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https://www.readbyqxmd.com/read/27926867/genomic-instability-is-induced-by-persistent-proliferation-of-cells-undergoing-epithelial-to-mesenchymal-transition
#1
Valentine Comaills, Lilian Kabeche, Robert Morris, Rémi Buisson, Min Yu, Marissa Wells Madden, Joseph A LiCausi, Myriam Boukhali, Ken Tajima, Shiwei Pan, Nicola Aceto, Srinjoy Sil, Yu Zheng, Tilak Sundaresan, Toshifumi Yae, Nicole Vincent Jordan, David T Miyamoto, David T Ting, Sridhar Ramaswamy, Wilhelm Haas, Lee Zou, Daniel A Haber, Shyamala Maheswaran
TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926865/tenascin-c-orchestrates-glioblastoma-angiogenesis-by-modulation-of-pro-and-anti-angiogenic-signaling
#2
Tristan Rupp, Benoit Langlois, Maria M Koczorowska, Agata Radwanska, Zhen Sun, Thomas Hussenet, Olivier Lefebvre, Devadarssen Murdamoothoo, Christiane Arnold, Annick Klein, Martin L Biniossek, Vincent Hyenne, Elise Naudin, Ines Velazquez-Quesada, Oliver Schilling, Ellen Van Obberghen-Schilling, Gertraud Orend
High expression of the extracellular matrix component tenascin-C in the tumor microenvironment correlates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C. We find that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, resulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogenesis...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926514/novel-amphiphilic-folic-acid-cholesterol-chitosan-micelles-for-paclitaxel-delivery
#3
Li-Chun Cheng, Yan Jiang, Yu Xie, Lu-Lu Qiu, Qing Yang, Hui-Yi Lu
In order to decrease the toxicity of paclitaxel (PTX) and increase the efficiency, we developed an amphiphilic PTX injection system using a biodegradable and biocompatible polymer synthesized by folic acid, cholesterol, and chitosan (FACC). This FACC-based polymer had a low critical concentration (64.13μg/ml) and could self-assemble in aqueous condition to form nanoscale micelles. The particle sizes of FACC-PTX micelles were 253.2±0.56 nm, the encapsulation efficiency and loading capacity of these FACC-PTX micelles were 65...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926505/antitumor-effect-of-combination-of-the-inhibitors-of-two-new-oncotargets-proton-pumps-and-reverse-transcriptase
#4
Luana Lugini, Ilaria Sciamanna, Cristina Federici, Elisabetta Iessi, Enrico Pierluigi Spugnini, Stefano Fais
Tumor therapy needs new approaches in order to improve efficacy and reduce toxicity of the current treatments. The acidic microenvironment and the expression of high levels of endogenous non-telomerase reverse transcriptase (RT) are common features of malignant tumor cells. The anti-acidic proton pump inhibitor Lansoprazole (LAN) and the non-nucleoside RT inhibitor Efavirenz (EFV) have shown independent antitumor efficacy. LAN has shown to counteract drug tumor resistance. We tested the hypothesis that combination of LAN and EFV may improve the overall antitumor effects...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925188/a-human-3d-in-vitro-model-to-assess-the-relationship-between-osteoporosis-and-dissemination-to-bone-of-breast-cancer-tumour-cells
#5
F Salamanna, V Borsari, S Brogini, P Torricelli, S Cepollaro, M Cadossi, M Fini
Despite consistent improvements in diagnostic and therapeutic strategies for breast cancer, up to 40% of patients will develop bone metastases. To reduce the morbidity and complications related with bone metastases, it is imperative to reduce their etiological factors. Osteoporosis, being characterized by a sudden estrogen deficiency, may provide a favorable condition for bone metastasis. This work, using a humanized 3D in vitro model, aims at evaluating the relationship between osteoporosis and breast cancer-derived bone metastases...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924972/protective-mechanisms-of-purified-polyphenols-from-pinecones-of-pinus-koraiensis-on-spleen-tissues-in-tumor-bearing-s180-mice-in-vivo
#6
Juanjuan Yi, Cuilin Cheng, Xiaoyu Li, Haitian Zhao, Hang Qu, Zhenyu Wang, Lu Wang
The previous study evaluated the antitumor activity and the underlying mechanism of the purified polyphenols from pinecones of Pinus koraiensis (PPP-40) using a tumor-bearing S180 mice model. This study was designed to evaluate the protective effects of PPP-40 on spleen tissues of S180 mice in vivo. Pretreatment with PPP-40 (150 mg per kg BW per D) could significantly inhibit tumor growth, enhance spleen index and prevent the decline of haematological parameters of S180 mice induced by the tumor microenvironment...
December 7, 2016: Food & Function
https://www.readbyqxmd.com/read/27924922/metabolic-adaptation-to-nutritional-stress-in-human-colorectal-cancer
#7
Masaaki Miyo, Masamitsu Konno, Naohiro Nishida, Toshinori Sueda, Kozo Noguchi, Hidetoshi Matsui, Hugh Colvin, Koichi Kawamoto, Jun Koseki, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Noriko Gotoh, Fumio Matsuda, Taroh Satoh, Tsunekazu Mizushima, Hiroshi Shimizu, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924676/bacterial-xenophagy-and-its-possible-role-in-cancer-a-potential-antimicrobial-strategy-for-cancer-prevention-and-treatment
#8
Xinbing Sui, Xiao Liang, Liuxi Chen, Chunming Guo, Weidong Han, Hongming Pan, Xue Li
Macroautophagy/autophagy is a conserved catabolic process through which cellular excessive or dysfunctional proteins and organelles are transported to the lysosome for terminal degradation and recycling. Over the past few years increasing evidence has suggested that autophagy is not only a simple metabolite recycling mechanism, but also plays a critical role in the removal of intracellular pathogens such as bacteria and viruses. When autophagy engulfs intracellular pathogens, the pathway is called 'xenophagy' because it leads to the elimination of foreign microbes...
December 7, 2016: Autophagy
https://www.readbyqxmd.com/read/27923328/modeling-stroma-induced-drug-resistance-in-a-tissue-engineered-tumor-model-of-ewing-sarcoma
#9
Marco Santoro, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Eric R Molina, Danielle Wu, Waldemar Priebe, Joseph A Ludwig, Antonios G Mikos
Three-dimensional (3D) tumor models are gaining traction in the research community given their capacity to mimic aspects of the tumor microenvironment absent in monolayer systems. In particular, the ability to spatiotemporally control cell placement within ex vivo 3D systems has enabled the study of tumor-stroma interactions. Furthermore, by regulating biomechanical stimuli, one can reveal how biophysical cues affect stromal cell phenotype and how their phenotype impacts tumor drug sensitivity. Both tumor architecture and shear force have profound effects on Ewing sarcoma (ES) cell behavior and are known to elicit ligand-mediated activation of the insulin-like growth factor-1 receptor (IGF-1R), thereby mediating resistance of ES cells to IGF-1R inhibitors...
December 6, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#10
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922590/neutrophils-are-essential-in-short-hairpin-rna-of-indoleamine-2-3-dioxygenase-mediated-antitumor-efficiency
#11
Kuan-Ting Liu, Yao-Hua Liu, Hsin-Liang Liu, Inn-Wen Chong, Meng-Chi Yen, Po-Lin Kuo
Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear...
December 6, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27920705/heterotopic-ossification-in-rectal-carcinoma-report-of-a-case-and-review-of-the-literature
#12
Jiro Shimazaki, Akira Takemura, Kiyotaka Nishida, Hideki Kajiyama, Mitsugi Shimoda, Shuji Suzuki
Heterotopic ossification in colorectal carcinoma is extremely rare. This report presents the case of a 57-year-old male who had undergone a low anterior resection following a diagnosis of rectal carcinoma. Histological examination showed heterotopic ossification in the tumor. The patient was referred to Ibaraki Medical Center, Tokyo Medical University, with a diagnosis of rectal carcinoma by a local physician. Abdominal computed tomography revealed thickening of the rectal wall with calcified deposits, and virtual colonoscopy showed stenosis with a mass in the rectum...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920023/il4-from-t-follicular-helper-cells-downregulates-antitumor-immunity
#13
Hidekazu Shirota, Dennis M Klinman, Shuku-Ei Ito, Hiroyasu Ito, Masato Kubo, Chikashi Ishioka
Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the LNs...
December 5, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27919940/vitamin-d-and-myofibroblasts-in-fibrosis-and-cancer-at-cross-purposes-with-tgf-%C3%AE-smad-signaling
#14
REVIEW
Shraga Shany, Ina Sigal-Batikoff, Sergio Lamprecht
The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D3 (henceforth referred to by the synonyms 1,25(OH)2D3, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)2D3 and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#15
Jacalyn Rosenblatt, David Avigan
PD-1/PD-L1 pathway is a negative regulator of immune activation that is up-regulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies but single agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma specific T cells and T cell activation via PD-1/PD-L1 blockade are currently being explored...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27919264/acidic-tumor-microenvironment-abrogates-the-efficacy-of-mtorc1-inhibitors
#16
Seraina Faes, Adrian P Duval, Anne Planche, Emilie Uldry, Tania Santoro, Catherine Pythoud, Jean-Christophe Stehle, Janine Horlbeck, Igor Letovanec, Nicolo Riggi, Nicolas Demartines, Olivier Dormond
BACKGROUND: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. METHODS: Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated...
December 5, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27919217/drug-delivery-nanoparticles-in-treating-chemoresistant-tumor-cells
#17
Giuseppina Barrera, Martina Daga, Benedetta Ferrara, Chiara Dianzani, Stefania Pizzimenti, Monica Argenziano, Roberta Cavalli, Francesco Trotta
Intrinsic or acquired chemoresistance represents the main obstacle to the successful treatment of cancer patients. Several mechanisms are involved in multidrug resistance: decreased uptake of hydrophilic drugs, increase of energy dependent efflux, alteration of the redox state, alteration of apoptotic pathways, and modification of the tumor microenvironment. In recent years, several types of nanoparticles have been developed to overcome these obstacles and improve the accumulation and release of drugs at the pathological site...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27917327/p53-mutation-critical-mediator-of-therapy-resistance-against-tumor-microenvironment
#18
Ali S Arbab, Meenu Jain, B R Achyut
No abstract text is available yet for this article.
October 2016: Biochemistry & Physiology
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#19
REVIEW
David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert, Hendrik Ungefroren
TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes...
November 30, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27916739/bioengineered-tumoral-microtissues-recapitulate-desmoplastic-reaction-of-pancreatic-cancer
#20
Virginia Brancato, Valentina Comunanza, Giorgia Imparato, Davide Corà, Francesco Urciuolo, Alessio Noghero, Federico Bussolino, Paolo A Netti
: Many of the existing three-dimensional (3D) cancer models in vitro fail to represent the entire complex tumor microenvironment composed of cells and extra cellular matrix (ECM) and do not allow a reliable study of the tumoral features and progression. In this paper we reported a strategy to produce 3D in vitro microtissues of pancreatic ductal adenocarcinoma (PDAC) for studying the desmoplastic reaction activated by the stroma-cancer crosstalk. Human PDAC microtissues were obtained by co-culturing pancreatic cancer cells (PT45) and normal or cancer-associated fibroblasts within biodegradable microcarriers in a spinner flask bioreactor...
December 1, 2016: Acta Biomaterialia
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