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https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#1
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28346381/multifaceted-applications-of-chitosan-in-cancer-drug-delivery-and-therapy
#2
REVIEW
Anish Babu, Rajagopal Ramesh
Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy...
March 27, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28345737/-meningeal-carcinomatosis-in-breast-cancer-from-diagnosis-to-treatment
#3
REVIEW
C Elm'hadi, Z Es Sbai, M Reda Khmamouche, M Toreis, R Tanz, H Errihani, M Ichou
The appearance of meningeal carcinomatosis in breast cancer is an event that is being reported increasingly more frequently in the literature. It seems to be related with the lengthening of the patients' lives, improved sensitivity to diagnostic imaging and impermeability of the blood-brain barrier to the chemotherapeutic agents. It is an evolutionary form that affirms the metastatic invasion of the subarachnoidal space and is correlated with limited survival. Its diagnosis is difficult, due to the lack of specificity of the clinical signs dominated by headaches, cognitive disorders and possible signs and symptoms of progressive focal lesions...
April 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28344814/the-role-of-chemotherapy-and-new-targeted-agents-in-the-management-of-primary-prostate-cancer
#4
Sanjeev Srinivas Kumar, Simon Pacey
While early treatment of primary prostate cancer is very effective, the incidence of primary prostate cancer continues to rise and therefore the detection of men with high-risk non-metastatic prostate cancer and their subsequent management is becoming increasingly important. There continues to be no molecularly-targeted or chemotherapeutic options with proven, statistically significant survival benefit in this setting. However, there are indications that further risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer, ultimately providing biological markers that could guide a more personalised approach to therapy selection...
December 2016: Journal of Clinical Urology
https://www.readbyqxmd.com/read/28343976/prophylactic-cranial-irradiation-versus-observation-in-patients-with-extensive-disease-small-cell-lung-cancer-a-multicentre-randomised-open-label-phase-3-trial
#5
Toshiaki Takahashi, Takeharu Yamanaka, Takashi Seto, Hideyuki Harada, Hiroshi Nokihara, Hideo Saka, Makoto Nishio, Hiroyasu Kaneda, Koichi Takayama, Osamu Ishimoto, Koji Takeda, Hiroshige Yoshioka, Motoko Tachihara, Hiroshi Sakai, Koichi Goto, Nobuyuki Yamamoto
BACKGROUND: Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer. However, because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses, concerns have been raised about these findings. We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer...
March 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28343282/effective-chemotherapy-of-heterogeneous-and-drug-resistant-early-colon-cancers-by-intermittent-dose-schedules-a-computer-simulation-study
#6
David E Axelrod, Sudeepti Vedula, James Obaniyi
PURPOSE: The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function...
March 25, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#7
Tikam Chand Dakal, Rajender Kumar, Dindial Ramotar
Human organic cation transporters (hOCTs) belong to solute carriers (SLC) 22 family of membrane proteins that play a central role in transportation of chemotherapeutic drugs for several clinical and pathological conditions, including cancer and diabetes. These transporters mediate drug transport; however, the precise mechanism of drug-binding and transport by them is not fully uncovered yet, partly due to unavailability of any crystal structure record. In this work, we performed a multi-phasic approach to compute the 3D structural models of seven human organic cation transporters (hOCTs) starting from primary protein sequence...
March 18, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28341137/targeting-hepatocellular-carcinoma-with-piperine-by-radical-mediated-mitochondrial-pathway-of-apoptosis-an-in-vitro-and-in-vivo-study
#8
Gunasekaran Vetrichelvi, Kannan Elangovan, S Niranjali Devaraj
Redox mediated cancer therapeutics are of immense interest in the recent decade due to their anticancer activity. Piperine is the principal alkaloid of black and long pepper. Although its anticancer activity has been reported in number of cancers , the precise molecular mechanism of action remains to be unravelled. Hence, in this study, for the first time, we delineated the mechanistic insight into the effect of piperine against hepatocellular carcinoma (HCC).MTT analysis determined the dose and time dependent cytotoxicity of piperine against Hep G2 cells...
March 21, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#9
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#10
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28339935/nephrotoxicity-of-anticancer-treatment
#11
Jolanta Malyszko, Klaudia Kozlowska, Leszek Kozlowski, Jacek Malyszko
Severe adverse systemic drug events occur commonly as a result of treatment of cancer patients. Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. A variety of renal disease and electrolyte disorders can result from the drugs that are used to treat malignant disease. The kidneys are a major elimination pathway for many antineoplastic drugs and their metabolites. Tumour lysis syndrome, an emergency in haematooncology, occurs most often after the initiation of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukaemia...
October 6, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339092/macc1-decreases-the-chemosensitivity-of-gastric-cancer-cells-to-oxaliplatin-by-regulating-fasn-expression
#12
Jiangman Duan, Lishan Chen, Minyu Zhou, Jingwen Zhang, Li Sun, Na Huang, Jianping Bin, Yulin Liao, Wangjun Liao
The effect of chemotherapeutic agents is limited as a result of drug resistance, which demands prompt solutions provided by clinical studies. To date, the underlying mechanisms of chemotherapy resistance are relatively unknown. Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and prognosis of gastric cancer (GC). Bioinformatic analysis revealed that MACC1 is positively associated with fatty acid synthase (FASN), a major enzyme of lipogenesis, and drives chemoresistance to oxaliplatin in GC...
March 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28337370/role-of-epidermal-growth-factor-receptor-in-lung-cancer-and-targeted-therapies
#13
REVIEW
Tie-Cheng Liu, Xin Jin, Yan Wang, Ke Wang
Lung cancer is the foremost cause of cancer-related deaths world-wide. Both, the major forms of lung cancer, Non-small cell lung cancer (NSCLC) and Small cell lung cancers (SCLC), have responded effectively to chemo-, radiation and adjuvant-therapies. Tumor removal through surgery also appeared as a good therapeutic strategy. However, these therapies demonstrated unfavourable side-effects, and hence novel drugs targeting lung cancer emerged essential. Activation of epidermal growth factor receptor (EGFR)-tyrosine kinases is a key reason for lung cancer progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337331/light-regulated-no-release-as-a-novel-strategy-to-overcome-doxorubicin-multidrug-resistance
#14
Konstantin Chegaev, Aurore Fraix, Elena Gazzano, Gamal Eldein F Abd-Ellatef, Marco Blangetti, Barbara Rolando, Sabrina Conoci, Chiara Riganti, Roberta Fruttero, Alberto Gasco, Salvatore Sortino
Nitric oxide (NO) release from a suitable NO photodonor (NOP) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (DOX). The strategy may thus increase DOX toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining DOX and NOP showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than DOX...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337141/%C3%AE-elemene-mechanistic-studies-on-cancer-cell-interaction-and-its-chemosensitization-effect
#15
REVIEW
Ziyu Jiang, Joe A Jacob, Dinesh S Loganathachetti, Prasannabalaji Nainangu, Baoan Chen
Over the past decade, screening and identifying novel compounds for their biomedical applications has become an upcoming area of research. Identifying the molecular mechanisms of these compounds has become an integral part of anticancer research. β-elemene, a sesquiterpene, is renowned for its anticancer activity against a variety of cell lines. Recent studies on β-elemene have elucidated that it possesses anti-proliferative effect on cancer cells by creating an apoptotic trigger. Interestingly, it also induces protective autophagy in some cancerous cell lines and is less cytotoxic compared to other widely accepted chemotherapeutic agents...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28336807/pmp22-regulates-self-renewal-and-chemoresistance-of-gastric-cancer-cells
#16
Wangyu Cai, Gang Chen, Qicong Luo, Jun Liu, Xiaofeng Guo, Tian Zhang, Fei Ma, Liang Yuan, Boan Li, Jianchun Cai
Cancer stem cells (CSCs) possess self-renewal and chemoresistance activities. However, the manner in which these features are maintained remains obscure. We sought to identify cell surface protein(s) that mark self-renewing and chemoresistant gastric cancer cells using the Explorer Antibody Microarray. We identified PMP22, a target gene of the Wnt/β-catenin pathway, as the most upregulated cell surface protein in gastric cancer xenografts exposed to cisplatin (DDP). PMP22 expression was markedly upregulated in tumorspheric cells and declined with differentiation...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28336457/synergistic-inhibition-of-migration-and-invasion-of-breast-cancer-cells-by-dual-docetaxel-quercetin-loaded-nanoparticles-via-akt-mmp-9-pathway
#17
Jing Li, Jun Zhang, Yiyue Wang, Xiao Liang, Zaitongguli Wusiman, Yunzhi Yin, Qi Shen
Metastasis impedes the successful chemotherapy for breast cancer. In this study, an Akt inhibitor (quercetin, Qu) was co-delivered with a chemotherapeutic agent (docetaxel, DTX) by using hyaluronic acid (HA)-modified nanoparticles (NPs) as vectors to block metastasis. Dual DTX/Qu-loaded HA/polylactic-co-glycolic acid-polyethyleneimine NPs (PP-HA/NPs) were prepared through a modified emulsion solvent evaporation technique. The particle size of PP-HA/NPs with narrow polydispersity was 209.8±10.8nm. Wound healing assay revealed that Qu co-delivery and HA modification elicited synergistic inhibitory effects on cell motility...
March 20, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#18
Hea Ry Oh, Hyun-Young Jo, James S Park, Dong-Eun Kim, Je-Yoel Cho, Pyung-Hwan Kim, Keun-Sik Kim
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA...
July 30, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334884/improvement-in-the-prognosis-of-ovarian-cancer-in-the-era-before-addition-of-molecular-targeting-therapy
#19
Takako Shimada, Toshiaki Saito, Mototsugu Shimokawa, Kumi Shimamoto, Shuhei Matsushita, Shinichiro Yamaguchi, Kazuya Ariyoshi, Masao Okadome
Objective: The prognosis of ovarian cancer has improved because of platinum- and taxane-containing chemotherapy. We investigated the 5-year disease-specific overall survival and prognostic factors of patients with advanced ovarian cancer to elucidate the change in clinical course of ovarian cancer with the advance of chemotherapy for patients who developed relapse in the era before the addition of molecular targeting therapy. Methods: We reviewed the clinical course of 134 patients with advanced ovarian cancer (FIGO Stage III and IV) treated in the past 11 years (1999-2010)...
February 24, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28334655/morpholine-or-methylpiperazine-and-salicylaldimine-based-heteroleptic-square-planner-platinum-ii-complexes-in%C3%A2-vitro-anticancer-study-and-growth-retardation-effect-on-e-%C3%A2-coli
#20
Faiz-Ur Rahman, Amjad Ali, Inam Ullah Khan, Hong-Quan Duong, Shang-Bo Yu, Yue-Jian Lin, Hui Wang, Zhan-Ting Li, Dan-Wei Zhang
Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II)2(bis-salicylaldimine)(morpholine)2Cl2C4a and Pt(II)2(bis-salicylaldimine)(methylpiperazine)2Cl2C4b were prepared...
March 18, 2017: European Journal of Medicinal Chemistry
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