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https://www.readbyqxmd.com/read/29151072/the-lactate-receptor-hcar1-gpr81-contributes-to-doxorubicin-chemoresistance-via-abcb1-transporter-up-regulation-in-human-cervical-cancer-hela-cells
#1
W Wagner, K D Kania, A Blauz, W M Ciszewski
The lactate receptor, also known as hydroxycarboxylic acid receptor 1 (HCAR1/GPR81), plays a vital role in cancer biology. Recently, HCAR1 was reported to enhance metastasis, cell growth, and survival of pancreatic, breast, and cervical cancer cells. This study showed, for the first time, the mechanism of HCAR1-mediated chemoresistance to doxorubicin through regulation of ABCB1 transporter. We observed the HCAR1 agonists L-lactate, D-lactate and 3,5-dihydroxybenzoic acid (DHBA) induced up-regulation of ABCB1...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29149832/optimizing-metal-based-chemotherapeutics-targeting-chemoresistance-related-patterns-in-molecular-tumor-immunology-and-immunosuppressive-tumor-networks
#2
Athanasios Salifoglou, Savvas Petanidis, Efrosini Kioseoglou
Tumor cell chemoresistance is a major challenge in cancer therapeutics. Major select metal-based drugs are potent anticancer agents yet they exhibit undesirable side-effects and are effective against only a few types of cancers. A need, therefore, arises for new metallodrugs with an improved spectrum of efficacy and lower toxicity. Development of anticancer drugs based on antitumor metals is currently a very active field, with considerable efforts having been made toward elucidating the mechanisms of immune action of complex metalloforms and optimizing their immunoregulatory bioactivity through appropriate structural modification...
November 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29149426/relationship-between-lat1-expression-and-resistance-to-chemotherapy-in-pancreatic-ductal-adenocarcinoma
#3
Bolag Altan, Kyoichi Kaira, Akira Watanabe, Norio Kubo, Pinjie Bao, Gantumur Dolgormaa, Erkhem-Ochir Bilguun, Kenichiro Araki, Yoshikatsu Kanai, Takehiko Yokobori, Tetsunari Oyama, Masahiko Nishiyama, Hiroyuki Kuwano, Ken Shirabe
PURPOSE: L-type amino acid transporter 1 (LAT1) is linked to tumor cell proliferation, angiogenesis, and survival in various human cancers. Although the expression of LAT1 was identified as a significant prognostic predictor after surgery in patients with pancreatic ductal adenocarcinoma (PDAC), little is known about the clinical significance of LAT1 as a chemotherapeutic resistance factor in PDAC. METHODS: A total of 110 patients with surgically resected PDAC were retrospectively reviewed as the training set...
November 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29146617/cure-in-advanced-renal-cell-cancer-is-it-an-achievable-goal
#4
Dhanusha Sabanathan, John J Park, Manuel Marquez, Louise Francisco, Natalie Byrne, Howard Gurney
BACKGROUND: Immunotherapy has historically been of interest in the management of metastatic renal cell cancer (mRCC) because of its relative chemoresistance and the reproducible but low incidence of spontaneous remission in metastatic disease. Recently, targeted immunotherapies in the form of checkpoint inhibitors have shown durable responses in approximately 20%-30% of patients with solid tumors, with a much more acceptable side-effect profile. Anti-programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 antibodies rely on the presence of host T cells in the tumor microenvironment to be stimulated in order to activate an antitumor response...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29145973/tak-ing-aim-at-chemoresistance-the-emerging-role-of-map3k7-as-a-target-for-cancer-therapy
#5
Raffaela Santoro, Carmine Carbone, Geny Piro, Paul J Chiao, Davide Melisi
Cellular drug resistance remains the main obstacle to the clinical efficacy of cancer chemotherapy. Alterations in key pathways regulating cell cycle checkpoints, apoptosis and Epithelial to Mesenchymal Transition (EMT), such as the Mitogen-activated protein kinase (MAPK) pathway, appear to be closely associated to cancer chemoresistance. Transforming growth factor-β (TGF-β)- activated kinase 1 (TAK1, also known as MAP3K7) is a serine/threonine kinase in the mitogen-activated protein kinase (MAP3K) family...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29144412/pancreatic-cancer-chemoresistance-to-gemcitabine
#6
REVIEW
Manoj Amrutkar, Ivar P Gladhaug
Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, ranks among the leading causes of cancer-related deaths in the Western world due to disease presentation at an advanced stage, early metastasis and generally a very limited response to chemotherapy or radiotherapy. Gemcitabine remains a cornerstone of PDAC treatment in all stages of the disease despite suboptimal clinical effects primarily caused by molecular mechanisms limiting its cellular uptake and activation and overall efficacy, as well as the development of chemoresistance within weeks of treatment initiation...
November 16, 2017: Cancers
https://www.readbyqxmd.com/read/29141914/proteotranscriptomics-reveal-signaling-networks-in-the-ovarian-cancer-microenvironment
#7
Thomas Worzfeld, Florian Finkernagel, Silke Reinartz, Anne Konzer, Till Adhikary, Andrea Nist, Thorsten Stiewe, Uwe Wagner, Mario Looso, Johannes Graumann, Rolf Müller
Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting cancer progression, chemoresistance and immuno-suppression. However, the underlying signaling mechanisms remain largely obscure.  To chart these signaling networks, we performed comprehensive proteomic and transcriptomic analyses of TU, TAT and TAM from ascites of ovarian cancer patients...
November 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29141558/modulation-of-cancer-metabolism-by-phytochemicals-a-brief-overview
#8
Danina Muntean, Sturza Adrian, Ioana Pavel, Oana Duicu
Despite tremendous research efforts for effective therapies, cancer remains the plague of the century and its burden is expected to increase worldwide in the near future. Metabolic reprogramming is a firmly established hallmark of all cancers, regardless their cellular or tissue origin, being a prerequisite for both tumor growth and invasion. Functional dependence of tumors on glycolysis and glutaminolysis and the crucial contribution of mitochondria to the tumor bioenergetic versatility are well recognized features and established therapeutic targets...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29141252/musashi1-promotes-non-small-cell-lung-carcinoma-malignancy-and-chemoresistance-via-activating-the-akt-signaling-pathway
#9
Yaoguo Lang, Xianglong Kong, Changjun He, Fengjiao Wang, Benkun Liu, Shibo Zhang, Jinfeng Ning, Kaibin Zhu, Shidong Xu
BACKGROUND/AIMS: Lung cancer is one of the leading causes for cancer mortality. The poor therapeutic outcome of non-small cell lung carcinoma (NSCLC) is mainly due to late diagnosis and chemoresistance. In this study, we investigated the role of Musashi1 (MSI1) in NSCLC malignancy and chemoresistance. METHODS: Colony formation, MTT, glucose uptake and lactate production assays were employed to study lung cancer cell malignancy and chemoresistance. RT-PCR and Western blotting were performed to detect mRNA and protein expressions of genes...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29138869/cepharanthine-exhibits-a-potent-anticancer-activity-in-p53-mutated-colorectal-cancer-cells-through-upregulation-of-p21waf1-cip1
#10
Arkornnut Rattanawong, Vilawan Payon, Wacharee Limpanasittikul, Chatikorn Boonkrai, Apiwat Mutirangura, Piyanuch Wonganan
Cepharanthine (CEP), a biscoclurine alkaloid isolated from Stephania cepharantha Hayata, has demonstrated anticancer activity in several different types of cancer cells. Colorectal cancer (CRC) is one of the most common cancers in both men and women. Mutated p53 in CRC was reported to be associated with resistance to commonly used chemotherapeutic agents including, 5‑fluorouracil, oxaliplatin and irinotecan. Many studies reported that mutation of p53 induced chemoresistance through several mechanisms, including induction of drug efflux, disruption of cell cycle regulation, evasion of apoptosis and upregulation of DNA repair...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138811/high-expression-of-mage-a9-contributes-to-stemness-and-malignancy-of-human-hepatocellular-carcinoma
#11
Youping Wei, Yanqin Wang, Jing Gong, Lihua Rao, Zhiwei Wu, Teng Nie, Dongling Shi, Liming Zhang
MAGE-A9, a well-characterized cancer testis antigen (CTA), belongs to a member of melanoma antigen gene (MAGE) family. In human malignancies, aberrant expression of MAGE genes correlated with poor clinical prognosis, increased tumor growth, metastases, and enrichment in stem cell populations of certain cancers. Cancer stem cells (CSCs) have been proposed to contribute to the major malignant phenotypes of liver cancer, including recurrence, metastasis and chemoresistance. However, expression and potential role of MAGE-A9 in liver cancer stem cells (LCSCs) still remain unclear...
November 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29137934/the-notch-pathway-is-activated-in-neoplastic-progression-in-esophageal-squamous-cell-carcinoma
#12
Daniel Lubin, Rosemarie Mick, Stuti G Shroff, Kristen Stashek, Emma Furth
The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial to mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters...
November 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/29137407/lncrna-snhg12-contributes-to-multidrug-resistance-through-activating-the-mapk-slug-pathway-by-sponging-mir-181a-in-non-small-cell-lung-cancer
#13
Pei Wang, Dong Chen, Hongbing Ma, Yong Li
Small nucleolar RNA host gene 12 (SNHG12), as one of the long non-coding RNAs (lncRNAs), plays an oncogenic role in various cancers, however, its role in the chemoresistance of non-small cell lung cancer (NSCLC) is unclear. In this study, we investigated the effect of SNHG12 on multidrug resistance (MDR) in NSCLC. The results showed that SNHG12 was high-expressed and miR-181a was low-expressed in NSCLC tumor tissues and cell lines. Knockdown of SNHG12 reversed the resistance to cisplatin, paclitaxel and gefitinib in A549/DDP, A549/PTX and PC9/AB2 cells through inducing cell apoptosis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137357/akr7a3-suppresses-tumorigenicity-and-chemoresistance-in-hepatocellular-carcinoma-through-attenuation-of-erk-c-jun-and-nf-%C3%AE%C2%BAb-signaling-pathways
#14
Raymond Kwok Kei Chow, Sarah Tsz-Kwan Sin, Ming Liu, Yan Li, Tim Hon Man Chan, Yangyang Song, Leilei Chen, Dora Lai-Wan Kwong, Xin-Yuan Guan
Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137332/long-noncoding-rna-xist-is-a-prognostic-factor-in-colorectal-cancer-and-inhibits-5-fluorouracil-induced-cell-cytotoxicity-through-promoting-thymidylate-synthase-expression
#15
Yang Xiao, Usenko Alexander Yurievich, Smorzhevskyi Valentyn Yosypovych
A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to 5-fluorouracil (5FU)-based treatment. Recent studies have shown that long non-coding RNAs (lncRNAs) are critical regulators in chemoresistance. By using the next generation HiSeq sequencing assay, we identified lncRNAs showing differential expression levels in 5FU resistant and non-resistant CRC patients. RT-qPCR was then performed for validation in tissues and serum samples, and lncRNA XIST was verified to be up-regulated in non-responding patients and have considerable diagnostic potential to identify responding patients from non-responding patients...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137250/molecular-chaperones-in-the-acquisition-of-cancer-cell-chemoresistance-with-mutated-tp53-and-mdm2-up-regulation
#16
Zuzanna Tracz-Gaszewska, Marta Klimczak, Przemyslaw Biecek, Marcin Herok, Marcin Kosinski, Maciej B Olszewski, Patrycja Czerwińska, Milena Wiech, Maciej Wiznerowicz, Alicja Zylicz, Maciej Zylicz, Bartosz Wawrzynow
Utilizing the TCGA PANCAN12 dataset we discovered that cancer patients with mutations in TP53 tumor suppressor and overexpression of MDM2 oncogene exhibited decreased survival post treatment. Interestingly, in the case of breast cancer patients, this phenomenon correlated with high expression level of several molecular chaperones belonging to the HSPA, DNAJB and HSPC families. To verify the hypothesis that such a genetic background may promote chaperone-mediated chemoresistance, we employed breast and lung cancer cell lines that constitutively overexpressed heat shock proteins and have shown that HSPA1A/HSP70 and DNAJB1/HSP40 facilitated the binding of mutated p53 to the TAp73α protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137236/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#17
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135607/targeting-the-perivascular-niche-in-brain-tumors
#18
Giorgio Seano
PURPOSE OF REVIEW: Brain tumors are composed of primary tumors of the central nervous system, such us glioblastoma (GBM), and secondary metastatic tumors, such as melanoma, non-Hodgkin lymphoma as well as lung and breast cancers. Brain tumors are highly deadly, and unfortunately not many improvements have been achieved to improve the survival of patients with brain tumors. Chemoradiation resistance is one of the most clinically relevant challenges faced in patients with brain tumors. The perivascular niche is one of the most relevant microenvironment hubs in brain tumors...
November 14, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29135088/the-role-of-toll-like-receptors-in-ovarian-cancer
#19
Vlad Gata, Ignat Florin Laurentiu
Ovarian cancer (OC) is the leading cause of death in gynecological malignancies in western countries. Chemoresistance represents a major issue and a better understanding of the interactions that take place within the tumor microenvironment is needed, such as the connection between inflammation and cancer. Toll like receptors (TLRs) are part of the basic mechanisms that are involved in the activation of the innate immune system, with extensive activation of various transcription factors, that subsequently lead to an adaptive immune response, making them key players that modulate the inflammatory response and tumor dynamics...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29133573/the-rars-mad1l1-fusion-gene-induces-cancer-stem-cell-like-properties-and-therapeutic-resistance-in-nasopharyngeal-carcinoma
#20
Qian Zhong, Zhihua Liu, Zhi-Rui Lin, Ze-Dong Hu, Li Yuan, Yan-Min Liu, Ai-Jun Zhou, Li-Hua Xu, Li-Juan Hu, Zi-Feng Wang, Xin Yuan Guan, Jia-Jie Hao, Vivian Wai Yan Lui, Ling Guo, Hai-Qiang Mai, Ming-Yuan Chen, Fei Han, Yun-Fei Xia, Jennifer R Grandis, Xing Zhang, Mu-Sheng Zeng
PURPOSE: Nasopharyngeal carcinoma (NPC) is most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. EXPERIMENTAL DESIGN: RNA-seq was applied to look for interchromosome translocation in NPC. PCR, FISH and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies...
November 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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