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Tumor growth factors in breast cancer

Michael Untch, Gunter von Minckwitz, Bernd Gerber, Christian Schem, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Sibylle Loibl
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308)...
March 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Xiaoli Wang, Wei Xiong, Yiyin Tang
Breast cancer is one of the most common metastatic tumor types. Reports have suggested that Tunicamycin may inhibit the aggressiveness of cancer cells by promoting their apoptosis. In the present study, the inhibitory effects of Tunicamycin were investigated and the potential molecular mechanism underlying the Tunicamycin-inhibited growth and aggressiveness of breast cancer cells was explored. In vitro assays demonstrated that Tunicamycin significantly inhibited growth and arrested the cell cycle of breast cancer cells in a dose-dependent manner, compared with control cells...
April 2018: Oncology Letters
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
Mi Hwa Heo, Hee Kyung Kim, Hansang Lee, Ji-Yeon Kim, Jin-Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Background/Aims: We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. Methods: We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016)...
March 16, 2018: Korean Journal of Internal Medicine
Ling Deng, Xuehua Zhu, Yun Sun, Jiemin Wang, Xiaorong Zhong, Jiayuan Li, Min Hu, Hong Zheng
Purpose: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. Materials and Methods: Tumors from five hundred and seven breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed...
March 15, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Emilie Clement, Hiroyuki Inuzuka, Naoe T Nihira, Wenyi Wei, Alex Toker
The PI3K-AKT kinase signaling pathway is frequently deregulated in human cancers, particularly breast cancer, where amplification and somatic mutations of PIK3CA occur with high frequency in patients. Numerous small-molecule inhibitors targeting both PI3K and AKT are under clinical evaluation, but dose-limiting toxicities and the emergence of resistance limit therapeutic efficacy. Various resistance mechanisms to PI3K inhibitors have been identified, including de novo mutations, feedback activation of AKT, or cross-talk pathways...
March 13, 2018: Science Signaling
J J Zhu, D C Jiao, J H Qiao, L N Wang, Y Z Ma, Z D Lu, Z Z Liu
Objective: To explore the expression of androgen receptor (AR) in the tissues as well as its association with the clinicopathological factors of primary breast cancer patients treated with neoadjuvant chemotherapy (NAC), and analyze the effect of AR in the prediction of pathologic complete response (PCR) rate. Method: A total of 668 breast cancer patients treated with NAC in Henan Cancer Hospital between March 2014 and June 2017 were retrospectively reviewed. The relationship of AR expression and clinicopathological characteristics was calculated using chi square test...
February 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Glenwood D Goss, Everett E Vokes, Michael S Gordon, Leena Gandhi, Kyriakos P Papadopoulos, Drew W Rasco, JuDee S Fischer, Katharine L Chu, William W Ames, Rajendar K Mittapalli, Ho-Jin Lee, Jiewei Zeng, Lisa A Roberts-Rapp, Lise I Loberg, Peter J Ansell, Edward B Reilly, Christopher J Ocampo, Kyle D Holen, Anthony W Tolcher
BACKGROUND: Epidermal growth factor receptor (EGFR) alterations are associated with multiple cancers. Current EGFR-directed therapies have led to increased efficacy but are associated with specific side effects. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) targets EGFR with a monoclonal antibody linked to a cytotoxin, and is highly tumor-specific. METHODS: This phase 1/2 study evaluated the safety, pharmacokinetics, and efficacy of depatux-m in patients who had advanced solid tumors with known wild-type EGFR overexpression, amplification, or mutated EGFR variant III...
March 13, 2018: Cancer
Pernilla Roswall, Matteo Bocci, Michael Bartoschek, Hong Li, Glen Kristiansen, Sara Jansson, Sophie Lehn, Jonas Sjölund, Steven Reid, Christer Larsson, Pontus Eriksson, Charlotte Anderberg, Eliane Cortez, Lao H Saal, Christina Orsmark-Pietras, Eugenia Cordero, Bengt Kristian Haller, Jari Häkkinen, Ingrid J G Burvenich, Elgene Lim, Akira Orimo, Mattias Höglund, Lisa Rydén, Holger Moch, Andrew M Scott, Ulf Eriksson, Kristian Pietras
Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas...
March 12, 2018: Nature Medicine
Wenjuan Ma, Yumei Zhao, Yu Ji, Xinpeng Guo, Xiqi Jian, Peifang Liu, Shandong Wu
RATIONALE AND OBJECTIVES: This study aimed to investigate whether quantitative radiomic features extracted from digital mammogram images are associated with molecular subtypes of breast cancer. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, we collected 331 Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 29 triple-negative, 45 human epidermal growth factor receptor 2 (HER2)-enriched, 36 luminal A, and 221 luminal B lesions...
March 8, 2018: Academic Radiology
Leticia Varella, Jame Abraham, Megan Kruse
Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF) that interferes with VEGF binding to its receptor on vascular endothelium. Bevacizumab has been approved for the treatment of various malignant tumors, and has been studied in combination with several cytotoxic agents in the treatment of breast cancer. In 2008, the US Food and Drug Administration granted accelerated approval for the use of bevacizumab in combination with weekly paclitaxel for first-line treatment of HER2-negative metastatic breast cancer...
August 2017: Seminars in Oncology
Michele Pellegrino, Pietro Rizza, Alessandra Nigro, Rosangela Ceraldi, Elena Ricci, Ida Perrotta, Saveria Aquila, Marilena Lanzino, Sebastiano Andò, Catia Morelli, Diego Sisci
Breast cancer (BC) is a complex and heterogeneous disease, with distinct histological features dictating the therapy. Although the clinical outcome of BC patients has been considerably improved, the occurrence of resistance to common endocrine and chemotherapy treatments remains the major cause of relapse and mortality. Thus, efforts in identifying new molecules to be employed in BC therapy are needed. As a "faster" alternative to reach this aim, we evaluated if Lamotrigine (LTG), a broadly used anticonvulsivant, could be "repurposed" as an antitumoral drug in BC...
March 9, 2018: Molecular Cancer Research: MCR
Xiaojie Zang, Guangji Wang, Qinngyun Cai, Xiao Zheng, Jingwei Zhang, Qianying Chen, Baojin Wu, Xiong Zhu, Haiping Hao, Fang Zhou
Multi-drug resistance (MDR) is a common limitation for the clinical use of microtubule-targeting chemotherapeutic agents and it is the main factor for poor prognoses in cancer therapy. Here, we report on deoxypodophyllotoxin (DPT), a promising microtubule inhibitor in phase I, as a promising candidate to circumvent the obstacle. DPT remarkably suppressed the tumor growth in xenograft mice bearing either Paclitaxel (PTX)-sensitive MCF-7/S or acquired resistance MCF-7/Adr (MCF-7/A) cells. Also, DPT exhibited a similar accumulation in both tumors, while PTX displayed much a lower accumulation in the resistant tumors...
March 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Jan Hauke, Judit Horvath, Eva Groß, Andrea Gehrig, Ellen Honisch, Karl Hackmann, Gunnar Schmidt, Norbert Arnold, Ulrike Faust, Christian Sutter, Julia Hentschel, Shan Wang-Gohrke, Mateja Smogavec, Bernhard H F Weber, Nana Weber-Lassalle, Konstantin Weber-Lassalle, Julika Borde, Corinna Ernst, Janine Altmüller, Alexander E Volk, Holger Thiele, Verena Hübbel, Peter Nürnberg, Katharina Keupp, Beatrix Versmold, Esther Pohl, Christian Kubisch, Sabine Grill, Victoria Paul, Natalie Herold, Nadine Lichey, Kerstin Rhiem, Nina Ditsch, Christian Ruckert, Barbara Wappenschmidt, Bernd Auber, Andreas Rump, Dieter Niederacher, Thomas Haaf, Juliane Ramser, Bernd Dworniczak, Christoph Engel, Alfons Meindl, Rita K Schmutzler, Eric Hahnen
The prevalence of germ line mutations in non-BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing...
March 9, 2018: Cancer Medicine
Maria Rosaria Ruocco, Angelica Avagliano, Giuseppina Granato, Valeria Imparato, Stefania Masone, Mariorosario Masullo, Rosarita Nasso, Stefania Montagnani, Alessandro Arcucci
Breast cancer is the most common cancer in women, which incidence has increased in recent years. It is constituted by very heterogeneous tissue characterized by an abnormal microenvironment regulating tumor progression and providing evasion from cancer therapies. Breast cancer associated fibroblasts (BCAFs) are the main cell type of breast cancer microenvironment and can represent up to 80 % of the tumor mass. In particular, BCAFs induce cancer initiation, proliferation, invasion and metastasis by undergoing an irreversible activation process associated with secretion of growth factors, cytokines, and paracrine interactions...
March 9, 2018: Current Medicinal Chemistry
Wenying Zhang, Qiongwei Wu, Chao Wang, Longtao Yang, Ping Liu, Chengbin Ma
Upregulation of A-kinase-interacting protein 1 (AKIP1) has been observed in breast and esophageal cancers, indicating that AKIP1 may be a potent oncogenic protein. However, the role of AKIP1 in cervical cancer still remains unknown. This study aimed to explore the role of AKIP1 in cervical cancer and to investigate the underlying mechanism of AKIP1 in tumor growth. Expression of AKIP1 in cervical cancer cells was determined by qRT-PCR and western blotting. Cell-Light EdU and colony formation assays were used to determine cell proliferation...
March 8, 2018: Molecular and Cellular Biochemistry
Annina Baumgartner, Christoph Tausch, Stefanie Hosch, Bärbel Papassotiropoulos, Zsuzsanna Varga, Christoph Rageth, Astrid Baege
BACKGROUND: Accuracy in predicting pathologic response to neoadjuvant chemotherapy (NACT) in breast cancer is essential for the determination of therapeutic efficacy and surgical planning. This study aimed to assess the precision of ultrasound (US) for predicting pathologic complete response (pCR = ypT0) after NACT. METHODS: This retrospective mono-center study included 124 invasive breast cancer patients treated with NACT. Patients received US before and after NACT with documentation of clinical partial response (cPR) and clinical complete response (cCR)...
March 5, 2018: Breast: Official Journal of the European Society of Mastology
Chhanda Bose, Sanjay Awasthi, Rajendra Sharma, Helen Beneš, Martin Hauer-Jensen, Marjan Boerma, Sharda P Singh
Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known...
2018: PloS One
Reza Dayer, Sadegh Babashah, Shirin Jamshidi, Majid Sadeghizadeh
Objective: Breast cancer is considered as a heterogeneous disease, characterized by different biological and phenotypic features which make its diagnosis and treatment challenging. The CXC chemokine receptor 4 (CXCR4) expression was found to be correlated with poor overall survival in invasive breast carcinoma patients. Here, we sought to investigate the expression levels of the CXCR4-CXC chemokine ligand 12 (CXCL12) chemokine axis and their association with clinicopathologic features and lymph node metastasis in invasive breast carcinoma...
January 2018: Journal of Cancer Research and Therapeutics
Leila Farahmand, Rezvan Esmaeili, Leila Eini, Keivan Majidzadeh-A
Purpose: Bone marrow-derived mesenchymal stem cells (MSCs) have the potential ability to differentiate into bone, muscle, fat, and cartilage lineage cells. Furthermore, MSCs are known to migrate into tumor-associated stroma of cancer. This tumor microenvironment consists of a dynamic network of growth factors, immune cells, fibroblasts, extracellular matrix, and MSCs. MSCs as nonhematopoietic stem cells affect tumor, epithelial cells by alteration proliferative capacity, morphology, and aggregation pattern of tumor cells...
January 2018: Journal of Cancer Research and Therapeutics
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