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Gemcitabine

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https://www.readbyqxmd.com/read/28088627/the-telomere-binding-protein-trf2-is-required-for-metronomic-therapeutic-effects-of-gemcitabine-and-capecitabine
#1
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Gemcitabine and capecitabine are two effective anticancer agents against solid tumors. The pharmacological mechanisms have been known as incorporation into DNA and thereby inhibition of DNA synthesis. When used as metronomic chemotherapy, they may inhibit angiogenesis and induce immunity. In our previous study, we showed that low-dose gemcitabine caused telomere shortening by stabilizing TRF2 that was required for XPF-dependent telomere loss. In this report, we established a SKOV3.ip1 ascites cell model. Tumor-bearing mice were treated with low-dose gemcitabine (GEM) or capecitabine (CAP)...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#2
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087305/circulating-interleukin-18-il-18-is-a-predictor-of-response-to-gemcitabine-based-chemotherapy-in-patients-with-pancreatic-adenocarcinoma
#3
Çiğdem Usul Afsar, Mehmet Karabulut, Senem Karabulut, Halil Alis, Murat Gonenc, Nergiz Dagoglu, Murat Serilmez, Faruk Tas
BACKGROUND: This study was conducted to investigate the serum levels of interleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. METHODS: Thirty-three patients with PA were studied. Serum samples were obtained on first admission before any treatment. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis...
January 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28086830/sigma-2-receptor-agonist-derivatives-of-1-cyclohexyl-4-3-5-methoxy-1-2-3-4-tetrahydronaphthalen-1-yl-propyl-piperazine-pb28-induce-cell-death-via-mitochondrial-superoxide-production-and-caspase-activation-in-pancreatic-cancer
#4
Maria Laura Pati, John R Hornick, Mauro Niso, Francesco Berardi, Dirk Spitzer, Carmen Abate, William Hawkins
BACKGROUND: Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of cancer related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective pancreatic cancer cells death. METHODS: We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect the viability of diverse pancreatic cancer cells (human cell lines BxPC3, AsPC1, Mia PaCa-2, and Panc1 and mouse Panc-02, KCKO and KP-02) and how this is reflected in vivo in a tumor model...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28081543/randomised-phase-ii-trial-of-irinotecan-plus-s-1-in-patients-with-gemcitabine-refractory-pancreatic-cancer
#5
T Ioka, Y Komatsu, N Mizuno, A Tsuji, S Ohkawa, M Tanaka, H Iguchi, A Ishiguro, M Kitano, T Satoh, T Yamaguchi, K Takeda, M Kida, K Eguchi, T Ito, M Munakata, T Itoi, J Furuse, C Hamada, Y Sakata
BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m(-2) on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS)...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28081540/efficacy-of-fluoropyrimidine-based-chemotherapy-in-patients-with-advanced-biliary-tract-cancer-after-failure-of-gemcitabine-plus-cisplatin-retrospective-analysis-of-321-patients
#6
Bum Jun Kim, Changhoon Yoo, Kyu-Pyo Kim, Jaewon Hyung, Seong Joon Park, Baek-Yeol Ryoo, Heung-Moon Chang
BACKGROUND: We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS). METHODS: We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCIS between December 2010 and June 2015. Among 748 patients treated with first-line GEMCIS, 321 (43%) subsequently received fluoropyrimidine-based second-line systemic chemotherapy...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28079819/efficacy-and-toxicity-of-different-concurrent-chemoradiotherapy-regimens-in-the-treatment-of-advanced-cervical-cancer-a-network-meta-analysis
#7
Zhan-Zhao Fu, Kun Li, Yong Peng, Yue Zheng, Li-Yan Cao, Yun-Jie Zhang, Yong-Mei Sun
OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of different concurrent chemoradiotherapy (CCRT) regimens in the treatment of advanced cervical cancer (CC) by adopting a network meta-analysis. METHODS: We searched PubMed and Cochrane Library from the inception of these databases to September 2016, and all cohort studies (CSs) related to different CCRT regimens in the treatment of CC were included. A network analysis was adopted to compare the combination of direct and indirect evidence, to analyze the odds ratio (OR), and to draw a surface under the cumulative ranking curve of the efficacy and toxicity of different CCRT regimens for CC...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079805/toxicities-of-different-first-line-chemotherapy-regimens-in-the-treatment-of-advanced-ovarian-cancer-a-network-meta-analysis
#8
Chang-Ping Qu, Gui-Xia Sun, Shao-Qin Yang, Jun Tian, Jin-Ge Si, Yi-Feng Wang
BACKGROUND: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. METHODS: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28078124/advanced-biliary-tract-cancer-clinical-outcomes-with-abc-02-regimen-and-analysis-of-prognostic-factors-in-a-tertiary-care-center-in-the-united-states
#9
Rishi Agarwal, Arun Sendilnathan, Nabeela Iffat Siddiqi, Shuchi Gulati, Abhimanyu Ghose, Changchun Xie, Olugbenga Olanrele Olowokure
BACKGROUND: Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC) based on the outcomes in ABC-02 trial. Multiple factors can affect outcomes in these patients. This retrospective review evaluates the University of Cincinnati experience with GC in advanced intrahepatic (IHC)/extrahepatic cholangiocarcinoma (EHC) and gall bladder carcinoma (GBC). METHODS: In this study approved by University of Cincinnati IRB, retrospective analysis of advanced BTC patients seen between 01/2008 and 01/2015 was done...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#10
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28074226/synergistic-effects-of-host-b7-h4-deficiency-and-gemcitabine-treatment-on-tumor-regression-and-anti-tumor-t-cell-immunity-in-a-mouse-model
#11
Joanne Leung, Philippe St-Onge, John Stagg, Woong-Kyung Suh
B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control...
January 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28072706/a-randomized-multicenter-phase-iii-study-of-gemcitabine-combined-with-capecitabine-versus-gemcitabine-alone-as-first-line-chemotherapy-for-advanced-pancreatic-cancer-in-south-korea
#12
Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Ho Gak Kim, Myung Hwan Noh, Sang Hyub Lee, Yong-Tae Kim, Hyo Jung Kim, Chang Duck Kim, Dong Ki Lee, Kwang Bum Cho, Chang Min Cho, Jong Ho Moon, Dong Uk Kim, Dae Hwan Kang, Young Koog Cheon, Ho Soon Choi, Tae Hyeon Kim, Jae Kwang Kim, Jieun Moon, Hye Jung Shin, Si Young Song
BACKGROUND: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy. METHODS: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m plus Gem 1000 mg/m by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks)...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28071891/dual-enzymatic-reaction-assisted-gemcitabine-delivery-systems-for-programmed-pancreatic-cancer-therapy
#13
Haijie Han, Daniel Valdeperez, Qiao Jin, Bin Yang, Zuhong Li, Yulian Wu, Beatriz Pelaz, Wolfgang J J Parak, Jian Ji
Dual enzymatic reactions were introduced to fabricate programmed gemcitabine (GEM) nanovectors for targeted pancreatic cancer therapy. Dual-enzyme sensitive GEM nanovectors were prepared by conjugation of matrix metalloproteinase-9 (MMP-9) detachable poly(ethylene glycol) (PEG), cathepsin B cleavable GEM, and targeting ligand CycloRGD to CdSe/ZnS quantum dots (QDs). The GEM nanovectors decorated with PEG corona could avoid nonspecific interactions and exhibit prolonged blood circulation time. After GEM nanovectors were accumulated in tumor tissue by the enhanced permeability and retention (EPR) effect, the PEG corona can be removed by overexpressed MMP-9 in tumor tissue and RGD would be exposed, which was capable of facilitating cellular internalization...
January 10, 2017: ACS Nano
https://www.readbyqxmd.com/read/28068240/does-unintentional-splenic-radiation-predict-outcomes-after-pancreatic-cancer-radiation-therapy
#14
Awalpreet S Chadha, Guan Liu, Hsiang-Chun Chen, Prajnan Das, Bruce D Minsky, Usama Mahmood, Marc E Delclos, Yelin Suh, Gabriel O Sawakuchi, Sam Beddar, Matthew H Katz, Jason B Fleming, Milind M Javle, Gauri R Varadhachary, Robert A Wolff, Christopher H Crane, Xuemei Wang, Howard Thames, Sunil Krishnan
PURPOSE: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28066957/overexpression-of-ribonucleotide-reductase-subunit-m1-protein-predicts-shorter-survival-in-metastatic-bladder-cancer-patients-treated-with-gemcitabine-containing-combination-chemotherapy
#15
Nagahide Matsumura, Yasushi Nakamura, Yasuo Kohjimoto, Satoshi Nishizawa, Kazuro Kikkawa, Akinori Iba, Yoshiki Kodama, Isao Hara
OBJECTIVES: To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen. METHODS: We studied 52 patients with metastatic bladder cancer treated with the gemcitabine and cisplatin regimen by evaluating the relationship between the expression of two biomarkers, ribonucleotide reductase subunit M1 and excision repair cross complementing 1, by immunohistochemistry and clinical outcomes. RESULTS: The patients with low expression of ribonucleotide reductase subunit M1 showed a higher objective response rate by the gemcitabine and cisplatin regimen than those with high expression of ribonucleotide reductase subunit M1 (80...
January 9, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28065502/neoadjuvant-and-adjuvant-chemotherapy-use-in-upper-tract-urothelial-carcinoma
#16
Andrew Cohen, Kristine Kuchta, Sangtae Park
OBJECTIVE: To determine trends in neoadjuvant and adjuvant chemotherapy use for upper tract urothelial cancer and assess its effects on survival. MATERIALS AND METHODS: We identified all patients diagnosed with upper tract urothelial cancer who underwent surgical treatment in the SEER-Medicare database from 2002 to 2011. We collected and analyzed patient demographic, clinical, and pathologic characteristics. We strictly defined neoadjuvant and adjuvant chemotherapy and studied patients who met such criteria...
January 5, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28065383/molecular-alterations-contributing-to-pancreatic-cancer-chemoresistance
#17
REVIEW
Azam Rajabpour, Farzad Rajaei, Ladan Teimoori-Toolabi
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related death all over the world. This disease is difficult to treat and patients have an overall 5-year survival rate of less than 5%. Although two drugs, gemcitabine (GEM) and 5-fluorouracil (5-FU) have been shown to improve the survival rate of patients systematically, they do not increase general survival to a clinically acceptable degree. Lack of ideal clinical response of pancreatic cancer patients to chemotherapy is likely to be due to intrinsic and acquired chemoresistance of tumor cells...
December 28, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28064436/mir-181b-5p-ets1-and-c-met-pathway-exacerbates-the-prognosis-of-pancreatic-ductal-adenocarcinoma-after-radiation-therapy
#18
Hideo Tomihara, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Takehiro Noda, Tadafumi Asaoka, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens exhibited remnant tumor cells, which indicated that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the epithelial-mesenchymal transition (EMT) and the presence of cancer stem cells (CSCs) were reported to be associated with resistance in various cancers...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28064300/primary-cutaneous-t-cell-lymphoma-gamma-delta-subtype
#19
Y K Guan, C C Gan
Primary cutaneous T-cell lymphoma gamma-delta subtype is an extremely rare entity of all the cutaneous T-cell lymphomas. Our case provides an insight on clinical behavior and treatment response with feasible effective combination chemotherapy. We believe this will be of great interest to clinicians when facing this difficult clinical entity. We present a case of a 66-year-old Malay man with a threeweek history of rapidly growing skin nodules and plaques which spread throughout his body. He was commenced on combination chemotherapy gemcitabine, etoposide, and carboplatin with near complete remission on completion of second cycle but he defaulted...
October 2016: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/28063799/phase-ii-trial-of-dose-dense-pemetrexed-gemcitabine-and-bevacizumab-in-patients-with-advanced-non-small-cell-lung-cancer
#20
Bryan J Schneider, Gregory P Kalemkerian, Shirish M Gadgeel, Manuel Valdivieso, Deborah M Hackstock, Wei Chen, Lance K Heilbrun, John C Ruckdeschel, Antoinette J Wozniak
INTRODUCTION: Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC. METHODS: This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (400 mg/m(2)), gemcitabine (1200 mg/m(2)), and bevacizumab (10 mg/kg), given every 14 days in patients with untreated, advanced NSCLC...
December 2, 2016: Clinical Lung Cancer
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