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triple-negative breast cancer

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https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#1
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27911956/adenosine-stimulate-proliferation-and-migration-in-triple-negative-breast-cancer-cells
#2
Miriam Fernandez-Gallardo, Ricardo González-Ramírez, Alejandro Sandoval, Ricardo Felix, Eduardo Monjaraz
Emerging evidence suggests that the adenosine (Ado) receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer...
2016: PloS One
https://www.readbyqxmd.com/read/27911269/the-matricellular-protein-cyr61-promotes-breast-cancer-lung-metastasis-by-facilitating-tumor-cell-extravasation-and-suppressing-anoikis
#3
Yu-Ting Huang, Qiang Lan, Girieca Lorusso, Nathalie Duffey, Curzio Rüegg
Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906684/phase-i-study-of-the-gamma-secretase-inhibitor-pf-03084014-in-combination-with-docetaxel-in-patients-with-advanced-triple-negative-breast-cancer
#4
Marzia A Locatelli, Philippe Aftimos, E Claire Dees, Patricia M LoRusso, Mark D Pegram, Ahmad Awada, Bo Huang, Rossano Cesari, Yuqiu Jiang, M Naveed Shaik, Kenneth A Kern, Giuseppe Curigliano
BACKGROUND: The NOTCH signaling pathway may be involved in the survival of stem cell-like tumor-initiating cells and contribute to tumor growth. In this phase Ib, open-label, multicenter study (NCT01876251), we evaluated PF-03084014, a selective gamma-secretase inhibitor in patients with advanced triple-negative breast cancer. METHODS: The dose-finding part was based on a 2×3 matrix design using the modified toxicity probability interval method. Oral PF-03084014 was administered twice daily continuously in combination with intravenous docetaxel given on day 1 of each 21-day cycle...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906681/sirna-mediated-suppression-of-collagen-type-iv-alpha-2-col4a2-mrna-inhibits-triple-negative-breast-cancer-cell-proliferation-and-migration
#5
He Jing Song, Guan Hong, Jianbo Yang, Zheng Duo, Fu Li, Chen Wei Cai, Luo Xue Ying, Mao You Sheng, Ou Yang YiWen, Pan Yue, Chang Zou
Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. Collagen type IV alpha 2 (COL4A2), a major component of the basement membrane, dynamically influences a wide range of biological processes, including cancer pathogenesis and progression. This study evaluated the effects of COL4A2 siRNA delivered by lentiviral vector to TNBC cells. COL4A2 siRNA lenti-viral vector was constructed and transfected into MDA-MB-231 and MDA-MB-468 cells. The COL4A2 mRNA levels were quantified by RT-PCR...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904868/predictive-ability-of-18-f-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-for-pathological-complete-response-and-prognosis-after-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer-patients
#6
Sachiko Kiyoto, Yoshifumi Sugawara, Kohei Hosokawa, Rieko Nishimura, Natsumi Yamashita, Shozo Ohsumi, Teruhito Mochizuki
OBJECTIVES: The mortality of patients with locally advanced triple-negative breast cancer (TNBC) is high, and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This retrospective study was designed and powered to investigate the ability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) to predict pathological response to NAC and prognosis after NAC. METHODS: The data of 32 consecutive women with clinical stage II or III TNBC from January 2006 to December 2013 in our institution who underwent FDG-PET/CT at baseline and after NAC were retrospectively analyzed...
2016: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/27904710/the-comt-rs165599-gene-polymorphism-contributes-to-chemotherapy-induced-cognitive-impairment-in-breast-cancer-patients
#7
Huaidong Cheng, Wen Li, Chen Gan, Bo Zhang, Qianqian Jia, Kai Wang
The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903149/obesity-and-breast-cancer-prognosis-evidence-challenges-and-opportunities
#8
Sao Jiralerspong, Pamela J Goodwin
Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#9
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902967/the-non-receptor-tyrosine-kinase-tnk2-ack1-is-a-novel-therapeutic-target-in-triple-negative-breast-cancer
#10
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Dhanashree S Kelkar, Mustafa A Bharbuiya, Pamela L Rojas, Vered Stearns, Edward Gabrielson, Pavani Malla, Saraswati Sukumar, Nupam P Mahajan, Akhilesh Pandey
Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers do not express estrogen receptor, progesterone receptor or HER2 receptor and hence are collectively classified as triple negative breast cancer (TNBC). These tumors are often relatively aggressive when compared to other types of breast cancer, and this issue is compounded by the lack of effective targeted therapy. In our previous phosphoproteomic profiling effort, we identified the non-receptor tyrosine kinase TNK2 as activated in a majority of aggressive TNBC cell lines...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#11
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#12
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899956/innovations-that-reach-the-patient-early-health-technology-assessment-and-improving-the-chances-of-coverage-and-implementation
#13
W H van Harten, V P Retèl
With growing concerns for the sustainability of the financial burden that health care-and especially cancer services-poses on the national budgets, the role of health economic analyses in coverage decisions is likely to grow. One of the strategies for the biomedical research field-also in oncology research-to foster coverage and health system implementation, is to anticipate this new role and to involve health technology assessment techniques earlier in various stages of translational research. In this article, we elaborate on the early involvement of health technology assessment in translational research and the concept of Coverage with Evidence Development in The Netherlands Cancer Institute and give two case examples that are currently ongoing: (1) tumour infiltrating lymphocytes therapy for metastatic melanoma; and (2) high-dose chemotherapy for BRCA1-like subgroup in triple-negative breast cancer...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27899251/improved-breast-cancer-cell-specific-intracellular-drug-delivery-and-therapeutic-efficacy-by-coupling-decoration-with-cell-penetrating-peptide-and-sp90-peptide
#14
Li-Qiang Fan, Guo-Xiu Du, Peng-Fei Li, Ming-Wei Li, Yao Sun, Li-Ming Zhao
Lack of satisfactory specificity towards tumor cells and poor intracellular delivery efficacy are the major drawbacks with conventional cancer chemotherapy. Conjugated anticancer drugs to targeting moieties e.g. to peptides with the ability to recognize cancer cells and to cell penetrating peptide can improve these characteristics, respectively. Combining a tumor homing peptide with an appropriate cell-penetrating peptide can enhance the tumor-selective internalization efficacy of the carrying cargo molecules...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27896700/fat4-functions-as-a-tumor-suppressor-in-triple-negative-breast-cancer
#15
Lingmi Hou, Maoshan Chen, Xiaobo Zhao, Jingdong Li, Shishan Deng, Jiani Hu, Hongwei Yang, Jun Jiang
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with biologic behavior with frequent distant metastasis. FAT tumor suppressor homolog 4 (FAT4), a cadherin-related protein, is involved in a variety of biological processes as a tumor suppressor; however, the role of FAT4 in TNBC is still unclear. The aim of our study was to identify the role of FAT4 in TNBC and examine the underlying molecular mechanisms. The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in a series of TNBC tissues...
November 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27895979/optical-redox-ratio-identifies-metastatic-potential-dependent-changes-in-breast-cancer-cell-metabolism
#16
Kinan Alhallak, Lisa G Rebello, Timothy J Muldoon, Kyle P Quinn, Narasimhan Rajaram
The development of prognostic indicators of breast cancer metastatic risk could reduce the number of patients receiving chemotherapy for tumors with low metastatic potential. Recent evidence points to a critical role for cell metabolism in driving breast cancer metastasis. Endogenous fluorescence intensity of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) can provide a label-free method for assessing cell metabolism. We report the optical redox ratio of FAD/(FAD + NADH) of four isogenic triple-negative breast cancer cell lines with varying metastatic potential...
November 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27895868/immunohistochemical-subtypes-of-breast-cancer-correlation-with-clinicopathological-and-radiological-factors
#17
Yu-Mee Sohn, Kyunghwa Han, Mirinae Seo
BACKGROUND: The relationship between biomarkers and imaging features is important because imaging findings can predict molecular features. OBJECTIVES: To investigate the relationship between clinicopathologic and radiologic factors and the immunohistochemical (IHC) profiles associated with breast cancer. PATIENTS AND METHODS: From December 2004 to September 2013, 200 patients (mean age, 56 years; range, 29 - 82 years) were diagnosed with breast cancer and underwent surgery at our institution...
October 2016: Iranian Journal of Radiology: a Quarterly Journal Published By the Iranian Radiological Society
https://www.readbyqxmd.com/read/27895745/evaluation-of-the-association-between-hif-1%C3%AE-and-her-2-expression-hormone-receptor-status-ki-67-expression-histology-and-tumor-fdg-uptake-in-breast-cancer
#18
Sevi M Sureyya Cerci, Kemal Kursat Bozkurt, Hasan Erol Eroglu, Celal Cerci, Evrim Erdemoglu, Pinar Talip Bulbul, Meltem Cetin, Recep Cetin, Ibrahim Metin Ciris, Mahmut Bulbul
The present study aimed to examine hypoxia-inducible factor (HIF)-1α expression and its association with glucose uptake in invasive breast cancer. In addition, connections between glucose uptake and several other prognostic parameters of breast cancer were studied. Between August 2013 and April 2015, 92 patients with biopsy-diagnosed breast cancer were subjected to (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. The primary tumor and nodal maximum standardized uptake values (SUVmax) were recorded, and HIF-1α expression and clinical parameters, including tumor mass, estrogen receptor (ER) and progesterone receptor (PgR) levels, human epidermal growth factor receptor-2 (HER-2), Ki-67 index, grade and histology, were analyzed...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#19
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#20
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
November 25, 2016: Cancer Letters
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