4 [Epub ahead of print].

PURPOSE: The aim of this study was to investigate the dosimetric and clinical effects of 4-dimensional computed tomography (4DCT)-based longitudinal dose accumulation in patients with locally advanced non-small cell lung cancer treated with standard-fractionated intensity-modulated radiation therapy (IMRT).

METHODS AND MATERIALS: Sixty-seven patients were retrospectively selected from a randomized clinical trial. Their original IMRT plan, planning and verification 4DCTs, and ∼4-month posttreatment follow-up CTs were imported into a commercial treatment planning system. Two deformable image registration algorithms were implemented for dose accumulation, and their accuracies were assessed. The planned and accumulated doses computed using average-intensity images or phase images were compared. At the organ level, mean lung dose and normal-tissue complication probability (NTCP) for grade ≥2 radiation pneumonitis were compared. At the region level, mean dose in lung subsections and the volumetric overlap between isodose intervals were compared. At the voxel level, the accuracy in estimating the delivered dose was compared by evaluating the fit of a dose versus radiographic image density change (IDC) model. The dose-IDC model fit was also compared for subcohorts based on the magnitude of NTCP difference (|ΔNTCP|) between planned and accumulated doses.

RESULTS: Deformable image registration accuracy was quantified, and the uncertainty was considered for the voxel-level analysis. Compared with planned doses, accumulated doses on average resulted in <1-Gy lung dose increase and <2% NTCP increase (up to 8.2 Gy and 18.8% for a patient, respectively). Volumetric overlap of isodose intervals between the planned and accumulated dose distributions ranged from 0.01 to 0.93. Voxel-level dose-IDC models demonstrated a fit improvement from planned dose to accumulated dose (pseudo-R[2] increased 0.0023) and a further improvement for patients with ≥2% |ΔNTCP| versus for patients with <2% |ΔNTCP|.

CONCLUSIONS: With a relatively large cohort, robust image registrations, multilevel metric comparisons, and radiographic image-based evidence, we demonstrated that dose accumulation more accurately represents the delivered dose and can be especially beneficial for patients with greater longitudinal response.

RevDate: 2023-08-07

Mooshage CM, Schimpfle L, Kender Z, et al (2023)

Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.

Clinical neuroradiology [Epub ahead of print].

INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.

METHODS: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K[trans]), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).

RESULTS: The K[trans] (HC 0.031 min[-1] ± 0.009, T2D 0.043 min[-1] ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with K[trans] (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and Vp (r = -0.57; p = 0.015) correlated negatively.

DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.

RevDate: 2023-08-07

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

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

bioRxiv : the preprint server for biology pii:2023.06.12.544550.

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

RevDate: 2023-08-04

Shoshani A, A Kor (2023)

The longitudinal impact of the COVID-19 pandemic on adolescents' internalizing symptoms, substance use, and digital media use.

European child & adolescent psychiatry [Epub ahead of print].

The present study examined the long-term effects of the COVID-19 pandemic on adolescent internalizing symptoms, substance use, and digital media use before and during the pandemic. A nationally representative longitudinal cohort of 3718 Israeli adolescents aged 12-16 at baseline completed measures of internalizing symptoms (anxiety, depression, and somatization), the prevalence of substance use (i.e., previous 30-day use of tobacco, alcohol, and cannabis), and average daily use of internet/television, video games, and social media. Social support and daily routines were assessed as potential protective factors for mental health. Data were collected in 10 public schools at four measurement points: before the Covid-19 outbreak (September 2019), after the first wave lockdown (May 2020), after the third wave lockdown (May 2021), and after the fifth wave of the pandemic (May 2022). Multi-level mixed models were used to analyze the longitudinal data. The results showed significant increases in internalizing symptoms, substance use (tobacco, alcohol, and cannabis), and daily screen time from the start of the study to the 33-month follow-up. Social support and daily routines moderated the increases in internalizing symptoms and digital media use. These findings highlight the need for public and educational mental health services to address the continuing impact of the pandemic on adolescents.

RevDate: 2023-08-03

Abdollahi E, H Mozdarani (2023)

Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.

Experimental and molecular pathology pii:S0014-4800(23)00016-3 [Epub ahead of print].

Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.

RevDate: 2023-08-02

Kishore A, Venkataramana L, Prasad DVV, et al (2023)

Enhancing the prediction of IDC breast cancer staging from gene expression profiles using hybrid feature selection methods and deep learning architecture.

Medical & biological engineering & computing [Epub ahead of print].

Prediction of the stage of cancer plays an important role in planning the course of treatment and has been largely reliant on imaging tools which do not capture molecular events that cause cancer progression. Gene-expression data-based analyses are able to identify these events, allowing RNA-sequence and microarray cancer data to be used for cancer analyses. Breast cancer is the most common cancer worldwide, and is classified into four stages - stages 1, 2, 3, and 4 [2]. While machine learning models have previously been explored to perform stage classification with limited success, multi-class stage classification has not had significant progress. There is a need for improved multi-class classification models, such as by investigating deep learning models. Gene-expression-based cancer data is characterised by the small size of available datasets, class imbalance, and high dimensionality. Class balancing methods must be applied to the dataset. Since all the genes are not necessary for stage prediction, retaining only the necessary genes can improve classification accuracy. The breast cancer samples are to be classified into 4 classes of stages 1 to 4. Invasive ductal carcinoma breast cancer samples are obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets and combined. Two class balancing techniques are explored, synthetic minority oversampling technique (SMOTE) and SMOTE followed by random undersampling. A hybrid feature selection pipeline is proposed, with three pipelines explored involving combinations of filter and embedded feature selection methods: Pipeline 1 - minimum-redundancy maximum-relevancy (mRMR) and correlation feature selection (CFS), Pipeline 2 - mRMR, mutual information (MI) and CFS, and Pipeline 3 - mRMR and support vector machine-recursive feature elimination (SVM-RFE). The classification is done using deep learning models, namely deep neural network, convolutional neural network, recurrent neural network, a modified deep neural network, and an AutoKeras generated model. Classification performance post class-balancing and various feature selection techniques show marked improvement over classification prior to feature selection. The best multiclass classification was found to be by a deep neural network post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with a Cohen-Kappa score of 0.303 and a classification accuracy of 53.1%. For binary classification into early and late-stage cancer, the best performance is obtained by a modified deep neural network (DNN) post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with an accuracy of 81.0% and a Cohen-Kappa score (CKS) of 0.280. This pipeline also showed improved multiclass classification performance on neuroblastoma cancer data, with a best area under the receiver operating characteristic (auROC) curve score of 0.872, as compared to 0.71 obtained in previous work, an improvement of 22.81%. The results and analysis reveal that feature selection techniques play a vital role in gene-expression data-based classification, and the proposed hybrid feature selection pipeline improves classification performance. Multi-class classification is possible using deep learning models, though further improvement particularly in late-stage classification is necessary and should be explored further.

RevDate: 2023-08-02

Cakir Y, Talu CK, Trabulus DC, et al (2023)

The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.

Indian journal of pathology & microbiology, 66(3):456-464.

BACKGROUND: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers.

AIM: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas.

MATERIALS AND METHODS: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs.

STATISTICAL ANALYSIS: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis.

RESULTS: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs.

CONCLUSIONS: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.

RevDate: 2023-08-01

Dao E, Gohla G, Williams P, et al (2023)

Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system.

Lasers in surgery and medicine [Epub ahead of print].

OBJECTIVE: This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated.

METHOD: In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue.

RESULTS: Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification.

CONCLUSION: With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.

RevDate: 2023-08-01

Shah MH, M Batool (2023)

Surviving the Test of Time: A Young Patient's Triumph Over Early-Onset Invasive Ductal Carcinoma and Its Recurrence a Decade Later.

Cureus, 15(7):e42613.

Breast cancer is a complex, heterogeneous disease with diverse clinical presentations and variable outcomes. In this report, we provide a detailed analysis of a case involving a 22-year-old woman diagnosed with invasive ductal carcinoma, highlighting the difficulties of managing breast cancer in young patients. Through the examination of this patient's 10-year journey, from the initial diagnosis to surgery, adjuvant therapy, and recurrence, we underline the crucial role of early detection, personalised treatment, and interdisciplinary cooperation in optimising patient outcomes. Overall, the case study serves as a compelling narrative, effectively highlighting the aggressive nature of breast cancer in younger individuals and underscoring the need to provide care that addresses the multifaceted dimensions of this disease.

RevDate: 2023-07-31

McFarland BJ, Luo A, X Wang (2023)

Male breast cancer: Report of two cases with bloody nipple discharge.

Radiology case reports, 18(9):3323-3330.

We report 2 rare cases of male breast cancer with bloody nipple discharge. Patient 1, a 32-year-old male, presented with a bloody nipple discharge from the left breast. Diagnostic workup revealed papillary ductal carcinoma in situ. Patient 1 underwent bilateral mastectomy with left axillary sentinel lymph node biopsy and has been doing well ever since. Patient 2, a 70-year-old male with concomitant metastatic prostate cancer, presented with a palpable right breast mass and with initially serous, then bloody nipple discharge. Diagnostic workup revealed invasive ductal carcinoma with ductal carcinoma in situ of the right breast. Patient 2 received aromatase inhibitor therapy prior to right total mastectomy with SLN biopsy followed by adjuvant tamoxifen therapy. Patient 2 recovered without complication for 2 years until metastatic disease recurrence was detected. This case report's purpose is to increase awareness and enhance understanding of the presentation, diagnosis, treatment, and outcomes of rare malignant pathologies.

RevDate: 2023-07-31

Grewal IS, T Rajagopal (2023)

Studying the Presentation of Paget Disease of the Breast.

Cureus, 15(6):e41057.

Paget disease of the breast is a rare breast cancer that accounts for 1-3% of all new presentations of breast cancer. It is characterized by an eczematous and ulcerative lesion of the nipple that may extend to the areola. Nearly 90% of cases are associated with underlying breast cancer. We report the presentation of Paget disease of the breast in a 41-year-old female, who presented due to a one-year history of an eczematous lesion of the left nipple area with no palpable mass, who was later found to have high-grade invasive ductal carcinoma treated with unilateral mastectomy and sentinel node biopsy.

RevDate: 2023-07-30

Amato S, Ramsey J, Ahern TP, et al (2023)

Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.

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

PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry.

METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle.

RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls.

CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.

RevDate: 2023-07-29

Hardt LM, Herrmann HJ, Reljic D, et al (2023)

Are Guideline Recommendations on Supportive Nutrition and Exercise Therapy for Cancer Patients Implemented in Clinical Routine? A National Survey with Real-Life Data.

Nutrients, 15(14):.

Malnutrition and cancer cachexia are highly prevalent comorbidities of cancer, limiting patients' quality of life and being relevant to prognosis. International and national clinical guidelines recommend supportive nutrition and exercise therapy for cancer patients. However, there is little current epidemiological evidence on the implementation of these guideline recommendations in clinical routine. To close this data gap, a national survey in Germany using an online questionnaire was conducted. There were 261 of a total of 5074 contacted hospitals and medical offices who participated in the survey (5.1% response rate). The data indicated that nutrition and exercise therapy for cancer patients is so far inadequately implemented, with 59% of the respondents reporting nutrition therapy as an integral part of oncological treatment, 66.7% having a nutrition specialist/team, and 65.1% routinely conducting a screening for nutritional status. Only half of the participants stated that there are defined goals in nutrition therapy. The majority of respondents (85.8%) generally recommend exercise therapy, but only a few of them provide specific offers at their own institution (19.6%) or at cooperation partners (31.7%). In order to implement the recommended combined nutrition and exercise therapy as part of regular care, there is a need for nationwide availability of multidisciplinary nutrition teams and targeted offers of individualized exercise therapy. Health policy support would be important to create the structural, financial, and staff conditions for appropriate guideline implementation in order to achieve the optimal treatment of cancer patients.

RevDate: 2023-07-29

Harnsoongnoen S, B Buranrat (2023)

Microwave Sensor for the Determination of DMSO Concentration in Water-DMSO Binary Mixture.

Micromachines, 14(7): pii:mi14071378.

This research aims to develop a microwave sensor to accurately measure the concentration of dimethyl sulfoxide (DMSO) in water-DMSO binary mixtures. The proposed sensor will utilize microwave frequency measurements to determine the DMSO concentration, providing a non-invasive and efficient method for analyzing DMSO solutions. The research will involve the design, fabrication, and testing of the sensor, as well as the development of an appropriate calibration model. The outcomes of this study will contribute to improved monitoring and quality control in various fields, including pharmaceuticals, chemical synthesis, and biomedical research. The binary mixtures of dimethyl sulfoxide (DMSO) and water with varying concentrations were investigated in the frequency range of 1 GHz to 5 GHz at room temperature using a microwave sensor. The proposed microwave sensor design was based on an interdigital capacitor (IDC) microstrip antenna loaded with a hexagonal complementary ring resonator (HCRR). The performance of the sensor, fabricated using the print circuit board (PCB) technique, was validated through simulations and experiments. The reflection coefficient (S11) and resonance frequency (Fr) of binary mixtures of DMSO and water solutions were recorded and analyzed for DMSO concentrations ranging from 0% v/v to 75% v/v. Mathematical models were developed to analyze the data, and laboratory tests showed that the sensor can detect levels of DMSO/water binary mixtures. The sensor is capable of detecting DMSO concentrations ranging from 0% v/v to 75% v/v, with a maximum sensitivity of 0.138 dB/% for S11 and ΔS11 and 0.2 MHz/% for Fr and ΔFr at a concentration of 50% v/v. The developed microwave sensor can serve as an alternative for detecting DMSO concentrations in water using a simple and cost-effective technique. This method can effectively analyze a wide range of concentrations, including highly concentrated solutions, quickly and easily.

RevDate: 2023-07-29

Faraz K, Dauce G, Bouhamama A, et al (2023)

Characterization of Breast Tumors from MR Images Using Radiomics and Machine Learning Approaches.

Journal of personalized medicine, 13(7): pii:jpm13071062.

Determining histological subtypes, such as invasive ductal and invasive lobular carcinomas (IDCs and ILCs) and immunohistochemical markers, such as estrogen response (ER), progesterone response (PR), and the HER2 protein status is important in planning breast cancer treatment. MRI-based radiomic analysis is emerging as a non-invasive substitute for biopsy to determine these signatures. We explore the effectiveness of radiomics-based and CNN (convolutional neural network)-based classification models to this end. T1-weighted dynamic contrast-enhanced, contrast-subtracted T1, and T2-weighted MR images of 429 breast cancer tumors from 323 patients are used. Various combinations of input data and classification schemes are applied for ER[+] vs. ER[-], PR[+] vs. PR[-], HER2[+] vs. HER2[-], and IDC vs. ILC classification tasks. The best results were obtained for the ER[+] vs. ER[-] and IDC vs. ILC classification tasks, with their respective AUCs reaching 0.78 and 0.73 on test data. The results with multi-contrast input data were generally better than the mono-contrast alone. The radiomics and CNN-based approaches generally exhibited comparable results. ER and IDC/ILC classification results were promising. PR and HER2 classifications need further investigation through a larger dataset. Better results by using multi-contrast data might indicate that multi-parametric quantitative MRI could be used to achieve more reliable classifiers.

RevDate: 2023-07-28

Rothschild HT, Clelland EN, Abel MK, et al (2023)

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.

Research square pii:rs.3.rs-3137103.

Purpose Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. Methods The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. Results In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC had more positive margins (10.6% versus 8.3%, p = 0.005). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. Conclusion Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

RevDate: 2023-07-27

Ding W, Ye D, Zhu H, et al (2023)

Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.

Clinical breast cancer pii:S1526-8209(23)00190-8 [Epub ahead of print].

INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial.

METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors.

RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS).

CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.

RevDate: 2023-07-27

Namikawa T, Yokota K, Maeda H, et al (2023)

Gastric and Bone Metastases Arising from Invasive Lobular Carcinoma With Ductal Carcinoma Occurring in one Breast Synchronously.

Anticancer research, 43(8):3701-3707.

BACKGROUND/AIM: We report the case of a patient with gastric and bone metastases arising from an invasive lobular carcinoma of the breast coexisting with ductal carcinoma at the same time.

CASE REPORT: A 68-year-old woman with gastric and right costal tumors was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed irregular, slightly elevated lesions extending from the gastric body to the antrum, and biopsy specimens revealed a poorly differentiated adenocarcinoma. Furthermore, abdominal contrast-enhanced computed tomography (CT) revealed extensive wall thickening with homogeneous enhancement in the stomach. 18F-2-deoxy-2-fluoro-glucose positron emission tomography (FDG-PET) showed intense FDG uptake in the right mammary gland and right third rib. Moreover, fine-needle aspiration of the third right rib lump and the right breast mass lesion was performed, and subsequent pathological investigations revealed metastatic adenocarcinoma and invasive ductal carcinoma, respectively. Immunohistochemical examination revealed that estrogen receptor was strongly positive (>95%) in breast cancer and focally positive (<5%) in gastric cancer with bone metastasis. In addition, another right breast tumor was detected by breast magnetic resonance imaging (MRI), and biopsy revealed invasive lobular carcinoma that matched the histological findings of bone and gastric lesions, including immunohistochemical examination. The patient was treated with an aromatase inhibitor, a CDK4/6 inhibitor, and a receptor activator of nuclear factor-kappa B ligand (RANKL) monoclonal antibody. She showed no symptoms or disease progression at 9-month follow-up after the initiation of systemic drug treatment.

CONCLUSION: Invasive lobular carcinoma can metastasize to the gastrointestinal tract, and new treatment developments are expected as more cases will accumulate in the future.

RevDate: 2023-07-27

Shoshani A (2023)

Longitudinal changes in children's and adolescents' mental health and well-being and associated protective factors during the COVID-19 pandemic.

Psychological trauma : theory, research, practice and policy pii:2023-93150-001 [Epub ahead of print].

OBJECTIVE: The COVID-19 pandemic has heightened children's and adolescents' risk of experiencing long-term mental health problems and a decline in subjective well-being. To better understand the longitudinal impact of COVID-19, this study explored the role of demographic variables and the potential moderating effects of social support and daily routines as resilience factors.

METHOD: A nationally representative, longitudinal cohort of 5,217 Israeli children and adolescents aged 10-15 at baseline completed measures of mental health symptoms, life satisfaction, positive and negative emotions, gratitude, social support, and daily routines. Data were collected in school at four measurement points: September 2019 (before the outbreak of COVID-19; N = 5,127), May 2020 (after the first lockdown; N = 4,698), May 2021 (after the third wave lockdown; N = 4,813), and May 2022 (after the fourth and fifth waves of the pandemic; N = 4,897). The data were analyzed using multilevel mixed models.

RESULTS: Significant increases in depression, anxiety, and panic along with decreases in psychological well-being were found as a function of time. These effects were moderated by age and gender. Participants with high social support and structured daily routines reported smaller increases in mental health symptoms than students with low social support or irregular daily routines.

CONCLUSION: There is a critical need for clinical and educational interventions for young people during this period to promote the resilience factors that can moderate well-being and counter the decline in mental health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

RevDate: 2023-07-27

Konishi K, Araya J, Nagabuchi M, et al (2023)

[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].

Gan to kagaku ryoho. Cancer & chemotherapy, 50(7):825-827.

Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.

RevDate: 2023-07-26

Bódis K, Bombrich M, Schön M, et al (2023)

Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.

Nutrition, metabolism, and cardiovascular diseases : NMCD pii:S0939-4753(23)00237-5 [Epub ahead of print].

BACKGROUND AND AIMS: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2[EK]; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.

METHODS AND RESULTS: Males with recent-onset type 2 diabetes with (TM6SF2[EK]: n = 16) or without (TM6SF2[EE]: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-[2]H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with [1]H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2[EK] had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2[EE]. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2[EE] only.

CONCLUSIONS: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.

RevDate: 2023-07-26

Lee SE, Yoon JH, Son NH, et al (2023)

Screening in Patients With Dense Breasts: Comparison of Mammography, Artificial Intelligence, and Supplementary Ultrasound.

AJR. American journal of roentgenology [Epub ahead of print].

Background: Screening mammography has decreased performance in patients with dense breasts. Supplementary screening ultrasound is a recommended option in such patients, although has yielded mixed results in prior investigation. Objective: To compare the performance characteristics of screening mammography alone, standalone artificial intelligence (AI), ultrasound alone, as well as mammography in combination with AI and/or ultrasound, in patients with dense breasts. Methods: This retrospective study included 1325 women (mean age, 53 years) with dense breasts who underwent both screening mammography and supplementary breast ultrasound within a 1-month interval from January 2017 to December 2017; prior mammogram and prior ultrasound were available for comparison in 91.2% and 91.8%, respectively. Mammography and ultrasound examinations were interpreted by one of 15 radiologists (5 staff; 10 fellows); clinical reports were used for the present analysis. A commercial AI tool was used to retrospectively evaluate mammographic examinations for presence of cancer. Screening performances were compared among mammography, AI, ultrasound, and test combinations, using generalized estimating equations. Benign diagnoses required ≥24 months of imaging stability. Results: Twelve cancers (6 invasive ductal carcinoma; 6 ductal carcinoma in situ) were diagnosed. Mammography, standalone AI, and ultrasound showed cancer detection rate (per 1000 patients) of 6.0, 6.8, and 6.0 (all p>.05); recall rate of 4.4%, 11.9%, and 9.2% (all p<.05); sensitivity of 96.2%, 88.7%, and 91.3% (all p>.05); specificity of 96.2%, 88.7%, and 91.3% (all p>.50); and accuracy of 95.9%, 88.5%, and 91.1% (all p<.05). Mammography with AI, mammography with ultrasound, and mammography with both ultrasound and AI showed CDR of 7.5, 9.1, and 9.1 (all p>.05); recall rate of 14.9, 11.7, and 21.4 (all p<.05); sensitivity of 83.3%, 100.0%, and 100.0% (all p>.05); specificity of 85.8%, 89.1%, and 79.4% (all p<.05); and accuracy of 85.7%, 89.2%, and 79.5% (all p<.05). Conclusion: Mammography with supplementary ultrasound showed higher accuracy, higher specificity, and lower recall rate in comparison to mammography with AI as well as in comparison to mammography with both ultrasound and AI. Clinical Impact: The findings fail to show benefit of AI with respect to screening mammography performed with supplementary breast ultrasound in patients with dense breasts.

RevDate: 2023-07-26

Kalantri P, K Lomashvili (2023)

Deruxtecan-Induced Reversible Fanconi Syndrome.

Cureus, 15(6):e40890.

Increasingly complex and constantly emerging cancer treatment protocols are associated with kidney toxicities. Data clearly demonstrate that when patients with cancer develop acute or chronic kidney disease, severe fluid and electrolyte abnormalities, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. We present a case of a 74-year-old woman with metastatic, recurrent ER+/PR-/HER2+ invasive ductal carcinoma of the right breast, status post bilateral mastectomies, chemotherapy, radiation therapy, and hormonal therapies, who were clinically stable on Trastuzumab/Pertuzumab maintenance for about a year. She then experienced disease progression. She was started on Trastuzumab+Deruxtecan (T-Dxt). However, due to worsening diarrhea of more than 12 episodes per day, decreased oral intake, weakness and weight loss, she got admitted to the hospital. Laboratory data showed hyponatremia, hypokalemia, non-anion gap metabolic acidosis, hypomagnesemia, and hypophosphatemia. These laboratory abnormalities were initially attributed to diarrhea. Renal losses were suspected when the electrolyte abnormalities did not correct despite improving diarrhea. Urine electrolytes were hence tested. There was evidence of Fanconi syndrome with glucosuria, proteinuria, and renal potassium and phosphorus wasting. Fanconi syndrome was attributed to the Deruxtecan component of the combination chemotherapy, as she was previously on Trastuzumab with no such abnormalities. The electrolyte abnormalities resolved over the course of a few months. To our knowledge, this is the first case of Fanconi syndrome due to T-Dxt.

RevDate: 2023-07-26

Li Y, Zhang Y, Zhou Z, et al (2023)

Predictive value of controlling nutritional status score in postoperative recurrence and metastasis of breast cancer patients with HER2-low expression.

Frontiers in oncology, 13:1116631.

BACKGROUND: To investigate the predictive value of controlling nutritional status (CONUT) score in Postoperative Recurrence and Metastasis of Breast Cancer Patients with HER2-Low Expression.

METHODS: The clinicopathological data of 697 female breast cancer patients who pathology confirmed invasive ductal carcinoma and surgery in Harbin Medical University Tumor Hospital from January 2014 to January 2017 were retrospectively analyzed. The relationship between CONUT score and various clinicopathological factors as well as prognosis was evaluated.

RESULTS: Based on the cut-off point of ROC curve, compared with the low CONUT score group, the high CONUT score group had worse 5-year RFS. In subgroup analysis, compared with the low CONUT group, the high CONUT group had worse prognosis at different TNM stages. Univariate and multivariate results showed that the low CONUT score group had better overall survival and recurrence-free survival than the high CONUT group.

CONCLUSION: CONUT score is an independent predictor of postoperative recurrence and metastasis in HER2-low breast cancer patients. It is may be used as an effective tool to predict the recurrence and metastasis of HER2-low breast cancer.

RevDate: 2023-07-25

Goldhaber NH, O'Keefe T, Kang J, et al (2023)

Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.

Annals of surgical oncology [Epub ahead of print].

BACKGROUND: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC).

METHODS: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared.

RESULTS: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity.

CONCLUSION: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the 'Choosing Wisely' criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.

RevDate: 2023-07-25

Choo ZY, AZ Xu (2023)

Predictors and outcomes of cutaneous metastatic breast carcinoma: a retrospective, single-institution review.

Archives of dermatological research [Epub ahead of print].

RevDate: 2023-07-25

Sanchez D, Bloomquist E, Wright H, et al (2023)

Immediate Nipple Reconstruction With Areolar Flaps After Nipple Excision.

Annals of plastic surgery, 91(2):211-214.

Nipple-sparing mastectomies (NSMs) have become a common surgical approach in the management of invasive breast cancers and ductal carcinoma in situ, and as a risk-reducing approach in genetically predisposed patients. The current standard of care in the management of positive nipple margin after NSM is total excision of the nipple-areola complex. In this article, we aimed to present a case series describing a novel approach to positive nipple margins with nipple-only excision and immediate nipple reconstruction using areolar flaps in patients who underwent NSM for noninvasive tumors. We conducted a retrospective review of patients who underwent NSM and were found to have positive nipple margins and underwent subsequent nipple excision with immediate areolar flap reconstruction. We identified 6 patients who underwent NSM and were found to have nipple margins-5 for ductal carcinoma in situ and 1 for invasive ductal carcinoma. These patients underwent nipple excision with immediate reconstruction using "sickle" flaps. We concluded that if nipple excision and immediate reconstruction with areolar sickle flaps can be performed, it results in good aesthetic outcomes without compromising oncologic results.

RevDate: 2023-07-22

D'Iorio A, Aiello EN, Amboni M, et al (2023)

Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.

Aging clinical and experimental research [Epub ahead of print].

BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.

METHODS: A retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.

RESULTS: The MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80).

DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.

RevDate: 2023-07-22

White D, Sadough Shahmirzadi M, B Boulmay (2023)

Multi-Phenotypic Breast Cancer Post-Radiotherapy for Hodgkin Lymphoma: A Case of Secondary Malignancy.

Journal of investigative medicine high impact case reports, 11:23247096231188251.

Morbidity and mortality associated with radiation-induced secondary malignancies (RISMs) have shifted treatment paradigms to minimize or eliminate radiation from treatment regimens. In this case, a 48-year-old woman was diagnosed with Hodgkin lymphoma (HL) and treated with radiotherapy in 2000. In 2018, she was diagnosed with ductal carcinoma in situ (DCIS) of the right breast and treated with a mastectomy. Soon after, she developed triple-negative invasive ductal carcinoma (IDC) in her reconstructed breast. The patient underwent a left lumpectomy, and pathology showed ER-/PR-/HER2+ IDC. This patient's multi-phenotypic DCIS and IDC presentation are suspected to be RISM due to her previous HL treatment regimen.

RevDate: 2023-07-21

Adachi Y, Asaga S, Kumamaru H, et al (2023)

Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National Cancer Database-Breast Cancer Registry.

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

PURPOSE: Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC.

METHODS: We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups.

RESULTS: For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases.

CONCLUSION: Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC.

RevDate: 2023-07-21

Tian Z, Yang Z, Jin M, et al (2023)

Identification of cytokine-predominant immunosuppressive class and prognostic risk signatures in glioma.

Journal of cancer research and clinical oncology [Epub ahead of print].

PURPOSE: The advent of immune checkpoint blockade (ICB) therapies this year has changed the way glioblastoma (GBM) is treated. Meanwhile, some patients with strong PD-L1 expression remain immune checkpoint resistant. To better understand the molecular processes that influence the immune environment, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to predict patient survival outcomes.

PATIENTS AND METHODS: Our study analyzed RNA-sequencing data from 178 GBM samples. Their unique gene expression patterns in the tumor microenvironment were analyzed by an unsupervised clustering algorithm. Through these expression patterns, a panel of T-cell exhaustion signatures, immunosuppressive cells, and clinical features correlates with immunotherapy response. The presence or absence of immune status and prognostic signatures was then validated with the test dataset.

RESULTS: 38.2% of GBM patients showed increased expression of anti-inflammatory cytokines, significant enrichment of T cell exhaustion signals, higher proportion of immunosuppressive cells (macrophages and CD4 regulatory T cells) and nine inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA). The immunodepleted class (IDC) was used to classify these immunocompromised individuals. Despite the high density of tumor-infiltrating lymphocytes shown by IDC, such patients have a poor prognosis. Although PD-L1 was highly expressed in IDC, it suggested that there might be ICB resistance. There are many IDC predictive signatures to discover.

CONCLUSION: PD-1 is strongly expressed in a novel immunosuppressive class of GBM, but this cluster may be resistant to ICB therapy. A comprehensive description of this drug-resistant tumor microenvironment could provide new insights into drug resistance mechanisms and improved immunotherapy techniques.

RevDate: 2023-07-21

Shi K, Liu XL, Guo Q, et al (2023)

TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.

PloS one, 18(7):e0285817 pii:PONE-D-23-07967.

BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.

METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.

RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.

CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.

RevDate: 2023-07-21

Zhang W, Yang L, Geng S, et al (2023)

Self-Supervised Time Series Representation Learning via Cross Reconstruction Transformer.

IEEE transactions on neural networks and learning systems, PP: [Epub ahead of print].

Since labeled samples are typically scarce in real-world scenarios, self-supervised representation learning in time series is critical. Existing approaches mainly employ the contrastive learning framework, which automatically learns to understand similar and dissimilar data pairs. However, they are constrained by the request for cumbersome sampling policies and prior knowledge of constructing pairs. Also, few works have focused on effectively modeling temporal-spectral correlations to improve the capacity of representations. In this article, we propose the cross reconstruction transformer (CRT) to solve the aforementioned issues. CRT achieves time series representation learning through a cross-domain dropping-reconstruction task. Specifically, we obtain the frequency domain of the time series via the fast Fourier transform (FFT) and randomly drop certain patches in both time and frequency domains. Dropping is employed to maximally preserve the global context while masking leads to the distribution shift. Then a Transformer architecture is utilized to adequately discover the cross-domain correlations between temporal and spectral information through reconstructing data in both domains, which is called Dropped Temporal-Spectral Modeling. To discriminate the representations in global latent space, we propose instance discrimination constraint (IDC) to reduce the mutual information between different time series samples and sharpen the decision boundaries. Additionally, a specified curriculum learning (CL) strategy is employed to improve the robustness during the pretraining phase, which progressively increases the dropping ratio in the training process. We conduct extensive experiments to evaluate the effectiveness of the proposed method on multiple real-world datasets. Results show that CRT consistently achieves the best performance over existing methods by 2%-9%. The code is publicly available at https://github.com/BobZwr/Cross-Reconstruction-Transformer.

RevDate: 2023-07-20

Chappidi MR, Sjöström M, Greenland NY, et al (2023)

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

European urology oncology pii:S2588-9311(23)00120-7 [Epub ahead of print].

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

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

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

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

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

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

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

RevDate: 2023-07-20

Chen BF, Tsai YF, Lien PJ, et al (2023)

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

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

PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry.

METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model.

RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05).

CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

RevDate: 2023-07-17

de Araújo RA, da Luz FAC, da Costa Marinho E, et al (2023)

The elusive Luminal B breast cancer and the mysterious chemokines.

Journal of cancer research and clinical oncology [Epub ahead of print].

PURPOSE: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients.

METHODS: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1β), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)].

RESULTS: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r =  0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1β/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases.

CONCLUSION: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH.

RevDate: 2023-07-14

Modena D, Moras ML, Sandrone G, et al (2023)

Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas.

Cancers, 15(13): pii:cancers15133453.

Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.

RevDate: 2023-07-14

Kang MK, Jiang F, Kim YJ, et al (2023)

CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs).

Cancers, 15(13): pii:cancers15133370.

[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.

RevDate: 2023-07-14

Su IL, YK Chen (2023)

Utility of FDG PET/CT in Patient with Synchronous Breast and Colon Cancer.

Diagnostics (Basel, Switzerland), 13(13): pii:diagnostics13132293.

The most common malignancy in women is breast cancer, and the second one is colon cancer. Synchronous breast and colon cancers are rare. Here, we reported a 60-year-old woman with a left breast mass for six months. Biopsy revealed an invasive ductal carcinoma. She underwent 2-[Fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan for evaluation of the extent of the disease. FDG PET/CT revealed an advanced left breast cancer with multiple metastases in both regional and distant lymph nodes (in left axilla level I/II, lower paratracheal region, and right lung hilum), bilateral lungs, and axial and proximal appendicular skeletons. An early staged synchronous colon cancer was detected incidentally on FDG PET/CT images. After endoscopic mucosal resection of colon cancer, she received palliative chemotherapy for breast cancer with a marked therapeutic response. The disease status of post-treated breast cancer remained relatively stationary for more than one year. Brain metastasis was noted afterward. Nevertheless, there was no evidence of colon cancer recurrence throughout her breast cancer disease course.

RevDate: 2023-07-13

Yang J, D Hussein Kadir (2023)

Data mining techniques in breast cancer diagnosis at the cellular-molecular level.

Journal of cancer research and clinical oncology [Epub ahead of print].

INTRODUCTION: Studies in the field of better diagnosis of breast cancer using machine learning and data mining techniques have always been promising. A new diagnostic method can detect the characteristics of breast cancer in the early stages and help in better treatment. The aim of this study is to provide a method for early detection of breast cancer by reducing human errors based on data mining techniques in medicine using accurate and rapid screening.

METHODOLOGY: The proposed method includes data pre-processing and image quality improvement in the first step. The second step consists of separating cancer cells from healthy breast tissue and removing outliers using image segmentation. Finally, a classification model is configured by combining deep neural networks in the third phase. The proposed ensemble classification model uses several effective features extracted from images and is based on majority vote. This model can be used as a screening system to diagnose the grade of invasive ductal carcinoma of the breast.

RESULTS: Evaluations have been done using two histopathological microscopic datasets including patients with invasive ductal carcinoma of the breast. With extracting high-level features with average accuracies of 92.65% and 93.34% in these two datasets, the proposed method has succeeded in quickly diagnosing and classifying breast cancer with high performance.

CONCLUSION: By combining deep neural networks and extracting features affecting breast cancer, the ability to diagnose with the highest accuracy is provided, and this is a step toward helping specialists and increasing the chances of patients' survival.

RevDate: 2023-07-13

Sasamoto M, Yamada A, Oshi M, et al (2023)

Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review.

Gland surgery, 12(6):853-859.

BACKGROUND: Spontaneous regression (SR) of cancer is a rare condition in which the cancer partially or completely disappears without treatment. We report a case of breast cancer with tumor regression and spontaneously induced T-cell-mediated immunological responses in a surgical specimen obtained after core needle biopsy (CNB).

CASE DESCRIPTION: A 52-year-old woman presented with a mass in the right breast. Mammography showed a high-density mass with fine serrated margins in the right lower outer quadrant. Breast ultrasonography showed an irregular hypoechoic mass with a maximum diameter of 22 mm. CNB was performed and revealed an invasive ductal carcinoma with negative estrogen receptors, positive progesterone receptors, and negative HER2 (1+). The Ki67 index was 70% to 80%. Luminal B cT2N1M0 stage IIB right breast cancer was diagnosed. Although preoperative chemotherapy was considered, surgery was selected because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection. A postoperative pathological analysis revealed a 20 mm × 10 mm × 10 mm mass. However, most areas of the mass regressed and appeared as necrotic tissue with no obvious invasive areas. Only intraductal extension was observed in one glandular duct. Axillary lymph node metastases were not observed. These results suggest that the tumor may have spontaneously regressed, possibly because of the CNB procedure. Follow-up without treatment was performed, and no recurrence occurred during 2 years after surgery.

CONCLUSIONS: Invasive ductal carcinoma may spontaneously regress after preoperative CNB.

RevDate: 2023-07-13

Tsunokake S, Iwabuchi E, Miki Y, et al (2023)

SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.

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

PURPOSE: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.

METHODS: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.

RESULTS: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.

CONCLUSION: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.

RevDate: 2023-07-12

Conway JRW, Dinç DD, Follain G, et al (2023)

IGFBP2 secretion by mammary adipocytes limits breast cancer invasion.

Science advances, 9(28):eadg1840.

The progression of noninvasive ductal carcinoma in situ to invasive ductal carcinoma for patients with breast cancer results in a significantly poorer prognosis and is the precursor to metastatic disease. In this work, we have identified insulin-like growth factor-binding protein 2 (IGFBP2) as a potent adipocrine factor secreted by healthy breast adipocytes that acts as a barrier against invasive progression. In line with this role, adipocytes differentiated from patient-derived stromal cells were found to secrete IGFBP2, which significantly inhibited breast cancer invasion. This occurred through binding and sequestration of cancer-derived IGF-II. Moreover, depletion of IGF-II in invading cancer cells using small interfering RNAs or an IGF-II-neutralizing antibody ablated breast cancer invasion, highlighting the importance of IGF-II autocrine signaling for breast cancer invasive progression. Given the abundance of adipocytes in the healthy breast, this work exposes the important role they play in suppressing cancer progression and may help expound upon the link between increased mammary density and poorer prognosis.

RevDate: 2023-07-12

Li S, Tong J, Li H, et al (2023)

L. pneumophila Infection Diagnosed by tNGS in a Lady with Lymphadenopathy.

Infection and drug resistance, 16:4435-4442.

We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.

RevDate: 2023-07-10

Cosar R, Sut N, Topaloglu S, et al (2023)

Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer.

PloS one, 18(7):e0283445 pii:PONE-D-22-33734.

PURPOSE: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups.

PATIENTS AND METHODS: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test.

RESULTS: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival.

CONCLUSION: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required.


RJR Experience and Expertise


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


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


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


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


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


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


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


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

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

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Collection of publications by R J Robbins

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

Research Gate page for R J Robbins

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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