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https://www.readbyqxmd.com/read/28538211/the-oxido-metabolic-driver-atf4-enhances-temozolamide-chemo-resistance-in-human-gliomas
#1
Daishi Chen, Manfred Rauh, Michael Buchfelder, Ilker Y Eyupoglu, Nicolai Savaskan
Malignant gliomas are devastating neoplasia with limited curative treatment options. Temozolomide (TMZ, Temcat®, Temodal® or Temodar®) is a first-line treatment for malignant gliomas but the development of drug resistance remains a major concern. Activating transcription factor 4 (ATF4) is a critical oxido-metabolic regulator in gliomas, and its role in the pathogenesis of TMZ-resistance remains elusive. We investigated the effect of TMZ on human glioma cells under conditions of enhanced ATF4 expression (ATF4OE) and ATF4 knock down (ATF4KD)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#2
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537902/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reverses-chemoresistance-in-human-ovarian-cancer-cells
#3
Jin-Long Hu, Xin-Long Hu, Ai-Ye Guo, Chao-Jie Wang, Yi-Yang Wen, Shun-Dong Cang
Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537899/nras-mutations-in-cutaneous-t-cell-lymphoma-ctcl-sensitize-tumors-towards-treatment-with-the-multikinase-inhibitor-sorafenib
#4
Michael K Kießling, Jan P Nicolay, Tabea Schlör, Claus-Detlev Klemke, Dorothee Süss, Peter H Krammer, Karsten Gülow
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance of the malignant T cells towards apoptosis that can be caused by NRAS mutations in late-stage patients. These mutations correlate with decreased overall survival, but sensitize the respective CTCL cells towards MEK-inhibition-induced apoptosis which represents a promising novel therapeutic target in CTCL. Here, we show that the multi-kinase inhibitor Sorafenib induces apoptosis in NRAS-mutated CTCL cells. CTCL cell lines and to a minor extent primary T cells from Sézary patients without NRAS mutations are also affected by Sorafenib-induced apoptosis suggesting a sensitizing role of NRAS mutations for Sorafenib-induced apoptosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537897/mek-inhibitors-cobimetinib-and-trametinib-regressed-a-gemcitabine-resistant-pancreatic-cancer-patient-derived-orthotopic-xenograft-pdox
#5
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Thinzar M Lwin, Ho Kyoung Hwang, Jonathan C Delong, Bryan M Clary, Michael Bouvet, Michiaki Unno, Robert M Hoffman
A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537895/interaction-of-glycosphingolipids-gd3-and-gd2-with-growth-factor-receptors-maintains-breast-cancer-stem-cell-phenotype
#6
Yuh-Jin Liang, Chen-Yu Wang, I-An Wang, Yi-Wen Chen, Li-Tzu Li, Chuang-Yu Lin, Ming-Yi Ho, Tsung-Lung Chou, Ya-Hui Wang, Shih-Pin Chiou, Yu-Ju Lin, John Yu
Many studies have suggested that disialogangliosides, GD2 and GD3, are involved in the development of various tumor types. However, the functional relationships between ganglioside expression and cancer development or aggressiveness are not fully described. GD3 is upregulated in approximately half of all invasive ductal breast carcinoma cases, and enhanced expression of GD3 synthase (GD3S, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase) in estrogen receptor-negative breast tumors, was shown to correlate with reduced overall patient survival...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537875/n-myc-downstream-regulated-gene-1-promotes-oxaliplatin-triggered-apoptosis-in-colorectal-cancer-cells-via-enhancing-the-ubiquitination-of-bcl-2
#7
Xiao Yang, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Luyang Zhang, Yanfeng Lv, Jing Sun, Minhua Zheng
N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535666/ddx53-regulates-cancer-stem-cell-like-properties-by-binding-to-sox-2
#8
Youngmi Kim, Minjeong Yeon, Dooil Jeoung
This study investigated the role of cancer/testis antigen DDX53 in regulating cancer stem cell-like properties. DDX53 shows co-expression with CD133, a marker for cancer stem cells. DDX53 directly regulates the SOX-2 expression in anticancer drug-resistant Malme3MR cells. DDX53 and miR-200bwere found to be involved in the regulation of tumor spheroid forming potential of Malme3M and Malme3MR cells. Furthermore, the self-renewal activity and the tumorigenic potential of Malme3M(R)-CD133 (+) cells were also regulated by DDX53...
May 2, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28535649/-cancer-associated-fibroblasts-regulate-the-chemoresistance-of-lung-cancer-cell-line-a549-via-sdf-1-secretion
#9
F Zou, Z H Zhang, Y T Zhang, J Q Zhao, X L Zhang, C L Wen, X Y Song, W M Zhou
Objective: To investigate whether cancer-associated- fibroblasts (CAF), the key component of tumor microenvironment, regulate the chemoresistant capacity of lung cancer cell line A549 through SDF-1 secretion. Methods: Primary cell isolation techniques was used to isolate cancer-associated-fibroblasts from lung cancer patients. MTT assay was applied to determine the proliferation and chemoresistance of A549 cells. Quantative PCR was used to detect the mRNA changes of Bcl-xL. Western blotting was used to detect the protein expression of Bcl-xL...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535439/critical-focus-on-mechanisms-of-resistance-and-toxicity-of-m-tor-inhibitors-in-pancreatic-neuroendocrine-tumors
#10
REVIEW
L Antonuzzo, M Del Re, V Barucca, F Spada, G Meoni, G Restante, R Danesi, F Di Costanzo, N Fazio
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms representing less than 2% of all pancreatic malignancies. The PI3K-AKT-mTOR pathway is often deregulated in pNETs and seems to play a key role in tumorigenesis. Everolimus, an inhibitor of the mTOR pathway, has demonstrated efficacy in the treatment of pNETs. Nevertheless de novo or acquired drug resistance is responsible for disease progression and represents a major obstacle to overcome by clinicians. Blocking the PI3K/AKT/mTOR pathway may cover the supposed main mechanisms of resistance to everolimus...
May 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28535418/a-study-of-peritoneal-metastatic-xenograft-model-of-colorectal-cancer-in-the-treatment-of-hyperthermic-intraperitoneal-chemotherapy-with-raltitrexed
#11
Cen Qiu, Yueqi Li, Xin Liang, Yingxue Qi, Yiyang Chen, Xianke Meng, Hongtu Zheng, Ye Xu, Sanjun Cai, Guoxiang Cai, Jianwen Liu
Peritoneal metastasis of colorectal cancer is one of the most incident and fateful diseases among relapse cases. It shows a certain resistance to systemic chemotherapy. The perfusion system in clinic is complex and hard to be used in fundamental researches. This study aims at evaluating the effect of an improved hyperthermic intraperitoneal chemotherapy with Raltitrexed used in tumor-bearing mice with peritoneal metastatic colorectal carcinoma. The results showed that no severe adverse effect was observed. All control animals developed extensive peritoneal and mesenteric metastatic nodes...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28535182/characterization-of-liver-injury-oval-cell-proliferation-and-cholangiocarcinogenesis-in-glutathione-s-transferase-a3-knockout-mice
#12
Dana R Crawford, Zoran Ilic, Ian Guest, Ginger L Milne, John D Hayes, Stewart Sell
We recently generated glutathione S-transferase (GST) A3 knockout (KO) mice as a novel model to study the risk factors for liver cancer. GSTA3 KO mice are sensitive to the acute cytotoxic and genotoxic effects of aflatoxin B1 (AFB1), confirming the crucial role of GSTA3 in resistance to AFB1. We now report histopathological changes, tumor formation, biochemical changes and gender response following AFB1 treatment as well as the contribution of oxidative stress. Using a protocol of weekly 0.5 mg AFB1/kg administration, we observed extensive oval (liver stem) cell (OC) proliferation within 1-3 weeks followed by microvesicular lipidosis, megahepatocytes, nuclear inclusions, cholangiomas, and small nodules...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28535001/standardization-of-a375-human-melanoma-models-on-chicken-embryo-chorioallantoic-membrane-and-balb-c-nude-mice
#13
Stefana Avram, Dorina-Elena Coricovac, Ioana Zinuca Pavel, Iulia Pinzaru, Roxana Ghiulai, Flavia Baderca, Codruta Soica, Danina Muntean, Daciana E Branisteanu, Demetrios A Spandidos, Aristides M Tsatsakis, Cristina Adriana Dehelean
Cutaneous melanoma is a metastatic disease characterized by high resistance to treatment, the incidence of which has alarmingly increased worldwide over the past years. A thorough characterization of tumor onset, progression and metastasis is compulsory to overcome the gaps existent in melanoma biology. The present study suggests a well‑established protocol and a detailed histological description of human melanoma models in ovo and in vivo obtained by the inoculation of A375 cells to chick embryo chorioallantoic membrane (CAM) and Balb/c nude mice...
May 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534969/the-cdc2-cdk1-inhibitor-purvalanol-a-enhances-the-cytotoxic-effects-of-taxol-through-op18-stathmin-in-non-small-cell-lung-cancer-cells-in%C3%A2-vitro
#14
Xian Chen, Ying Liao, Dan Long, Ting Yu, Fang Shen, Xuechi Lin
Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534965/cucurbitacin%C3%A2-b-induces-autophagy-and-apoptosis-by-suppressing-cip2a-pp2a-mtorc1-signaling-axis-in-human-cisplatin-resistant-gastric-cancer-cells
#15
Xuewen Liu, Chao Duan, Juanli Ji, Te Zhang, Xiaoning Yuan, Yunfei Zhang, Wenjing Ma, Jingyuan Yang, Linsen Yang, Zhiguo Jiang, Huiliang Yu, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534509/a-novel-interaction-of-pak4-with-ppar%C3%AE-to-regulate-nox1-and-radiation-induced-epithelial-to-mesenchymal-transition-in-glioma
#16
D Kesanakurti, D Maddirela, Y K Banasavadi-Siddegowda, T-H Lai, Z Qamri, N K Jacob, D Sampath, S Mohanam, B Kaur, V K Puduvalli
Tumor recurrence in glioblastoma (GBM) is, in part, attributed to increased epithelial-to-mesenchymal transition (EMT) and enhanced tumor cell dissemination in adjacent brain parenchyma after ionizing radiation (IR). EMT is associated with aggressive behavior, increased stem-like characteristics and treatment resistance in malignancies; however, the underlying signaling mechanisms that regulate EMT are poorly understood. We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534338/-application-and-development-of-patient-derived-tumor-xenograft-model-in-translational-medicine-of-tumor
#17
Zhenqiang Wang, Zhenggang Zhu
Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28534251/sequencing-of-alk-inhibitors-in-alk-non-small-cell-lung-cancer
#18
REVIEW
Shirish M Gadgeel
Major therapeutic advances have occurred over the last several years in the management of advanced ALK+ NSCLC patients. Crizotinib was the first agent approved for the management of ALK+ NSCLC patients after it demonstrated significantly greater clinical benefit compared to chemotherapy. Several next generation ALK inhibitors have demonstrated clinical benefit in patients with crizotinib refractory NSCLC patients including in the CNS. Based on available data, therapy with a next generation ALK inhibitor can be initiated following therapy with crizotinib without any assessment of the molecular mechanisms of resistance...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28533948/radiosensitization-effect-of-hsa-mir-138-2-3p-on-human-laryngeal-cancer-stem-cells
#19
Ying Zhu, Li-Yun Shi, Yan-Min Lei, Yan-Hong Bao, Zhao-Yang Li, Fei Ding, Gui-Ting Zhu, Qing-Qing Wang, Chang-Xin Huang
BACKGROUND: Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28533658/checkpoint-inhibitors-in-gastrointestinal-cancers-expectations-and-reality
#20
EDITORIAL
Hampig Raphael Kourie, Samer Tabchi, Marwan Ghosn
Immune checkpoint inhibitors represent revolutionary anti-cancer agents, being rapidly approved in different malignancies and settings. Gastrointestinal (GI) cancers represent a wide variety of tumors with specific characteristics and different responses to various therapeutic alternatives; while some are chemo-sensitive others are chemo-resistant and only respond to more aggressive cytotoxic regimens, targeted therapies or a combination of both. Preliminary results of immune checkpoint inhibitors in some GI cancers are promising, namely in hepatocellular carcinoma, anal cancers and microsatellite instability high colorectal cancers...
May 7, 2017: World Journal of Gastroenterology: WJG
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