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gemcitabine resistance

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https://www.readbyqxmd.com/read/29344648/effect-of-midkine-on-gemcitabine-resistance-in-biliary-tract-cancer
#1
Yongliang Lu, Bing Yan, Huihui Guo, Li Qiu, Xinrong Sun, Xiang Wang, Qian Shi, Ying Bao
Gemcitabine‑based chemotherapy is one of the most effective and commonly used chemotherapeutic regimens for biliary tract cancer (BTC). However, development of resistance to this drug limits its efficacy. The present study aimed to explore the effects of midkine (MDK) on the resistance of BTC cells to gemcitabine. Cell viability and proliferation were measured by a Cell Counting Kit‑8 assay and 5‑ethynyl‑2'‑deoxyuridine staining, respectively. Western blot analysis was used to detect the expression of E‑cadherin and vimentin...
January 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344636/analysis-of-the-prolonged-infusion-of-dfp-10917-a-deoxycytidine-analog-as-a-therapeutic-strategy-for-the-treatment-of-human-tumor-xenografts-in-vivo
#2
Kenzo Iizuka, Chun Zhang, Kokoro Eshima, Cheng Jin, Kiyoshi Eshima, Masakazu Fukushima
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofranocyl-cytosine (DFP-10917, CNDAC) is a 2'-deoxycytidine analog with antitumor activity against various tumor cells. However, a clinically available therapeutic regimen for this compound needs to be established and its functional mechanisms in relation to the dosing schedule need to be clarified. In this study, we evaluated the antitumor activity and toxicity of DFP-10917 by varying the dose and administration schedule in human solid tumor and leukemia xenografts in vivo...
January 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344142/isolation-and-identification-of-tumor-initiating-cell-properties-in-human-gallbladder-cancer-cell-lines-using-the-marker-cluster-of-differentiation-133
#3
Jiwei Yu, Zhaohui Tang, Wei Gong, Mingdi Zhang, Zhiwei Quan
The present study aimed to isolate and identify the properties of the cluster of differentiation (CD)133+ subset in human gallbladder cancer cells. The CD133+ and CD133- subpopulations of the GBC-SD cell line were separated using immunomagnetic separation, and the biological features of the two subpopulations were analyzed in vitro and in vivo. In particular, the present study aimed to determine whether the two subpopulations were resistant to anti-tumor reagents and to identify the underlying molecular mechanisms involved...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344124/molecular-biological-characterization-and-drug-sensitivity-of-chidamide-resistant-non-small-cell-lung-cancer-cells
#4
Song'e Luo, Kai Ma, Hongxia Zhu, Shuren Wang, Mei Liu, Weina Zhang, Shufang Liang, Ningzhi Xu
Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical trials for various types of hematological and solid tumors. Although acquired resistance is common in chemotherapy, the mechanism of resistance to chidamide is poorly characterized. The goal of the present study was to explore, in detail, the mechanism for the induced resistance to chidamide, and investigate a potential cross-resistance to other chemotherapeutic drugs. A549 cells were exposed to gradually increasing chidamide concentrations to establish a chidamide-resistant non-small cell lung cancer cell line (A549-CHI-R)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29339176/the-absence-of-class-iii-%C3%AE-tubulin-is-predictive-of-a-favorable-response-to-nab-paclitaxel-and-gemcitabine-in-patients-with-unresectable-pancreatic-ductal-adenocarcinoma
#5
Akihisa Kato, Aya Naiki-Ito, Itaru Naitoh, Kazuki Hayashi, Takahiro Nakazawa, Shuya Shimizu, Yuji Nishi, Fumihiro Okumura, Inoue Tadahisa, Hiroki Takada, Hiromu Kondo, Michihiro Yoshida, Satoru Takahashi, Takashi Joh
The combined administration of nab-paclitaxel and gemcitabine (nab-P + Gem) is a standard chemotherapy for unresectable pancreatic ductal adenocarcinoma (UR-PDAC); thus, a predictive biomarker to identify patients best suited for nab-P + Gem therapy would be useful. Class III β-tubulin (TUBB3) has been reported to be a predictive marker for taxane resistance in various tumors. However, the correlation between TUBB3 expression and the response to nab-P + Gem in patients with UR-PDAC has not been evaluated. We retrospectively reviewed 75 patients with UR-PDAC who received nab-P + Gem...
January 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/29329575/microrna-200a-confers-chemoresistance-by-antagonizing-tp53inp1-and-yap1-in-human-breast-cancer
#6
San-Jian Yu, Liu Yang, Qi Hong, Xia-Ying Kuang, Gen-Hong Di, Zhi-Ming Shao
BACKGROUND: Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial-mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. METHODS: Breast cancer cells transfected with mimic or inhibitor for miR-200a was assayed for chemoresistance in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR) in breast cancer patients treated with preoperative chemotherapy...
January 12, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29329547/microfluidic-co-culture-of-pancreatic-tumor-spheroids-with-stellate-cells-as-a-novel-3d-model-for-investigation-of%C3%A2-stroma-mediated-cell-motility-and-drug-resistance
#7
Ji-Hyun Lee, Seul-Ki Kim, Iftikhar Ali Khawar, Su-Yeong Jeong, Seok Chung, Hyo-Jeong Kuh
BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance...
January 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#8
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29301792/therapy-educated-mesenchymal-stem-cells-enrich-for-tumor-initiating-cells
#9
Michael Timaner, Nitzan Letko-Khait, Ruslana Kotsofruk, Madeleine Benguigui, Ofrat Beyar-Katz, Chen Rachman-Tzemach, Ziv Raviv, Tomer Bronshtein, Marcelle Machluf, Yuval Shaked
Stromal cells residing in the tumor microenvironment contribute to the development of therapy resistance. Here we show that chemotherapy-educated mesenchymal stem cells (MSCs) promote therapy resistance via crosstalk with tumor-initiating cells (TICs), a resistant tumor cell subset that initiates tumorigenesis and metastasis. In response to gemcitabine chemotherapy, MSCs colonized pancreatic adenocarcinomas in large numbers and resided in close proximity to TICs. Furthermore, gemcitabine-educated MSCs promoted the enrichment of TICs in vitro and enhance tumor growth in vivo...
January 4, 2018: Cancer Research
https://www.readbyqxmd.com/read/29299930/difluoromethylornithine-combined-with-a-polyamine-transport-inhibitor-is-effective-against-gemcitabine-resistant-pancreatic-cancer
#10
Sarah B Gitto, Veethika Pandey, Jeremiah L Oyer, Alicja J Copik, Frederick C Hogan, Otto Phanstiel, Deborah A Altomare
Pancreatic ductal adenocarcinoma (PDAC) is highly chemo-resistant and has an extremely poor patient prognosis, with a survival rate at five years of <8%. There remains an urgent need for innovative treatments. Targeting polyamine biosynthesis through inhibition of ornithine decarboxylase with difluoromethylornithine (DFMO) has had mixed clinical success due to tumor escape via an undefined transport system, which imports exogenous polyamines and sustains intracellular polyamine pools. Here, we tested DFMO in combination with a polyamine transport inhibitor (PTI), Trimer44NMe, against Gemcitabine-resistant PDAC cells...
January 4, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29296182/microrna-410-3p-attenuates-gemcitabine-resistance-in-pancreatic-ductal-adenocarcinoma-by-inhibiting-hmgb1-mediated-autophagy
#11
Junjie Xiong, Dan Wang, Ailin Wei, Nengwen Ke, Yichao Wang, Jie Tang, Sirong He, Weiming Hu, Xubao Liu
Gemcitabine-based chemotherapy is the most common treatment option for pancreatic ductal adenocarcinoma (PDAC). However, it offers little therapeutic value in many cases due to the rapid development of chemoresistance. MicroRNAs (miRNAs) have been found to play pivotal roles in the chemotherapeutic resistance of PDAC. We found that miR-410-3p was significantly down-regulated in human pancreatic cancer xenograft (HPCx) tumor tissues from gemcitabine-treated mice. Low miR-410-3p expression correlated with gemcitabine resistance in HPCx tumors and PDAC cells as well as poor prognosis in PDAC patients...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29277822/bevacizumab-added-to-moderate-dose-chemotherapy-for-refractory-uterine-cancer
#12
Howard W Bruckner, Daniel Gurell, Azriel Hirschfeld
BACKGROUND/AIM: Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs. PATIENTS AND METHODS: Eligible patients (n=9) had high-grade endometrial tumors and had failed standard chemotherapy...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29274141/acquired-resistance-of-pten-deficient-cells-to-parp-inhibitor-and-ara-c-mediated-by-53bp1-loss-and-samhd1-overexpression
#13
Yu-Ting Wang, Bo Yuan, Hua-Dong Chen, Lin Xu, Yu-Nan Tian, Ao Zhang, Jin-Xue He, Ze-Hong Miao
With increasing uses of PARP inhibitors (PARPis) for cancer therapy, understanding their resistance is becoming urgent. However, acquired PARPi resistance in the PTEN-deficient background is poorly understood. We generated 3 PARPi-resistant PTEN-deficient glioblastoma U251 variants separately with olaparib (U251/OP), talazoparib (U251/TP) and simmiparib (U251/SP). These variants displayed consistent resistance (2.46~71.78-fold) to all 5 PARPis including niraparib and rucaparib and showed higher degrees of resistance to the PARPis to which the parental cells were more sensitive...
December 22, 2017: Cancer Science
https://www.readbyqxmd.com/read/29248457/malnutrition-in-pancreatic-ductal-adenocarcinoma-pda-dietary-pancreatic-enzymes-improve-short-term-health-but-stimulate-tumor-growth
#14
Yalda Zolghadri, Shreoshi Pal Choudhuri, Ozhan Ocal, Somayeh Layeghi- Ghalehsoukhteh, Feaven Berhe, Michael A Hale, Thomas M Wilkie
Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that resists efforts to identify better chemotherapeutics. PDA is associated with chronic pancreatitis and acinar cell dedifferentiation. This reduces enzyme production by the exocrine pancreas, resulting in digestive insufficiencies. Malabsorption of partially digested food can cause bloating, overfilled intestines, abdominal pain, excessive feces, steatorrhea, and malnutrition. These maladies affect quality of life and restrict treatment options for pancreatitis and PDA...
December 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29238973/demethylzeylasteral-zst93-inhibits-cell-growth-and-enhances-cell-chemosensitivity-to-gemcitabine-in-human-pancreatic-cancer-cells-via-apoptotic-and-autophagic-pathways
#15
Feng Wang, Xiaodong Tian, Zhengkui Zhang, Yongsu Ma, Xuehai Xie, Jian Liang, Chunxin Yang, Yinmo Yang
The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis, and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. Demethylzeylasteral (ZST93) is a novel triterpenoid monomer extracted from the xylem of Tripterygium roots. This study aimed to assess the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells...
December 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29233971/implication-of-4e-bp1-protein-dephosphorylation-and-accumulation-in-pancreatic-cancer-cell-death-induced-by-combined-gemcitabine-and-trail
#16
Androulla Elia, Ricky Henry-Grant, Charlotte Adiseshiah, Catherine Marboeuf, Rebecca J Buckley, Michael J Clemens, Satvinder Mudan, Stéphane Pyronnet
Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1...
December 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29232464/treatment-of-recurrent-ovarian-cancer
#17
S Pignata, S C Cecere, A Du Bois, P Harter, F Heitz
Despite optimal surgery and appropriate first-line chemotherapy, ∼70%-80% of patients with epithelial ovarian cancer will develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29221990/molecular-and-cellular-mechanisms-of-chemoresistance-in-pancreatic-cancer
#18
REVIEW
Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients...
November 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29218103/microrna-429-sensitizes-pancreatic-cancer-cells-to-gemcitabine-through-regulation-of-pdcd4
#19
Gang Yu, Benli Jia, Yunsheng Cheng, Lianbang Zhou, Bo Qian, Zhining Liu, Yong Wang
One of the features for pancreatic cancer is that it is often resistant to chemotherapy treatment, which is one of the major hindrances in the treatment of this malignancy. Previous studies indicated that the microRNAs (miRNAs) could mediate resistance of tumor cells to chemotherapy drug in the cancer progression. In the present study, we are aimed to examine whether microRNA-429 was involved in mediating the chemo-resistance of pancreatic cancer cells to gemcitabine. Firstly, a gemcitabine-resistant pancreatic cancer cell line (SW1990/GZ) derived from cell line (SW1990) was constructed and found to possess a decreased expression of miR-429 when it is compared to the original cell line...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29201179/gemcitabine-treatment-causes-resistance-and-malignancy-of-pancreatic-cancer-stem-like-cells-via-induction-of-lncrna-hotair
#20
Li Wang, Ping Dong, Weiguo Wang, Mingquan Huang, Bole Tian
Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma of the pancreas, despite the high risk of chemoresistance as a major disadvantage. In the past few years, significant advances have been made in the field of pancreatic cancer stem-like cells (CSCs) and their critical roles in drug resistance, invasion and metastasis, which are tightly regulated by long non-coding RNAs (lncRNAs). The present study demonstrated that HOX antisense intergenic RNA (HOTAIR) is not different between the pancreatic cancer cell line PANC-1 and its enriched CSC sub-population...
November 2017: Experimental and Therapeutic Medicine
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