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Tumor microenviroment

Ziwen Zhang, Detao Tao, Ping Zhang, Xue Liu, Yuchao Zhang, Jie Cheng, Hua Yuan, Laikui Liu, Hongbing Jiang
BACKGROUND: Hyaluronan synthases (HAS) control the biosynthesis of hyaluronan (HA) and critically modulate the tumor microenviroment. Cancer-associated fibroblasts (CAFs) affect the progression of a tumor by remolding the matrix. However, little is known about the role of HAS from CAFs in this process. This study aimed to determine the role of hyaluronan synthase 2 (HAS2) from CAFs in the progression of oral squamous cell carcinoma (OSCC) invasion. METHODS: HAS isoforms 1, 2, and 3 in paired sets of CAFs and normal fibroblasts (NFs) were examined by real-time PCR, and the expression of HAS2 and α-SMA in OSCC tissue sections was further evaluated using immunohistochemical staining...
November 25, 2016: Journal of Experimental & Clinical Cancer Research: CR
Gang Wang, Xing-Li Fu, Jun-Jie Wang, Rui Guan, Xiang-Jun Tang
Glioblastoma multiforme is a common primary brain tumor, which exhibits an imbalance between glioma cell growth and glucose metabolism. Recent discoveries have found the multiple pathways and downstream genes are involved in the dysregulated metabolic pathway allows tumor to start and progress, which is critical to the patients with glioblastoma associated with significant systemic and immunosuppression. Moreover, immune microenvironment is considered a major obstacle to generating an effective antitumor immune response...
May 12, 2016: Current Cancer Drug Targets
Zeming Chen, Jaymin M Patel, Philip W Noble, Cesar Garcia, Zhangyong Hong, James E Hansen, Jiangbing Zhou
Strategies to target nanoparticles to tumors that rely on surface modification with ligands that bind molecules overexpressed on cancer cells or the tumor neovasculature suffer from a major limitation: with delivery of toxic agents the amount of molecules available for targeting decreases with time; consequently, the efficiency of nanoparticle delivery is reduced. To overcome this limitation, here we propose an autocatalytic tumor-targeting mechanism based on targeting extracellular DNA (exDNA). exDNA is enriched in the tumor microenviroment and increases with treatment with cytotoxic agents, such as doxorubicin (DOX), due to release of DNA by dying tumor cells...
September 13, 2016: Oncotarget
Tomoki Nakashima
Receptor activator of nuclear factor-κB ligand(RANKL),a transmembrane protein of the tumor necrosis factor(TNF) superfamily cytokine, currently provides a paradigm that enables the molecular understanding of the linkage among bone metabolism, organization of lymphoid tissues, establishment of the thymic microenviroment, thermoregulation, metabolic regulation, mammary gland development and tumorigenesis. Here we summarize the recent progress in the understanding of RANKL biology by focusing on the investigation of RANKL expressing cells/organs, signaling and related diseases in the context of the newly established interdisciplinary field of osteonetwork...
August 2016: Clinical Calcium
Giuseppe Musumeci, Carla Loreto, Salvatore Giunta, Venerando Rapisarda, Marta Anna Szychlinska, Rosa Imbesi, Alessandro Castorina, Tiziana Annese, Sergio Castorina, Paola Castrogiovanni, Domenico Ribatti
Angiogenesis plays a crucial role in progression of pleural malignant mesothelioma. A significantly increased incidence of pleural mesothelioma has been attributed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. In this study, we have investigated the expression of CD68-positive macrophages, tryptase-positive mast cells and CD31 positive areas, as expression of microvascular density, in lung tissue of sheeps exposed to fluoro-edenite fibers vs controls, by immunohistochemical, morphometric and Western blot analysis...
August 1, 2016: Experimental Cell Research
Ian S Brown
The perineural space is a compartment located between the nerve axons, supporting cells and tissues, and the epineural fibrous sheath. Tumor cells invade this space in response to a complex interplay of trophic factors in the local microenviroment. This attraction of tumor cells to nerves is referred to as neurotropism. The perineural space provides a conduit for tumor spread beyond the primary site of tumor occurrence. Perineural tumor growth is of two types: perineural invasion, affecting small unnamed nerves; and perineural spread, affecting larger, named nerves and presenting with clinical symptoms related to the involved nerve...
April 2016: Journal of Neurological Surgery. Part B, Skull Base
Zengshan Li
Gastroenteropancreatic neuroendocrine neoplasms are a rare, heterogeneous group of neoplasms. The incidence has increased greatly during the past 40 years, partially due to the advanced endoscopic and imaging techniques. As a type of neoplasm with the specific morphology and immunophenotype, its nomenclature and classification have also been changed considerably over the past 40 years, from the past "carcinoid" to the current "neuroendocrine neoplasm". WHO currently recommends two-tiered classification, neuroendocrine tumors and neuroendocrine cancer, according to the differentiation, morphology and proliferation index...
January 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Begoña Comin-Anduix, Helena Escuin-Ordinas, Francisco Javier Ibarrondo
The immune checkpoint therapy is a relatively recent strategy that aims to tweak the immune system to effectively attack cancer cells. The understanding of the immune responses and their regulation at the intracellular level and the development of fully humanized monoclonal antibodies are the pillars of an approach that could elicit durable clinical responses and even remission in some patients with cancer. Most of the immune checkpoints that regulate the T-cell responses (activation and inhibition) operate through proteins present on the cytoplasmic membrane of the immune cells...
2016: OncoTargets and Therapy
Kamil Wdowiak, Wojciech Spychałowicz, Marcin Fajkis, Jerzy Wojnar
Galectins are a family of lectins characterized by an affinity for β-galactosides through the carbohydrate recognition domain (CRD). The extracellular and intracellular presence of Galectins has been described. Their activity and functions are mainly attributed to cell type. The tumor microenviroment is a complex milieu connected with immunosupression, angiogenesis and hypoxic compartments. The studies of interactions between Glycans-Lectins are highly advanced and promising. We are not able to explain the pathogenesis of many diseases only by protein-protein interactions, that is why in these studies is a chance to find a new therapeutic targets...
February 14, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Wantong Song, Zhaohui Tang, Na Shen, Haiyang Yu, Yanjie Jia, Dawei Zhang, Jian Jiang, Chaoliang He, Huayu Tian, Xuesi Chen
A poly(l-glutamic acid) graft polyethylene glycol-cisplatin complex (PGA-CisPt) performs well in reducing the toxicity of free cisplatin and greatly enhances the accumulation and retention of cisplatin in solid tumors. However, there is a lack of effective treatment options for cisplatin-resistant tumors. A major reason for this is the dense PEG shell, which ensures that the PGA-CisPt maintains a long retention time in the blood that may result in it bypassing the tumor cells or failing to be endocytosed within the tumor microenvironment...
June 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jin Hong, Yan Mao, Xiaosong Chen, Li Zhu, Jianrong He, Weiguo Chen, Yafen Li, Lin Lin, Xiaochun Fei, Kunwei Shen
Inflammation and tumor immune microenviroment are critical factors for prognosis in numerous cancers. The aim of this study was to determine the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in breast cancer. We performed a retrospective analysis of 487 patients diagnosed with primary breast cancer at Shanghai Ruijin hospital from January 2009 to December 2010. Hematological parameters before surgery, clinicopathological data, and survival status were obtained. Survival analysis was used to evaluate the prognostic value of NLR...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiaokun Bian, Yuanquan Si, Min Zhang, Ran Wei, Xiaomin Yang, Hao Ren, Guixi Zheng, Chuanxin Wang, Yi Zhang
It is known that chronic HBV infection (CHB) is the major risk factor for hepatocellular carcinoma (HCC) because CHB could not only cause liver tumorigenesis but also lead to change of local microenviroment and lower immune response to infected and cancerous cells (immune tolerance). Human leucocyte antigen-G (HLA-G) belongs to a non-classic MHC-I family and was considered to be an immune tolerance molecule, which could bind to immunosuppressive receptors of natural killer cell (NK) and T cells and trigger immunosuppressive signaling...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Angela Rynne-Vidal, José Antonio Jiménez-Heffernan, Concepción Fernández-Chacón, Manuel López-Cabrera, Pilar Sandoval
Solid tumors are complex and unstructured organs that, in addition to cancer cells, also contain other cell types. Carcinoma-associated fibroblasts (CAFs) represent an important population in the tumor microenviroment and participate in several stages of tumor progression, including cancer cell migration/invasion and metastasis. During peritoneal metastasis, cancer cells detach from the primary tumor, such as ovarian or gastrointestinal, disseminate through the peritoneal fluid and colonize the peritoneum. Tumor cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity, then colonizing the submesothelial compact zone where CAFs accumulate...
2015: Cancers
Kyle Crassini, Stephen P Mulligan, O Giles Best
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Despite significant advances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor (BCR) and cytokine receptors...
August 16, 2015: World Journal of Clinical Cases
Catalin Vlad, Paul Kubelac, Andrea Onisim, Alexandru Irimie, Patriciu Achimas-Cadariu
Ovarian cancer (OC) is the second most common gynecological cancer and the deadliest in industrialized countries, with poor outcomes that indicate an urgent need to provide a greater insight into the molecular mechanisms underlying OC. Insights into the complex tumor microenviroment show that besides tumor islets, OC biomarkers can derive from newly formed blood vessels that have endothelial cells with a different molecular signature in comparison with their normal counterparts. In this view, recent research has been able to highlight promising candidates such as CDCP1 and ADAM12...
May 2015: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Wei Li, Rong-Rui Liang, Chong Zhou, Meng-Yao Wu, Lian Lian, Gao-Feng Yuan, Ming-Yun Wang, Xin Xie, Liu-Mei Shou, Fei-Ran Gong, Kai Chen, Wei-Ming Duan, Min Tao
OBJECTIVE: Angiogenesis is a critical step of breast cancer metastasis. Oncogenic Ras promotes the remodeling of cancer microenviroment. Tumor-associated macrophages (TAMs) are a prominent inflammatory cell population emerging in the microenviroment and facilitating the angiogenesis and metastasis. In the present study, we tried to investigate the relationship between the expression of Ras and infiltration of TAM, both of which could further promote angiogenesis. METHODS: Expressions of Ras, CD68 and CD34 were assessed by immunohistochemistry...
2015: Cancer Cell International
Ziming Du, Malak Abedalthagafi, Ayal A Aizer, Allison R McHenry, Heather H Sun, Mark-Anthony Bray, Omar Viramontes, Revaz Machaidze, Priscilla K Brastianos, David A Reardon, Ian F Dunn, Gordon J Freeman, Keith L Ligon, Anne E Carpenter, Brian M Alexander, Nathalie Y Agar, Scott J Rodig, Elizabeth M Bradshaw, Sandro Santagata
There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry...
March 10, 2015: Oncotarget
Xin-Yu Wu, Rui-Tai Fan, Xin-Hui Yan, Jing Cui, Jun-Ling Xu, Hao Gu, Yong-Ju Gao
Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment...
March 2015: Molecular Medicine Reports
Qinghua Hu, Lingjin Huang, Xuyuan Kuang, Heng Zhang, Guoqiang Ling, Xuliang Chen, Kejiang Li, Zhenghao Deng, Jianhua Zhou
Insulin-like growth factor binding protein 2 (IGFBP2) is involved in the progression of many epithelial cancers. However, its role in non-small cell lung cancer (NSCLC), another type of epithelial cancer, remains unclear. We detected IGFBP2 expression using immunohistochemistry in surgically resected tumors from 110 NSCLC patients, 37 of which had metastases. The positive rate of IGFBP2 expression was compared between the metastatic and the non-metastatic group, and correlations of IGFBP2 expression with metastasis and overall survival were analyzed...
June 2014: Clinical & Experimental Metastasis
Weicai Chen, Yuanyuan Yuan, Du Cheng, Jifeng Chen, Lu Wang, Xintao Shuai
Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co-delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to silence drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. This study aims at effective co-delivery of siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG-PAsp(AED)-PDPA consisting of pH-sensitive poly(2-(diisopropyl amino)ethyl methacrylate) (PDPA), reduction-sensitive poly(N-(2,2'-dithiobis(ethylamine)) aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and assembled into a core-shell structural micelle which encapsulated doxorubicin (DOX) in its pH-sensitive core and the siRNA-targeting anti-apoptosis BCL-2 gene (BCL-2 siRNA) in a reduction-sensitive interlayer...
July 9, 2014: Small
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