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https://www.readbyqxmd.com/read/28739697/z-360-suppresses-tumor-growth-in-mia-paca-2-bearing-mice-via-inhibition-of-gastrin-induced-anti-apoptotic-effects
#1
Yoshihiro Shiomi, Makoto Yoshimura, Kazumasa Kuki, Yuko Hori, Takao Tanaka
BACKGROUND/AIM: The aim of the study was to evaluate the anti-tumor mechanism of Z-360, a gastrin/cholecystokinin-2 receptor (CCK2R) antagonist, in MIA PaCa-2 cells and in a subcutaneous xenograft mice model. MATERIALS AND METHODS: The anti-tumor effects of Z-360 and/or gemcitabine were monitored using a MIA PaCa-2 xenograft model. The effect of Z-360 on apoptosis in the model was examined by TUNEL staining and real-time PCR analysis and the effect in MIA PaCa-2 cells stably expressing human CCK2R was also evaluated by caspase-3/7 activity...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739504/improved-metabolic-stability-and-therapeutic-efficacy-of-a-novel-molecular-gemcitabine-phospholipid-complex
#2
Chander Parkash Dora, Varun Kushwah, Sameer S Katiyar, Pradeep Kumar, Viness Pillay, Sarasija Suresh, Sanyog Jain
The aim of the present research is to increase lipid solubility, metabolic stability and therapeutic efficacy of water soluble gemcitabine (GEM) via phospholipid complex (PC) formation. A novel phospholipid complex of GEM was successfully prepared and optimized. Physical interaction of GEM with phospholipid was evaluated by DSC, FT-IR, (1)H NMR, (31)P-NMR and P-XRD. SEM images of GEM-PC showed rough structure and TEM images of diluted aqueous dispersion of GEM-PC showed micellar structure. In silico study also revealed the significant interaction between drug and phospholipid...
July 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28738680/photothermal-effect-enhanced-cascade-targeting-strategy-for-improved-pancreatic-cancer-therapy-by-gold-nanoshell-mesoporous-silica-nanorod
#3
Ruifang Zhao, Xuexiang Han, Yiye Li, Hai Wang, Tianjiao Ji, Yuliang Zhao, Guangjun Nie
Pancreatic cancer, one of the leading causes of cancer-related mortality, is characterized by desmoplasia and hypovascular cancerous tissue, with a 5-year survival rate of less than 8%. To overcome the severe resistance of pancreatic cancer to conventional therapies, we synthesized gold nanoshell-coated rod-like mesoporous silica (GNRS) nanoparticles which integrated cascade tumor targeting (mediated by photothermal effect and molecular receptor binding) and photothermal treatment-enhanced gemcitabine chemotherapy, under mild near infrared laser irradiation condition...
July 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28736643/comparison-of-efficacy-and-toxicity-of-folfirinox-and-gemcitabine-with-nab-paclitaxel-in-unresectable-pancreatic-cancer
#4
Tetsuhito Muranaka, Masaki Kuwatani, Yoshito Komatsu, Kentaro Sawada, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Satoshi Yuki, Yoshimasa Kubota, Kimitoshi Kubo, Shuhei Kawahata, Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
BACKGROUND: Irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) and the combination regimen of gemcitabine and nanoparticle albumin-bound paclitaxel (GnP) (nab-PTX) improve the prognosis of patients with metastatic pancreatic cancer. However, no study has compared the efficacy of the two regimens. We compared retrospectively the efficacy and safety of the two regimens in patients with unresectable pancreatic cancer. METHODS: Thirty-eight patients with unresectable locally advanced or metastatic pancreatic cancer received FOLFIRINOX or GnP as first-line chemotherapy between December 2013 and September 2015...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736642/gemcitabine-nab-paclitaxel-as-second-line-therapy-following-folfirinox-in-metastatic-advanced-pancreatic-cancer-retrospective-analysis-of-response
#5
Khanh T Nguyen, Aparna Kalyan, H Scott Beasley, Aatur D Singhi, Weijing Sun, Herbert J Zeh, Daniel Normolle, Nathan Bahary
BACKGROUND: Given the tolerability of nPG in first-line therapy, we desired to evaluate the response and toxicity profiles of second-line gemcitabine with nab-paclitaxel (nPG) following FOLFIRINOX. Methods: We retrospectively identified 30 patients who received first-line FOLFIRINOX for unresectable or metastatic pancreatic adenocarcinoma followed by second-line nPG. Response was evaluated by RECIST criteria and carbohydrate antigen 19-9 (CA19-9) change. RESULTS: Median age was 63 years with 77% percent having metastatic disease...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736631/shifting-paradigm-of-developing-biologics-for-the-treatment-of-pancreatic-adenocarcinoma
#6
REVIEW
Ying Zeng, Agnieszka A Rucki, Xu Che, Lei Zheng
Pancreatic adenocarcinoma is still widely considered as a deadly disease even though there are substantial therapeutic developments in the past decade. Using combinational chemotherapy regimens, represented by gemcitabine plus nab-paclitaxel and FOLFIRINOX, was able to improve overall survival in patients with advanced disease to a limited extent. It has been a challenge to develop targeted therapies that are focused on the neoplasm cells of pancreatic adenocarcinoma. Recently, targeting the stroma and immune compartments of pancreatic adenocarcinoma has shown promising results...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28733542/use-of-a-genome-wide-haploid-genetic-screen-to-identify-treatment-predicting-factors-a-proof-of-principle-study-in-pancreatic-cancer
#7
Yuk Ting Ma, Sarah M Leonard, Naheema Gordon, Jennifer Anderton, Claire James, David Huen, Ciaran B Woodman, Daniel H Palmer
The ability to develop a comprehensive panel of treatment predicting factors would significantly improve our ability to stratify patients for cytotoxic or targeted therapies, and prevent patients receiving ineffective treatments. We have investigated if a recently developed genome-wide haploid genetic screen can be used to reveal the critical mediators of response to anticancer therapy. Pancreatic cancer is known to be highly resistant to systemic therapy. Recently epigenetic changes have been shown to be a key determinant in the maintenance of subpopulations of cancer cells with high-level resistance to cytotoxic therapy...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#8
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733220/pan-mtor-inhibitor-mln0128-is-effective-against-intrahepatic-cholangiocarcinoma-induced-in-mice-by-akt-and-yap-co-expression
#9
Shanshan Zhang, Xinhua Song, Dan Cao, Zhong Xu, Biao Fan, Li Che, Junjie Hu, Bin Chen, Mingjie Dong, Maria G Pilo, Antonio Cigliano, Katja Evert, Silvia Ribback, Frank Dombrowski, Rosa M Pascale, Antonio Cossu, Gianpaolo Vidili, Alberto Porcu, Maria M Simile, Giovanni M Pes, Gianluigi Giannelli, John Gordan, Lixin Wei, Matthias Evert, Wenming Cong, Diego F Calvisi, Xin Chen
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy without effective treatment options. MLN0128, a second-generation pan-mTOR inhibitor, shows efficacy for multiple tumor types. METHODS: We established a novel ICC mouse model via hydrodynamic transfection of activated forms of AKT (myr-AKT) and Yap (YapS127A) protooncogenes (that will be referred to as AKT/YapS127A). Genetic approaches were applied to study the requirement of mTORC1 and mTORC2 in mediating AKT/YapS127A driven tumorigenesis...
July 18, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28732877/enhanced-antitumor-activity-of-gemcitabine-by-polysaccharide-induced-nk-cell-activation-and-immune-cytotoxicity-reduction-in-vitro-vivo
#10
Xin Xie, Yiran Zhou, Xue Wang, Jian Guo, Jingwen Li, Hongye Fan, Jie Dou, Baiyong Shen, Changlin Zhou
The polysaccharide SEP has been reported to activate NK and T cells via TLR2/4. Here, the combination of gemcitabine (GEM) and SEP against HepG-2 was investigated. SEP apparently enhanced antitumor activity of gemcitabine against liver cancer through stimulating NKG2D and DAP10/Akt pathway to activate NK cells. The NKG2D upregulation could improve the sensitivity of NK-92 cells targeting to its ligand MICA expressed on HepG-2 cells. Meanwhile, GEM up-regulated MICA expression and attenuated soluble MICA secretion through inhibiting ADAM10 expression, which in turn enhanced the cytotoxicity of NK-92 cells against cancer cells...
October 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28728891/impact-of-adjuvant-chemotherapy-on-survival-in-patients-with-intrahepatic-cholangiocarcinoma-a-multi-institutional-analysis
#11
Bradley N Reames, Fabio Bagante, Aslam Ejaz, Gaya Spolverato, Andrea Ruzzenente, Matthew Weiss, Sorin Alexandrescu, Hugo P Marques, Luca Aldrighetti, Shishir K Maithel, Carlo Pulitano, Todd W Bauer, Feng Shen, George A Poultsides, Oliver Soubrane, Guillaume Martel, Bas G Koerkamp, Alfredo Guglielmi, Endo Itaru, Timothy M Pawlik
BACKGROUND: The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database. METHODS: 1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS)...
July 17, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28724327/gemcitabine-hydrochloride-loaded-liposomes-and-nanoparticles-comparison-of-encapsulation-efficiency-drug-release-particle-size-and-cytotoxicity
#12
Tahir Emre Yalcin, Sibel Ilbasmis-Tamer, Burçin Ibisoglu, Aysun Özdemir, Mustafa Ark, Sevgi Takka
The aim of this study is to formulate and compare the physicochemical properties of negatively-charged liposomes and poly-lactide-co-glycolide (PLGA) nanoparticles loaded with gemcitabine hydrochloride. The influence of the formulation variables on the liposome and nanoparticle properties on particle size, zeta potential, encapsulation efficiency and drug release were evaluated. Although the PEGylated nanoparticles and PEGylated liposomes were of the same size (∼200 nm), the encapsulation efficiency was 1...
July 20, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28722678/optimal-adjuvant-chemotherapy-for-resected-pancreatic-adenocarcinoma-a-systematic-review-and-network-meta-analysis
#13
Jian-Bo Xu, Bin Jiang, Ya Chen, Fu-Zhen Qi, Jian-Huai Zhang, Hang Yuan
Adjuvant chemotherapy improves survival in patients with resected pancreatic cancer but the optimal regimen remains unclear. We aim to compare all possible adjuvant chemotherapy in terms of overall survival and toxic effects. Pubmed, Trial registries and Cochrane library databases for randomized controlled trials were searched until November 2016. Thirteen trials were included for network analysis and the hazard ratios (HRs) for survival and odds ratios for toxic effects were assessed via Aggregate Data Drug Information System software...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722661/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#14
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722177/metformin-induced-alterations-in-nucleotide-metabolism-cause-5-fluorouracil-resistance-but-gemcitabine-susceptibility-in-oesophageal-squamous-cell-carcinoma
#15
Charissa Mynhardt, Leonard Howard Damelin, Rupal Jivan, Jade Peres, Sharon Prince, Robin Bruce Veale, Demetra Mavri-Damelin
5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than 5-fold and 6-fold respectively, as assessed by MTT assay...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28720574/fructose-1-6-bisphosphatase-inhibits-erk-activation-and-bypasses-gemcitabine-resistance-in-pancreatic-cancer-by-blocking-iqgap1-mapk-interaction
#16
Xin Jin, Yunqian Pan, Liguo Wang, Tao Ma, Lizhi Zhang, Amy H Tang, Daniel D Billadeau, Heshui Wu, Haojie Huang
Dysregulation of the mitogen-activated protein kinase (MAPK) pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and extracellular signaling-regulated kinases (ERK). Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28719890/effect-of-neoadjuvant-nab-paclitaxel-plus-gemcitabine-therapy-on-overall-survival-in-patients-with-borderline-resectable-pancreatic-cancer-a-prospective-multicenter-phase-ii-trial-nac-ga-trial
#17
Ken-Ichi Okada, Toshio Shimokawa, Seiko Hirono, Manabu Kawai, Masayuki Sho, Sohei Satoi, Ippei Matsumoto, Hidetoshi Eguchi, Yoshiaki Murakami, Suguru Yamada, Mariko Doi, Hiroki Yamaue
We conducted a prospective multicenter phase II trial of patients with borderline resectable pancreatic carcinoma to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival (OS). The clinical trial primarily evaluated OS time from the first day of protocol therapy as a primary endpoint. The secondary endpoints were recurrence-free survival from the first day of protocol therapy, safety of the protocol therapy (adverse effect), morbidity based on the Clavien Dindo classification of more than III, response rate, preoperative/postoperative tumor marker (CA 19-9, CEA), rate of normalization, reduction rate of the maximum standardized uptake value on positron emission tomography-computed tomography (limited to institutions where positron emission tomography-computed tomography was available), chemotherapeutic effect grade based on Evans' classification, resection rate, R0 resection rate, surgical data (operative time, blood loss, transfusion, postoperative hospital day), overall morbidity rates (reoperation, rate of readmission, mortality), patient rate in postoperative adjuvant therapy (entry rate, completion rate), dose intensity, quality of life regarding fatigue and malaise assessed by the questionnaire of FACIT-F (Japanese version), and peripheral sensory neuropathy assessed by the questionnaire of the FACT/GOG-NTX subscale (version 4; Japanese version)...
July 19, 2017: Oncology
https://www.readbyqxmd.com/read/28719220/egfr-targeted-cationic-polymeric-mixed-micelles-for-co-delivery-of-gemcitabine-and-mir-205-for-treating-advanced-pancreatic-cancer
#18
Goutam Mondal, Saud Almawash, Amit Kumar Chaudhary, Ram I Mahato
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy...
July 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28717760/pilot-survey-of-breast-cancer-management-in-sub-saharan-africa
#19
Verna D N K Vanderpuye, Olufunmilayo I Olopade, Dezheng Huo
PURPOSE: To understand the current state of breast cancer management in sub-Saharan Africa. METHODS: We conducted an anonymous online survey of breast cancer management among African Organization for Research and Treatment in Cancer (AORTIC) members by using a 42-question structured questionnaire in both English and French in 2013. RESULTS: Twenty members from 19 facilities in 14 countries responded to the survey. Twelve members (60%) belonged to a multidisciplinary breast cancer team...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28716944/potent-competitive-inhibition-of-human-ribonucleotide-reductase-by-a-nonnucleoside-small-molecule
#20
Md Faiz Ahmad, Intekhab Alam, Sarah E Huff, John Pink, Sheryl A Flanagan, Donna Shewach, Tessianna A Misko, Nancy L Oleinick, William E Harte, Rajesh Viswanathan, Michael E Harris, Chris Godfrey Dealwis
Human ribonucleotide reductase (hRR) is crucial for DNA replication and maintenance of a balanced dNTP pool, and is an established cancer target. Nucleoside analogs such as gemcitabine diphosphate and clofarabine nucleotides target the large subunit (hRRM1) of hRR. These drugs have a poor therapeutic index due to toxicity caused by additional effects, including DNA chain termination. The discovery of nonnucleoside, reversible, small-molecule inhibitors with greater specificity against hRRM1 is a key step in the development of more effective treatments for cancer...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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