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https://www.readbyqxmd.com/read/28819116/silencing-of-tgf-%C3%AE-1-in-tumor-cells-impacts-mmp-9-in-tumor-microenvironment
#1
Lakisha D Moore-Smith, Tatyana Isayeva, Joo Hyoung Lee, Andra Frost, Selvarangan Ponnazhagan
Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816139/total-mesorectal-excision-versus-local-excision-after-favorable-response-to-preoperative-chemoradiotherapy-in-early-clinical-t3-rectal-cancer-a-propensity-score-analysis
#2
Young Seob Shin, Chang Sik Yu, Jin-Hong Park, Jin Cheon Kim, Seok-Byung Lim, In Ja Park, Tae Won Kim, Yong Sang Hong, Kyu-Pyo Kim, Sang Min Yoon, Ji Hyeon Joo, Jong Hoon Kim
PURPOSE: To compare oncological outcomes of total mesorectal excision (TME) and local excision (LE) in patients with "early" clinical T3 rectal cancer who received preoperative chemoradiotherapy (PCRT). METHODS AND MATERIALS: "Early" clinical T3 rectal cancer was radiologically defined as tumors with extramural extension of <5 mm without mesorectal fascia involvement and lateral lymph node metastasis. Patients with "early" clinical T3 rectal cancer who received PCRT followed by TME or LE between January 2007 and December 2013 were retrospectively analyzed...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28815347/the-tumor-stromal-ratio-as-a-strong-prognosticator-for-advanced-gastric-cancer-patients-proposal-of-a-new-tsnm-staging-system
#3
Chunwei Peng, Jiuyang Liu, Guifang Yang, Yan Li
BACKGROUND: Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. METHODS: Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed...
August 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#4
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813110/trait-vs-state-anxiety-in-different-threatening-situations
#5
Pollyana Caldeira Leal, Tiago Costa Goes, Luiz Carlos Ferreira da Silva, Flavia Teixeira-Silva
Objective: Anxiety as a uni- or multidimensional construct has been under discussion. The unidimensional approach assumes that there is a general trait anxiety, which predisposes the individuals to increases in state anxiety in various threatening situations. In this case, there should be a correlation between state and trait anxiety in any situation of threat. Therefore, the aim of this study was to investigate the correlation between trait and state anxiety in participants exposed to two different anxiogenic situations: interpersonal threat (Video-Monitored Stroop Test - VMST) and physical threat (third molar extraction - TME)...
August 14, 2017: Trends in Psychiatry and Psychotherapy
https://www.readbyqxmd.com/read/28809532/transient-and-local-expression-of-chemokine-and-immune-checkpoint-traps-to-treat-pancreatic-cancer
#6
Lei Miao, Jingjing Li, Qi Liu, Richard Feng, Manisit Das, C Michael Lin, Tyler J Goodwin, Oleksandra Dorosheva, Rihe Liu, Leaf Huang
Pancreatic tumor is known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (Kd = 4.1 nM and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and injected IV to mice bearing orthotopic pancreatic cancer...
August 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/28807001/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#7
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806945/tumor-microenvironment-conditions-alter-akt-and-na-h-exchanger-nhe1-expression-in-endothelial-cells-more-than-hypoxia-alone-implications-for-endothelial-cell-function-in-cancer
#8
A K Pedersen, J Mendes Lopes de Melo, N Mørup, K Tritsaris, S F Pedersen
BACKGROUND: Chronic angiogenesis is a hallmark of most tumors and takes place in a hostile tumor microenvironment (TME) characterized by hypoxia, low nutrient and glucose levels, elevated lactate and low pH. Despite this, most studies addressing angiogenic signaling use hypoxia as a proxy for tumor conditions. Here, we compared the effects of hypoxia and TME conditions on regulation of the Na(+)/H(+) exchanger NHE1, Ser/Thr kinases Akt1-3, and downstream effectors in endothelial cells...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28805874/microfluidic-modeling-of-the-biophysical-microenvironment-in-tumor-cell-invasion
#9
Yu Ling Huang, Jeffrey E Segall, Mingming Wu
Tumor cell invasion, whether penetrating through the extracellular matrix (ECM) or crossing a vascular endothelium, is a critical step in the cancer metastatic cascade. Along the way from a primary tumor to a distant metastatic site, tumor cells interact actively with the microenvironment either via biomechanical (e. g. ECM stiffness) or biochemical (e.g. secreted cytokines) signals. Increasingly, it is recognized that the tumor microenvironment (TME) is a critical player in tumor cell invasion. A main challenge for the mechanistic understanding of tumor cell-TME interactions comes from the complexity of the TME, which consists of extracellular matrices, fluid flows, cytokine gradients and other cell types...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28803344/outcome-one-year-after-robot-assisted-rectal-cancer-surgery-a-consecutive-cohort-study
#10
Sanne Harsløf, Anders Stouge, Niels Thomassen, Sissel Ravn, Søren Laurberg, Lene Hjerrild Iversen
PURPOSE: The aim of this study was to investigate outcome after robot-assisted rectal cancer surgery (RARCS). We focused on conversion rate, postoperative complications, pathological evaluation (adequacy of resection margins), and bowel function (low anterior resection syndrome (LARS)) 1 year after surgery. METHODS: An observational study of prospectively registered patients with data obtained from medical records. Data comprise the initial 208 rectal cancer patients operated with robot-assisted surgery at a single Danish university hospital from October 2011 to October 2014...
August 13, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28791370/tumor-associated-macrophages-induce-the-expression-of-foxq1-to-promote-epithelial-mesenchymal-transition-and-metastasis-in-gastric-cancer-cells
#11
Jian Guo, Yan Yan, Yu Yan, Qinyue Guo, Mingxin Zhang, Jia Zhang, David Goltzman
Gastric cancer (GC) is one of the most common malignancies, and is the second leading cause of cancer-related deaths worldwide. Macrophages infiltrated in the tumor microenvironment (TME) called tumor-associated macrophages (TAMs) are key orchestrators in TME. In GC, it has been reported that infiltration of TAMs is associated with epithelial-mesenchymal transition (EMT)-related proteins in human GC tissues, but the exactly mechanism has not been clarified. In the present study, we aimed to elucidate the underlying mechanism of TAMs on GC cells...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28790030/notch-shapes-the-innate-immunophenotype-in-breast-cancer
#12
Qiang Shen, Brenda Cohen, Weiyue Zheng, Ramtin Rahbar, Bernard Martin, Kiichi Murakami, Sara Lamorte, Patrycja Thompson, Hal Berman, Juan Carlos Zúñiga-Pflücker, Pamela S Ohashi, Michael Reedijk
Notch activation, which is associated with basal-like breast cancer (BLBC), normally directs tissue patterning, suggesting that it may shape the tumor microenvironment (TME). Here we show that Notch in tumor cells regulates the expression of two powerful pro-inflammatory cytokines, IL1β and CCL2, and the recruitment of tumor-associated macrophages (TAMs). Notch also regulates TGFβ-mediated activation of tumor cells by TAMs, closing a Notch-dependent paracrine signaling loop between these two cell types. We use a novel mouse model in which Notch can be regulated in spontaneous mammary carcinoma to confirm that IL1β and CCL2 production, and macrophage recruitment are Notch-dependent...
August 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28780935/metabolic-regulation-of-tregs-in-cancer-opportunities-for-immunotherapy
#13
REVIEW
Haiping Wang, Fabien Franco, Ping-Chih Ho
The promising outcomes observed in cancer immunotherapy are evidence that the immune system provides a powerful arsenal for the restriction of tumor outgrowth; however, the immunosuppressive tumor microenvironment (TME) is known to impair antitumor immunity and impede the efficacy of cancer immunotherapies. Regulatory T cells (Tregs), which prevent overt immune responses and autoimmunity, accumulate aberrantly in some types of tumor to suppress antitumor immunity and support the establishment of an immunosuppressive microenvironment...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28759044/inhibition-of-colony-stimulating-factor-1-receptor-abrogates-microenvironment-mediated-therapeutic-resistance-in-gliomas
#14
D Yan, J Kowal, L Akkari, A J Schuhmacher, J T Huse, B L West, J A Joyce
Glioblastomas represent the most aggressive glioma grade and are associated with a poor patient prognosis. The current standard of care, consisting of surgery, radiation and chemotherapy, only results in a median survival of 14 months, underscoring the importance of developing effective new therapeutic strategies. Among the challenges in treating glioblastomas are primary resistance and the rapid emergence of recurrent disease, which can result from tumor cell-intrinsic mechanisms in addition to tumor microenvironment (TME)-mediated extrinsic resistance...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28752076/molecular-machineries-of-ph-dysregulation-in-tumor-microenvironment-potential-targets-for-cancer-therapy
#15
REVIEW
Mohammad Reza Asgharzadeh, Jaleh Barar, Mohammad M Pourseif, Morteza Eskandani, Mojtaba Jafari Niya, Mohammad Reza Mashayekhi, Yadollah Omidi
Introduction: Cancer is an intricate disorder/dysfunction of cells that can be defined as a genetic heterogeneity in human disease. Therefore, it is characterized by several adaptive complex hallmarks. Among them, the pH dysregulation appears as a symbol of aberrant functions within the tumor microenvironment (TME). In comparison with normal tissues, in the solid tumors, we face with an irregular acidification and alkalinization of the extracellular and intracellular fluids. Methods: In this study, we comprehensively discussed the most recent reports on the hallmarks of solid tumors to provide deep insights upon the molecular machineries involved in the pH dysregulation of solid tumors and their impacts on the initiation and progression of cancer...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28750018/pancreatic-cancer-cell-fibroblast-co-culture-induces-m2-like-macrophages-that-influence-therapeutic-response-in-a-3d-model
#16
Janina Kuen, Diana Darowski, Tobias Kluge, Meher Majety
Pancreatic cancer (PC) remains one of the most challenging solid tumors to treat with a high unmet medical need as patients poorly respond to standard-of-care-therapies. Prominent desmoplastic reaction involving cancer-associated fibroblasts (CAFs) and the immune cells in the tumor microenvironment (TME) and their cross-talk play a significant role in tumor immune escape and progression. To identify the key cellular mechanisms induce an immunosuppressive tumor microenvironment, we established 3D co-culture model with pancreatic cancer cells, CAFs and monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28742692/oncologic-outcome-and-morbidity-in-the-elderly-rectal-cancer-patients-after-preoperative-chemoradiotherapy-and-total-mesorectal-excision-a-multi-institutional-and-case-matched-control-study
#17
Soo-Y Sung, Hong S Jang, Sung H Kim, Jae U Jeong, Songmi Jeong, Jin H Song, Mi J Chung, Hyeon M Cho, Hyung J Kim, Jun-Gi Kim, In K Lee, Jong H Lee
OBJECTIVE: To determine the toxicity and oncologic outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in the elderly (≥70 yrs) and younger (<70 yrs) rectal cancer patients. BACKGROUND: Sufficient data for elderly rectal cancer patients who received definitive trimodality have not been accumulated yet. PATIENTS AND METHODS: A total of 1232 rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this study...
July 24, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28740384/tumor-microenvironment-dual-responsive-core-shell-nanoparticles-with-hyaluronic-acid-shield-for-efficient-co-delivery-of-doxorubicin-and-plasmid-dna
#18
Tianqi Wang, Xiaoyue Yu, Leiqiang Han, Tingxian Liu, Yongjun Liu, Na Zhang
As the tumor microenvironment (TME) develops, it is critical to take the alterations of pH value, reduction and various enzymes of the TME into consideration when constructing the desirable co-delivery systems. Herein, TME pH and enzyme dual-responsive core-shell nanoparticles were prepared for the efficient co-delivery of chemotherapy drug and plasmid DNA (pDNA). A novel pH-responsive, positively charged drug loading material, doxorubicin (DOX)-4-hydrazinobenzoic acid (HBA)-polyethyleneimine (PEI) conjugate (DOX-HBA-PEI, DHP), was synthesized to fabricate positively charged polyion complex inner core DHP/DNA nanoparticles (DDN)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28739758/laparoscopic-assisted-transanal-total-mesorectal-excision-for-middle-low-rectal-carcinoma-a-clinical-study-of-19-cases
#19
Hong-Wei Yao, Guo-Cong Wu, Ying-Chi Yang, Lan Jin, Zhi-Peng Zhang, Ning Chen, Zhong-Tao Zhang
AIM: To explore the safety, feasibility and short-term outcomes of laparoscopic-assisted transanal total mesorectal excision (La-TaTME) of middle-low rectal carcinoma. MATERIALS AND METHODS: This retrospective research collected and analyzed the clinical data of 19 patients diagnosed with middle and low rectal carcinoma who underwent La-TaTME from August 2015 to February 2017. RESULTS: No case was converted to laparotomy. In none of the enrolled cases, did the circumferential resection margin test positive by histopathology examination...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28733738/robot-assisted-total-mesorectal-excision-for-rectal-cancer-case-matched-comparison-of-short-term-surgical-and-functional-outcomes-between-the-da-vinci-xi-and-si
#20
Luca Morelli, Gregorio Di Franco, Simone Guadagni, Leonardo Rossi, Matteo Palmeri, Niccolò Furbetta, Desirée Gianardi, Matteo Bianchini, Giovanni Caprili, Cristiano D'Isidoro, Franco Mosca, Andrea Moglia, Alfred Cuschieri
BACKGROUND: Robotic rectal resection with da Vinci Si has some technical limitations, which could be overcome by the new da Vinci Xi. We compare short-term surgical and functional outcomes following robotic rectal resection with total mesorectal excision for cancer, with the da Vinci Xi (Xi-RobTME group) and the da Vinci Si (Si-RobTME group). METHODS: The first consecutive 30 Xi-RobTME were compared with a Si-RobTME control group of 30 patients, selected using a one-to-one case-matched methodology from our prospectively collected Institutional database, comprising all cases performed between April 2010 and September 2016 by a single surgeon...
July 21, 2017: Surgical Endoscopy
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