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Tumor growth factors in breast cancer

Marie-Julie Nokin, Florence Durieux, Paul Peixoto, Barbara Chiavarina, Olivier Peulen, Arnaud Blomme, Andrei Turtoi, Brunella Costanza, Nicolas Smargiasso, Dominique Baiwir, Jean L Scheijen, Casper G Schalkwijk, Justine Leenders, Pascal De Tullio, Elettra Bianchi, Marc Thiry, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Edwin De Pauw, Philippe Delvenne, Dominique Belpomme, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion...
October 19, 2016: ELife
Domenico Ribatti, Beatrice Nico, Simona Ruggieri, Roberto Tamma, Giovanni Simone, Anita Mangia
Several data support a central role for angiogenesis in breast cancer growth and metastasis. Observational studies have demonstrated that microvascular density (MVD) is a prognostic factor in invasive breast cancer, whereas others reached the opposite conclusion. Vascular endothelial growth factor is the most important angiogenic factor with proven significance in breast cancer, as it has been assessed in both experimental and clinical studies. Triple-negative breast cancer (TNBC) is a type of breast cancer which lacks estrogen, progesterone, and HER-2/neu receptors...
October 2016: Translational Oncology
Egidio Iorio, Maria José Caramujo, Serena Cecchetti, Francesca Spadaro, Giulia Carpinelli, Rossella Canese, Franca Podo
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. (1)H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment...
2016: Frontiers in Oncology
Ciara M Kelly, Yelena Y Janjigian
Gastric cancer is a biologically heterogeneous tumor. The identification of human epidermal growth factor receptor-2 (HER2) biomarker overexpression in gastric cancer represented a significant step towards unraveling the molecular complexity of this disease. Trastuzumab in combination with chemotherapy, in the first-line setting of patients with metastatic, HER2-positive gastric and gastroesophageal, represents the first targeted therapeutic to demonstrate improvement in response rate and survival in gastric cancer...
October 2016: Journal of Gastrointestinal Oncology
Mariko Okamoto, Ai Asamura, Ko Tanaka, Takefumi Soeda, Kyo Watanabe, Hiroyuki Mizuguchi, Teruo Ikeda
Adenovirus (Ad) vectors are widely used in cancer gene therapies. However, compared to human patients, relatively limited information is available on gene transduction efficiency or cell-specific cytotoxicity in canine tumor cells transduced with Ad vectors. Since epidermal growth factor receptor (EGFR) is highly expressed on canine breast tumor cells, we sought to develop an Ad vector based on the RGD fiber-mutant adenovirus vector (AdRGD) that expresses canine caspase 3 under the control of EGFR promoter...
October 16, 2016: Veterinary Research Communications
Jalal Poorolajal, Nahid Nafissi, Mohammad Esmaeil Akbari, Hossein Mahjub, Nader Esmailnasab, Ebrahim Babaee
BACKGROUND: We conducted this study to estimate the prevalence of biomarkers, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) among patients with breast cancer and to explore their effects on disease mortality. METHODS: We conducted this registry-based retrospective cohort study in Tehran, in 2014, using the data on 1622 patients with breast cancer, diagnosed pathologically and registered with the Comprehensive Cancer Control Center from 1998 to 2013...
October 2016: Archives of Iranian Medicine
Rico D Bense, Christos Sotiriou, Martine J Piccart-Gebhart, John B A G Haanen, Marcel A T M van Vugt, Elisabeth G E de Vries, Carolien P Schröder, Rudolf S N Fehrmann
BACKGROUND: Not all breast cancer patients benefit from neoadjuvant or adjuvant therapy, resulting in considerable undertreatment or overtreatment. New insights into the role of tumor-infiltrating immune cells suggest that their composition, as well as their functionality, might serve as a biomarker to enable optimal patient selection for current systemic therapies and upcoming treatment options such as immunotherapy. METHODS: We performed several complementary unbiased in silico analyses on gene expression profiles of 7270 unrelated tumor samples of nonmetastatic breast cancer patients with known clinical follow-up...
January 2017: Journal of the National Cancer Institute
Wafa Khaali, Khalid Moumad, El Khalil Ben Driss, Abdellatif Benider, Wided Ben Ayoub, Mokhtar Hamdi-Cherif, Kada Boualga, Elham Hassen, Marilys Corbex, Meriem Khyatti
BACKGROUND: Genetic susceptibility plays a key role in the development of nasopharyngeal carcinoma (NPC) and in fact the disease presents with an unusually high incidence in certain regions of the world like North Africa. We investigated the association between polymorphism of the Transforming growth factor-β1 (TGF-β1) and risk of NPC in North Africa. TGF-β1 is a multifunctional cytokine that acts as both a tumor suppressor and a stimulator of cancer development; it has been shown to influence risk of numerous other carcinomas including lung, breast and prostate cancer...
October 12, 2016: BMC Medical Genetics
Grace Gar-Lee Yue, Sida Xie, Julia Kin-Ming Lee, Hin-Fai Kwok, Si Gao, Yin Nian, Xiao-Xiao Wu, Chun-Kwok Wong, Ming-Hua Qiu, Clara Bik-San Lau
Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida (Chinese herb "shengma") which could inhibit the growth of breast cancer cells. Nevertheless, the effect of actein on angiogenesis, which is an essential step for tumor growth and metastasis, has never been reported. Hence, this study aimed to investigate the in vitro and in vivo effects of actein on angiogenesis using human microvascular endothelial cells (HMEC-1), matrigel plug and tumor-bearing mouse models. Our results showed that actein significantly inhibited the proliferation, reduced the migration and motility of endothelial cells, and it could suppress the protein expressions of VEGFR1, pJNK and pERK, suggesting that JNK/ERK pathways were involved...
October 12, 2016: Scientific Reports
Huiping Shi, Weili Zhang, Qiaoming Zhi, Min Jiang
In the era of new and mostly effective molecular targeted therapies, human epidermal growth factor receptor 2 positive (HER2+) cancers are still intractable diseases. Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor, has greatly improved breast cancer prognosis in recent years after the initial introduction of trastuzumab (Herceptin). However, clinical evidence indicates the existence of both primary unresponsiveness and secondary lapatinib resistance, which leads to the failure of this agent in HER2+ cancer patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hee-Chul Shin, Wonshik Han, Hyeong-Gon Moon, In-Ae Park, Dong-Young Noh
PURPOSE: We investigated the prognostic impact of discordance between the receptor status of primary breast cancers and corresponding metastases. METHODS: A total 144 patients with breast cancer and distant metastasis were investigated. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of primary tumor and corresponding metastases were assessed. Tumor phenotype according to receptor status was classified as triple-negative phenotype (TNP) or non-TNP...
September 2016: Journal of Breast Cancer
Sang Byung Bae, Hyun Deuk Cho, Mee-Hye Oh, Ji-Hye Lee, Si-Hyong Jang, Soon Auck Hong, Junhun Cho, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Han Jo Kim, Hyun Ju Lee
PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas...
September 2016: Journal of Breast Cancer
Laura Nogués, Clara Reglero, Verónica Rivas, Alicia Salcedo, Vanesa Lafarga, Maria Neves, Paula Ramos, Marta Mendiola, Alberto Berjón, Kostas Stamatakis, Xiao Zhen Zhou, Kun Ping Lu, David Hardisson, Federico Mayor, Petronila Penela
In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators...
October 1, 2016: EBioMedicine
Balazs T Nemeth, Zoltan V Varga, Wen Jin Wu, Pal Pacher
Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20% to 25% of human breast cancers, which is associated with aggressive tumor growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumors. Although initial trials indicated high efficacy and a favorable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in prior trials utilizing trastuzumab...
October 7, 2016: British Journal of Pharmacology
Nathalie Reix, Charlotte Malina, Marie-Pierre Chenard, Jean-Pierre Bellocq, Stéphanie Delpous, Sébastien Molière, Anthony Sevrin, Karl Neuberger, Catherine Tomasetto, Carole Mathelin
PURPOSE: We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression. METHODS: We prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up...
November 2016: Breast Cancer Research and Treatment
Jian-Li Gao, Yan-Mei Shui, Wei Jiang, En-Yi Huang, Qi-Yang Shou, Xin Ji, Bai-Cheng He, Gui-Yuan Lv, Tong-Chuan He
Hypoxic in the tumor mass is leading to the myeloproliferative-like disease (leukemoid reaction) and anemia of body, which characterized by strong extensive extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes essential for EMH processes including enhanced blood cell production and angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro...
September 30, 2016: Oncotarget
Jeff Johnson, Michael Choi, Farnaz Dadmanesh, Bingchen Han, Ying Qu, Yi Yu-Rice, Xiao Zhang, Sanjay Bagaria, Clive Taylor, Armando E Giuliano, Farin Amersi, Xiaojiang Cui
Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2...
September 30, 2016: Oncotarget
Galina Kochneva, Galina Sivolobova, Anastasiya Tkacheva, Antonina Grazhdantseva, Olga Troitskaya, Anna Nushtaeva, Anastasiya Tkachenko, Elena Kuligina, Vladimir Richter, Olga Koval
Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor models. In this study our goal was to generate a double recombinant vaccinia virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L-IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia growth factor genes...
September 30, 2016: Oncotarget
Jieqiong Liu, Kai Chen, Wen Jiang, Kai Mao, Shunrong Li, Min Ji Kim, Qiang Liu, Lisa K Jacobs
PURPOSE: To study the impact of hormone receptor (HR)- and human epidermal growth factor receptor 2 (HER2)-defined subtypes on survival of inflammatory breast cancer (IBC), and to determine whether sensitivity to neoadjuvant chemotherapy (NAC) varies with subtypes in a large IBC population. METHODS: We analyzed 593 IBCs with known HR/HER2 statuses between 2010 and 2011 from National Cancer Database. We compared pathologic complete response (pCR) rates among four molecular subtypes by Chi-square test...
October 4, 2016: Journal of Cancer Research and Clinical Oncology
Angélica Morales, Sumiko Morimoto, Felipe Vilchis, Natsuko Taniyama, Claudia J Bautista, Carlos Robles, Enrique Bargalló
Vascular endothelial growth factor (VEGF) is important in the growth and metastasis of cancer cells. In 2001, another angiogenic factor, endocrine gland-derived VEGF (EG-VEGF), was characterized and sequenced. EG-VEGF activity appears to be restricted to endothelial cells derived from endocrine glands. At the molecular level, its expression is regulated by hypoxia and steroid hormones. Although VEGF and EG-VEGF are structurally different, they function in a coordinated fashion. Since the majority of mammary tumors are hormone-dependent, it was hypothesized that EG-VEGF would be expressed in these tumors, and therefore, represent a potential target for anti-angiogenic therapy...
October 2016: Oncology Letters
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