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https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#1
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29153879/remodeling-the-tumor-microenvironment-with-emerging-nanotherapeutics
#2
REVIEW
Qin Chen, Guangxuan Liu, Shuo Liu, Hongyan Su, Yue Wang, Jingyu Li, Cong Luo
The tumor microenvironment (TME) has profound impacts on cancer progression and remodeling of the TME has emerged as a strategy to facilitate cancer therapy. Recently, great progress in TME modulation has been made, especially with the rapid developments in nanomedicine. In this review we outline the latest advances in remodeling of the TME based on nanotherapeutics. First, novel strategies developed to modulate the tumor extracellular matrix (ECM) are discussed, including disruption, mimicking, and intervening in tumor ECM fabrication...
November 15, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#3
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132215/in-vivo-molecular-epr-based-spectroscopy-and-imaging-of-tumor-microenvironment-and-redox-using-functional-paramagnetic-probes
#4
Valery V Khramtsov
<i><b>Significance:</b></i> A key role of the tumor microenvironment (TME) in cancer progression, treatment resistance and as a target for therapeutic intervention is increasingly appreciated. Among physiological components of the TME are tissue hypoxia, acidosis, high reducing capacity, elevated concentrations of intracellular glutathione (GSH) and interstitial inorganic phosphate (Pi). Noninvasive <i>in vivo</i> assessment of these parameters provide unique insights into biological processes in TME, and may serve as a tool for pre-clinical screening of anticancer drugs and optimizing TME-targeted therapeutic strategies...
November 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29130232/-clinical-study-of-preserving-left-colic-artery-during-laparoscopic-total-mesorectal-excision-for-the-treatment-of-rectal-cancer
#5
Xiaolan You, Yuanjie Wang, Zhiyi Chen, Wenqi Li, Ning Xu, Guiyuan Liu, Xiaojun Zhao, Chuanjiang Huang
OBJECTIVE: To evaluate the feasibility, safety, radicality and short-term outcome of preserving left colic artery (LCA) during laparoscopic total mesorectal excision (TME) for the treatment of rectal cancer. METHODS: From January 2013 to December 2016,136 patients with mid-lower rectal cancer received laparoscopic TME in the Gastrointestinal Surgery Department of Taizhou People's Hospital of Jiangsu Province. Patients with rectal tumor within 10 cm to the anal verge were enrolled into the study...
October 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/29130229/-discovery-anatomy-and-clinical-significance-of-the-mesorectal-finish-line-of-total-mesorectal-excision
#6
Pan Chi, Xiaojie Wang, Guoxian Guan, Huiming Lin, Ying Huang, Weizhong Jiang
OBJECTIVE: To investigate the surgical endpoint of separation of mesorectum during total mesorectal excision (TME), suggesting the concept of "terminal line", in order to perform above separation better for middle-low rectal cancer. METHODS: Gross anatomy of mesorectum endpoint from 81 surgical specimens of low anterior resection (LAR, 5 to 6 cm of distance from low margin of cancer to anal edge) and 71 surgical specimens of abdominal perineal resection(APR, <5 cm of distance from low margin of cancer to anal edge) was observed...
October 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/29129292/targeting-myeloid-cells-in-the-tumor-sustaining-microenvironment
#7
REVIEW
Jonathan Schupp, Franziska K Krebs, Niklas Zimmer, Emily Trzeciak, Detlef Schuppan, Andrea Tuettenberg
Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden...
November 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29124406/selective-lateral-pelvic-lymph-node-dissection-a-comparative-study-of-the-robotic-versus-laparoscopic-approach
#8
Hye Jin Kim, Gyu-Seog Choi, Jun Seok Park, Soo Yeun Park, Hee Jae Lee, In Taek Woo, In Kyu Park
BACKGROUND: Lateral pelvic lymph node dissection (LPND) is a challenging procedure due to its technical difficulty and higher incidence of surgical morbidity. We compared short-term outcomes between laparoscopic and robotic LPND in patients with rectal cancer. METHODS: Between May 2006 and December 2014, prospectively collected data from consecutive patients undergoing robotic or laparoscopic total mesorectal excision (TME) with LPND were retrospectively compared...
November 9, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/29117945/adipocytes-sequester-and-metabolize-the-chemotherapeutic-daunorubicin
#9
Xia Sheng, Jean-Hugues Parmentier, Jonathan Tucci, Hua Pei, Omar Cortez-Toledo, Christina M Dieli-Conwright, Matthew J Oberley, Michael Neely, Etan Orgel, Stan G Louie, Steven D Mittelman
Obesity is associated with poorer outcome for many cancers. Previously, we observed that adipocytes protect acute lymphoblastic leukemia (ALL) cells from the anthracycline, daunorubicin. In this study, it is determined whether adipocytes clear daunorubicin from the tumor microenvironment (TME). Intracellular daunorubicin concentrations were evaluated using fluorescence. Daunorubicin and its largely inactive metabolite, daunorubicinol, were analytically measured in media, cells, and tissues using liquid chromatography/mass spectrometry (LC/MS)...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29115421/gene-expression-profiles-and-protein%C3%A2-protein-interaction-networks-during-tongue-carcinogenesis-in-the-tumor-microenvironment
#10
Wei Sun, Zeting Qiu, Wenqi Huang, Minghui Cao
Oral tongue squamous cell carcinoma (OTSCC) has a high incidence and is associated with a high mortality rate. Studies regarding the potential molecular mechanism of OTSCC in the tumor microenvironment (TME) are required. The present study aimed to perform bioinformatic analysis to identify important nodes, clusters and functional pathways during tongue carcinogenesis in the TME. After downloading the gene expression data of GSE42780, differentially expressed genes (DEGs) among carcinoma, dysplastic and normal samples in epithelia and fibroblasts were identified using the affy and limma packages with R version 3...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111350/metabolic-changes-in-tumor-cells-and-tumor-associated-macrophages-a-mutual-relationship
#11
Romana T Netea-Maier, Johannes W A Smit, Mihai G Netea
In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs)...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29101570/transanal-total-mesorectal-excision-pathological-results-of-186-patients-with-mid-and-low-rectal-cancer
#12
F Borja de Lacy, Jacqueline J E M van Laarhoven, Romina Pena, María Clara Arroyave, Raquel Bravo, Miriam Cuatrecasas, Antonio M Lacy
BACKGROUND: Transanal total mesorectal excision (TaTME) seems to be a valid alternative to the open or laparoscopic TME. Quality of the TME specimen is the most important prognostic factor in rectal cancer. This study shows the pathological results of the largest single-institution series published on TaTME in patients with mid and low rectal cancer. METHODS: We conducted a retrospective cohort study of all consecutive patients with rectal cancer, treated by TaTME between November 2011 and June 2016...
November 3, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/29101162/ex-vivo-profiling-of-pd-1-blockade-using-organotypic-tumor-spheroids
#13
Russell W Jenkins, Amir R Aref, Patrick H Lizotte, Elena Ivanova, Susanna Stinson, Chensheng W Zhou, Michaela Bowden, Jiehui Deng, Hongye Liu, Diana Miao, Meng Xiao He, William Walker, Gao Zhang, Tian Tian, Chaoran Cheng, Zhi Wei, Sangeetha Palakurthi, Mark Bittinger, Hans Vitzthum, Jong Wook Kim, Ashley Merlino, Max Quinn, Chandrasekar Venkataramani, Joshua A Kaplan, Andrew Portell, Prafulla C Gokhale, Bart Phillips, Alicia Smart, Asaf Rotem, Robert E Jones, Lauren Keogh, Maria Anguiano, Lance Stapleton, Zhiheng Jia, Michal Barzily-Rokni, Israel Cañadas, Tran C Thai, Marc R Hammond, Raven Vlahos, Eric S Wang, Hua Zhang, Shuai Li, Glenn J Hanna, Wei Huang, Mai P Hoang, Adriano Piris, Jean-Pierre Eliane, Anat O Stemmer-Rachamimov, Lisa Cameron, Mei-Ju Su, Parin Shah, Benjamin Izar, Manisha Thakuria, Nicole R LeBoeuf, Guilherme Rabinowits, Viswanath Gunda, Sareh Parangi, James M Cleary, Brian C Miller, Shunsuke Kitajima, Rohit Thummalapalli, Benchun Miao, Thanh U Barbie, Vivek Sivathanu, Joshua Wong, William G Richards, Raphael Bueno, Charles H Yoon, Juan Miret, Meenhard Herlyn, Levi A Garraway, Eliezer M Van Allen, Gordon J Freeman, Paul T Kirschmeier, Jochen H Lorch, Patrick A Ott, F Stephen Hodi, Keith T Flaherty, Roger D Kamm, Genevieve M Boland, Kwok-Kin Wong, David Dornan, Cloud Peter Paweletz, David A Barbie
Ex vivo systems that incorporate features of the tumor microenvironment (TME) and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations, and respond to ICB in short-term 3-dimensional microfluidic culture...
November 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29100742/outcome-of-neoadjuvant-chemoradiation-in-mri-staged-locally-advanced-rectal-cancer-retrospective-analysis-of-123-chinese-patients
#14
Shing Fung Lee, Chi Leung Chiang, Francis Ann Shing Lee, Yiu Wah Wong, Chi Ming Poon, Frank Chi Sing Wong, Stewart Yuk Tung
BACKGROUND: For advanced rectal cancer with involved or threatened mesorectal fascia (MRF), current standard is pre-operative long course chemoradiotherapy (PLCRT) with either capecitabine or 5-fluorouracil (5-FU). However, few Chinese data on its clinical outcome are available, especially for those with pelvic MRI staging. METHODS: Between Jan-2009 and Oct-2014, 123 consecutive patients with biopsy proven adenocarcinoma of rectum, all with pelvic MRI staging, selected for PLCRT after multi-disciplinary team discussion were recruited...
November 1, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29098433/effect-of-transanal-total-mesorectal-excision-for-rectal-cancer-comparison-of-short-term-outcomes-with-laparoscopic-and-open-surgeries
#15
Sharaf Karim Perdawood, Benjamin Sejr Thinggaard, Maya Xania Bjoern
OBJECTIVE: To compare short-term results of total mesorectal excision (TME) for mid and low rectal cancer, achieved by transanal (TaTME), laparoscopic (LaTME), and open (OpTME) approaches. BACKGROUND: The impact of TaTME on the surgical treatment of mid and low rectal cancer has yet to be clarified. METHODS: This is a case-matched study, based on data from a prospectively maintained database of patients who underwent TaTME from May 2015 to March 2017, and a retrospective chart review of patients who underwent LaTME and OpTME in the previous period...
November 2, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/29098333/synthesis-of-multirecognition-magnetic-molecularly-imprinted-polymer-by-atom-transfer-radical-polymerization-and-its-application-in-magnetic-solid-phase-extraction
#16
Xiang-Jin Kong, Chao Zheng, Yao-Han Lan, Shuai-Shuai Chi, Qian Dong, Hao-Long Liu, Chao Peng, Lin-Yi Dong, Liang Xu, Xian-Hua Wang
In this work, we reported an effective method for the synthesis of a multirecognition magnetic molecularly imprinted polymer (MMIP) with atom transfer radical polymerization (ATRP), using 2,4-diamino-6-methyl-1,3,5-triazine as pseudo-template. The resulting MMIP was characterized in detail by Fourier transform-infrared (FT-IR) spectra, scanning electron microscopy (SEM), thermogravimetic analysis (TGA), and vibrating sample magnetometry (VSM). These results indicated the successful synthesis of MMIP with sufficient thermal stability and magnetic properties...
November 2, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29097420/combination-of-cd40-agonism-and-csf-1r-blockade-reconditions-tumor-associated-macrophages-and-drives-potent-antitumor-immunity
#17
Karla R Wiehagen, Natasha M Girgis, Douglas H Yamada, Andressa A Smith, Szeman Ruby Chan, Iqbal S Grewal, Michael Quigley, Raluca I Verona
Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with agonist anti-CD40 treatment confers superior antitumor efficacy and increased survival compared with monotherapy treatment in preclinical tumor models. Concurrent CSF-1R blockade and CD40 agonism lead to profound changes in the composition of immune infiltrates, causing an overall decrease in immunosuppressive cells and a shift toward a more inflammatory milieu...
November 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29094389/antiferromagnetic-pyrite-as-the-tumor-microenvironment-mediated-nanoplatform-for-self-enhanced-tumor-imaging-and-therapy
#18
Zhongmin Tang, Huilin Zhang, Yanyan Liu, Dalong Ni, Hua Zhang, Jiawen Zhang, Zhenwei Yao, Mingyuan He, Jianlin Shi, Wenbo Bu
Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH-sensitive imaging, acidity-sensitive starving therapy, and hydrogen peroxide-activated chemotherapy, etc. Herein, a novel TME-mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self-enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i...
November 2, 2017: Advanced Materials
https://www.readbyqxmd.com/read/29093724/efficient-crispr-cas9-genome-editing-of-phytoene-desaturase-in-cassava
#19
John Odipio, Titus Alicai, Ivan Ingelbrecht, Dmitri A Nusinow, Rebecca Bart, Nigel J Taylor
CRISPR/Cas9 has become a powerful genome-editing tool for introducing genetic changes into crop species. In order to develop capacity for CRISPR/Cas9 technology in the tropical staple cassava (Manihot esculenta), the Phytoene desaturase (MePDS) gene was targeted in two cultivars using constructs carrying gRNAs targeting two sequences within MePDS exon 13. After Agrobacterium-mediated delivery of CRISPR/Cas9 reagents into cassava cells, both constructs induced visible albino phenotypes within cotyledon-stage somatic embryos regenerating on selection medium and the plants regenerated therefrom...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29079339/exhaustion-of-t-lymphocytes-in-the-tumor-microenvironment-significance-and-effective-mechanisms
#20
REVIEW
Mohammad Davoodzadeh Gholami, Gholam Ali Kardar, Yousef Saeedi, Sahel Heydari, Johan Garssen, Reza Falak
T lymphocytes play crucial roles in adaptive immune responses to tumors. However, due to different tolerance mechanisms and inhibitory effects of the tumor microenvironment (TME) on T cells, responses to tumors are insufficient. In fact, cellular and molecular suppressive mechanisms repress T cell responses in the TME, resulting in senescent, anergic and exhausted lymphocytes. Exhaustion is a poor responsive status of T cells, with up-regulated expression of inhibitory receptors, decreased production of effective cytokines, and reduced cytotoxic activity...
October 10, 2017: Cellular Immunology
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