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tumor micro environment

Alicia Martı Nez-González, Gabriel F Calvo, Jose M Ayuso, Ignacio Ochoa, Luis J Fernández, Víctor M Pérez-García
This chapter explores the use of mathematical models as promising and powerful tools to understand the complexity of tumors and their, frequently, hypoxic environment. We focus on gliomas, which are primary brain tumors derived from glial cells, mainly astrocytes and/or oligodendrocytes. A variety of mathematical models, based on ordinary and/or partial differential equations, have been developed both at the micro and macroscopic levels. The aim here is to describe in a quantitative way key physiopathological mechanisms relevant in these types of malignancies and to suggest optimal therapeutical strategies...
2016: Advances in Experimental Medicine and Biology
Shrikant Pradhan, Divyank Mahajan, Prabhjot Kaur, Namita Pandey, Chandresh Sharma, Tapasya Srivastava
Non-small cell lung cancer (NSCLC), comprising 85% of lung cancer cases, has been associated with resistance to chemo/radiotherapy. The hypoxic tumor micro-environment, where insufficient vasculature results in poor drug penetrance and sub-optimal chemotherapy in the tumor interiors contributes heavily to this resistance. Additionally, epigenetic changes in tumorigenic cells also change their response to different forms of therapy. In our study, we have investigated the effectiveness of a combination of cisplatin with scriptaid [a pan-Histone Deacetylase inhibitor (HDACi)] in a model that mimics the tumor microenvironment of hypoxia and sub-lethal chemotherapy...
September 30, 2016: Oncotarget
Xianping Lu, Zhiqiang Ning, Zhibin Li, Haixiang Cao, Xinhao Wang
Peripheral T-cell lymphoma (PTCL) is a set of rare and highly heterogeneous group of mature T- and NK-cell neoplasms associated with poor outcomes and lack of standard and effective therapies. The total number of newly diagnosed cases of PTCL yearly in China is estimated about 50,000. Chidamide (CS055) is a novel and orally active benzamide class of histone deacetylase (HDAC) inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, the enzymes that are involved and play an important role in tumor initiation and development in both tumor cells and their surrounding micro-environment...
August 2016: Intractable & Rare Diseases Research
Wen Zhong, Chengping Hu
Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis "seed and soil", that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well...
September 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Matthew J Ware, Vazrik Keshishian, Justin J Law, Jason C Ho, Carlos A Favela, Paul Rees, Billie Smith, Sayeeduddin Mohammad, Rosa F Hwang, Kimal Rajapakshe, Cristian Coarfa, Shixia Huang, Dean P Edwards, Stuart J Corr, Biana Godin, Steven A Curley
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic/stromal reaction, which contributes to the poor clinical outcome of this disease. Therefore, greater understanding of the stroma development and tumor-stroma interactions is highly required. Pancreatic stellate cells (PSC) are myofibroblast-like cells located in exocrine areas of the pancreas, which as a result of inflammation produced by PDAC migrate and accumulate in the tumor mass, secreting extracellular matrix components and producing the dense PDAC stroma...
November 2016: Biomaterials
Serena Zilio, Paolo Serafini
Neutrophils are the most abundant circulating blood cell type in humans, and are the first white blood cells recruited at the inflammation site where they orchestrate the initial immune response. Although their presence at the tumor site was recognized in the 1970s, until recently these cells have been neglected and considered to play just a neutral role in tumor progression. Indeed, in recent years neutrophils have been recognized to play a dual role in tumor development by either assisting the growth, angiogenesis, invasion, and metastasis or by exerting tumoricidal action directly via the secretion of antitumoral compounds, or indirectly via the orchestration of antitumor immunity...
September 9, 2016: Vaccines
Caroline Moyret-Lalle, Roxane Pommier, Charlotte Bouard, Ebticem Nouri, Geoffrey Richard, Alain Puisieux
Metastatic dissemination consists of a sequence of events resulting in the invasion by cancer cells of tissues located away from the primary tumour. This process is highly inefficient, since each event represents an obstacle that only a limited number of cells can overcome. However, two biological phenomena intrinsically linked with tumour development facilitate the dissemination of cancer cells throughout the body and promote the formation of metastases, namely the genetic diversity of cancer cells within a given tumour, which arises from their genetic instability and from successive clonal expansions, and cellular plasticity conveyed to the cells by micro-environmental signals...
August 2016: Médecine Sciences: M/S
Feifei Teng, Xiangjiao Meng, Xin Wang, Jupeng Yuan, Sujing Liu, Dianbin Mu, Hui Zhu, Li Kong, Jinming Yu
PURPOSE: Currently, adjuvant chemotherapy is recommended for patients with high risk stage I non-small cell lung cancer (NSCLC). However, identifying high risk patients remains a challenge. This study aims to identify the patient cohorts more likely to benefit from adjuvant chemotherapy based on the tumor micro-immune environment. RESULTS: CD8+TILs significantly associated with disease-free survival (DFS) and overall survial (OS) (p=0.002; 0.040). Patients with high risk factors may also predict shorter DFS (P=0...
September 1, 2016: Oncotarget
Alexandre E Escargueil, Soizic Prado, Ambre Dezaire, Jean Clairambault, Annette K Larsen, Daniele G Soares
Despite the efficacy of most cancer therapies, drug resistance remains a major problem in the clinic. The eradication of the entire tumor and the cure of the patient by chemotherapy alone are rare, in particular for advanced disease. From an evolutionary perspective, the selective pressure exerted by chemotherapy leads to the emergence of resistant clones where resistance can be associated with many different functional mechanisms at the single cell level or can involve changes in the tumor micro-environment...
August 31, 2016: Current Pharmaceutical Design
Xiang Qi, Kevin Tak-Pan Ng, Yan Shao, Chang Xian Li, Wei Geng, Chang Chun Ling, Yuen Yuen Ma, Xiao Bing Liu, Hui Liu, Jiang Liu, Wai Ho Yeung, Chung Mau Lo, Kwan Man
BACKGROUND AND AIMS: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth. GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study. Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation. METHODS: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established...
2016: Theranostics
Todd B Shelper, Carrie J Lovitt, Vicky M Avery
Pancreatic cancer continues to have one of the poorest prognoses among all cancers. The drug discovery efforts for this disease have largely failed, with no significant improvement in survival outcomes for advanced pancreatic cancer patients over the past 20 years. Traditional in vitro cell culture techniques have been used extensively in both basic and early drug discovery; however, these systems offer poor models to assess emerging therapeutics. More predictive cell-based models, which better capture the cellular heterogeneity and complexities of solid pancreatic tumors, are urgently needed not only to improve drug discovery success but also to provide insight into the tumor biology...
September 2016: Assay and Drug Development Technologies
Geert Bultynck
Bone metastases of tumor cells are a common and life-threatening feature of a variety of late-stage cancers, including breast cancers. However, until now, much less has been known about the intrinsic anti-metastatic properties of the bones and how these could be exploited to prevent or treat bone metastases. Very recently, native Cx43 hemichannels present in osteocytes have been identified as important anti-metastatic signaling complexes by establishing high local extracellular ATP levels. Moreover, bisphosphonate drugs, applied as adjuvant therapies in the treatment of breast cancer patients and bone diseases, are known to display anti-metastatic properties...
August 2016: Biochimica et Biophysica Acta
Nicole Michelson, Jordina Rincon-Torroella, Alfredo Quiñones-Hinojosa, Jeffrey P Greenfield
Studies of inflammatory mediators have established the tumor micro-environment as a driver of oncogenesis. This inflammatory milieu often precedes cancer, however recent data also point to the ability of oncogenic changes to induce inflammatory responses that are later harnessed by the tumor to survive and proliferate. In this review, we propose that the IDH1 mutation, present in the majority of low-grade gliomas (LGGs), initiates an inflammatory cascade that is ultimately hijacked by the tumor. Glioma infiltrating macrophages and microglia (GIMs) are polarized to the M2 phenotype, subverting the host's adaptive immune response, and fostering a tumor milieu ripe for angiogenesis, migration, and metastasis...
August 15, 2016: Journal of Neuroimmunology
Yu-Chih Chen, Zhixiong Zhang, Shamileh Fouladdel, Yadwinder Deol, Patrick N Ingram, Sean P McDermott, Ebrahim Azizi, Max S Wicha, Euisik Yoon
Considerable evidence suggests that cancer stem-like cells (CSCs) are critical in tumor pathogenesis, but their rarity and transience has led to much controversy about their exact nature. Although CSCs can be functionally identified using dish-based tumorsphere assays, it is difficult to handle and monitor single cells in dish-based approaches; single cell-based microfluidic approaches offer better control and reliable single cell derived sphere formation. However, like normal stem cells, CSCs are heavily regulated by their microenvironment, requiring tumor-stromal interactions for tumorigenic and proliferative behaviors...
August 7, 2016: Lab on a Chip
F-Y Fu, B-Y Chen, L-L Chen, F-L Zhang, Y-K Luo, F Jun
OBJECTIVE: As the impairment of myocardial micro-environments with local inflammatory reactions due to coronary micro-embolization (CME) reduces the survival of transplanted stem cells (SCs). We hypothesized that rosuvastatin treatment could improve the SC survival and enhance their therapeutic effects. MATERIALS AND METHODS: Rat bone marrow-derived mesenchymal stem cells (BMSCs) were infected with lentivirus carrying the green fluorescent protein (GFP) gene. To develop a CME model, rats were injected with a suspension of microthrombotic particles (MTPs) into the left ventricle to obstruct the ascending aorta...
June 2016: European Review for Medical and Pharmacological Sciences
Kelly E Burns, Tanner P McCleerey, Damien Thévenin
Positively charged antimicrobial peptides have become promising agents for the treatment of cancer by inducing apoptosis though their preferential binding and disruption of negatively charged membranes, such as the mitochondrial membrane. (KLAKLAK)2 is such a peptide but due to its polarity, it cannot cross the cellular membrane and therefore relies on the use of a delivery agent. For targeted delivery, previous studies have relied on cell penetrating peptides, nanoparticles or specific biomarkers. Herein, we investigated the first use of pHLIP to selectively target and directly translocate (KLAKLAK)2 into the cytoplasm of breast cancer cells, based on the acidic tumor micro-environment...
2016: Scientific Reports
Yung-Shin Sun
Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC) chips...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S Di Biase, V D Longo
Most tumors are generated and evolve under high-nutrient conditions, yet therapy does not include dietary changes generating a hostile environment for cancer cells. Because fasting promotes the most drastic change in the levels of plasma macro- and micro-nutrients, and consequently in glucose and growth factors, it has the potential to maximize cancer cell sensitization.
May 2016: Molecular & Cellular Oncology
Arnela Redzović, Renata Dobrila Dintinjana, Antica Duletić Nacinović
In human organism development is a very complex and highly regulated system that enables the functional balance of each organ in a whole body. Disorders and tumor micro-environment weaken host immune system that is not able to recognize the tumor as a unknown body and fight against its uncontrollable forces. Tumor avoids the immune system in a way that promotes immunosuppression and orientation cytokine production towards Th2 immune responses which are responsible for infection appearances. Some of infectious agents (viruses) can cause oncogene activation and inhibition of tumor suppressor genes...
April 2016: Collegium Antropologicum
Jelena Ivanovska, Tobias Zehnder, Pablo Lennert, Bapi Sarker, Aldo R Boccaccini, Arndt Hartmann, Regine Schneider-Stock, Rainer Detsch
Hydrogels are an important class of biomaterials as they could mimic the extracellular matrix (ECM). Among the naturally occurring biopolymers, alginate and gelatin are extensively used for many biomedical applications. For developing biofabrication constructs as three-dimensional (3D) cell culture models, realistic imaging of cell spreading and proliferation inside the hydrogels represents a major challenge. Therefore, we aimed to establish a system that can mimic the structural architecture, composition, and biological functions of the ECM for cancer research approaches...
July 2016: Tissue Engineering. Part C, Methods
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