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31 Jul 2021 at 01:44
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Bibliography on: Invasive Ductal Carcinoma


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

RJR: Recommended Bibliography 31 Jul 2021 at 01:44 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: 2021-07-30

Sazawal S, Ryckman KK, Mittal H, et al (2021)

Using AMANHI-ACT cohorts for external validation of Iowa new-born metabolic profiles based models for postnatal gestational age estimation.

Journal of global health, 11:04044 pii:jogh-11-04044.

Background: Globally, 15 million infants are born preterm and another 23.2 million infants are born small for gestational age (SGA). Determining burden of preterm and SGA births, is essential for effective planning, modification of health policies and targeting interventions for reducing these outcomes for which accurate estimation of gestational age (GA) is crucial. Early pregnancy ultrasound measurements, last menstrual period and post-natal neonatal examinations have proven to be not feasible or inaccurate. Proposed algorithms for GA estimation in western populations, based on routine new-born screening, though promising, lack validation in developing country settings. We evaluated the hypothesis that models developed in USA, also predicted GA in cohorts of South Asia (575) and Sub-Saharan Africa (736) with same precision.

Methods: Dried heel prick blood spots collected 24-72 hours after birth from 1311 new-borns, were analysed for standard metabolic screen. Regression algorithm based, GA estimates were computed from metabolic data and compared to first trimester ultrasound validated, GA estimates (gold standard).

Results: Overall Algorithm (metabolites + birthweight) estimated GA to within an average deviation of 1.5 weeks. The estimated GA was within the gold standard estimate by 1 and 2 weeks for 70.5% and 90.1% new-borns respectively. Inclusion of birthweight in the metabolites model improved discriminatory ability of this method, and showed promise in identifying preterm births. Receiver operating characteristic (ROC) curve analysis estimated an area under curve of 0.86 (conservative bootstrap 95% confidence interval (CI) = 0.83 to 0.89); P < 0.001) and Youden Index of 0.58 (95% CI = 0.51 to 0.64) with a corresponding sensitivity of 80.7% and specificity of 77.6%.

Conclusion: Metabolic gestational age dating offers a novel means for accurate population-level gestational age estimates in LMIC settings and help preterm birth surveillance initiatives. Further research should focus on use of machine learning and newer analytic methods broader than conventional metabolic screen analytes, enabling incorporation of region-specific analytes and cord blood metabolic profiles models predicting gestational age accurately.

RevDate: 2021-07-29

Deng Y, Li FL, Qin HY, et al (2021)

[Application Test of the AI-Automatic Diagnostic System for Ki-67 in Breast Cancer].

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition, 52(4):693-697.

Objective: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results.

Methods: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient (ICC) was used to evaluate the correlation.

Results: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal.

Conclusion: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.

RevDate: 2021-07-29

Meyer D, Kames J, Bar H, et al (2021)

Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.

Genome medicine, 13(1):122.

BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.

METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.

RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.

CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.

RevDate: 2021-07-29

Fan T, Wang CQ, Li XT, et al (2021)

MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 31(8):937-940.

OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.

STUDY DESIGN: An experimental study.

PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.

METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT⁃PCR.

RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para⁃carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2) is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.

CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.

RevDate: 2021-07-28

Chung HL, Tso HH, Middleton LP, et al (2021)

Axillary Nodal Metastases in Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma: Comparison of Node Detection and Morphology by Ultrasound.

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

Background: Invasive lobular carcinoma is more subtle on imaging compared with invasive ductal carcinoma; nodal metastases may also differ on imaging between these. Objective: To determine whether invasive lobular carcinoma and invasive ductal carcinoma differ in the detection rate by ultrasound (US) of metastatic axillary nodes and in metastatic nodes' US characteristics. Methods: This retrospective study included 695 women (median age 53 years) with breast cancer in a total of 723 breasts (76 lobular, 586 ductal, 61 mixed), with biopsy-proven axillary nodal metastases and who underwent pretreatment US. A single breast radiologist reviewed US images in patients with suspicious nodes on US and classified node number, size, and morphology. Morphologic assessment used a previously described classification based on the relationship between node cortex and hilum. Nodal findings were compared between lobular and ductal carcinoma. A second radiologist independently classified node morphology in 241 cancers to assess interreader agreement. Results: A total of 99 metastatic axillary nodes (15 lobular, 66 ductal, 18 mixed) were not visualized on US and were diagnosed by surgical biopsy. The remaining 624 metastatic nodes (61 lobular, 520 ductal, 43 mixed) were visualized on US and diagnosed by US-guided FNA. Thus, US detected the metastatic nodes in 80.3% for lobular carcinoma versus 88.7% for ductal carcinoma (p=.04). Among metastatic nodes detected by US, retrospective review identified ≥3 abnormal nodes in 50.8% of lobular carcinoma versus 69.2% of ductal carcinoma (p=.003); node size was ≤2.0 cm in 65.6% for lobular carcinoma versus 47.3% for ductal carcinoma (p=.03); morphology was type III/IV (diffuse cortical thickening without hilar mass effect) rather than type V/VI (marked cortical thickening with hilar mass effect) in 68.9% for lobular carcinoma versus 28.8% for ductal carcinoma (p<.001). Interreader agreement assessment for morphology exhibited kappa coefficient of 0.63 (95% CI, 0.54-0.73). Conclusion: US detects a lower percentage of nodal metastases in lobular than ductal carcinoma. Nodal metastases in lobular carcinoma more commonly show diffuse cortical thickening and with less hilar mass effect. Clinical Impact: A lower threshold may be warranted to recommend biopsy of suspicious axillary nodes detected on US in patients with lobular carcinoma.

RevDate: 2021-07-28

Demir S, Nawroth PP, Herzig S, et al (2021)

Emerging Targets in Type 2 Diabetes and Diabetic Complications.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment-or even the prevention-of type 2 diabetes along with its complications.

RevDate: 2021-07-28

Lopez Salazar V, Karikari RA, Li L, et al (2021)

WITHDRAWN: Adipocyte Deletion of ADAM17 Leads to Insulin Resistance in Association with Age and HFD in Mice.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35 Suppl 1:.

Withdrawal: Valeria Lopez Salazar, Rhoda Anane Karikari, Lun Li, Rabih El-Merahbi, Maria Troullinaki, Moya Wu, Tobias Wiedemann, Alina Walth, Manuel Gil Lozano, Maria Rohm, Stephan Herzig, Anastasia Georgiadi. Adipocyte Deletion of ADAM17 Leads to Insulin Resistance in Association with Age and HFD in Mice (2021). The FASEB Journal. 35:s1. doi: 10.1096/fasebj.2021.35.S1.00447. The above abstract, published online on May 14, 2021 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, FASEB, and Wiley Periodicals Inc. The withdrawal is due to a request made by the authors prior to publication. The Publisher apologizes that this abstract was published in error.

RevDate: 2021-07-29

Ramani SK, Rastogi A, Nair N, et al (2021)

Hyperechoic Lesions on Breast Ultrasound: All Things Bright and Beautiful?.

The Indian journal of radiology & imaging, 31(1):18-23.

Ultrasound (US) lexicon of the Breast Imaging Reporting and Data System (BI-RADS) defines an echogenic breast mass as a lesion that is hyperechoic in comparison with subcutaneous adipose tissue. However, at sonography, only 0.6 to 5.6% of breast masses are echogenic and the majority of these lesions are benign. approximately, 0.5% of malignant breast lesions appear hyperechoic. The various benign pathologic entities that appear echogenic on US are lipoma, hematoma, seroma, fat necrosis, abscess, pseudoangiomatous stromal hyperplasia, galactocele, etc. The malignant diagnoses that may present as hyperechoic lesions on breast US are invasive ductal carcinoma, invasive lobular carcinoma, metastasis, lymphoma, and angiosarcoma. Echogenic breast masses need to be correlated with mammographic findings and clinical history. Lesions with worrisome features such as a spiculated margin, interval enlargement, interval vascularity, or association with suspicious microcalcifications on mammography require biopsy. In this article, we would like to present a pictorial review of patients who presented to our department with echogenic breast masses and were subsequently found to have various malignant as well as benign etiologies on histopathology.

RevDate: 2021-07-28

Rafiq MT, Hamid MSA, Hafiz E, et al (2021)

Feasibility and acceptability of instructions of daily care in overweight and obese knee osteoarthritis participants.

INTRODUCTION: Knee osteoarthritis (OA) is a weight-bearing joint disease and more common in the overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of instructions of daily care (IDC) on pain, mobility and body mass index (BMI) among knee OA participants who are overweight or obese.

MATERIAL AND METHOD: The study was an open-label randomized controlled trial of six-weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six-weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.

RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05), The results of descriptive statistics showed a significantly higher satisfaction score to participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.

CONCLUSION: The IDC are effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.

RevDate: 2021-07-27

Offermann A, Joerg V, Hupe MC, et al (2021)

CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia.

Human pathology pii:S0046-8177(21)00128-3 [Epub ahead of print].

High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of CDK19 by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole tissue sections, and compared CDK19 levels between HGPIN, PCa and adjacent benign glands. In addition, CDK19 was compared to AMACR expression in a subset of intraductal carcinomas (IDC) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists we suggest CDK19 as diagnostic biomarker for HGPIN.

RevDate: 2021-07-27

Andrén P, Jakubovski E, Murphy TL, et al (2021)

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part II: psychological interventions.

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

Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011-2019 and a manual search for the years 2019-2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.

RevDate: 2021-07-23

Ikeda J, Ohe C, Ohsugi H, et al (2021)

Association of intraductal carcinoma of the prostate detected by initial histological specimen and neuroendocrine prostate cancer: A report of three cases.

We present three cases of neuroendocrine prostate cancer (NEPC) and histologically investigate the association of intraductal carcinoma of the prostate (IDC-P) and NEPC. Case 1 was a 76-year-old man who had NEPC identified by repeated biopsy specimens when his prostate-specific antigen (PSA) level became elevated 8 years after the initiation of androgen deprivation therapy (ADT). Case 2 was a 70-year-old man who had NEPC detected when multiple bone metastases were found 3 years after the initiation of ADT. Case 3 was a 70-year-old man who was diagnosed with NEPC based on histological examination of transurethral resected specimens. The histological findings in these three cases showed mixed neuroendocrine carcinoma-acinar adenocarcinoma with various proportions of both components. In all three cases, the neuroendocrine carcinoma components were positive for synaptophysin and chromogranin A, whereas the adenocarcinoma components were positive for PSA and NKX3.1. When we retrospectively reviewed the initial hematoxylin and eosin-stained slides, IDC-P was detected in all three cases. Furthermore, we collected nine additional cases of NEPC and found that all six cases with initial biopsy specimens available had an IDC-P component. Detecting IDC-P on initial histological specimens of the prostate may predict transformation to NEPC.

RevDate: 2021-07-23

Chen X, Li X, Wang J, et al (2021)

Breast invasive ductal carcinoma diagnosis with a three-miRNA panel in serum.

Biomarkers in medicine [Epub ahead of print].

Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials & methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.

RevDate: 2021-07-27

Wang D, Zhang J, Jin J, et al (2021)

Rapid global path planning algorithm for unmanned surface vehicles in large-scale and multi-island marine environments.

PeerJ. Computer science, 7:e612.

A global path planning algorithm for unmanned surface vehicles (USVs) with short time requirements in large-scale and complex multi-island marine environments is proposed. The fast marching method-based path planning for USVs is performed on grid maps, resulting in a decrease in computer efficiency for larger maps. This can be mitigated by improving the algorithm process. In the proposed algorithm, path planning is performed twice in maps with different spatial resolution (SR) grids. The first path planning is performed in a low SR grid map to determine effective regions, and the second is executed in a high SR grid map to rapidly acquire the final high precision global path. In each path planning process, a modified inshore-distance-constraint fast marching square (IDC-FM2) method is applied. Based on this method, the path portions around an obstacle can be constrained within a region determined by two inshore-distance parameters. The path planning results show that the proposed algorithm can generate smooth and safe global paths wherein the portions that bypass obstacles can be flexibly modified. Compared with the path planning based on the IDC-FM2 method applied to a single grid map, this algorithm can significantly improve the calculation efficiency while maintaining the precision of the planned path.

RevDate: 2021-07-24

Freche D, Naim-Feil J, Hess S, et al (2020)

Phase-Amplitude Markers of Synchrony and Noise: A Resting-State and TMS-EEG Study of Schizophrenia.

Cerebral cortex communications, 1(1):tgaa013.

The electroencephalogram (EEG) of schizophrenia patients is known to exhibit a reduction of signal-to-noise ratio and of phase locking, as well as a facilitation of excitability, in response to a variety of external stimuli. Here, we demonstrate these effects in transcranial magnetic stimulation (TMS)-evoked potentials and in the resting-state EEG. To ensure veracity, we used 3 weekly sessions and analyzed both resting-state and TMS-EEG data. For the TMS responses, our analysis verifies known results. For the resting state, we introduce the methodology of mean-normalized variation to the EEG analysis (quartile-based coefficient of variation), which allows for a comparison of narrow-band EEG amplitude fluctuations to narrow-band Gaussian noise. This reveals that amplitude fluctuations in the delta, alpha, and beta bands of healthy controls are different from those in schizophrenia patients, on time scales of tens of seconds. We conclude that the EEG-measured cortical activity patterns of schizophrenia patients are more similar to noise, both in alpha- and beta-resting state and in TMS responses. Our results suggest that the ability of neuronal populations to form stable, locally, and temporally correlated activity is reduced in schizophrenia, a conclusion, that is, in accord with previous experiments on TMS-EEG and on resting-state EEG.

RevDate: 2021-07-26

Ahmed F, Adnan M, Malik A, et al (2021)

Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.

PloS one, 16(7):e0255243 pii:PONE-D-21-14182.

Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient's data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients' biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.

RevDate: 2021-07-24

Yan Z, Qu J, Li Z, et al (2021)

NEK7 Promotes Pancreatic Cancer Progression And Its Expression Is Correlated With Poor Prognosis.

Frontiers in oncology, 11:705797.

The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis.

RevDate: 2021-07-24

Keelara AG, Satish C, Rudresh HK, et al (2021)

Rotter's Lymph Nodes-Do We Really Need to Remove During Axillary Clearance?.

Indian journal of surgical oncology, 12(2):397-400.

Surgical management of node positive breast cancer requires axillary dissection. Interpectoral nodes (IPNs) or Rotter's nodes removal is controversial as there is hardly any tissue in this region. IPNs involvement is rarely seen among breast cancer patients. Developing an effective protocol for surgical management of axilla is necessary for uniformity, to reduce the risk of regional recurrence and to avoid the morbidity of interpectoral lymphatic tissue clearance. This study aimed to evaluate the detection of lymph nodes in Rotter's region and positive metastasis rate of IPNs in patients with node positive breast cancer for analyzing the prognostic and therapeutic value of IPN excision during axillary clearance. Fifty-six patients undergoing axillary clearance, aged ≥ 18 years, were studied. Patients with recurrence or those who underwent neoadjuvant chemotherapy were excluded. Baseline investigations were done pre-operatively along with core needle biopsy, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 status. Association between IPN status, age, and clinicopathological parameters were assessed by Kruskal Wallis and Chi-square test using R v 3.6.0. P value of ≤ 0.05 was considered statistically significant. Majority of patients had upper outer quadrant tumor location (22/56), and the most common histopathological type was invasive ductal carcinoma (46/56). IPNs were identified in 35.71% (20/56) of 56 patients, with metastasis prevalence of 27.27% (9/33 node positive patients). Patients having IPN metastasis had larger tumor size, later TNM classification, lower ER/PR, and higher Ki-67 positivity. Dissection of IPNs can be practiced routinely during axillary clearance and should be subjected to histopathological examination separately.

RevDate: 2021-07-22

Okcu O, Öztürk Ç, Şen B, et al (2021)

Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters.

Annals of diagnostic pathology, 54:151792 pii:S1092-9134(21)00092-7 [Epub ahead of print].

BACKGROUND AND OBJECTIVE: Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases.

MATERIALS AND METHODS: 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed.

RESULTS: We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis.

CONCLUSION: Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.

RevDate: 2021-07-22

Elgazar A, Awad AK, Mnadal D, et al (2021)

Synchronous breast invasive ductal carcinoma and clear cell renal carcinoma: case report and a review of literature.

Journal of surgical case reports, 2021(7):rjab317 pii:rjab317.

Multiple primary tumors' incidence is rare, yet more rare is the incidence of multiple primary malignant tumors. Co-occurring tumors can be divided into synchronous and non-synchronous. Synchronous tumors are those tumors that present within a period not >6 months from each other. To define synchronous malignant tumors: metastasis should not be present, both tumors have to show criteria of malignancy, and they should differ pathologically from each other. Breast cancer is the most common tumor to be associated with other primaries especially; colorectal cancer, endometrial and ovarian cancer, yet the occurrence of invasive ductal carcinoma with clear cell renal cancer is uncommon. In our case, we present a 59-year-old female with invasive ductal carcinoma and clear cell renal carcinoma.

RevDate: 2021-07-21

Muley C, A Bartelt (2021)

Fuse your mitochondria, lose appetite: an anorexic, anti-obesity sphingolipid.

EMBO molecular medicine [Epub ahead of print].

Aberrant production of ceramides, the precursors of complex sphingolipids, is a hallmark of obesity and strongly linked to metabolic dysfunction (Meikle and Summers 2017). Ceramides are formed by recycling or de novo synthesis from sphingosine and a fatty acid side chain moiety. The side chain length determines lipotoxicity of ceramides, as those composed of C16:0 or C18:0 side chains are toxic whereas those with C24:0 or C24:1 are not (Meikle and Summers 2017). Counteracting the deleterious effects of high-fat diets (HFDs) rich in saturated fat either by inhibiting synthesis or by promoting degradation of ceramides mitigates insulin resistance and ectopic lipid accumulation (Meikle and Summers 2017). However, drugs that safely and selectively target ceramide metabolism have failed to translate into metabolic benefit in human trials so far.

RevDate: 2021-07-21

Horiguchi J, Nakashoji A, Kawahara N, et al (2021)

Chemotherapy resumption in breast cancer patient after COVID-19.

Surgical case reports, 7(1):170.

BACKGROUND: While many studies have verified the effect of recent anti-cancer treatment in patients with COVID-19, there are no data on the optimal time for cancer treatment resumption, as well as the safety of chemotherapy in COVID-19 patients. As many cancer patients are recovering from COVID-19, there is an urgent need for reliable clinical information. Herein, we report a case of invasive ductal carcinoma in which we were able to successfully resume chemotherapy after infection with SAR-CoV-2.

CASE PRESENTATION: The patient was a 38-year-old non-smoking Japanese woman with no significant medical history. She had fever on days 5 and 6 of her second course of adjuvant FEC therapy, and on day 7, she tested positive for SARS-CoV-2 by RT-PCR. She was hospitalized for 11 days. We resumed the therapy on day 25 after discharge, as she had no remaining clinical symptoms. The patient completed four courses of the initial chemotherapy without any major adverse events nor the recurrence of COVID-19, and subsequently completed four courses of docetaxel as her second regimen therapy.

CONCLUSIONS: Evaluating the risk for each patient is essential when resuming anti-cancer therapy in cancer patient's post-COVID-19.

RevDate: 2021-07-19

Ren X, Ju Y, Wang C, et al (2021)

MARCKS on Tumor-Associated Macrophages is Correlated with Immune Infiltrates and Poor Prognosis in Hepatocellular Carcinoma.

Cancer investigation [Epub ahead of print].

BACKGROUND: Hepatocellular carcinoma is the fourth most common cause of cancer-related death. However, the cross-talk between tumor immune microenvironment and hepatocellular carcinoma (HCC) remains unclear.

MATERIAL AND METHODS: We analyzed the expression of miR-143-3p in exosomes from different HCC cell lines. Differentially expressed genes (DEGs) in Tumor-associated macrophages (TAMs) co-cultured with HCC cell lines were overlapped with miR-143-3p target genes. We used the Oncomine, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) databases to assess Myristoylated alanine-rich C-kinase substrate (MARCKS) expression in various types of cancers. The relationship between patient clinicopathological characteristics and MARCKS expression level was identified using the Kaplan-Meier plotter database. Last, we analyzed how MARCKS expression correlated with immune infiltration makers using the TCGA database, Tumor IMmune Estimation Resource (TIMER), and Gene Expression Profiling Interactive Analysis (GEPIA).

RESULTS: Exosomal miR-143-3p was elevated after IL-6 treatment in the HCC cell line. MARCKS, a target gene of miR-143-3p, was up-regulated in Tumor-associated macrophages co-cultured with high-metastatic-potential HCC cell line. MARCKS expression was identified as significantly correlated with outcome in multiple types of cancer, especially in HCC. High MARCKS expression level was associated with poorer overall survival (OS), Progress-free survival (PFS), and also with patient gender, race, hepatitis virus background, stage, grade, AJCC_T, and vascular invasion. MARCKS was positively associated with levels of T follicular helper cells (TFH) (R = .48, p < .001), T helper type 2 (Th2) cells (R = .47, p < .001), macrophages (R = .41, p ≤ .001), T helper cells (R = .40, p < .001), T helper type 1 (Th1) cells (R = .38, p < .001), T cells (R = .34, p < .001), NK CD56bright cells (R = .34, p < .001) and immature DC (iDC) (R = .33, p < .001), and negatively associated with levels of T helper 17 (Th17) cells. Also, MARCKS may influence the M2 polarization and immune escape.

CONCLUSION: The present study suggests that MARCKS on TAMs is associated with poor prognosis and immune cell infiltration in HCC.

RevDate: 2021-07-19

Qi H, Schmöhl F, Li X, et al (2021)

Reduced Acrolein Detoxification in akr1a1a Zebrafish Mutants Causes Impaired Insulin Receptor Signaling and Microvascular Alterations.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a-/- zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a-/- larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. Akr1a1a-/- larvae display impaired glucose homeostasis and angiogenic retina hyaloid vasculature, which are caused by reduced acrolein detoxification ability and increased internal ACR concentration. The effects of acrolein on hyaloid vasculature can be reversed by acrolein-scavenger l-carnosine treatment. In adult akr1a1a-/- mutants, impaired glucose tolerance accompanied by angiogenic retina vessels and glomerular basement membrane thickening, consistent with an early pathological appearance in diabetic retinopathy and nephropathy, are observed. Thus, the data strongly suggest impaired ACR detoxification and elevated ACR concentration as biomarkers and inducers for diabetes and diabetic complications.

RevDate: 2021-07-19

Haque W, Verma V, Adeberg S, et al (2021)

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer.

Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology, 26(3):341-351 pii:rpor-26-3-341.

Background: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.

Materials and methods: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.

Results: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER-/HER2- disease had worse OS than patients with ER+/HER2- disease, for both patients treated with SRS and for patients treated with WBRT.

Conclusions: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.

RevDate: 2021-07-19

Gortman A, Aherne NJ, Westhuyzen J, et al (2021)

Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up.

Molecular and clinical oncology, 15(3):178.

Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.

RevDate: 2021-07-17

Considine B, Adeniran A, ME Hurwitz (2021)

Current Understanding and Management of Intraductal Carcinoma of the Prostate.

Current oncology reports, 23(9):110.

PURPOSE OF REVIEW: This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts.

RECENT FINDINGS: The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.

RevDate: 2021-07-16

Scolozzi V, Giancipoli RG, Macciomei MC, et al (2021)

Cavernous Hemangioma: A Potential Pitfall at Delayed 18F-FDG PET/CT Scan.

Clinical nuclear medicine pii:00003072-900000000-95936 [Epub ahead of print].

ABSTRACT: We report the case of a 72-year-old woman who underwent neoadjuvant chemotherapy, right quadrantectomy (invasive ductal carcinoma, G3, pT2pN1pMx), and adjuvant radiotherapy. Two years later, a follow-up CT revealed a hepatic nodule of approximately 1 cm suspected for metastasis. 18F-FDG PET/CT was performed for restaging. Standard total-body 18F-FDG PET/CT acquisition showed no abnormal 18F-FDG uptake in the hepatic nodule. A delayed 18F-FDG PET/CT acquisition of upper abdomen was performed at 180 minutes postradiopharmaceutical injection and showed increased 18F-FDG uptake in the hepatic nodule. After nodule resection, the histological examination proved a cavernous hemangioma.

RevDate: 2021-07-15

Coşkun Bilge A, Aydın H, Bostancı IE, et al (2021)

Comparison of the Magnetic Resonance Imaging Findings of Paget's Disease of the Breast and Malignant Tumor Invasion of the Nipple-Areola Complex.

European journal of breast health, 17(3):265-273 pii:47937.

Objective: We aimed to investigate the distinction between Paget's disease of the breast (PDB) and malignant tumor invasion of nipple-areolar complex (MTION) with Magnetic resonance imaging (MRI) findings without the need for skin punch biopsy.

Materials and Methods: MRI findings of 16 patients with pathologically proven PDB and 11 patients with pathologically proven MTION were reviewed retrospectively. MRI images were assessed for nipple morphological changes; areolar-periareolar skin changes; thickness, classification, and kinetic characteristics of the nipple-areolar complex (NAC) enhancement; morphological pattern, size, and pathological diagnosis of concomitant malignant lesions; kinetic characteristics of the concomitant malignant lesions enhancement; continuity of enhancement between the nipple and closest concomitant malignant lesion; similarity of enhancement kinetics of the NAC and concomitant malignant lesions; and nipple-to-malignant lesion distance in both patient groups.

Results: Areolar-periareolar skin thickening was statistically different between the patient groups. Enhancement kinetic pattern was classified as persistent in four patients with MTION and plateau in seven patients with PDB. Moreover, NAC enhancement kinetic characteristics were statistically different between the groups. Invasive ductal carcinoma was detected in three patients with PDB and five patients with MTION. A statistically significant difference in malignant lesion pathological types was detected between the patient groups.

Conclusion: The significant MRI findings in patients with MTION diagnosed as invasive ductal carcinoma were areolar-periareolar skin thickening and asymmetric NAC enhancement with persistent kinetics pattern. In patients diagnosed with ductal carcinoma in situ, a plateau pattern of asymmetric NAC enhancement without any areolar-periareolar skin changes on MRI may indicate PDB.

RevDate: 2021-07-14

Lifshin U, M Mikulincer (2021)

Further evidence for motivated helplessness in the context of the COVID-19 outbreak: the case of Argentina before and during the pandemic.

The Journal of social psychology [Epub ahead of print].

According to the motivated helplessness hypothesis, a sense of helplessness in coping with threats in a specific domain can serve an anxiety-buffering function. The purpose of this study was to test this hypothesis in the context of the coronavirus (COVID-19) pandemic in Argentina, using data collected before and during the pandemic. Findings supported the motivated helplessness hypothesis: Whereas feelings of helplessness to avoid being infected with COVID-19 were positively related to fear of being infected with COVID-19 and state anxiety before the pandemic, these feelings were negatively related to fear of being infected (and not directly related to state anxiety) during the pandemic. These findings demonstrate the specificity of the motivated helplessness effect and further establish this effect in the context of the COVID-19 pandemic.

RevDate: 2021-07-14

Naffouje SA, Sabesan A, Hoover SJ, et al (2021)

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

Annals of surgical oncology [Epub ahead of print].

INTRODUCTION: We aim to analyze survival outcomes for sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in human epidermal growth factor receptor (HER2)+ infiltrative ductal carcinoma (IDC) that demonstrate complete clinical response (cCR) to neoadjuvant systemic therapy (NAST) after initial presentation with clinical N1 (cN1) disease.

METHODS: NCDB 2004-2017 was utilized for the analysis. Female patients with unilateral HER2+ IDC, stage cT1-T4 cN1, who demonstrated cCR to NAST with reported definitive axillary surgical management were included. Patients were propensity score matched, and overall survival (OS) was compared. Cox regression analysis was used to identify survival predictors.

RESULTS: 6453 patients were selected, of whom 2461 (38.1%) had SLNB and 3992 (69.1%) had ALND as definitive axillary surgical management. The trend of SLNB utilization increased from 20% in 2012 to 50% in 2017. A total of 2454 patients were matched from each group with adequate adjustment for all variables. There was no difference in OS between SLNB versus ALND (84.03 ± 0.36 versus 84.62 ± 0.42 months; p = 0.522). Cox regression identified age, cT stage, primary tumor response to NAST, ypN+, and endocrine therapy as significant OS predictors. In subgroup analysis of patients with ypN+ who had SLNB as a definitive procedure, primary tumor response to NAST and continuation of adjuvant chemotherapy were associated with improved OS.

CONCLUSION: In cN1 HER2+ IDC patients who demonstrate cCR to NAST, SLNB is a reasonable definitive procedure for axillary management with comparable OS outcomes to ALND. However, higher-level data are required to determine the appropriate management in the case of ypN+.

RevDate: 2021-07-14

Cernusco NLV, Bianco PD, Romano M, et al (2021)

Long-Term Outcomes Using Electron IOERT APBI for Early Stage Breast Cancer: The Verona University Hospital Experience.

Clinical breast cancer pii:S1526-8209(21)00143-9 [Epub ahead of print].

METHODS AND MATERIALS: From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status.

RESULTS: With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively.

CONCLUSION: Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.

RevDate: 2021-07-13

Shoshani A, S Yaari (2021)

Parental Flow and Positive Emotions: Optimal Experiences in Parent-Child Interactions and Parents' Well-Being.

Journal of happiness studies pii:427 [Epub ahead of print].

Flow is a mental state of thorough absorption and concentration in an activity, in which intrinsic motivation and enjoyment are maximized, and the individual achieves optimal performance. This study investigated how daily flow experiences during parents' interactions with their children contribute to parental well-being. The Day Reconstruction Method was completed by 832 employed Israeli parents of children aged 2 to 12, who reconstructed their experiences on three different working days over three weeks, and rated their levels of flow, as well as positive and negative affect for each experience. Participants also completed measures of subjective well-being and parental satisfaction and efficacy. The results indicated that parents' flow experiences during interactions with their children were positively related to parents' positive affect, self-efficacy and satisfaction, and greater subjective well-being. The findings underscore the importance for parental well-being of daily optimal experiences with their children.

RevDate: 2021-07-12

Dabiri C, Hotton J, Wehbe K, et al (2021)

Assessment of the Grisotti oncoplastic procedure for the management of central breast tumors.

The breast journal [Epub ahead of print].

INTRODUCTION: The Grisotti technique consists to excise central breast tumor with nipple areolar and mobilize a dermo-glandular flap which is de-epithelized in order to reshape the breast and recreate an areola. The objective was to assess oncological results, postoperative side-effects, and patient and surgeon satisfaction rates resulting from this technique.

MATERIALS AND METHODS: From September 2016 to December 2019, 38 patients have been treated with a central breast tumor using the Grisotti technique.

RESULTS: The mean age was 61.6 ± 11. The median body mass index was 27 kg/m² [20-42]. Thirty one patients benefited from a sentinel lymph node dissection. Preoperative histology found a majority of invasive ductal carcinomas (IDC) (71%). There were no intraoperative complications, and the average operating time was 90 min [60-200]. Postoperative histology found IDC associated with ductal carcinoma in situ in 28 patients. The surgical margins were invaded in two patients (reoperated by mastectomy after adjuvant treatment) and invasion of a margin of less than 1 mm in another six patients (supplemented by re-excision). The main postoperative complications were an abscess of the operating site and a partial necrosis of the neo-areola. The appearance of the breasts after radiotherapy gives a high satisfaction rate, both for patients and for surgeons.

CONCLUSION: The Grisotti technique is an easily reproducible procedure without major complications. It makes it possible to perform a carcinological satisfactory central lumpectomy, correction of the central glandular defect, and reconstruction of a new areola.

RevDate: 2021-07-13

Lin Q, Chen X, Meng F, et al (2021)

Multi-organ metastasis as destination for breast cancer cells guided by biomechanical architecture.

American journal of cancer research, 11(6):2537-2567.

A majority of breast cancer patients die of widespread aggressive multidrug-resistant tumors. Aspartate β-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase and oncofetal antigen involved in embryogenesis. To illustrate if ASPH could be targeted for metastatic breast cancer, embedded and on-top three-dimensional (3-D) cultures, 3-D invasion, mammosphere formation, immunofluorescence, immunohistochemistry, Western blot, co-IP and microarray were conducted. In vitro metastasis was developed to imitate how cancer cells invade basement membrane at the primary site, transendothelially migrate, consequently colonize and outgrow at distant sites. Orthotopic and experimental pulmonary metastatic (tail vein injection) murine models were established using stable breast cancer cell lines. Cox proportional hazards regression models and Kaplan-Meier plots were applied to assess clinical outcome of breast cancer patients. In adult non-cancerous breast tissue, ASPH is undetectable. Pathologically, ASPH expression re-emerged at ductal carcinoma in situ (DCIS), and enhanced with disease progression, from early-stage invasive ductal carcinoma (IDC) to late-stage carcinoma. ASPH at moderate to high levels contribute to aggressive molecular subtypes, early relapse or more frequent progression and metastases, whereas substantially shortened overall survival and disease-free survival of breast cancer patients. Through direct physical interactions with A disintegrin and metalloproteinase domain-containing protein (ADAM)-12/ADAM-15, ASPH could activate SRC cascade, thus upregulating downstream components attributed to multifaceted metastasis. ASPH-SRC axis initiated pro-invasive invadopodium formation causing breakdown/disorganization of extracellular matrix (ECM), simultaneously potentiated epithelial-mesenchymal transition (EMT), induced cancer stem cell markers (CD44 and EpCAM), enhanced mammosphere formation and intensified 3-dimentional invasion. Oncogenic SRC upregulated matrix metallopeptidases (MMPs) were assembled by invadopodia, acting as executive effectors for multi-step metastasis. ASPH-SRC signal guided multi-organ metastases (to lungs, liver, bone, spleen, lymph nodes, mesentery or colon) in immunocompromised mice. Malignant phenotypes induced by ASPH-SRC axis were reversed by the third-generation small molecule inhibitor (SMI) specifically against β-hydroxylase activity of ASPH in pre-clinical models of metastatic breast cancer. Collectively, ASPH could activate ADAMs-SRC-MMPs cascades to promote breast cancer tumor progression and metastasis. ASPH could direct invadopodium construction as a biomechanical sensor and pro-metastatic outlet. ASPH-mediated cancer progression could be specifically/efficiently subverted by SMIs of β-hydroxylase activity. Therefore, ASPH emerges as a therapeutic target for breast cancer.

RevDate: 2021-07-13

Sato F, Shimomura A, Nakayama K, et al (2021)

Breast Cancer Treatment in a Patient with Decubitus Ulcer Infection Secondary to Spina Bifida: Surgical Resection versus Neoadjuvant Chemotherapy.

Case reports in oncology, 14(2):944-949.

Spina bifida (SB) is a congenital neural tube defect that often presents with neurological disability and decubitus ulcers. A 66-year-old woman with SB presented to our hospital with decubitus ulcers and was treated by a plastic surgeon. She was referred to our department because of a mass measuring 5 × 4 cm in the superolateral quadrant of the right breast. The size of the right axillary lymph node (LN) was 2 × 1 cm. A core-needle biopsy revealed an invasive ductal carcinoma. Total mastectomy and axillary LN dissection were planned. However, 2 days prior to surgery, the size of the mass and the LN rapidly increased to 7 × 4 cm and 3 × 2 cm, respectively. Furthermore, the enlarged LN was close to the thoracodorsal artery. Since complete resection was difficult, neoadjuvant chemotherapy was also administered. On day 11 of neoadjuvant chemotherapy, the patient was febrile and developed a decubitus ulcer infection at the buttock. The neutrophil count was within normal limits; thus, she was not diagnosed with febrile neutropenia. Follow-up computed tomography revealed a shrinking of the mass to 5 × 4 cm after the first cycle of neoadjuvant chemotherapy. After 17 days of antibiotic therapy and drainage, total mastectomy and axillary LN dissection were performed. Due to the risk of recurrence of infection, adjuvant chemotherapy was discontinued and hormone therapy was initiated. In conclusion, indications for chemotherapy should be carefully evaluated in SB patients with lower limb paralysis and decubitus ulcers.

RevDate: 2021-07-13
CmpDate: 2021-07-13

Hirabayashi M, Ozawa M, Kako S, et al (2021)

[Pancreatic adenocarcinoma:a case containing a cyst enclosing a dilated tubular gland duct].

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 118(7):679-685.

This case report describes a 73-year-old woman with pancreatic adenocarcinoma who had undergone a colectomy for colorectal cancer in 1995 and a right mastectomy and axillary dissection for breast cancer in 2013. In January 2019, a tumor, approximately 20mm in diameter, was detected in the pancreatic body. It contained a cyst noted to have delayed perfusion towards the center on abdominal computed tomography. On T1-weighted magnetic resonance imaging (MRI), almost the entire tumor exhibited low intensity. On T2-weighted MRI, however, the tumor center displayed high intensity, the tumor wall displayed low intensity, and the outermost layer displayed high intensity. On endoscopic ultrasound, the tumor center displayed low echo density, the tumor wall had a slightly elevated echo density, and the outermost layer had a low echo density. A distal pancreatectomy was performed for a suspected metastatic pancreatic cancer, pancreatic neuroendocrine neoplasm, or invasive ductal carcinoma without tubular adenocarcinoma. Histopathological examination revealed that the tumor cells had formed atypical tubular gland ducts with a fibrous stroma in the background. The lesion differed from the histopathological findings of her previous colorectal and breast cancers, and it was ultimately diagnosed as a pancreatic ductal adenocarcinoma. The lumen of the cyst was covered with tumor cells identical to those of the atypical tubular gland ducts in the tumor parenchyma, suggesting that the cyst was a dilated tubular gland duct.

RevDate: 2021-07-11

Maida A, Zota A, Vegiopoulos A, et al (2021)

Corrigendum to "Dietary protein dilution limits dyslipidemia in obesity through FGF21-driven fatty acid clearance" [The Journal of Nutritional Biochemistry 57 (2018) 189-196].

RevDate: 2021-07-13

Bodner E, Bergman YS, Ben-David B, et al (2021)

Vaccination anxiety when vaccinations are available: The role of existential concerns.

Stress and health : journal of the International Society for the Investigation of Stress [Epub ahead of print].

This study examined how existential fears are related to COVID-19 vaccination anxiety and followed the Terror Management Theory (TMT) by examining the contribution of two existential concerns, subjective nearness-to-death (SNtD) and death anxiety, to COVID-19 vaccination anxiety during the first month of COVID-19 vaccinations. Data were collected during January 2021, when Israel was in lockdown, from a convenience sample of 381 Jewish Israelis (M = 55.39, SD = 17.17). Participants completed questionnaires examining demographics, SNtD, death anxiety and COVID-19 vaccination anxiety. A hierarchical regression analysis examined the connections between these variables and COVID-19 vaccination anxiety while controlling for demographics and for receiving COVID-19 vaccinations. In line with the hypotheses, SNtD and death anxiety were each positively associated with COVID-19 vaccination anxiety, and death anxiety levels moderated the positive connection between SNtD and COVID-19 vaccination anxiety, as this association was not significant for individuals with low death anxiety. The findings of this study provide preliminary evidence concerning the role of death anxiety in moderating the effect that SNtD has on COVID-19 vaccination anxiety. These findings are in line with the TMT and justify further investigation and may be utilized in future research in order to address COVID-19 vaccination anxiety more effectively.

RevDate: 2021-07-13

Chiong F, Wasef MS, Liew KC, et al (2021)

The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.

BMC infectious diseases, 21(1):671.

BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB.

METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality.

RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups.

CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.

RevDate: 2021-07-12

Samanta A, A Sarkar (2021)

Altered expression of ERK, Cytochrome-c, and HSP70 triggers apoptosis in Quinacrine-exposed human invasive ductal carcinoma cells.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 139:111707.

Invasive ductal carcinoma (IDC) is the most recurrent cancer, accounting for 80% of all breast cancers worldwide. Originating from the milk duct, it eventually invades the fibrous tissue of the breast outside the duct, proliferation takes 1-2 months for each division. Quinacrine (QC), an FDA-approved small molecule, has been shown to have anti-cancer activity in numerous cancerous cell lines through diverse pathways; ultimately leading to cell death. Here, we have investigated the mode of action of QC in MCF7 cells. This study demonstrated the modulation of cellular cytoskeleton, such as the formation of distinct filopodial and lamellipodial structures and spikes, through the regulation of small-GTPases. We also observed that QC induces a signaling cascade by inducing apoptotic cell death by increasing ROS generation and altering HSP70 expression; which presumably involves ERK regulation. Our findings show that QC could be an attractive chemotherapeutic agent having a "shotgun" nature with potential of inducing different signaling pathways leading to apoptotic cell death. This opens new avenues for research on developing QC as an effective therapeutic agent for the treatment of invasive ductal carcinomas.

RevDate: 2021-07-12

Xu Z, Kurek A, Cannon SB, et al (2021)

Predictions from algorithmic modeling result in better decisions than from data modeling for soybean iron deficiency chlorosis.

PloS one, 16(7):e0240948 pii:PONE-D-20-30550.

In soybean variety development and genetic improvement projects, iron deficiency chlorosis (IDC) is visually assessed as an ordinal response variable. Linear Mixed Models for Genomic Prediction (GP) have been developed, compared, and used to select continuous plant traits such as yield, height, and maturity, but can be inappropriate for ordinal traits. Generalized Linear Mixed Models have been developed for GP of ordinal response variables. However, neither approach addresses the most important questions for cultivar development and genetic improvement: How frequently are the 'wrong' genotypes retained, and how often are the 'correct' genotypes discarded? The research objective reported herein was to compare outcomes from four data modeling and six algorithmic modeling GP methods applied to IDC using decision metrics appropriate for variety development and genetic improvement projects. Appropriate metrics for decision making consist of specificity, sensitivity, precision, decision accuracy, and area under the receiver operating characteristic curve. Data modeling methods for GP included ridge regression, logistic regression, penalized logistic regression, and Bayesian generalized linear regression. Algorithmic modeling methods include Random Forest, Gradient Boosting Machine, Support Vector Machine, K-Nearest Neighbors, Naïve Bayes, and Artificial Neural Network. We found that a Support Vector Machine model provided the most specific decisions of correctly discarding IDC susceptible genotypes, while a Random Forest model resulted in the best decisions of retaining IDC tolerant genotypes, as well as the best outcomes when considering all decision metrics. Overall, the predictions from algorithmic modeling result in better decisions than from data modeling methods applied to soybean IDC.

RevDate: 2021-07-12

Samson J, Derlipanska M, Zaheed O, et al (2021)

Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.

BMC cancer, 21(1):790.

BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.

METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.

RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.

CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.

RevDate: 2021-07-08

Loft A, Alfaro AJ, Schmidt SF, et al (2021)

Liver-fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication.

Cell metabolism pii:S1550-4131(21)00275-8 [Epub ahead of print].

Liver fibrosis is a strong predictor of long-term mortality in individuals with metabolic-associated fatty liver disease; yet, the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely understood. Using cell-type-resolved genomics, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a network of fibrosis-activated transcription factors, as exemplified by the transcription factor Elf-3 (ELF3) and zinc finger protein GLIS2 (GLIS2). Indeed, ELF3- and GLIS2-controlled fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell gene programs. Thus, interconnected transcription factor networks not only promoted hepatocyte dysfunction but also directed the intra-hepatic crosstalk necessary for NASH and fibrosis progression, implying that molecular "hub-centered" targeting strategies are superior to existing mono-target approaches as currently used in NASH therapy.

RevDate: 2021-07-08

Muthumani K, Xu Z, Jeong M, et al (2021)

Preexisting vs. de novo antibodies against SARS-CoV-2 in individuals without or with virus infection: impact on antibody therapy, vaccine research and serological testing.

Translational medicine communications, 6(1):13.

The causative agent of the ongoing pandemic in the world is SARS-CoV-2. The research on SARS-CoV-2 has progressed with lightning speed on various fronts, including clinical research and treatment, virology, epidemiology, drug development, and vaccine research. Recent studies reported that sera from healthy individuals, who were confirmed negative for SARS-CoV-2 by RT-PCR method, tested positive for antibodies against spike and nucleocapsid proteins of SARS-CoV-2. Further, such antibodies also exhibited neutralizing activity against the virus. These observations have prompted us to prepare a commentary on this topic. While the preexisting antibodies are likely to protect against SARS-CoV-2 infection, they may also complicate serological testing results. Another unknown is the influence of preexisting antibodies on immune responses in individuals receiving vaccines against SARS-CoV-2. The commentary identifies the potential limitations with the serological tests based on spike and nucleocapsid proteins as these tests may overestimate the seroprevalence due to cross-reactive antibodies. The inclusion of tests specific to SARS-CoV-2 (such as RBD of spike protein) could overcome these limitations.

RevDate: 2021-07-13

Zeigerer A (2021)

NAFLD - A rising metabolic disease.

RevDate: 2021-07-12

Fosko NK, Davis CH, Koshenkov VP, et al (2021)

Simultaneous primary invasive breast carcinoma and ipsilateral cutaneous melanoma of the back: Surgical approach and considerations, a case report.

International journal of surgery case reports, 84:106155 pii:S2210-2612(21)00657-X [Epub ahead of print].

INTRODUCTION AND IMPORTANCE: A patient presented with ipsilateral, synchronous primary malignancies of left upper back melanoma and left breast invasive ductal carcinoma. This complex presentation was managed with a multidisciplinary approach.

CASE PRESENTATION: A 61-year-old female presented with multiple cutaneous lesions, revealed to be several foci of melanoma in situ as well as a T4b melanoma of the left upper back. On staging work up, a left breast malignancy was incidentally discovered. Genetic testing did not delineate a relevant mutation to explain the synchronous malignancies. Multidisciplinary surgical planning entailed consideration of the lymphatic drainage patterns of the lesions, with both the upper back melanoma and breast carcinoma expected to drain to the left axilla. Ultimately, simultaneous resections of both malignancies were performed as well as concomitant left sentinel lymph node biopsies utilizing dual tracer technique.

CLINICAL DISCUSSION: Currently, cases of synchronous primary cutaneous melanoma and independent, ipsilateral primary breast carcinoma have not been examined, and thus surgical considerations for axillary staging in this circumstance have not been discussed. The existing literature instead explores the incidence and operative challenges of one malignancy following the other after an interval of time.

CONCLUSION: This case highlights the utility of a multidisciplinary team for complex oncologic presentations and discusses a creative surgical approach to address two simultaneous primary malignancies involving the left breast and ipsilateral skin of the back. This case emphasizes an exceedingly rare presentation and serves as an important example to educate medical professionals on the innovative and team-based approach to treatment.

RevDate: 2021-07-12

Pariyar M, Johns A, Thorne RF, et al (2021)

Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.

Neoplasia (New York, N.Y.), 23(8):743-753 pii:S1476-5586(21)00040-3 [Epub ahead of print].

Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.

RevDate: 2021-07-13

Jones BM, S Green (2021)

Modern radiation techniques in early stage breast cancer for the breast radiologist.

Clinical imaging, 80:19-25 pii:S0899-7071(21)00281-3 [Epub ahead of print].

Partial breast irradiation (PBI) and ultra-hypofractionated whole breast irradiation (uWBI) are contemporary alternatives to conventional and standard hypofractionated whole breast irradiation (WBI), which shorten treatment from 3 to 6 weeks to 1-2 weeks for select patients. PBI and accelerated PBI (APBI) can be delivered with external beam radiation (3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT)), intraoperative radiation (IORT), or brachytherapy. These new radiation techniques offer the advantage of convenience and lower cost, which ultimately improves access to care. Globally, the COVID 19 pandemic has accelerated APBI/PBI and ultra-hypofractionated regimens into routine practice for carefully selected patients. Recent long-term data from randomized controlled trials (RCTs) have demonstrated these techniques are safe and effective in suitable patients demonstrating equivalent or improved local recurrence, acute/late toxicity, and cosmesis. PBI and APBI should be limited to low risk unifocal invasive ductal carcinoma and ductal carcinoma in situ with tumor size < 2 cm, clear margins (≥2 mm), ER+, and negative nodes. Based on the results from UK Fast-Forward and UK FAST ultra-hypofractionated breast radiation can be safely employed for early stage node negative patients, but is not yet considered an international standard of care. In this review, authors will appraise recent data for these shorter course radiation treatment regimens, as well as, considerations for breast radiologists including surveillance imaging and radiographic findings.

RevDate: 2021-07-06

Carpinello O, Aserlind A, Chang F, et al (2020)

Fertility preservation in an oncology patient who presented with positive human chorionic gonadotropin.

F&S reports, 1(1):51-53.

Objective: To report the case of a woman who presented for fertility preservation before breast cancer treatment who was found to be pregnant with an undesired pregnancy.

Design: Case report.

Setting: Single infertility practice.

Patient: A 28-year-old woman with a new diagnosis of grade 3 invasive ductal carcinoma of the breast was planning to undergo oocyte cryopreservation and was found to be pregnant with an undesired pregnancy. She underwent a medical termination at a gestational age of 5 weeks 4 days. Neither the patient nor her oncology team wished to delay treatment more than was necessary. The physician and patient decided to initiate controlled ovarian hyperstimulation (COH) before her human chorionic gonadotropin (hCG) returned to normal.

Interventions: COH in the setting of a positive quantitative hCG.

Main Outcome Measures: Number of metaphase II (MII) oocytes cryopreserved; doses of Gonal-F and Menopur; serum E2, follicle-stimulating hormone, luteinizing hormone, hCG levels.

Results: COH began 7 days after passing the products of conception. Baseline labs demonstrated hCG at 222 mIU/mL, follicle-stimulating hormone at <0.10 mIU/mL, luteinizing hormone at <1.10 mIU/mL, and E2 at 147 pg/mL. She was started on an antagonist protocol with the use of 150 IU Gonal F and 75 IU Menopur. She was triggered on stimulation day 14 with 5,000 U hCG, and her peak E2 was 5,924 pg/mL. She ultimately had 18 oocytes retrieved, 12 of which were MII, one MI, and five germinal vesicle. All were vitrified.

Conclusions: COH can be achieved in the setting of low positive hCG levels with subsequent successful oocyte maturation. The threshold for hCG trigger to be ineffective in the setting of a positive hCG has yet to be determined.

RevDate: 2021-07-06

Sprenger J, Murray C, Lad J, et al (2021)

Toward a quantitative method for estimating tumour-stroma ratio in breast cancer using polarized light microscopy.

Biomedical optics express, 12(6):3241-3252.

The tumour-stroma ratio (TSR) has been explored as a useful source of prognostic information in various cancers, including colorectal, breast, and gastric. Despite research showing potential prognostic utility, its uptake into the clinic has been limited, in part due to challenges associated with subjectivity, reproducibility, and quantification. We have recently proposed a simple, robust, and quantifiable high-contrast method of imaging intra- and peri-tumoural stroma based on polarized light microscopy. Here we report on its use to quantify TSR in human breast cancer using unstained slides from 40 patient samples of invasive ductal carcinoma (IDC). Polarimetric results based on a stromal abundance metric correlated well with pathology designations, showing a statistically significant difference between high- and low-stroma samples as scored by two clinical pathologists. The described polarized light imaging methodology shows promise for use as a quantitative, automatic, and standardizable tool for quantifying TSR, potentially addressing some of the challenges associated with its current estimation.

RevDate: 2021-07-06

Abedi SM, Mardanshahi A, R Zeanali (2021)

Added diagnostic value of SPECT to evaluate bone metastases in breast cancer patients with normal whole body bone scan.

Caspian journal of internal medicine, 12(3):290-293.

Background: In this research, we aimed to survey the added value of single photon emission computed tomography (SPECT) in comparison with planar whole body bone scan to visualize bone metastatic lesions in patients with breast cancer.

Methods: A total of 80 patients with breast cancer (invasive ductal carcinoma) were examined with planar whole body bone scan and SPECT imaging using 99mTc-labelled methylene diphosphonate (99mTc-MDP). The patients with abnormal uptakes in SPECT imaging were also investigated with magnetic resonance imaging (MRI).

Results: Among these 80 patients with normal whole body bone SPECT scan, 19 (23.25%) of them revealed abnormal 99mTc-MDP uptake in skeleton. Furthermore, these 19 patients were subjected to MRI and 3 (3.75%) of them were confirmed with metastatic bone lesion.

Conclusion: The obtained data suggest that SPECT possess the added diagnostic over planar whole body bone scan.

RevDate: 2021-07-05

Avau F, Chintinne M, Baudry S, et al (2021)

Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.

Breast disease pii:BD210001 [Epub ahead of print].

Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.

RevDate: 2021-07-05

Timbres J, Moss C, Mera A, et al (2021)

Survival Outcomes in Invasive Lobular Carcinoma Compared to Oestrogen Receptor-Positive Invasive Ductal Carcinoma.

Cancers, 13(12):.

Invasive lobular breast cancer (ILC) accounts for 10-15% of breast cancers and has distinct characteristics compared with the more common invasive ductal carcinoma (IDC). Studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neo-adjuvant chemotherapy, but it is not clear how this affects long-term survival. Patients at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2016 diagnosed with ER+ IDC or ER+ ILC were eligible for inclusion. Kaplan-Meier plots and Cox proportional-hazards regression models were used for analysis. There was no difference in overall survival comparing ER+ ILC to ER+ IDC (OR: 0.94, 95% CI: 0.83, 1.04) with a median follow-up time of 8.3 years compared to 8.4 years in IDC. However, ER+HER2- ILC had worse survival compared to ER+HER2- IDC in those that received chemotherapy (OR: 1.46, 95% CI: 1.06, 2.01). Here, median follow-up time was 7.0 years in ILC compared to 8.1 years in IDC. These results indicate worse overall survival after chemotherapy (neo-adjuvant and adjuvant) in ILC compared to ER+HER2- IDC even when correcting for tumour grade, age, size, and nodal involvement, but validation is needed in a larger study population.

RevDate: 2021-07-05

Gulde S, Wiedemann T, Schillmaier M, et al (2021)

Gender-Specific Efficacy Revealed by Head-to-Head Comparison of Pasireotide and Octreotide in a Representative In Vivo Model of Nonfunctioning Pituitary Tumors.

Cancers, 13(12):.

Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors' proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal Sstr3 expression was significantly higher in the former group. It is noteworthy that female human NFPTs patients also have a trend towards higher SSTR3 expression. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.

RevDate: 2021-07-05

Itani MM, Nassar FJ, Tfayli AH, et al (2021)

A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer.

International journal of molecular sciences, 22(11):.

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.

RevDate: 2021-07-05

Madhavan BK, Han Z, Singh B, et al (2021)

Elevated Expression of the RAGE Variant-V in SCLC Mitigates the Effect of Chemotherapeutic Drugs.

Cancers, 13(11):.

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy with a very high mortality rate. A prominent part of this is because these carcinomas are refractory to chemotherapies, such as etoposide or cisplatin, making effective treatment almost impossible. Here, we report that elevated expression of the RAGE variant-V in SCLC promotes homology-directed DNA DSBs repair when challenged with anti-cancer drugs. This variant exclusively localizes to the nucleus, interacts with members of the double-strand break (DSB) repair machinery and thus promotes the recruitment of DSBs repair factors at the site of damage. Increased expression of this variant thus, promotes timely DNA repair. Congruently, the tumor cells expressing high levels of variant-V can tolerate chemotherapeutic drug treatment better than the RAGE depleted cells. Our findings reveal a yet undisclosed role of the RAGE variant-V in the homology-directed DNA repair. This variant thus can be a potential target to be considered for future therapeutic approaches in advanced SSLC.

RevDate: 2021-07-12

Solomon Z, Mikulincer M, Ohry A, et al (2021)

Prior trauma, PTSD long-term trajectories, and risk for PTSD during the COVID-19 pandemic: A 29-year longitudinal study.

Journal of psychiatric research, 141:140-145 pii:S0022-3956(21)00405-2 [Epub ahead of print].

This study assessed the contributions of prior war captivity trauma, the appraisal of the current COVID-19 danger and its resemblance to the prior trauma, and long-term trajectories of posttraumatic stress disorder (PTSD) to risk for PTSD during the COVID-19 pandemic. Capitalizing on a 29-year longitudinal study with four previous assessments, two groups of Israeli veterans - ex-Prisoners-of-War (ex-POWs) of the 1973 Yom Kippur War and comparable combat veterans of the same war - were reassessed during the COVID-19 pandemic. Previous data were collected on their PTSD trajectory 18, 30, 35, and 42 years after the war and exposure to stressful life events after the war. Currently, we collected data on their PTSD during the COVID-19 pandemic and their appraisal of similarities of past trauma with the current pandemic. Previously traumatized ex-POWs were found to be more vulnerable and had significantly higher rates of PTSD and more intense PTSD during the current pandemic than comparable combat veterans. Moreover, veterans in both groups who perceived the current adversity (captivity, combat) as hindering their current coping were more likely to suffer from PTSD than veterans who perceived it as a facilitating or irrelevant experience. In addition, chronic and delayed trajectories of PTSD among ex-POWs increased the risk for PTSD during the pandemic, and lifetime PTSD mediated the effects of war captivity on PTSD during the current pandemic. These findings support the stress resolution perspective indicating that the response to previous trauma - PTSD and its trajectories - increased the risk of PTSD following subsequent exposure to stress.

RevDate: 2021-07-12

Sela Y, Bar-Or RL, Kor A, et al (2021)

The Internet addiction test: Psychometric properties, socio-demographic risk factors and addictive co-morbidities in a large adult sample.

Addictive behaviors, 122:107023 pii:S0306-4603(21)00208-2 [Epub ahead of print].

The Internet Addiction Test (IAT) (Young, 1998) is one of the most utilized diagnostic instruments to evaluate internet addiction. Despite the wide use of IAT in research and clinical settings, there is lack of an empirical validation of this scale among a largescale adult population. The present study aimed to: (1) investigate the psychometric properties of a Hebrew version of the IAT among large-scale Israeli adult sample. (2) Assess the socio-demographic characteristics of individuals who suffer from IA. (3) Assess the co-morbidity of IA in relation to substance and behavioral addictions. A cross sectional study was conducted, by constructing a representative sample (N = 4035) of the Jewish adult (18-70 y/o, M = 40.5, SD = 14.5) population in Israel. Participants responded an online survey, that measured IAT, socio-demographic characteristics, substance and behavioral addictions. Results showed that two-factor model (Emotional and Cognitive Preoccupation with the Internet and Loss of Control and Interference with Daily Life) has good psychometric properties and fits the data well. Young age, not being married (Risk Ratio [RR] = 1.98, 95% CI [1.51-2.63]), and having a low socio-economic status (RR = 1.41, 95% CI [1.05-1.90]) were found to be associated with IA. Drug (RR = 4.50, 95% CI [2.89-7.01]) and alcohol (RR = 3.54, 95% CI [1.50-5.42]) use disorders were associated with IA. High co-morbidity between behavioral addictions and IA was also found (RR = 15.24, 95% CI [11.17-20.78]). Overall, results show that the Hebrew version of the IAT is a valid and reliable instrument, and provide a comprehensive picture of IA prevalence and profile in adult Israeli sample.

RevDate: 2021-07-01

Abdelsattar JM, Afridi FG, Dai Z, et al (2021)

The Effect of Lumpectomy and Cavity Shave Margin Status on Recurrence and Survival in Breast-Conserving Surgery.

The American surgeon [Epub ahead of print].

BACKGROUND/OBJECTIVE: Cavity shave margins (CSMs) decrease rate of positive margins and need for re-excision. Recurrence data following breast-conserving surgery (BCS) are not always available in large cancer registries. We sought to define our recurrence and survival data in BCS with routine excision of CSMs.

METHODS: A single institution, 10-year retrospective review of breast cancer patients who underwent BCS with routine CSMs was conducted. Cavity shave margin technique was standard. Cox proportional hazard analyses and the Kaplan-Meier method were used to estimate recurrence and survival.

RESULTS: Breast-conserving surgery with CSM was performed in 839 patients. Re-excision rate to achieve negative margins was 8.5%. Fifty-two patients (75%) underwent margin re-excision vs 18 patients (25%) underwent salvage mastectomy. Positive margin rate stratified by tumor histology was highest for invasive lobular carcinoma followed by mixed invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), followed by pure DCIS and lowest for IDC. Length of follow-up was (4.7 ± 2.6, years). Overall recurrence rate (locoregional and systemic) was 4.3%: highest in patients with negative lumpectomy margin but positive CSM (L-S+ = 15%) followed by positive lumpectomy and CSMs (L+S+ = 14%), followed by patients with positive lumpectomy margin but negative CSMs (L+S- = 13%) and lowest for negative lumpectomy and CSM (L-S- = 5%), (P = .0008). There was no difference in 5-year breast cancer-specific survival between the 4 subgroups: 96% for L-S-, 86.7% L-S+, 94.7% L+S+ and 90% L+S- (P = .094).

CONCLUSIONS: Recurrence following BCS with CSMs can be stratified based on both lumpectomy and cavity shave margin positivity. Routine excision of CSMs allows identification of these patient subsets.

RevDate: 2021-07-01

Gity M, Jafari M, Olfatbakhsh A, et al (2021)

Assessment of Ultrasound Features and BI-RADS Categories of Malignant Breast Masses in Women ≤40.

Archives of Iranian medicine, 24(5):383-389.

BACKGROUND: To evaluate ultrasound (US) characteristics and BI-RADS (Breast imaging-reporting and data system) of malignant breast masses in women <40 years and to compare with older patients.

METHODS: In a retrospective, descriptive-analytical study, we assessed the US images and BI-RADS category of 78 malignant masses with a final pathology of invasive ductal carcinoma (IDC, NOS type).

RESULTS: Overall, the most frequent US descriptors of IDC were indistinct margin (45%), irregular shaped (63.5%), posterior shadowing (38.8%), heterogeneous internal echogenicity (56.3%) and non-parallel orientation (76.3%). In this study, most malignant masses of young patients were categorized as BI-RADS 4a while in the older patients (over 40), they were mostly BI-RADS 4b and 5 with P=0.03 and odds ratio (OR) of 2.57 (95% confidence interval (CI), 0.74-8.8). In addition, the mean dimension of the mass in young cases was greater (18.3 mm) compared with older patients (13.2 mm) with P value of 0.04 and OR of 3.8 (95% CI, 1.1-13.4).

CONCLUSION: Similar to previous studies, malignant masses were diagnosed in greater dimensions in younger cases which may be due to the delay in diagnosis, the rapid growth of the tumor and the absence of routine screening guidelines. Radiologists should be aware of the possibility of malignancy in palpable slightly suspicious masses (BI-RADS 4A) in young cases.

RevDate: 2021-07-01

Tahmasebi S, Almayali AMJ, Arasteh P, et al (2021)

Determinants of Prognosis in Triple-Negative Breast Cancer: Report from a Large Breast Cancer Registry.

Archives of Iranian medicine, 24(4):280-288.

BACKGROUND: The outcome of patients with triple-negative breast cancer (TNBC) is highly dependent on demographic factors and ethnicity. We aimed to evaluate the clinicopathological determinants of prognosis among women with TNBC using data from one of the largest breast cancer (BC) registries.

METHODS: A total of 6145 patients with BC from our referral center were evaluated from 1995 to 2018, among whom 523 had TNBC. The baseline, menstrual and reproductive, treatment and pathology related characteristics were evaluated.

RESULTS: Among TNBC patients, the rate of stage 3 and 4 BC (29.9% vs. 14.4% and 7.8% vs. 0% for stage 3 and 4, respectively; P<0.001), invasive ductal carcinoma (90.7% vs. 75.6%; P=0.004), nodal involvement (46.7% vs. 33.4%; P=0.026), mastectomy (57.3% vs. 37.8%; P=0.001) and axillary node dissection (76.7% vs. 59.8%; P=0.019) was significantly higher in the group that developed recurrence. Disease-free-survival was 80.6% (157.76 ± 9.48 months) and overall-survival was 90.1% (182.73 ± 3.28 months). For death, stage 3 BC (compared to stages 0 and 1 as base) showed a higher risk of earlier death (adjusted HR: 4.191, 95% CI=1.392-12.621; P=0.011). For recurrence, stage 3 BC (adjusted HR: 1.044, 95% CI=1.209-6.673; P=0.017) (compared to stages 0 and 1 as base) showed significantly higher risk for developing earlier recurrence. Moreover, those who had invasive ductal carcinoma (compared to other types of BCs) had a higher risk for developing earlier recurrence (adjusted HR: 3.307, 95% CI=1.191-0.724; P=0.012).

CONCLUSION: BC stage plays a significant role in both earlier recurrence and earlier mortality among patients with TNBC.

RevDate: 2021-07-02

Uenaka N, Yamamoto S, Sato S, et al (2021)

Primary breast lymphoma initially diagnosed as invasive ductal carcinoma: A case report.

Clinical case reports, 9(6):e04189.

A malignant tumor in the breast may not be conclusive of breast cancer. It is important to keep the possibility of primary breast lymphoma in rare scenarios. For the diagnosis of primary breast lymphoma, immunohistochemical staining is necessary.

RevDate: 2021-07-02

Almomen A, Arafah M, Alwhaibi M, et al (2021)

Ceramide expression in relation to breast cancer molecular subtypes in Saudi women.

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 29(6):609-615.

Background/Introduction: Despite advances in the diagnosis and management of breast cancer (BC), it is still associated with high mortality rates. New biomarkers are being developed for the diagnosis, treatment, and prediction of responses of BC. Ceramide (CER), a bioactive sphingolipid, has emerged recently as a useful diagnostic tool in several types of tumors. In this study, we evaluated CER expression in invasive BC and assessed its relation to the molecular subtypes of BC.

Materials and methods: The clinical data and histopathological slides of 50 patients with invasive ductal carcinoma were retrieved and reviewed. The cases were then stained with a mouse monoclonal anti-ceramide antibody. Pearson correlation was used to assess the correlation between CER percentage and intensity and other clinical and pathological variables.

Results: CER expression showed a direct relationship with estrogen and progesterone receptors Allred scores. However, it showed an inverse relation with tumor grade, HER2/neu status and Ki-67 index.

Conclusions: CER expression is likely to be associated with luminal BC molecular subtypes. However, more research is needed to confirm these results and to explore its relation to the different clinical outcomes, including response to treatment and prognosis.

RevDate: 2021-06-30

Badjatia N, Haymore J, Voorhees ME, et al (2021)

Development of a Resting Energy Expenditure Estimation in Patients Undergoing Targeted Temperature Management with a Surface Gel Pad Temperature Modulating Device.

Therapeutic hypothermia and temperature management [Epub ahead of print].

Targeted temperature management (TTM) directly impacts energy expenditure via temperature modulation and shivering associated with temperature modulating devices. We hypothesized that resting energy expenditure (REE) can be accurately estimated utilizing data obtained from a surface gel pad temperature modulating device (TMD) and demographic factors. Baseline demographic data, along with concurrent temperature, sedation, and shivering data, and indirect calorimetry (IDC) were collected from patients undergoing TTM. The data from the IDC and temperature modulation device (TMD) were synchronized and averaged over 60-second intervals to provide simultaneous comparisons. Heat transfer (calories) was calculated from the TMD by an equation that assessed water temperature from the TMD to the patient, water temperature returning to the TMD, water flow rates, and device mode. A linear regression model was used to determine factors associated with REE as measured by IDC. A difference in the mean between REE and estimated REE was used to assess accuracy. There were 48 assessments conducted in 40 subjects [mean (standard deviation)] age: 58 (14) years, 60% female, body surface area (BSA): 2.0 ± 0.3 who underwent simultaneous assessments. Target temperature was 36-37°C in 75%, with a median Bedside Shivering Assessment Score of 0 (range 0-2). Factors associated with REE on multivariable linear regression included older age (p < 0.001), male sex (p = 0.004), higher BSA (p < 0.001), higher patient temperature (p < 0.001), and lower heat transfer (p = 0.003). Adjusted prediction coefficients from this model were then tested against REE by a Bland-Altman analysis. The difference between difference in resting energy estimation (REEdiff) and measured REE by IDC was 6.2 calories/min (REEdiff: 95% confidence interval: -14.1 calories, 26.5 calories, p = 0.5). We believe that the heat transfer data from the TMD coupled with clinical characteristics of patients can be utilized to calculate the REE for every minute of TTM. These data can be utilized to mitigate the consequences of shivering and malnutrition during TTM.

RevDate: 2021-07-01

Greulich F, Mechtidou A, Horn T, et al (2021)

Protocol for using heterologous spike-ins to normalize for technical variation in chromatin immunoprecipitation.

STAR protocols, 2(3):100609.

Quantifying differential genome occupancy by chromatin immunoprecipitation (ChIP) remains challenging due to variation in chromatin fragmentation, immunoprecipitation efficiencies, and intertube variability. In this protocol, we add heterologous spike-ins from Drosophila chromatin as an internal control to the mice chromatin before immunoprecipitation to normalize for technical variation in ChIP-qPCR or ChIP-seq. The choice of spike-in depends on the evolutionary conservation of the protein of interest and the antibody used. For complete details on the use and execution of this protocol, please refer to Greulich et al. (2021).

RevDate: 2021-07-08
CmpDate: 2021-07-08

Mayopoulos GA, Ein-Dor T, Li KG, et al (2021)

COVID-19 positivity associated with traumatic stress response to childbirth and no visitors and infant separation in the hospital.

Scientific reports, 11(1):13535.

As the novel coronavirus (COVID-19) has spread globally, a significant portion of pregnant and delivering women were infected with COVID-19. While emerging studies examined birth outcomes in COVID-19 positive women, knowledge of the psychological experience of childbirth and maternal wellness remains lacking. This matched-control survey-based study included a sample of women recruited during the first wave of the pandemic in the US who gave birth in the previous six months. Women reporting confirmed/suspected COVID-19 (n = 68) during pregnancy or childbirth were matched on background factors with women reporting COVID-19 negativity (n = 2,276). We found nearly 50% of COVID positive women endorsed acute traumatic stress symptoms at a clinical level in response to childbirth. This group was more than twice as likely to endorse acute stress and to have no visitors during maternity hospitalization than COVID negative women; they were also less likely to room-in with newborns. The COVID positive group reported higher levels of pain in delivery, lower newborn weights, and more infant admission to neonatal intensive care units. Our findings suggest COVID-19 affected populations are at increased risk for traumatic childbirth and associated risk for psychiatric morbidity. Attention to delivering women's wellbeing is warranted during the pandemic.

RevDate: 2021-07-01
CmpDate: 2021-07-01

Danzinger S, Hielscher N, Izsó M, et al (2021)

Invasive lobular carcinoma: clinicopathological features and subtypes.

The Journal of international medical research, 49(6):3000605211017039.

OBJECTIVE: To analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors.

METHODS: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC).

RESULTS: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (+), have a lower proliferation rate (Ki67 <14%), and a higher pathological T stage (pT2-4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ER+, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1-3) was significantly more frequent with ILC versus IDC.

CONCLUSIONS: Our data suggest that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.

RevDate: 2021-06-29

Zhao J, Sun G, Zhu S, et al (2021)

Circulating tumor DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.

BJU international [Epub ahead of print].

OBJECTIVES: To investigate the genetic alterations of prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P).

MATERIALS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients of prostate adenocarcinoma (PAC) with IDC-P and 84 cases without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored.

RESULTS: Totally, we identified 29.8% (48/161) and 21.4% (18/84) patients with and without IDC-P harbored genomic alterations in DNA repair pathway, respectively (P=0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carries (11.8% [19/161] vs. 2.4% [2/84], P=0.024). Germline BRCA2 and somatic CDK12 defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs. 0% and CDK12: 6.8% [11/161] vs. 1.2% [1/84]). Patients with IDC-P had a distinct AR pathway alteration, characterized by an enrichment of NCOR2 mutations against patients with pure PAC (21.1% [34/161] vs. 6.0% [5/84], P=0.004). Increased AR alterations were detected in patients harbouring tumors with IDC-P proportion≥10% versus cohort with IDC-P proportion<10% (6.4% [5/78] vs. 18.1% [15/83], P=0.045). For IDC-P carries, TP53 mutation was associated with shorter castration-resistant free survival (median 10.9-Mo vs. 28.9-Mo, P=0.026), and BRCA2 alteration was related to rapid PSA progression for those receiving abiraterone treatment (median 9.1-Mo vs 11.9-Mo, P=0.036).

CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumors with IDC-P, highlighting the potential therapeutic strategies for this patient population.

RevDate: 2021-07-05

Fedorov A, Longabaugh WJR, Pot D, et al (2021)

NCI Imaging Data Commons.

Cancer research pii:0008-5472.CAN-21-0950 [Epub ahead of print].

The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot{trade mark, serif}. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of de-identified imaging data and to support integrated analyses with non-imaging data. We achieve this goal by co-locating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research.

RevDate: 2021-07-13

Aftab F, Ahmed I, Ahmed S, et al (2021)

Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.

PLoS medicine, 18(6):e1003644 pii:PMEDICINE-D-20-05504.

BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.

METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.

CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.

TRIAL REGISTRATION: The study is not a clinical trial.

RevDate: 2021-06-28

Zilcha-Mano S, Dolev-Amit T, Fisher H, et al (2021)

Patients' individual differences in implicit and explicit expectations from the therapist as a function of attachment orientation.

Journal of counseling psychology pii:2021-61031-001 [Epub ahead of print].

Patients' attachment orientation was found to be an important predictor of the process and outcome of psychotherapy. The present study is the first to examine whether patients' attachment orientation toward significant others predicts their implicit and explicit expectations from the therapist, and whether this effect is moderated by the extent to which the therapist has become an attachment figure. In two studies (N = 308), we developed measures of implicit (lexical decision task) and explicit expectations from therapist, and tested the presence of individual differences in expectations as a function of the patients' attachment orientation, early and late in treatment. Whereas individuals higher on attachment anxiety did not report having fewer positive expectations from therapist early in treatment, they showed lower accessibility of positive expectations when measured implicitly. As treatment progressed, the extent to which the therapist has become an attachment figure may mitigate the adverse effects of pretreatment attachment anxiety. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

RevDate: 2021-07-10

Uomori T, Horimoto Y, Takanashi M, et al (2021)

Cerebral hemorrhage due to amyloid angiopathy that was difficult to differentiate from breast cancer metastasis: a case report.

Surgical case reports, 7(1):150.

BACKGROUND: Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non-neoplastic lesions, such as cerebral hemorrhage. Meanwhile, there are various causes of cerebral hemorrhage; a major one is cerebral amyloid angiopathy (CAA). With the advancement of imaging technology, CAA-related cerebral hemorrhage can be more precisely diagnosed with magnetic resonance imaging (MRI), but definitive diagnosis of CAA can only be made based on pathological assessment. Herein, we report a case of consciousness disorder appearing during adjuvant therapy for breast cancer. We initially considered that the patient's cerebral hemorrhage was due to a metastatic tumor, but based on excisional biopsy, she was diagnosed with CAA.

CASE PRESENTATION: A 73-year-old Japanese woman underwent curative surgery for left breast cancer. Her disease was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma (pStage IIB). While receiving adjuvant treatment, she developed disorientation, and emergent imaging revealed multiple cerebral hemorrhages. There was no apparent enhancement in the cerebral parenchyma on MRI, and differential diagnosis included hemorrhage due to a metastatic tumor, intravascular large B-cell lymphoma, CAA and thrombotic intracranial bleeding. After hospitalization, the bleeding lesion enlarged, resulting in cerebral hernia, and she needed emergency drainage surgery. The tissue surrounding the hemorrhage was pathologically assessed, and she was diagnosed with CAA. Although we initially suspected the lesion to be a metastatic tumor from breast cancer, there were no tumorous cells.

CONCLUSION: Atypical MRI findings made diagnosis difficult in this case, but it should be considered for differential diagnosis when multiple cerebral hemorrhages in elderly patients are observed, especially in cases with symptoms such as transient multifocal neurological deficits and dementia.

RevDate: 2021-06-29

Picillo M, Ricciardi C, Tepedino MF, et al (2021)

Gait Analysis in Progressive Supranuclear Palsy Phenotypes.

Frontiers in neurology, 12:674495.

The objective of the present study was to describe gait parameters of progressive supranuclear palsy (PSP) phenotypes at early stage verifying the ability of gait analysis in discriminating between disease phenotypes and between the other variant syndromes of PSP (vPSP) and Parkinson's disease (PD). Nineteen PSP (10 PSP-Richardson's syndrome, five PSP-parkinsonism, and four PSP-progressive gait freezing) and nine PD patients performed gait analysis in single and dual tasks. Although phenotypes showed similar demographic and clinical variables, Richardson's syndrome presented worse cognitive functions. Gait analysis demonstrated worse parameters in Richardson's syndrome compared with the vPSP. The overall diagnostic accuracy of the statistical model during dual task was almost 90%. The correlation analysis showed a significant relationship between gait parameters and visuo-spatial, praxic, and attention abilities in PSP-Richardson's syndrome only. vPSP presented worse gait parameters than PD. Richardson's syndrome presents greater gait dynamic instability since the earliest stages than other phenotypes. Computerized gait analysis can differentiate between PSP phenotypes and between vPSP and PD.

RevDate: 2021-06-29

Baharav S, Nitsan G, BM Ben-David (2021)

Commentary: Working Memory Load Affects Processing Time in Spoken Word Recognition: Test Retest Reliability of the E-WINDMIL Eyetracking Paradigm.

Frontiers in neuroscience, 15:663930.

RevDate: 2021-06-26

March DS, Hurt AW, Grantham CE, et al (2021)

A Cost-Effective Analysis of the CYCLE-HD Randomized Controlled Trial.

Kidney international reports, 6(6):1548-1557.

Introduction: No formal cost-effectiveness analysis has been performed for programs of cycling exercise during dialysis (intradialytic cycling [IDC]). The objective of this analysis is to determine the effect of a 6-month program of IDC on health care costs.

Methods: This is a retrospective formal cost-effectiveness analysis of adult participants with end-stage kidney disease undertaking in-center maintenance hemodialysis enrolled in the CYCLE-HD trial. Data on hospital utilization, primary care consultations, and prescribed medications were extracted from medical records for the 6 months before, during, and after a 6-month program of thrice-weekly IDC. The cost-effectiveness analysis was conducted from a health care service perspective and included the cost of implementing the IDC intervention. The base-case analyses included a 6-month "within trial" analysis and a 12-month "within and posttrial" analysis considering health care utilization and quality of life (QoL) outcomes.

Results: Data from the base-case within trial analysis, based on 109 participants (n = 56 control subjects and n = 53 IDC subjects) showed a reduction in health care utilization costs between groups, favoring the IDC group, and a 73% chance of IDC being cost-effective compared with control subjects at a willingness to pay of £20,000 and £30,000 per quality-adjusted life year (QALY) gained. When QoL data points were extrapolated forward to 12 months, the probability of IDC being cost-effective was 93% and 94% at £20,000 and £30,000 per QALY gained. Sensitivity analysis broadly confirms these findings.

Conclusion: A 6-month program of IDC is cost-effective and the implementation of these programs nationally should be a priority.

RevDate: 2021-06-24

Nkadimeng MV, Makombe G, Mapiye O, et al (2021)

A gross margin analysis for Nguni cattle farmers in Limpopo Province, South Africa.

PloS one, 16(6):e0253657 pii:PONE-D-21-03815.

Factors such as increases in population, urbanization, growth in per capita income and changes in consumer taste and preferences are causing gradual increases in livestock product consumption and demand. South Africa is addressing this predicted increase in livestock products demand by commercializing smallholder livestock producers. The Limpopo Industrial Development Corporation (IDC) Nguni Cattle Development Project is an example of such effort. The economic performance of these efforts needs to be evaluated. We use gross margin analysis to evaluate the performance of the Limpopo IDC Nguni Cattle Development Project. Additionally, we use regression analysis to identify factors influencing gross margins. Our results indicate that although smallholders show potential to commercialize, they lack commercial farming experience and require that a strong extension support system be used as one of the strategies to improve profitability. We also noted that individual farmers were more profitable than group farmers. Multiple regression analysis shows that three variables could be used to stimulate gross margin among the Limpopo IDC Nguni Cattle Development Project farmers. These are herd size, distance to market and farm size. Since farm size is a given, policy should focus on assisting farmers to build their herds and to have better access to markets.

RevDate: 2021-06-22

Sugie M, Takahara T, Ohashi A, et al (2021)

Presence of corpora amylacea among prostate cancer cells: an unrecognised feature of intraductal carcinoma of the prostate.

Pathology pii:S0031-3025(21)00235-X [Epub ahead of print].

Corpora amylacea (CA) is usually present in benign prostatic ducts and acini, and its presence is considered suggestive of negative or low-risk prostate cancer. The clinicopathological definition of CA among prostate cancer cells (CAPCCs)-described as CA entirely surrounded by invasive cancer cells-has not been discussed. As intraductal carcinoma of the prostate (IDC-P) is a well-known adverse prognostic factor in prostate cancer, this study aimed to elucidate the relationship between CAPCC and IDC-P. We enrolled 366 patients who underwent robotic-assisted radical prostatectomies between 2012 and 2018 at Aichi Medical University Hospital. All surgical specimens were independently reviewed by two genitourinary pathologists. The median age of the patients was 68.5 years; the median serum prostate-specific antigen was 6.49 ng/mL. IDC-P was observed in 143 (39.1%) patients, while the presence of CAPCC was observed in 47 cases (12.8%). Patients with CAPCC were associated with more advanced clinical and pathological T stages, as well as Gleason scores, than those without CAPCC (p=0.018, p<0.001, p=0.036). Notably, the presence of CAPCC was significantly associated with the presence of IDC-P (39 cases) and a high Gleason score compared with the absence of CAPCC (12 cases) (p<0.001 and p=0.036, respectively). The presence of CAPCC is an adverse pathological feature, often closely related to IDC-P. Therefore, CAPCC may be a surrogate finding to detect IDC-P via haematoxylin and eosin staining.

RevDate: 2021-07-12

Gandolfi M, Fiorio M, Geroin C, et al (2021)

Motor dual task with eyes closed improves postural control in patients with functional motor disorders: A posturographic study.

Gait & posture, 88:286-291 pii:S0966-6362(21)00226-5 [Epub ahead of print].

BACKGROUND: Functional motor disorders (FMD) are highly disabling neurological conditions in which postural control deficits increase the risk of falls and disability in performing daily living activities. Scattered evidence suggests that such disturbances may depend on abnormal attentional focus and might improve with distraction.

RESEARCH QUESTION: How do motor and cognitive dual tasks performed under two different sensory conditions shape postural control in patients with FMD.

METHODS: This posturographic study involved 30 patients with FMD (age, 45.20 ± 14.57 years) and 30 healthy controls (age, 41.20 ± 16.50 years). Postural parameters were measured with eyes open, and eyes closed in quiet stance (single task) and on a motor dual task (m-DT) and a calculation (cognitive) dual task (c-DT). The dual task effect (DTE, expressed in percentage) on motor and cognitive performance was calculated for sway area, length of Center of Pressure (CoP), and velocity of CoP displacement.

RESULTS: There was a statistically significant three-way interaction between task, condition, and group for the DTE on sway area (p = 0.03). The mean sway area DTE on the motor task in the eyes-closed condition was increased by 70.4 % in the healthy controls, while it was decreased by 1% in the patient group (p = 0.003). No significant three-way interaction was observed for the DTE on length of CoP and velocity of CoP displacement.

SIGNIFICANCE: This study provides novel preliminary evidence for the benefit of a simple motor dual task in the eyes closed condition as a way to improve postural control in patients with FMD. These findings are relevant for the management of postural control disorders in patients with FMD.

RevDate: 2021-07-02

DeCoste RC, Carter MD, Barnes PJ, et al (2021)

Independent primary cutaneous and mammary apocrine carcinomas with neuroendocrine differentiation: Report of a case and literature review.

Cutaneous apocrine carcinomas share common features with their counterparts in the breast; hence, metastatic mammary carcinoma must be excluded before such lesions can be designated primary cutaneous neoplasms. Primary tumors from either source rarely exhibit neuroendocrine differentiation. We report a case of a 72-year-old female with a painless 1.2-cm scalp nodule. An incisional biopsy revealed dermal involvement by an invasive apocrine carcinoma juxtaposed to a benign apocrine cystic lesion. Immunohistochemically, the carcinoma expressed neuroendocrine proteins including synaptophysin, chromogranin, and CD56. A primary cutaneous apocrine carcinoma with neuroendocrine differentiation was favored, but additional investigations to exclude breast origin were recommended. These revealed a 1.1-cm nodule in the right breast, which proved to be an invasive ductal carcinoma, morphologically and immunophenotypically similar to the scalp lesion. This confounded the case, yet factors militating against metastatic breast carcinoma to skin included (a) the small size of the mammary tumor, (b) absence of other metastatic disease, and (c) juxtaposition of the scalp carcinoma to a putative benign precursor. Molecular studies were undertaken to resolve the diagnostic quandary. Single nucleotide polymorphism microarray analysis revealed distinct patterns of chromosomal copy number alterations in the two tumors, supporting the concept of synchronous and unusual primary neoplasms.

RevDate: 2021-06-22

Munawar S, Haider R, Ali SM, et al (2021)

Triple-Negative Metaplastic Breast Carcinoma: Association of Epidermal Growth Factor Receptor Expression With Prognostic Parameters and Clinical Outcome.

Cureus, 13(5):e15006.

Introduction Metaplastic breast carcinoma (MBC) is one of the rare special subtypes of breast carcinoma associated with poor prognostic features compared with invasive ductal carcinoma. Moreover, therapeutic options are limited in MBC owing to frequent triple-negative profiles of these tumors. Epidermal growth factor receptor (EGFR) is a proto-oncogene that is overexpressed in many human cancers, and is a potential therapeutic target. Therefore, in this study, we evaluated the expression of EGFR in MBC by immunohistochemistry, and its association with clinicopathological and prognostic parameters. Methods We conducted a retrospective observational study in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, over a period of seven years. A total of 61 cases with a histopathological diagnosis of MBC were included in the study. All slides were reviewed by histopathologists for diagnostic confirmation. Histopathological parameters, such as tumor size, grade, and nodal metastasis, were recorded. The representative tissue blocks were also retrieved and immunohistochemical studies were performed for cytokeratin 5/6 (CK5/6), Ki67, and EGFR. Results The mean age of the patients was 44.48 ± 13.01 years. The mean tumor size was 5.72 ± 2.72 cm, with most of the cases belonging to tumor (T)-stage T3. Axillary metastasis was present in 57.4% cases, and the perinodal extension was present in 11.5% cases. Most tumors were grade III (85.2%), with a mean Ki67 index of 39.67% ± 20.38%. Most of the cases were nonbasal (83.6%), owing to the absent CK5/6 expression. Tumor recurrence was noted in 14.8% cases, with a median follow-up of 43 (13-83) months and median disease-free survival of 36 (12-60) months. Positive EGFR expression was noted in 52.5% cases. A significant association of EGFR expression was noted with tumor grade, mean Ki67 index, axillary metastasis, and nodal (N)-stage. Cases with positive EGFR expression were found to have higher grade (grade III), with higher Ki67 index, higher frequency of axillary metastasis, and higher N-stage. Moreover, cases with positive EGFR expression had lower disease-free survival compared to cases with negative EGFR expression. Conclusion We found that a significant proportion of triple-negative MBC expressed EGFR. Moreover, EGFR overexpression was associated with poor pathological parameters and lower disease-free survival. Therefore, EGFR can be considered a potential prognostic biomarker and therapeutic target in triple-negative MBC; however, the correlation between gene amplification and protein overexpression is required to better uncover the role of EGFR as a therapeutic target.

RevDate: 2021-07-06

Abascal-Junquera JM, Fumadó-Ciutat L, Gasa-Galmes B, et al (2021)

Concomitant intraductal carcinoma of the prostate and response to hormonal therapy in metastatic prostate carcinoma.

Actas urologicas espanolas, 45(6):455-460.

INTRODUCTION AND OBJECTIVE: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini. We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.

PATIENTS AND METHODS: We retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.

RESULTS: Mean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (P = .007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (P = .05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (P = .001). In the multivariate analysis, adenocarcinoma subtype was statistically significant P .014, CI 95% (HR 0.058, 0.006-0.56) CONCLUSIONS: IDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. Once IDC-P is identified, clinicians could extrapolate the relative poor response to hormonal therapy. Consequently, follow-up of these patients in this scenario should be more strict.

RevDate: 2021-07-10

Nakamura T, Okabe K, Hirayama S, et al (2021)

Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.

Nucleic acids research, 49(12):7154-7163.

Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.

RevDate: 2021-06-16

Rocha SR, CAV Marques (2021)

Functional capacity of women with breast neoplasm undergoing palliative chemotherapy.

Revista da Escola de Enfermagem da U S P, 55:e03714 pii:S0080-62342021000100449.

OBJECTIVE: To evaluate the functional capacity of women with breast neoplasm undergoing palliative chemotherapy.

METHOD: Cross-sectional study with an analysis of medical records of women with breast cancer undergoing palliative chemotherapy.

RESULTS: Out of one hundred evaluated records, most registered 50 years or older (66%), primary education (53%), an income of 1 to 2 minimum wages (87%), invasive ductal carcinoma (95%), positive hormone receptor (64%), and histological grade 1 and 2 (57%). Performance status 0 (49%), 1 (39%), and 2 (12%) were prevalent; these imply, respectively, active patients, with mild and moderate activity restriction. One to four chemotherapy schemes were associated with the inappetence (p =0.00) and weight loss (p =0.001) symptoms. The main complications were neuropathy (31%), medullary compression syndrome (21%), neutropenia (9%), and death (28%).

CONCLUSION: Out of the analyzed women, 88% presented functional capacity 0 and 1, had no or mild restriction of daily activities, were multiply treated, and manifested manageable symptoms. Others, however, presented moderate to severe clinical complications during the treatment, progressing to exclusive palliative care or death.

RevDate: 2021-06-16

Akhavan AA, Wirtz EC, Ollila DW, et al (2021)

An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab: A Case Report and Review of the Literature.

Plastic and reconstructive surgery pii:00006534-990000000-00222 [Epub ahead of print].

SUMMARY: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.

RevDate: 2021-06-16

Rachamim L, Nacasch N, I Sinay (2021)

Complicated Grief, Depression, Health and Attachment Style in First Degree Relatives of Individuals with a Chronic Psychotic Disorders.

Community mental health journal [Epub ahead of print].

Complicated grief (CG) is a form of unrelenting grief after the death of a loved one. However, family members of individuals who suffer from Schizophrenia, Schizoaffective disorders and Bipolar disorder may experience symptoms of CG even though their loved one is still alive. The present study assessed CG and risk factors for CG in first degree relatives of individuals with severe chronic mental illness. The incidence of CG was examined in 78 parents, siblings, adult children and spouses recruited through organizations and social media that provide support services for individuals suffering from mental illness and their families. High rates of CG (39.7%) were found in this group. CG was associated with a higher prevalence of posttraumatic and depression symptoms and poorer physical health. These findings may contribute to heightening therapists' awareness of the importance of assessing, acknowledging and resolving CG in the family members of patients with chronic psychotic disorders.

RevDate: 2021-06-29
CmpDate: 2021-06-17

Bai Y, Tao X, Xu C, et al (2021)

Diagnosis and treatment of chylous leakage after modified radical mastectomy for breast cancer: a case report.

The Journal of international medical research, 49(6):3000605211021375.

The post-operative complication of chylous leakage after breast cancer is relatively rare, and few clinical studies have been published. We report a 64-year-old woman with chylous leakage following modified radical mastectomy. We describe the patient's diagnostic and treatment process in detail. The patient was diagnosed with grade II (left) breast invasive ductal carcinoma. Post-operatively, the patient's chest wall and axilla were pressurized, and negative pressure drainage was initiated. On the fifth post-operative day, the drainage from the chest wall and axilla increased significantly, and the patient developed chylous leakage on the eighth postoperative day. We injected meglumine diatrizoate (100 mL) and elemene (10 mL) into the patient's axilla, and the chylous leakage gradually resolved 18 days post-operatively. In this report, we focus on managing a case of chylous leakage after modified radical mastectomy for breast cancer. Meglumine diatrizoate combined with elemene is a possible treatment for the management of this rare complication.

RevDate: 2021-06-15

Kayadibi Y, Ucar N, Kaya MF, et al (2021)

Characterization of Suspicious Microcalcifications on Mammography Using 2D Shear-Wave Elastography.

Ultrasound in medicine & biology pii:S0301-5629(21)00219-2 [Epub ahead of print].

Our aim was to investigate the correlations between the findings of two-dimensional shear-wave elastography (2D-SWE) and the histopathologic results of microcalcifications (MCs) visualized using ultrasonography (USG). Fifty people with suspicious MCs without accompanying mass were evaluated. They underwent USG and 2D-SWE before USG-guided tru-cut biopsy. SWE values and histopathologic features were compared statistically. The variables between groups were analyzed using the Mann-Whitney U test. Receiver operating characteristic analysis was performed and cut-off values determined to discriminate malignancy, invasiveness and high grade. Pathology confirmed 27 malignant lesions (18 invasive ductal carcinomas, one invasive lobular and eight ductal carcinomas in situ) and 23 benign ones. There was a statistically significant difference between the SWE values of malignant and benign MCs (p < 0.001). The diagnostic performance of SWE for malignancy, invasiveness and high grade were as follows, repectively: sensitivity (93%, 83%, 88%), specificity (91%, 88%, 53%), positive predictive value (93%, 94%, 44%), negative predictive value (91%, 70%, 90%) and area under the curve (0.952, 0.885, 0.776). Cut-off values were determined as 57 kPa for malignancy, 124 kPa for invasiveness and 124.5 kPa for high grade. In conclusion, SWE is a useful method in clinical practice for characterizing MCs that can be visualized with USG.

RevDate: 2021-06-13

Gnangnon B, Duraisingh MT, CO Buckee (2021)

Deconstructing the parasite multiplication rate of Plasmodium falciparum.

Trends in parasitology pii:S1471-4922(21)00110-0 [Epub ahead of print].

Epidemiological indicators describing population-level malaria transmission dynamics are widely used to guide policy recommendations. However, the determinants of malaria outcomes within individuals are still poorly understood. This conceptual gap partly reflects the fact that there are few indicators that robustly predict the trajectory of individual infections or clinical outcomes. The parasite multiplication rate (PMR) is a widely used indicator for the Plasmodium intraerythrocytic development cycle (IDC), for example, but its relationship to clinical outcomes is complex. Here, we review its calculation and use in P. falciparum malaria research, as well as the parasite and host factors that impact it. We also provide examples of metrics that can help to link within-host dynamics to malaria clinical outcomes when used alongside the PMR.

RevDate: 2021-07-08

Fortunato A, Mallo D, Rupp SM, et al (2021)

A new method to accurately identify single nucleotide variants using small FFPE breast samples.

Briefings in bioinformatics pii:6296507 [Epub ahead of print].

Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.

RevDate: 2021-06-12

Bin Kanner Y, Ganoth A, Y Tsfadia (2021)

Extracellular mutation induces an allosteric effect across the membrane and hampers the activity of MRP1 (ABCC1).

Scientific reports, 11(1):12024.

Dynamic conformational changes play a major role in the function of proteins, including the ATP-Binding Cassette (ABC) transporters. Multidrug Resistance Protein 1 (MRP1) is an ABC exporter that protects cells from toxic molecules. Overexpression of MRP1 has been shown to confer Multidrug Resistance (MDR), a phenomenon in which cancer cells are capable to defend themselves against a broad variety of drugs. In this study, we used varied computational techniques to explore the unique F583A mutation that is known to essentially lock the transporter in a low-affinity solute binding state. We demonstrate how macro-scale conformational changes affect MRP1's stability and dynamics, and how these changes correspond to micro-scale structural perturbations in helices 10-11 and the nucleotide-binding domains (NBDs) of the protein in regions known to be crucial for its ATPase activity. We demonstrate how a single substitution of an outward-facing aromatic amino acid causes a long-range allosteric effect that propagates across the membrane, ranging from the extracellular ECL5 loop to the cytoplasmic NBD2 over a distance of nearly 75 Å, leaving the protein in a non-functional state, and provide the putative allosteric pathway. The identified allosteric structural pathway is not only in agreement with experimental data but enhances our mechanical understanding of MRP1, thereby facilitating the rational design of chemosensitizers toward the success of chemotherapy treatments.

RevDate: 2021-06-08

Icht M, Zukerman G, Ben-Itzchak E, et al (2021)

Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta-analysis study.

Autism research : official journal of the International Society for Autism Research [Epub ahead of print].

Daily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) experience difficulties in identification of spoken emotions. We conducted a meta-analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer-reviewed journal articles) comparing individuals with ASD-without-ID (N = 614) and typically-developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF-ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD-without-ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new-look on emotion processing in ASD-without-ID. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions and target improved performance with complex emotions. LAY SUMMARY: Individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta-analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions.

RevDate: 2021-06-11

Netzer O, Heimler B, Shur A, et al (2021)

Backward spatial perception can be augmented through a novel visual-to-auditory sensory substitution algorithm.

Scientific reports, 11(1):11944.

Can humans extend and augment their natural perceptions during adulthood? Here, we address this fascinating question by investigating the extent to which it is possible to successfully augment visual spatial perception to include the backward spatial field (a region where humans are naturally blind) via other sensory modalities (i.e., audition). We thus developed a sensory-substitution algorithm, the "Topo-Speech" which conveys identity of objects through language, and their exact locations via vocal-sound manipulations, namely two key features of visual spatial perception. Using two different groups of blindfolded sighted participants, we tested the efficacy of this algorithm to successfully convey location of objects in the forward or backward spatial fields following ~ 10 min of training. Results showed that blindfolded sighted adults successfully used the Topo-Speech to locate objects on a 3 × 3 grid either positioned in front of them (forward condition), or behind their back (backward condition). Crucially, performances in the two conditions were entirely comparable. This suggests that novel spatial sensory information conveyed via our existing sensory systems can be successfully encoded to extend/augment human perceptions. The implications of these results are discussed in relation to spatial perception, sensory augmentation and sensory rehabilitation.

RevDate: 2021-07-06

Maitre T, Ok V, Calin R, et al (2021)

Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.

Therapeutic advances in respiratory disease, 15:17534666211003012.

BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors.

METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded.

RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p = 0.03), the absence of smoking or emphysema (p = 0.05), Staphylococcus aureus (p = 0.001) or Streptococcus spp. (p = 0.05) isolation, and the smaller size of their abscess (p = 0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p = 0.02), particularly when they spontaneously discharged (p = 0.04). Relapses were more frequent in patients with emphysema (p = 0.04) and when Haemophilus influenzae was isolated (p = 0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p = 0.02), and in those who received antibiotics during less than 6 weeks (p = 0.05).

CONCLUSION: A duration of antibiotic treatment of less than 6 weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.

RevDate: 2021-07-12

Busheri L, Dixit S, Nare S, et al (2021)

Breast cancer biobank from a single institutional cohort in an urban setting in india: Tumor characteristics and survival outcomes.

Cancer treatment and research communications, 28:100409 pii:S2468-2942(21)00107-6 [Epub ahead of print].

BACKGROUND: A breast cancer biobank with retrospectively collected patient data and FFPE tissue samples was established in 2018 at Prashanti Cancer Care Mission, Pune, India. It runs a cancer care clinic with support from a single surgeon's breast cancer practice. The clinical data and tissue sample collection is undertaken with appropriate patient consent following ethical approval and guidelines.

METHODS: The biobank holds clinical history, diagnostic reports, treatment and follow-up information along with FFPE tumor tissue specimens, adjacent normal and, in few cases, contralateral normal breast tissue. Detailed family history and germline mutational profiles of eligible and consenting patients and their relatives are also deposited in the biobank.

RESULTS: Here, we report the first audit of the biobank. A total number of 994 patients with breast disease have deposited consented clinical records in the biobank. The majority of the records (80%, n = 799) are of patients with infiltrating ductal carcinoma (IDC). Of 799 IDC patients, 434 (55%) have deposited tumor tissue in the biobank with consent. In addition, germline mutation profiles of 84 patients and their family members are deposited. Follow-up information is available for 85% of the 434 IDC patients with an average follow-up of 3 years.

CONCLUSION: The biobank has aided the initiation of translational research at our center in collaboration with eminent institutes like IISER Pune and SJRI Bangalore to evaluate profiles of breast cancer in an Indian cohort. The biobank will be a valuable resource to the breast cancer research community, especially to understand South Asian profiles of breast cancer.

RevDate: 2021-06-10

Joachim-Célestin M, Chara R, SB Montgomery (2021)

Living Near an Immigration Detention Center: Impact on Latinas' Health.

Journal of immigrant and minority health [Epub ahead of print].

There is ample evidence that exposure to Immigration and Customs Enforcement (ICE) activities could widen Latinas' health disparities. Whether or not residing near an ICE detention center (IDC) further impacts their health is unknown. During nationwide increased ICE activities Latinas (N=45) attended an intervention at two separate sites: one near and another one far from an IDC. A focus group discussion and an interview were conducted using a grounded theory approach. Quantitative data were collected and analyzed. Participants residing near an IDC benefited less from the intervention and reported changes in anxiety levels and in mobility, and a sense of powerlessness. They also requested resources to respond to ICE overreach and broadcasting of their reality. Our results suggest that proximity to IDCs impacts immigrant communities and public health programming, which is inevitably embedded in political realities. These need to be addressed when providing much needed interventions.

RevDate: 2021-06-07

Badak B, Aykanat NEB, Kacar S, et al (2021)

Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.

Annali italiani di chirurgia, 10: pii:S0003469X21035648 [Epub ahead of print].

BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell.

MATERIAL METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method.

RESULT: 250 μM astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients.

CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results.

KEY WORDS: Breast, cancer, metastasis.

RevDate: 2021-06-08

Wang Y, Liang F, Zhou Y, et al (2021)

Sharp Downregulation of Hub Genes Associated With the Pathogenesis of Breast Cancer From Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.

Frontiers in oncology, 11:634569.

Introduction: Breast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.

Methods: Laser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.

Results: Two modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e-07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e-12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.

Conclusions: Five hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.

RevDate: 2021-07-03

Thompson HK, PJ Spicer (2021)

Recurrent breast cancer diagnosis delayed by COVID-19 pandemic.

Radiology case reports, 16(9):2450-2453.

We describe the case of a 64-year-old female with a no relevant medical history. Screening mammography in March 2020 demonstrated calcifications in the right breast, and a diagnostic mammogram was recommended. In the months that followed, the patient experienced tissue changes in the right breast but avoided returning to the facility as the COVID-19 pandemic worsened. The patient returned for a diagnostic mammogram in September of 2020, which indicated suspicious lymph nodes and an increase in calcifications. Further analysis through ultrasound-guided core biopsy ultimately led to a right mastectomy and lymph node biopsy, which were performed in October 2020. Pathology results confirmed the diagnosis of invasive ductal carcinoma with lobular features.

RevDate: 2021-06-05

Ahmed M, Frederickson J, Khan K, et al (2021)

Rhabdomyolysis After Total Abdominal Hysterectomy Requiring Urgent Hemodialysis Due to Hyperkalemia.

Cureus, 13(4):e14757.

A 63-year-old woman with a past medical history of invasive ductal carcinoma of the breast, status post lumpectomy and chemoradiation, 15 cm left inguinal-femoral enlarged lymph node consistent with high-grade serous carcinoma of the ovary and 4.7 cm right adnexal mass underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection with cystoscopy and bilateral ureteral catheter placement. There was no intraoperative complication. After surgery, patient's urine output decreased, and she developed acute kidney injury (AKI). Initially, it was thought that her reduced output might be due to surgery/anesthesia. She also developed arm and leg weakness raising suspicion for stroke. The neurological workup was unremarkable for any acute abnormality. Her creatinine kinase (CK) level was >20,000 u/l consistent with rhabdomyolysis. She was hydrated aggressively and required hemodialysis due to hyperkalemia. During the hospital course, her kidney function improved, and rhabdomyolysis resolved, and she did not require dialysis after discharge.


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

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