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gemcitabine resistance

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https://www.readbyqxmd.com/read/29792309/metabolic-and-physiologic-imaging-biomarkers-of-the-tumor-microenvironment-predict-treatment-outcome-with-radiation-or-a-hypoxia-activated-prodrug-in-mice
#1
Shingo Matsumoto, Shun Kishimoto, Keita Saito, Yoichi Takakusagi, Jeeva P Munasinghe, Nallathamby Devasahayam, Charles Hart, Robert J Gillies, James B Mitchell, Murali C Krishna
Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here we define two imaging biomarkers that predict differences in tumor response to therapy: 1) partial oxygen pressure (pO2), measured by EPR imaging; and 2) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa-2, and Su...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#2
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29781033/microarray-analysis-of-circular-rna-expression-profiles-associated-with-gemcitabine-resistance-in-pancreatic-cancer-cells
#3
Chao Xu, Yue Yu, Fei Ding
Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29772221/mir-301a-plays-a-pivotal-role-in-hypoxia-induced-gemcitabine-resistance-in-pancreatic-cancer
#4
Guangtao Luo, Xiang Xia, Xiaofeng Wang, Kundong Zhang, Jun Cao, Tao Jiang, Qian Zhao, Zhengjun Qiu
Hypoxia is a hallmark of pancreatic cancer (PC) and is associated with gemcitabine resistance. However, the mechanisms underlying hypoxia-induced gemcitabine resistance in PC remain greatly unknown. Our previous work showed that miR-301a, a hypoxia-sensitive miRNA, is involved in PC metastasis under hypoxia via regulation of its target gene P63. Here, we showed that miR-301a was upregulated in a NF-κB independent manner under hypoxia and promoted gemcitabine resistance under hypoxic conditions in vitro. In addition, TAp63, a member of the P63 family, reversed hypoxia-induced gemcitabine resistance by promoting degradation of HIF-1α...
May 14, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29768008/striking-a-balance-between-carbonate-carbamate-linkage-bond-and-reduction-sensitive-disulfide-bond-bearing-linker-for-tailored-controlled-release-in-situ-covalently-albumin-binding-gemcitabine-prodrugs-promote-bioavailability-and-tumor-accumulation
#5
Huicong Zhang, Kuanglei Wang, Kexin Na, Dan Li, Zhenbao Li, Dongyang Zhao, Lu Zhong, Menglin Wang, Longfa Kou, Cong Luo, Haotian Zhang, Qiming Kan, Huaiwei Ding, Zhonggui He, Jin Sun
To address the challenge of rapid enzyme inactivation, poor tumor targeting, acquired drug resistance in gemcitabine (GEM) application, we report two groups of maleimide-functionalised GEM prodrugs conjugating covalently in situ with cys-34 of blood-circulating albumin, resulting in macromolecular prodrugs after intravenous administration. Specially, tailored and accurate controlled release was achieved through different combinations of linkage bonds relatively stable and labile (carbamate and carbonate, respectively) and linkers with or without insertion of a disulfide bond...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767464/platinum-resistant-recurrent-ovarian-cancer-with-long-survival-on-bevacizumab-and-gemcitabine
#6
Shinichi Komiyama, Tsuyoki Kugimiya, Chiaki Takeya, Rena Takahashi, Kaneyuki Kubushiro
Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin...
May 16, 2018: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/29765509/resveratrol-induced-downregulation-of-naf-1-enhances-the-sensitivity-of-pancreatic-cancer-cells-to-gemcitabine-via-the-ros-nrf2-signaling-pathways
#7
Liang Cheng, Bin Yan, Ke Chen, Zhengdong Jiang, Cancan Zhou, Junyu Cao, Weikun Qian, Jie Li, Liankang Sun, Jiguang Ma, Qingyong Ma, Huanchen Sha
NAF-1 (nutrient-deprivation autophagy factor-1), which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF-1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF-1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29752079/gemcitabine-loaded-gold-nanospheres-mediated-by-albumin-for-enhanced-anti-tumor-activity-combining-with-ct-imaging
#8
Zhiming Wang, Lina Chen, Zhongyun Chu, Chusen Huang, Yuankui Huang, Nengqin Jia
Currently, the development of a more effective therapy approach overcoming the resistance to chemotherapy for lung cancer still faces great challenges and requires further investigation. Herein, we fabricated gemcitabine (Gem) loaded gold nanospheres mediated by bovine serum albumin (Au@BSA) for the efficient delivery of therapeutic agents into the human pulmonary carcinoma cells (A549) and simultaneous computed tomography (CT) imaging. These nanoparticles (Au@BSA) with an approximate diameter of 10 nm were single crystals and prepared through a protein-directed facile one-pot synthesis via the reduction of chloroauric acid (HAuCl4 ) utilizing bovine serum albumin (BSA) as the stabilizer...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29749405/natural-compound-oblongifolin-c-confers-gemcitabine-resistance-in-pancreatic-cancer-by-downregulating-src-mapk-erk-pathways
#9
Yang Li, Zhichao Xi, Xiaoqiong Chen, Shuangfan Cai, Chen Liang, Zhen Wang, Yingyi Li, Hongsheng Tan, Yuanzhi Lao, Hongxi Xu
Gemcitabine (GEM)-induced drug resistance is the major reason for the failure of chemotherapy in pancreatic cancer (PC). In this study, we found that Oblongifolin C (OC) efficiently inhibited PC cell proliferation by inducing G0/G1 arrest and apoptosis. Also, our mechanism study demonstrated that OC re-sensitized the GEM-resistant PC cells through the ubiquitin-proteasome-dependent degradation of Src, and then downregulating the MAPK pathway. Knockdown of Src plus OC resulted in a greater inhibitory effect in GEM-resistant PC cells...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29742358/application-of-integrated-drug-screening-kinome-analysis-to-identify-inhibitors-of-gemcitabine-resistant-pancreatic-cancer-cell-growth
#10
Linas J Krulikas, Ian M McDonald, Benjamin Lee, Denis O Okumu, Michael P East, Thomas S K Gilbert, Laura E Herring, Brian T Golitz, Carrow I Wells, Allison D Axtman, William J Zuercher, Timothy M Willson, Dmitri Kireev, Jen Jen Yeh, Gary L Johnson, Antonio T Baines, Lee M Graves
Continuous exposure of a pancreatic cancer cell line MIA PaCa-2 (MiaS ) to gemcitabine resulted in the formation of a gemcitabine-resistant subline (MiaR ). In an effort to discover kinase inhibitors that inhibited MiaR growth, MiaR cells were exposed to kinase inhibitors (PKIS-1 library) in a 384-well screening format. Three compounds (UNC10112721A, UNC10112652A, and UNC10112793A) were identified that inhibited the growth of MiaR cells by more than 50% (at 50 nM). Two compounds (UNC10112721A and UNC10112652A) were classified as cyclin-dependent kinase (CDK) inhibitors, whereas UNC10112793A was reported to be a PLK inhibitor...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29739052/mechanism-comparison-of-gemcitabine-and-dasatinib-resistant-pancreatic-cancer-by-integrating-mrna-and-mirna-expression-profiles
#11
Zongjing Chen, Liang Zhao, Keqing Shi, Bicheng Chen
BACKGROUND: Pancreatic cancer is one of the most lethal cancers with limited treatment options. Gemcitabine has been the standard drug for patients with advanced pancreatic cancer. Dasatinib is a competitive inhibitor of Src kinase, which has shown promise in treatment of pancreatic cancer. Several studies have revealed the drug resistant mechanism of gemcitabine or dasatinib in human cancers; however, few reports focused on the different mechanisms of gemcitabine and dasatinib resistance in pancreatic cancer...
May 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29727019/bitter-melon-juice-exerts-its-efficacy-against-pancreatic-cancer-via-targeting-both-bulk-and-cancer-stem-cells
#12
Deepanshi Dhar, Gagan Deep, Sushil Kumar, Michael F Wempe, Komal Raina, Chapla Agarwal, Rajesh Agarwal
Pancreatic cancer (PanC) is one of the deadliest malignancies worldwide and frontline treatment with gemcitabine becomes eventually ineffective due to increasing PanC resistance, suggesting additional approaches are needed to manage PanC. Recently, we have shown the efficacy of bitter melon juice (BMJ) against PanC cells, including those resistant to gemcitabine. Since cancer stem cells (CSCs) are actively involved in PanC initiation, progression, relapse and drug-resistance, here we assessed BMJ ability in targeting pancreatic cancer-associated cancer stem cells (PanC-CSCs)...
May 4, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29715094/combined-gemcitabine-and-metronidazole-is-a-promising-therapeutic-strategy-for-cancer-stem-like-cholangiocarcinoma
#13
Makoto Kawamoto, Masayo Umebayashi, Hiroto Tanaka, Norihiro Koya, Sinichiro Nakagawa, Ken Kawabe, Hideya Onishi, Masafumi Nakamura, Takashi Morisaki
BACKGROUND/AIM: Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). MATERIALS AND METHODS: We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29701272/dck-negatively-regulates-the-nrf2-are-axis-and-ros-production-in-pancreatic-cancer
#14
Qiangsheng Hu, Yi Qin, Jinfeng Xiang, Wensheng Liu, Wenyan Xu, Qiqing Sun, Shunrong Ji, Jiang Liu, Zheng Zhang, Quanxing Ni, Jin Xu, Xianjun Yu, Bo Zhang
OBJECTIVES: Decreased deoxycytidine kinase (dCK) expression is a reported indicator of gemcitabine efficacy in pancreatic cancer, due to the impact of this kinase on gemcitabine metabolism. The transcription factor NF-E2 p45-related factor 2 (NRF2, also called Nfe2l2), a master regulator of redox homoeostasis, has been reported to tightly control the expression of numerous ROS-detoxification genes and participates in drug resistance. However, the contribution of dCK to the NRF2 signalling axis has seldom been discussed and needs investigation...
April 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29700299/epigenetic-reprogramming-using-5-azacytidine-promotes-an-anti-cancer-response-in-pancreatic-adenocarcinoma-cells
#15
Luc Gailhouste, Lee Chuen Liew, Izuho Hatada, Hitoshi Nakagama, Takahiro Ochiya
Curative management of pancreatic adenocarcinoma is limited because this malignancy remains resistant to most chemotherapeutic drugs. Strategies that reverse epigenetic alterations offer a unique opportunity for cancer cell reprogramming, which is valuable for development of new treatments. The aim of this work was to reprogram pancreatic ductal adenocarcinoma (PDAC) cells toward a less aggressive and drug-responsive phenotype. The process applied is called "epigenetic reprogramming". To evaluate the efficiency of PDAC epigenetic reprogramming, we assessed tumor growth and drug response in PANC-1 cells after exposure to non-cytotoxic doses of the demethylating agent 5-azacytidine (5-AZA)...
April 27, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29695571/heat-shock-protein-27-expression-in-eus-fna-samples-can-predict-gemcitabine-sensitivity-in-pancreatic-cancer
#16
Michitaka Kawano, Seiji Kaino, Shogo Amano, Shuhei Shinoda, Shigeyuki Suenaga, Manabu Sen-Yo, Isao Sakaida
BACKGROUND/AIM: Gemcitabine (GEM) sensitivity can help select the appropriate treatment for pancreatic cancer. We examined the association between HSP27 expression and GEM sensitivity. MATERIALS AND METHODS: A total of 19 patients with unresectable pancreatic cancer who underwent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) were enrolled and treated with GEM alone. We measured the expression of heat shock protein 27 (HSP27) and phosphorylated HSP27(p-HSP27) in EUS-FNA samples and evaluated the effects of GEM treatment...
May 2018: In Vivo
https://www.readbyqxmd.com/read/29693166/hypoxia-induced-autophagy-promotes-gemcitabine-resistance-in-human-bladder-cancer-cells-through-hypoxia-inducible-factor-1%C3%AE-activation
#17
Xiaoyu Yang, Hubin Yin, Yunzhi Zhang, Xinyuan Li, Hang Tong, Yizhou Zeng, Quan Wang, Weiyang He
Overcoming the chemoresistance of bladder cancer is a pivotal obstacle in clinical treatments. Hypoxia widely exists in solid tumors and has been demonstrated to contribute to chemoresistance through hypoxia-inducible factor 1α (HIF‑1α)-mediated autophagy in several types of cancer. However, it is unclear whether HIF‑1α-mediated autophagy and chemoresistance occur in bladder cancer. The present study demonstrated that HIF‑1α was overexpressed in 20 bladder cancer tissues compared with matched paracarcinoma tissues...
April 24, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29685527/survival-of-patients-with-non-resectable-chemotherapy-resistant-colorectal-cancer-liver-metastases-undergoing-conventional-lipiodol-based-transarterial-chemoembolization-ctace-palliatively-versus-neoadjuvantly-prior-to-percutaneous-thermal-ablation
#18
Thomas J Vogl, Maximilian Lahrsow, Moritz H Albrecht, Renate Hammerstingl, Zachary M Thompson, Tatjana Gruber-Rouh
PURPOSE: To determine overall (OS) and progression-free survival (PFS) for cTACE alone and in combination with percutaneous thermal ablation in patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases (CRLM). MATERIAL AND METHODS: The study included 452 patients undergoing 2654 repetitive cTACE treatments of CRLM. 233 patients were treated palliatively using only cTACE, whereas 219 patients were treated with cTACE in a neoadjuvant intend with subsequent thermal ablation (either microwave ablation or laser-induced thermotherapy)...
May 2018: European Journal of Radiology
https://www.readbyqxmd.com/read/29674277/long-noncoding-rna-foxd2-as1-accelerates-the-gemcitabine-resistance-of-bladder-cancer-by-sponging-mir-143
#19
Qing An, Liyang Zhou, Nan Xu
Increasing evidences have proved that long noncoding RNAs (lncRNAs) modulate the tumorigenesis of bladder cancer involved in multiple pathophysiological processes. In the study, we investigate the role of lncRNA FOXD2-AS1 in the gemcitabine (GEM) resistant bladder cancer and explore its potential mechanism. Results showed that lncRNA FOXD2-AS1 was high-expressed in gemcitabine-resistant bladder cancer cells. In vitro experiments, FOXD2-AS1 knockdown suppressed the 50% inhibitive concentration (IC50) of gemcitabine, drug-resistance related genes (MDR1, MRP2, LRP1) expression, invasion and ABCC3 protein expression in gemcitabine-resistant bladder cancer cells (T24/GEM, 5637/GEM)...
April 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29623758/targeting-altered-cancer-methionine-metabolism-with-recombinant-methioninase-rmetase-overcomes-partial-gemcitabine-resistance-and-regresses-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model-of-pancreatic-cancer
#20
Kei Kawaguchi, Kentaro Miyake, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Thinzar M Lwin, Takashi Higuchi, Tasuku Kiyuna, Masuyo Miyake, Hiromichi Oshiro, Michael Bouvet, Michiaki Unno, Robert M Hoffman
Pancreatic cancer is a recalcitrant disease. Gemcitabine (GEM) is the most widely-used first-line therapy for pancreatic cancer, but most patients eventually fail. Transformative therapy is necessary to significantly improve the outcome of pancreatic cancer patients. Our and other's previous work has demonstrated tumors have an elevated requirement for methionine and are susceptible to methionine restriction. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of pancreatic cancer to determine the efficacy of recombinant methioninase (rMETase) to effect methionine restriction and thereby overcome GEM-resistance...
April 6, 2018: Cell Cycle
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