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https://www.readbyqxmd.com/read/28224609/mir-181-elevates-akt-signaling-by-co-targeting-phlpp2-and-inpp4b-phosphatases-in-luminal-breast-cancer
#1
Michaela Strotbek, Simone Schmid, Ismael Sànchez-Gonzàlez, Melanie Boerries, Hauke Busch, Monilola A Olayioye
The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d post-transcriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28221401/s%C3%A3-mre-prognos-f%C3%A3-r-unga-kvinnor-med-br%C3%A3-stcancer-fr%C3%A3-gest%C3%A3-llningar-s%C3%A3-som-fertilitet-och-graviditet-viktiga-att-beakta
#2
Irma Fredriksson, Hanna Fredholm
Breast cancer in young women is uncommon, but the second most frequent cause of death in this age group. Young women with breast cancer have a worse prognosis than middle-aged women, with a higher risk of local recurrence, distant disease and breast cancer death. This can partly be explained by diagnosis at a later stage, and a higher proportion of tumors with unfavourable characteristics. However, in women with tumors of the luminal B subtype, low age remained an independent prognostic factor of DDFS and LRFS after correction for stage, tumor characteristics and treatment...
February 14, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28218902/retinoic-acid-directs-breast-cancer-cell-state-changes-through-regulation-of-tet2-pkc%C3%AE-pathway
#3
M-J Wu, M R Kim, Y-S Chen, J-Y Yang, C-J Chang
The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARβ-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#4
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28216075/-androgen-receptors-in-breast-cancer-expression-value-and-therapeutic-prospects
#5
REVIEW
Delphine Héquet, Slim Mzoughi, Roman Rouzier, Ernesto Guccione
Triple-negative (TN) breast cancer are characterized by lack of estrogen receptor (OR) and progesterone receptor (PR) expression, and the absence of overexpression of human epidermal growth factor receptor 2 (HER2). It is a heterogeneous group of tumors with a more pejorative prognosis than other subtypes of breast cancer. Androgen receptors (AR) are nuclear receptors whose expression varies from 80 to 85% of primary breast cancers and 60 to 75% of metastatic cancers. Among the TN breast cancers, the luminal androgen receptor (LAR) subtype expresses AR more frequently, up to 53% of the cases...
February 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28214007/-impact-of-her2%C3%A2-and-brca1-2%C3%A2-status-in-high-dose-chemotherapy-and-autologous-stem-cells-transplantation-in-the-treatment-of-breast-cancer-the-institut-paoli-calmettes-experience
#6
Laurys Boudin, Christian Chabannon, Patrick Sfumato, Renaud Sabatier, François Bertucci, Carole Tarpin, Magali Provansal, Gilles Houvenaeghel, Eric Lambaudie, Agnes Tallet, Michel Resbeut, Emmanuelle Charafe-Jauffret, Boris Calmels, Claude Lemarie, Jean-Marie Boher, Jean-Marc Extra, Patrice Viens, Anthony Gonçalves
INTRODUCTION: Studies evaluating chemotherapy high dose chemotherapy with autologous haematopoietic stem cell transplantation (HDC-ACSH) in the treatment of metastatic (MBC), locally advanced (LABC) and inflammatory (IBC) breast cancer have in common lack of biomarker information, in particular the HER2 status. PATIENTS AND METHODS: All consecutive female patients treated for breast cancer with HDC and AHSCT at Institut Paoli Calmettes between 2003 and 2012 were included...
February 14, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28211079/gata3-expression-in-triple-negative-breast-cancers
#7
David J Byrne, Siddhartha Deb, Elena A Takano, Stephen B Fox
AIMS: GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types including breast and urotheilial carcinomas making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. METHODS AND RESULTS: We investigated GATA3 protein expression in a 106 primary triple negative breast carcinomas (100 basal-like, 6 non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823)...
February 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28208987/bcl6-mrna-expression-level-in-invasive-duct-carcinoma-not-otherwise-specified
#8
Eman Badr, Eman Masoud, Asmaa Gaber Abdou, Marwa Serag Eldien
INTRODUCTION: B-Cell Lymphoma 6 (BCL6) has an oncogenic role in tumourigenesis of various malignancies. It represses genes involved in terminal differentiation and plays complementary role with Signal Transducer and Activator of Transcription 3 (STAT3) in triple-negative breast cancer cellular function. AIM: To evaluate the expression of BCL6 in cancer breast and determine its correlation with the clinico-pathological features including the molecular subtype of breast carcinoma...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28205537/her2-alterations-in-muscle-invasive-bladder-cancer-patient-selection-beyond-protein-expression-for-targeted-therapy
#9
Bernhard Kiss, Alexander W Wyatt, James Douglas, Veronika Skuginna, Fan Mo, Shawn Anderson, Diana Rotzer, Achim Fleischmann, Vera Genitsch, Tetsutaro Hayashi, Maja Neuenschwander, Christine Buerki, Elai Davicioni, Colin Collins, George N Thalmann, Peter C Black, Roland Seiler
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205042/screening-relevant-age-threshold-of-70%C3%A2-years-and-older-is-a-stronger-determinant-for-the-choice-of-adjuvant-treatment-in-breast-cancer-patients-than-tumor-biology
#10
E C Inwald, O Ortmann, M Koller, F Zeman, F Hofstädter, M Evert, G Brockhoff, M Klinkhammer-Schalke
PURPOSE: The 70-year threshold determines whether patients are eligible or not for the breast cancer screening program in Germany. It is not known whether this age threshold also influences the choice of adjuvant treatment and ultimate outcome. METHODS: 3463 patients were analyzed from the clinical cancer registry Regensburg (Germany) with primary, non-metastatic invasive breast cancer diagnosed between 2000 and 2012. The distribution of tumor biological subtypes was evaluated in breast cancer patients both in those eligible for screening (ESG, 50-69 years) and those not eligible for screening (NESG, ≥70 years)...
February 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28202520/evolution-of-cancer-stem-like-cells-in-endocrine-resistant-metastatic-breast-cancers-is-mediated-by-stromal-microvesicles
#11
Pasquale Sansone, Marjan Berishaj, Vinagolu K Rajasekhar, Claudio Ceccarelli, Qing Chang, Antonio Strillacci, Claudia Savini, Lauren Shapiro, Robert Bowman, Chiara Mastroleo, Sabrina De Carolis, Laura Daly, Alberto Benito-Martin, Fabiana Perna, Nicola Fabbri, John H Healey, Enzo Spisni, Monica Cricca, David Lyden, Massimiliano Bonafé, Jacqueline Bromberg
The hypothesis that microvesicle (MV)-mediated microRNA transfer converts non-cancer stem cells into cancer stem cells (CSCs) leading to therapy resistance remains poorly investigated. Here we provide direct evidence supporting this hypothesis, by demonstrating how MV derived from cancer associated fibroblasts (CAF) transfer miR-221 to promote hormonal therapy resistance (HTR) in models of luminal breast cancer. We determined that CAF-derived MV horizontally transferred miR221 to tumor cells and, in combination with hormone therapy activated an ERlo/Notchhi feed-forward loop responsible for the generation of CD133hi CSC...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28195084/calretinin-expression-as-a-reliable-prognostic-marker-in-different-molecular-subtypes-of-breast-carcinoma
#12
Mayada Saad Farrag, Amro Awad El-Karef, Maha Mohammed Amin, Nagwa Mokhtar Helal, Omar Farouk Ali, Nesrine Saad Farrag
BACKGROUND: Calretinin (CR), a known mesothelial marker, is expressed in both epithelial and mesenchymal malignancies including breast cancer. AIMS: We aimed to measure the frequency of CR expression in correlation with other clinicopathological parameters of different molecular subtypes of invasive breast carcinoma and to study its prognostic implications in this common cancer. STUDY DESIGN: Tissue microarrays were constructed from 225 tissue samples of breast carcinoma cases...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28194538/the-influences-of-peritumoral-lymphatic-invasion-and-vascular-invasion-on-the-survival-and-recurrence-according-to-the-molecular-subtypes-of-breast-cancer
#13
Ki-Tae Hwang, Young A Kim, Jongjin Kim, A Jung Chu, Ji Hyun Chang, So Won Oh, Kyu Ri Hwang, Young Jun Chai
PURPOSE: We aimed to compare the influences of lymphatic invasion (LI) and vascular invasion (VI) on survival and recurrence according to the molecular subtypes of breast cancer. METHODS: We retrospectively analyzed data on 820 breast cancer patients and assessed overall survival (OS) and disease-free survival (DFS) according to LI and VI using the Kaplan-Meier estimator and the Cox proportional hazards model. RESULTS: Both positive LI and positive VI showed inferior OS and DFS compared with negative LI and negative VI (all p < 0...
February 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28194227/bone-metastasis-risk-factors-in-breast-cancer
#14
REVIEW
Catarina Pulido, Inês Vendrell, Arlindo R Ferreira, Sandra Casimiro, André Mansinho, Irina Alho, Luís Costa
Bone is the single most frequent site for bone metastasis in breast cancer patients. Patients with bone-only metastasis have a fairly good prognosis when compared with patients with visceral disease. Nevertheless, cancer-induced bone disease carries an important risk of developing skeletal related events that impact quality of life (QoL). It is therefore particularly important to stratify patients according to their risk of developing bone metastasis. In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28194015/induced-p53-loss-in-mouse-luminal-cells-causes-clonal-expansion-and-development-of-mammary-tumours
#15
Luwei Tao, Dongxi Xiang, Ying Xie, Roderick T Bronson, Zhe Li
Most breast cancers may have a luminal origin. TP53 is one of the most frequently mutated genes in breast cancers. However, how p53 deficiency contributes to breast tumorigenesis from luminal cells remains elusive. Here we report that induced p53 loss in Krt8(+) mammary luminal cells leads to their clonal expansion without directly affecting their luminal identity. All induced mice develop mammary tumours with 9qA1 (Yap1) and/or 6qA2 (Met) amplification(s). These tumours exhibit a mammary stem cell (MaSC)-like expression signature and most closely resemble claudin-low breast cancer...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28192598/overall-survival-and-the-response-to-radiotherapy-among-molecular-subtypes-of-breast-cancer-brain-metastases-treated-with-targeted-therapies
#16
Jacob A Miller, Rupesh Kotecha, Manmeet S Ahluwalia, Alireza M Mohammadi, Samuel T Chao, Gene H Barnett, Erin S Murphy, Michael A Vogelbaum, Lilyana Angelov, David M Peereboom, John H Suh
BACKGROUND: The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. METHODS: Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis...
February 13, 2017: Cancer
https://www.readbyqxmd.com/read/28187434/interface-between-breast-cancer-cells-and-the-tumor-microenvironment-using-platelet-rich-plasma-to-promote-tumor-angiogenesis-influence-of-platelets-and-fibrin-bundles-on-the-behavior-of-breast-tumor-cells
#17
Sheila Siqueira Andrade, Joana Tomomi Sumikawa, Eloísa Dognani Castro, Fabricio Pereira Batista, Edgar Paredes-Gamero, Lilian Carolina Oliveira, Izabel Monastério Guerra, Giovani Bravin Peres, Renan Pelluzzi Cavalheiro, Luiz Juliano, Afonso Pinto Nazário, Gil Facina, Siu Mui Tsai, Maria Luiza Vilela Oliva, Manoel João Batista Castello Girão
Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187177/a-comparison-of-ki-67-counting-methods-in-luminal-breast-cancer-the-average-method-vs-the-hot-spot-method
#18
Min Hye Jang, Hyun Jung Kim, Yul Ri Chung, Yangkyu Lee, So Yeon Park
In spite of the usefulness of the Ki-67 labeling index (LI) as a prognostic and predictive marker in breast cancer, its clinical application remains limited due to variability in its measurement and the absence of a standard method of interpretation. This study was designed to compare the two methods of assessing Ki-67 LI: the average method vs. the hot spot method and thus to determine which method is more appropriate in predicting prognosis of luminal/HER2-negative breast cancers. Ki-67 LIs were calculated by direct counting of three representative areas of 493 luminal/HER2-negative breast cancers using the two methods...
2017: PloS One
https://www.readbyqxmd.com/read/28187033/prognostic-significance-of-stromal-versus-intratumoral-infiltrating-lymphocytes-in-different-subtypes-of-breast-cancer-treated-with-cytotoxic-neoadjuvant-chemotherapy
#19
Thaer Khoury, Vidya Nagrale, Mateusz Opyrchal, Xuan Peng, Dan Wang, Song Yao
BACKGROUND: The aim of the study was to investigate if there were differences in associations of stromal versus intratumoral tumor infiltrating lymphocytes (TILs) with pathology complete response (pCR) among breast cancer (BC) subtypes treated with neoadjuvant therapy. MATERIALS AND METHODS: The hematoxylin and eosin slides of BC-core biopsy consecutive cases (n=331) were reviewed from a single institution between 2000 and 2014. TIL-stroma (TIL-str) was scored from 0% to 100%...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28185173/ovarian-function-suppression-in-premenopausal-women-with-early-stage-breast-cancer
#20
REVIEW
Matteo Lambertini, Lucia Del Mastro, Giulia Viglietti, Noam F Pondé, Cinzia Solinas, Evandro de Azambuja
Breast cancers arising in young women are biologically more aggressive, and most of these patients are candidates to receive aggressive treatments that include the use of chemotherapy. As most of these tumors express the hormone receptors (i.e., luminal disease), these patients are also candidates to adjuvant endocrine therapy. Chemotherapy-induced amenorrhea showed to be prognostic in young patients with luminal breast cancer. However, the role of ovarian function suppression (OFS) in addition to standard adjuvant treatments has been largely debated over the past years...
January 2017: Current Treatment Options in Oncology
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