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tumor micro environment

Sara Nikoofal-Sahlabadi, Maryam Matbou Riahi, Kayvan Sadri, Ali Badiee, Amin Reza Nikpoor, Mahmoud Reza Jaafari
CpG oligodeoxynucleotides (CpG-ODN), a common immune stimulator and vaccine adjuvant, was reported to switch Tumor Associated Macrophages (TAMs) from M2 to M1 phenotype inducing anti-tumor responses. Liposomes are of the successfully applied carriers for CpG-ODN. The aim of present study was design and preparation of a liposomal formulation containing phosphodiester CpG-ODN, evaluation of its effect on macrophages responses, and subsequent antitumor responses in mice. Liposomal formulations containing phosphodiester CpG-ODN or non-CpG-ODN were prepared and characterized...
April 13, 2018: European Journal of Pharmaceutical Sciences
Chunhai Su, Hui Li, Wenbo Gao
Fructose is now such an important component of human diets, and several studies have found that some cancer cells could utilize fructose to overcome low glucose micro-environment, but the study on the role of fructose in glioma is rare. To explore the role of fructose in glioma, we detected the proliferation and colony formation ability of glioma cells in fructose medium, and found that the abilities of proliferation and colony formation of glioma cells in fructose medium were similar with abilities in glucose medium, however, fructose just partly restored proliferation ability of normal glial cells...
April 13, 2018: Biochemical and Biophysical Research Communications
Tiziana Vaisitti, Francesca Arruga, Silvia Deaglio
Targeting adenosine triphosphate (ATP) metabolism and adenosinergic signaling in cancer is gaining momentum, as increasing evidence is showing their relevance in tumor immunology and biology. Chronic lymphocytic leukemia (CLL) results from the expansion of a population of mature B cells that progressively occupies the bone marrow (BM), the blood, and peripheral lymphoid organs. Notwithstanding significant progress in the treatment of these patients, the cure remains an unmet clinical need, suggesting that novel drugs or drug combinations are needed...
April 12, 2018: International Journal of Molecular Sciences
Amit Pathak
Motile cells sense the stiffness of their extracellular matrix (ECM) through adhesions and respond by modulating the generated forces, which in turn lead to varying mechanosensitive migration phenotypes. Through modeling and experiments, cell migration speed is known to vary with matrix stiffness in a biphasic manner, with optimal motility at an intermediate stiffness. Here, we present a two-dimensional cell model defined by nodes and elements, integrated with subcellular modeling components corresponding to mechanotransductive adhesion formation, force generation, protrusions and node displacement...
April 12, 2018: Physical Biology
Charles J Cho, Hyo Jeong Kang, Yeon-Mi Ryu, Young Soo Park, Hui Jeong Jeong, Young-Mi Park, Hyun Lim, Jeong Hoon Lee, Ho June Song, Hwoon-Yong Jung, Sang-Yeob Kim, Seung-Jae Myung
BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein-Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS...
April 7, 2018: Gastric Cancer
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
Kerem Ben-Meir, Nira Twaik, Michal Baniyash
Myeloid derived suppressor cells (MDSCs) are immature myeloid cells characterized by diverse phenotypes and functions. They impair effector functions of immune cells and promote tumor growth, angiogenesis, and tissue damage. In pathologies characterized by chronic inflammation, MDSCs are arrested in their immature state and migrate from the bone marrow to the periphery and to the site of inflammation, where they mediate immunosuppression. When reaching new environments, which exhibit a different array of cytokines, chemokines, and pro-inflammatory mediators, MDSCs sense and adapt to the altered micro-environment by virtue of acquiring different suppressive features/functions that involve changing their cell fate, surface receptors, metabolism and intracellular as well as secreted molecules...
March 31, 2018: Current Opinion in Immunology
Leonardo Vinícius Monteiro de Assis, Maria Nathália Moraes, Keila Karoline Magalhães-Marques, Gabriela Sarti Kinker, Sanseray da Silveira Cruz-Machado, Ana Maria de Lauro Castrucci
The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h...
April 3, 2018: International Journal of Molecular Sciences
Venus Dalal, Raman Kumar, Sunesh Kumar, Alpana Sharma, Lalit Kumar, J B Sharma, K K Roy, Neeta Singh, Perumal Vanamail
BACKGROUND: Ovarian cancer is represented with significantly higher mortality rate predominately due to asymptomatic behaviour during initial disease course and at diagnosis majority patients already progressed to advanced stage. Acellular fraction of ascites in epithelial ovarian cancer (EOC) has been suggested to promote growth of tumor cells by providing ambient micro-environment for their proliferation. This acellular fraction contains multiple growth factors including IL-6 and VEGF-A, which were exploited to establish their bio-marker significance in EOC patients...
March 20, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Stefan Benke, Benedikt Agerer, Lisa Haas, Martin Stöger, Alexander Lercher, Lisa Gabler, Izabella Kiss, Sara Scinicariello, Walter Berger, Andreas Bergthaler, Anna C Obenauf, Gijs A Versteeg
Tripartite motif (TRIM) proteins have been shown to play important roles in cancer development and progression by modulating cell proliferation or resistance from cell death during non-homeostatic stress conditions found in tumor micro-environments. In this study, we set out to investigate the importance for cellular fitness of the virtually uncharacterized family member TRIM52. The human TRIM52 gene has arisen recently in evolution, making it unlikely that TRIM52 is required for basic cellular functions in normal cells...
March 2, 2018: Oncotarget
Priscilla Coutinho Romualdo, Marília P Lucisano, Francisco Wanderley G Paula-Silva, Graziela B Leoni, Manoel D Sousa-Neto, Raquel Assed B Silva, Lea Assed B Silva, Paulo Nelson-Filho
INTRODUCTION: The aim of this study was to evaluate the gene expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and cathepsin K in apical periodontitis (AP) and the volume of lesions in ovariectomized and sham-operated rats. METHODS: Twenty 12-week-old female Wistar rats were subjected to ovariectomy (OVX) or sham surgery. After 9 weeks, access cavities were prepared in the maxillary and mandibular first molars, pulp tissue was removed, and canals were exposed to the oral environment during 21 days for the induction of AP...
March 14, 2018: Journal of Endodontics
A Boussommier-Calleja, Y Atiyas, K Haase, M Headley, C Lewis, R D Kamm
Metastasis is the leading cause of cancer-related deaths. Recent developments in cancer immunotherapy have shown exciting therapeutic promise for metastatic patients. While most therapies target T cells, other immune cells, such as monocytes, hold great promise for therapeutic intervention. In our study, we provide primary evidence of direct engagement between human monocytes and tumor cells in a 3D vascularized microfluidic model. We first characterize the novel application of our model to investigate and visualize at high resolution the evolution of monocytes as they migrate from the intravascular to the extravascular micro-environment...
March 5, 2018: Biomaterials
Ming Chen, Ju-Tao Wang, Hua-Wu Gao, Sheng-Ping Lei, Yong-Heng Zhu
This paper was aimed to investigate the relationship between autophagy and NLRP3 inflammasome activation by studying the effect oftotal flavonoids in Scutellaria barbata (TF-SB) on autophagy in tumor cells and NLRP3 inflammasome, and to provide experimental evidence for further study of the anti-tumor mechanism of TF-SB. Mielanoma models were established by inoculating B16-F1 cell line to mice, and then were randomly divided into 5 groups (n=10 in each group): model control, positive control control(Rap, 1...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Guido Gambara, Manuela Gaebler, Ulrich Keilholz, Christian R A Regenbrecht, Alessandra Silvestri
Recent advances in next-generation sequencing and other omics technologies capable to map cell fate provide increasing evidence on the crucial role of intra-tumor heterogeneity (ITH) for cancer progression. The different facets of ITH, from genomic to microenvironmental heterogeneity and the hierarchical cellular architecture originating from the cancer stem cell compartment, contribute to the range of tumor phenotypes. Decoding these complex data resulting from the analysis of tumor tissue complexity poses a challenge for developing novel therapeutic strategies that can counteract tumor evolution and cellular plasticity...
2018: Frontiers in Pharmacology
Ioannis A Voutsadakis
BACKGROUND: The interplay between the immune system and cancer cells has come to the forefront of cancer therapeutics, with novel immune blockade inhibitors being approved for the treatment of an increasing list of cancers. However, the majority of cancer patients still display or develop resistance to these promising drugs. It is possible that cancer stem cells (CSCs) are contributing to this therapeutic resistance. Although CSCs usually represent a small percentage of the total number of cancer cells, they are endowed with the ability of self-renewal and to produce differentiated progeny...
February 22, 2018: Cellular Oncology (Dordrecht)
Hongfei Ji, Xingjian Niu, Lei Yin, Yiran Wang, Lan Huang, Qijia Xuan, Liru Li, Han Zhang, Jingtong Li, Yue Yang, Weiwei An, Qingyuan Zhang
BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival...
2018: Cellular Physiology and Biochemistry
Chad Tang, Brian Hobbs, Ahmed Amer, Xiao Li, Carmen Behrens, Jaime Rodriguez Canales, Edwin Parra Cuentas, Pamela Villalobos, David Fried, Joe Y Chang, David S Hong, James W Welsh, Boris Sepesi, Laurence Court, Ignacio I Wistuba, Eugene J Koay
With increasing use of immunotherapy agents, pretreatment strategies for identifying responders and non-responders is useful for appropriate treatment assignment. We hypothesize that the local immune micro-environment of NSCLC is associated with patient outcomes and that these local immune features exhibit distinct radiologic characteristics discernible by quantitative imaging metrics. We assembled two cohorts of NSCLC patients treated with definitive surgical resection and extracted quantitative parameters from pretreatment CT imaging...
January 31, 2018: Scientific Reports
Rahila Rahimova, Simon Fontanel, Corinne Lionne, Lars Peter Jordheim, Suzanne Peyrottes, Laurent Chaloin
The ecto-5'-nucleotidase CD73 plays an important role in the production of immune-suppressive adenosine in tumor micro-environment, and has become a validated drug target in oncology. Indeed, the anticancer immune response involves extracellular ATP to block cell proliferation through T-cell activation. However, in the tumor micro-environment, two extracellular membrane-bound enzymes (CD39 and CD73) are overexpressed and hydrolyze efficiently ATP into AMP then further into immune-suppressive adenosine. To circumvent the impact of CD73-generated adenosine, we applied an original bioinformatics approach to identify new allosteric inhibitors targeting the dimerization interface of CD73, which should impair the large dynamic motions required for its enzymatic function...
January 29, 2018: PLoS Computational Biology
Zhenqiang Gong, Jiachi Ma, He Su, Tiankang Guo, Hui Cai, Quan Chen, Xiaodan Zhao, Jianbo Qi, Jianbo Du
BACKGROUND: Interleukin-1 alpha (IL-1α) plays an important role in tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the interactions of tumor cells and their micro-environment is poorly understood. We have evaluated the role of IL-1RA in the metastatic process as well as the mutual or reciprocal actions between gastric cancer cells and stromal cells...
January 17, 2018: International Journal of Clinical Oncology
Ling Li, Suleixin Yang, Linjiang Song, Yan Zeng, Tao He, Ning Wang, Chuan Yu, Tao Yin, Li Liu, Xiawei Wei, Qinjie Wu, Yuquan Wei, Li Yang, Changyang Gong
Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been widely applied in cancer treatment. However, in most cases, the tissue penetration depth of NIR light is not sufficient and thus photothermal therapy is unable to completely eradicate deep, seated tumors inevitably leading to recurrence of the tumor. Due to this significant limitation of NIR, improved therapeutic strategies are urgently needed. Methods: We developed an endogenous vaccine based on a novel nanoparticle platform for combinatorial photothermal ablation and immunotherapy...
2018: Theranostics
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