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https://www.readbyqxmd.com/read/29928434/downregulation-of-glutathione-s-transferase-a1-suppressed-tumor-growth-and-induced-cell-apoptosis-in-a549-cell-line
#1
Huan Liu, Zhouping Yang, Linquan Zang, Guixiang Wang, Sigui Zhou, Guifang Jin, Zhicheng Yang, Xuediao Pan
Glutathione S-transferase A1 (GSTA1) is a phase II detoxification enzyme and serves a crucial role in anti-cancer drug resistance. In our previous study, GSTA1 was identified to be highly expressed in various subtypes of non-small-cell lung cancer cell lines compared with human embryonic lung fibroblast cell line MRC-5. The aim of the present study was to investigate the effect of GSTA1 expression on the proliferation and apoptosis of A549 cells. GSTA1 expression was knocked down or with overexpressed using lentivirus particles...
July 2018: Oncology Letters
https://www.readbyqxmd.com/read/29927319/dietary-fat-stimulates-pancreatic-cancer-growth-and-promotes-fibrosis-of-the-tumor-microenvironment-through-the-cholecystokinin-receptor
#2
Sandeep Nadella, Julian Burks, Abdulhameed Al-Sabban, Gloria Inyang, Juan Wang, Robin D Tucker, Marie E Zamanis, William Bukowski, Narayan Shivapurkar, Jill P Smith
The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat to aid in digestion, and plasma CCK levels are elevated with the consumption of high fat diets. CCK is also a trophic peptide for the pancreas and has also been shown to stimulate growth of pancreatic cancer. In the current investigation, we studied the influence of a diet high in saturated fat on growth of pancreatic cancer in syngeneic murine models before the mice became obese to exclude the confounding factors associated with obesity...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29924913/mir-27b-3p-is-involved-in-doxorubicin-resistance-of-human-anaplastic-thyroid-cancer-cells-via-targeting-ppar%C3%AE
#3
Yuan Xu, Yi-Fan Han, Bing Ye, Yin-Long Zhang, Jian-Da Dong, Shao-Jun Zhu, Jiong Chen
Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumors. In order to investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells...
June 20, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29921887/asiatic-acid-enhances-intratumor-delivery-and-the-antitumor-effect-of-pegylated-liposomal-doxorubicin-by-reducing-tumor-stroma-collagen
#4
Luo Fang, Si-Si Kong, Li-Ke Zhong, Can-Ming Wang, Yu-Jia Liu, Hai-Ying Ding, Jiao Sun, Yi-Wen Zhang, Fan-Zhu Li, Ping Huang
Tumor-targeted drug delivery systems (Tt-DDSs) are proposed as a promising strategy for cancer care. However, the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Tt-DDS. In order to investigate the effect of asiatic acid (AA) on antitumor effect of pegylated liposomal doxorubicin (PLD) by attenuating stroma-collagen, colon cancer xenograft mice (SW620 cell line) were treated by PLD, AA, or combined regimes, respectively; the collagen levels were estimated by Sirius red/fast green dual staining and immunohistochemistry (IHC) staining; the intratumor exposure of doxorubicin was visualized by ex vivo fluorescence imaging and quantified by HPLC/MS analysis...
June 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29921731/cancer-associated-fibroblasts-affect-intratumoral-cd8-and-foxp3-t-cells-via-interleukin-6-in-the-tumor-microenvironment
#5
Takuya Kato, Kazuhiro Noma, Toshiaki Ohara, Hajime Kashima, Yuki Katsura, Hiroaki Sato, Satoshi Komoto, Ryoichi Katsube, Takayuki Ninomiya, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
PURPOSE: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression. EXPERIMENTAL DESIGN: 140 cases of esophageal cancer were analyzed for CAFs and CD8+ or forkhead box protein 3 (FoxP3+ ) TILs by immunohistochemistry. We analyzed cytokines using murine or human fibroblasts and cancer cells...
June 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29921235/tgf-%C3%AE-signaling-promotes-tumor-vasculature-by-enhancing-the-pericyte-endothelium-association
#6
Justin Zonneville, Alfiya Safina, Alexander M Truskinovsky, Carlos L Arteaga, Andrei V Bakin
BACKGROUND: The breast cancer microenvironment promotes tumor vascularization through the complex interactions involving tumor-associated fibroblasts (TAFs). Emerging data indicate that TAFs increase production and signaling by TGF-β cytokines, while the role of TGF-β signaling in the regulation of tumor blood vessels is not fully understood. The current study presents evidence that TAFs enhance the organization of tumor blood capillaries, and TGF-β signaling plays an important role in this response...
June 19, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29920670/urokinase-plasminogen-activator-protects-periodontal-ligament-fibroblast-from-oxidative-induced-apoptosis-and-dna-damage
#7
M S Ahmad Akhoundi, A Rokn, R Bagheri, N Momeni, M Hodjat
BACKGROUND AND OBJECTIVE: Urokinase-plasminogen activator (uPA) is a serine protease expressed at high basal level in normal gingival cervical fluid. Despite its known pathologic role in tissue proteolysis in periodontitis, little is known concerning uPA physiological function in oral tissue. Recent evidence in cancer cells has implicated the uPA system in DNA repair and anti-apoptotic pathways. This study is aimed to evaluate the protective function of urokinase against oxidative DNA damage in periodontal ligament (PDL) fibroblast, and to propose a new biological role for uPA in oral cavity...
June 19, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29917165/hgf-derived-from-cancer%C3%A2-associated-fibroblasts-promotes-vascularization-in-gastric-cancer-via-pi3k-akt-and-erk1-2-signaling
#8
Xusheng Ding, Wenqi Xi, Jun Ji, Qu Cai, Jinling Jiang, Min Shi, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Cancer‑associated fibroblasts (CAFs) are predominate cells in tumor stroma and play a key role in tumor progression. Hepatocyte growth factor (HGF) is a cytokine mainly derived from fibroblasts. In the present study, we reported that HGF significantly promoted angiogenesis of human umbilical vein endothelial cells (HUVECs) and vasculogenic mimicry (VM) formation of gastric cancer cells, respectively, by increasing cell proliferation and migration. In addition, mosaic vessels formed by HUVECs and gastric cancer cells were also increased with treatment of recombinant human HGF and conditioned medium from CAFs...
June 18, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29915722/new-therapies-and-immunological-findings-in-cutaneous-t-cell-lymphoma
#9
REVIEW
Kazuyasu Fujii
Primary cutaneous lymphomas comprise a group of lymphatic malignancies that occur primarily in the skin. They represent the second most common form of extranodal non-Hodgkin's lymphoma and are characterized by heterogeneous clinical, histological, immunological, and molecular features. The most common type is mycosis fungoides and its leukemic variant, Sézary syndrome. Both diseases are considered T-helper cell type 2 (Th2) diseases. Not only the tumor cells but also the tumor microenvironment can promote Th2 differentiation, which is beneficial for the tumor cells because a Th1 environment enhances antitumor immune responses...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29909276/quantitative-analysis-reveals-that-actin-and-src-family-kinases-regulate-nuclear-yap1-and-its-export
#10
Nil Ege, Anna M Dowbaj, Ming Jiang, Michael Howell, Steven Hooper, Charles Foster, Robert P Jenkins, Erik Sahai
The transcriptional regulator YAP1 is critical for the pathological activation of fibroblasts. In normal fibroblasts, YAP1 is located in the cytoplasm, while in activated cancer-associated fibroblasts, it is nuclear and promotes the expression of genes required for pro-tumorigenic functions. Here, we investigate the dynamics of YAP1 shuttling in normal and activated fibroblasts, using EYFP-YAP1, quantitative photobleaching methods, and mathematical modeling. Imaging of migrating fibroblasts reveals the tight temporal coupling of cell shape change and altered YAP1 localization...
June 8, 2018: Cell Systems
https://www.readbyqxmd.com/read/29909028/tunable-spr-based-remote-actuation-of-bimetallic-core-shell-nanoparticles-coated-stimuli-responsive-polymer-for-switchable-chemo-photothermal-synergistic-cancer-therapy
#11
Mitra Amoli-Diva, Rasoul Sadighi-Bonabi, Kamyar Pourghazi
New dual light/temperature-responsive nanocarriers were synthesized using bimetallic plasmonic Au-Ag and Ag-Au nanoparticles (NPs) as cores of vehicles which subsequently functionalized with a UCST-based poly acrylamide-co-acrylonitrile using reversible addition-fragmentation chain transfer for spatiotemporally controlled chemo-photothermal synergistic cancer therapy. The bimetallic cores were assigned to sense wavelengths close to the localized SPR of monometallic NP shell to produce heat which not only can increase the surrounding temperature over the UCST of polymer to open the its valves and promote drug diffusion, but also can kill cancerous cells through photothermal effects with increasing in environment temperature nearly 18 °C after about 5 min radiation...
June 14, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29909021/nf%C3%AE%C2%BAb-in-pancreatic-stellate-cells-reduces-infiltration-of-tumors-by-cytotoxic-t-cells-and-killing-of-cancer-cells-via-upregulation-of-cxcl12
#12
Bharti Garg, Bhuwan Giri, Shrey Modi, Vrishketan Sethi, Iris Castro, Oliver Umland, Yuguang Ban, Shweta Lavania, Rajinder Dawra, Sulagna Banerjee, Selwyn Vickers, Nipun B Merchant, Steven Xi Chen, Eli Gilboa, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
BACKGROUND & AIMS: Immunotherapies are ineffective against pancreatic cancer. We investigated whether the activity of nuclear factor (NF)κB in pancreatic stromal cells contributes to an environment that suppresses anti-tumor immune response. METHODS: Pancreata of C57BL/6 or Rag1-/- mice were given pancreatic injections of a combination of KrasG12D/+; Trp53 R172H/+; Pdx-1cre (KPC) pancreatic cancer cells and pancreatic stellate cells (PSCs) extracted from C57BL/6 (control) or mice with disruption of the gene encoding the NFkB p50 subunit (Nfkb1 or p50-/- mice)...
June 14, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29908438/targeting-rna-polymerase-i-transcription-machinery-in-cancer-cells-by-a-novel-monofunctional-platinum-based-agent
#13
Zhen-Lei Zhang, Chun-Lai Zhao, Qian Chen, Kai Xu, Xin Qiao, Jing-Yuan Xu
Aberrant ribosome biogenesis and enlarged nucleoli have long been used by pathologists as a marker of aggressive tumors. Suppression of RNA polymerase I (Pol I) transcription machinery within the nucleolus could be a direct way to trigger the nucleolar stress and to inhibit the rapid proliferation of cancer cells. Here we modified cisplatin with an analogue of the selective inhibitor of RNA polymerase I-mediated transcription BMH-21 to develop a novel platinum-based Pol I selective inhibitor. We show that this novel monofunctional platinum-based agent, P1-B1, had enhanced antitumor activity of up to 17-fold greater than the clinical drug cisplatin in cisplatin-resistant non-small cell lung cancer cells...
June 1, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29907957/laminin-%C3%AE-1-orchestrates-vegfa-functions-in-the-ecosystem-of-colorectal-carcinoma
#14
E Mammadova-Bach, T Rupp, C Spenlé, I Jivkov, P Shankaranarayanan, A Klein, L Pisarsky, A Méchine-Neuville, G Cremel, M Kedinger, O De Wever, N Ambartsumian, S Robine, E Pencreach, D Guenot, P Simon-Assmann, J G Goetz, G Orend, O Lefebvre
Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation...
June 15, 2018: Biology of the Cell
https://www.readbyqxmd.com/read/29906389/biotin-tagged-polysaccharide-vesicular-nanocarriers-for-receptor-mediated-anticancer-drug-delivery-in-cancer-cells
#15
Nilesh Umakant Deshpande, Manickam Jayakannan
Biotin-conjugated multi-stimuli-responsive polysaccharide vesicular nanocarriers are designed and developed, for the first time, to accomplish receptor-mediated endocytosis in cancer cells and to deliver anticancer drugs at the intracellular compartments. For this purpose, a new renewable hydrophobic unit was custom designed with redox-degradable disulphide and enzyme-biodegradable aliphatic ester chemical linkages and it was conjugated along with biotin on the dextran backbone. The dextran derivative self-assembled into nanovesicles of < 200 nm in size which were characterized by dynamic and static light scattering, electron and atomic force microscopes...
June 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29906225/scleraxis-regulates-twist1-and-snai1-expression-in-epithelial-to-mesenchymal-transition
#16
Danah S Al-Hattab, Hamza A Safi, Raghu S Nagalingam, Rushita A Bagchi, Matthew Taras Stecy, Michael Paul Czubryt
Numerous physiological and pathological events, from organ development to cancer and fibrosis, are characterized by Epithelial-to-Mesenchymal Transition (EMT), whereby adherent epithelial cells convert to migratory mesenchymal cells. During cardiac development, pro-epicardial organ epithelial cells undergo EMT to generate fibroblasts. Subsequent stress or damage induces further phenotype conversion of fibroblasts to myofibroblasts, causing fibrosis via synthesis of excessive extracellular matrix. We previously showed that the transcription factor scleraxis is both sufficient and necessary for the conversion of cardiac fibroblasts to myofibroblasts, and found that scleraxis knockout reduced cardiac fibroblast number by 50%, possibly via EMT attenuation...
June 15, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29905606/the-effect-of-the-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-and-paclitaxel-treatment-on-full-thickness-wound-healing-in-mice
#17
Joseph H Marcotte, Deviney A Rattigan, Robin F Irons, Kevin W Cahill, Ping Zhang, Shaohua Chang, Kiavash R Koko, John P Gaughan, Jeffrey P Carpenter, Spencer A Brown, Tulin Budak-Alpdogan
INTRODUCTION: Neoadjuvant chemotherapy prior to lumpectomy or mastectomy for breast cancer challenges wound healing. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been shown to work synergistically with paclitaxel in vitro and in preclinical studies. In addition, our laboratory has demonstrated that SAHA treatment decreases paclitaxel-associated stem cell toxicity, modulates inflammatory response, and promotes wound healing in injured fibroblast cells. Our goal was to determine if combined SAHA and paclitaxel treatment would improve wound healing in an in vivo full-thickness murine model, without altering antitumor effect...
June 13, 2018: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29904943/fgf9-induced-ovarian-cancer-cell-invasion-involves-vegf-a-vegfr2-augmentation-by-virtue-of-ets1-upregulation-and-metabolic-reprogramming
#18
Rahul Bhattacharya, Susri Ray Chaudhuri, Sib S Roy
Ovarian cancer (OC) renders its lethality to enhanced metastasis and late detection. A plethora of growth factors including Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) stimulated signaling pathways regulate the invasive/metastatic behavior of ovarian tumors contributing to its aggressiveness. Autocrine VEGF-functioning by virtue of upregulated VEGFR2 contributes to the invasiveness of OC cells by modulating the MMPs. Studies have highlighted the interaction between FGF and VEGF signaling pathways during angiogenesis...
June 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29903916/insulin-like-growth-factor-1-receptor-stabilizes-the-etv6-ntrk3-chimeric-oncoprotein-by-blocking-its-kpc1-rnf123-mediated-proteasomal-degradation
#19
Cristina E Tognon, Bo Rafn, Naniye Malli Cetinbas, Takumi Kamura, Genny Trigo, Barak Rotblat, Fumihiko Okumura, Masaki Matsumoto, Christine Chow, Monika Davare, Michael Pollak, Thibault Mayor, Poul H Sorensen
Many oncogenes, including chimeric oncoproteins, require insulin-like growth factor 1 receptor (IGF1R) for promoting cell transformation. The ETS variant 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) (EN) chimeric tyrosine kinase is expressed in mesenchymal, epithelial, and hematopoietic cancers and requires the IGF1R axis for transformation. However, current models of IGF1R-mediated EN activation are lacking mechanistic detail. We demonstrate here that IGF-mediated IGF1R stimulation enhances EN tyrosine phosphorylation and that blocking IGF1R activity or decreasing protein levels of the adaptor protein insulin receptor substrate 1/2 (IRS1/2) results in rapid EN degradation...
June 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29902528/divergent-mechanisms-of-metabolic-dysfunction-drive-fibroblast-and-t-cell-senescence
#20
Lauren A Callender, Elizabeth C Carroll, Emilia A Bober, Sian M Henson
The impact of cellular senescence during ageing is well established, however senescence is now recognised to play a role in a variety of age related and metabolic diseases, such as cancer, autoimmune and cardiovascular diseases. It is therefore crucial to gain a better understanding of the mechanisms that control cellular senescence. In recent years our understanding of the intimate relationship between cell metabolism, cell signalling and cellular senescence has greatly improved. In this review we discuss the differing roles of glucose and protein metabolism in both senescent fibroblast and CD8+ T-cells, and explore the impact cellular metabolism has on the senescence-associated secretory phenotype (SASP) of these cell types...
June 11, 2018: Ageing Research Reviews
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