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https://www.readbyqxmd.com/read/29341150/effect-of-akt-activation-and-experimental-pharmacological-inhibition-on-responses-to-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#1
F C Koyama, C M Lopes Ramos, F Ledesma, V A F Alves, J M Fernandes, B B Vailati, G P São Julião, A Habr-Gama, J Gama-Rodrigues, R O Perez, A A Camargo
BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT. METHODS: Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal verge...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29340219/a-novel-hybrid-promoter-are-htert-for-cancer-gene-therapy
#2
S V Kalinichenko, M V Shepelev, P N Vikhreva, I V Korobko
describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the human GCLM gene promoter. The hybrid promoter retains the tumor specificity of the basal hTERT promoter but is characterized by an enhanced transcriptional activity in cancer cells with abnormal activation of the Nrf2 transcription factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein induced a more pronounced death of cancer cells either upon treatment with 5-fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as compared to the hTERT promoter...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29340092/first-line-dose-dense-chemotherapy-with-docetaxel-cisplatin-folinic-acid-and-5-fluorouracil-dcf-plus-panitumumab-in-patients-with-locally-advanced-or-metastatic-cancer-of-the-stomach-or-gastroesophageal-junction-final-results-and-biomarker-analysis-from-an
#3
Gianluca Tomasello, Nicola Valeri, Michele Ghidini, Elizabeth C Smyth, Wanda Liguigli, Laura Toppo, Rodolfo Mattioli, Alessandra Curti, Jens C Hahne, Federica M Negri, Stefano Panni, Margherita Ratti, Silvia Lazzarelli, Fabiana Gerevini, Chiara Colombi, Andrea Panni, Massimo Rovatti, Leonardo Treccani, Mario Martinotti, Rodolfo Passalacqua
Background: Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. Methods: HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340058/a-multicenter-prospective-phase-ii-study-of-first-line-modified-folfirinox-for-unresectable-advanced-pancreatic-cancer
#4
Kensaku Yoshida, Takuji Iwashita, Shinya Uemura, Akinori Maruta, Mitsuru Okuno, Nobuhiro Ando, Keisuke Iwata, Junji Kawaguchi, Tsuyoshi Mukai, Masahito Shimizu
Background: FOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance. Aims: To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339440/repurposing-tin-mesoporphyrin-as-an-immune-checkpoint-inhibitor-shows-therapeutic-efficacy-in-preclinical-models-of-cancer
#5
Tamara Muliaditan, James W Opzoomer, Jonathan Caron, Mary Okesola, Paris Kosti, Sharanpreet Lall, Mieke Van Hemelrijck, Francesco Dazzi, Andrew Tutt, Anita Grigoriadis, Cheryl Gillett, Stephen F Madden, Joy M Burchell, Shahram Kordasti, Sandra S Diebold, James Spicer, James N Arnold
PURPOSE: Unprecedented clinical outcomes have been achieved in a variety of cancers by targeting immune checkpoint molecules. This preclinical study investigates heme oxygenase-1 (HO-1), an immune suppressive enzyme that is expressed in a wide variety of cancers, as a potential immune checkpoint target in the context of a chemotherapy-elicited anti-tumor immune response. We evaluate repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy targeting hepatic HO in the clinic for the treatment of hyperbilirubinaemia, as an immune checkpoint blockade therapy for the treatment of cancer...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29339374/multicenter-evaluation-of-a-new-closed-system-drug-transfer-device-in-reducing-surface-contamination-by-antineoplastic-hazardous-drugs
#6
Sylvia B Bartel, Timothy G Tyler, Luci A Power
PURPOSE: Results of a study to evaluate the effectiveness of a recently introduced closed system drug-transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. METHODS: Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil)...
January 16, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29339282/probing-the-interaction-of-two-chemotherapeutic-drugs-of-oxali-palladium-and-5-fluorouracil-simultaneously-with-milk-carrier-protein-of-%C3%AE-lactoglobulin
#7
Amineh Leilabadi-Asl, Adeleh Divsalar, Ali Akbar Saboury, Kazem Parivar
β-Lactoglobulin (βLG) is a basic element of globular carrier protein, which is the major protein in the whey of ruminant milk and is of main interest in the dairy industry. In the present study, the simultaneous effects of both of the important anticancer drugs of 5-fluorouracil (5-FU) and oxali-palladium, on the structure of βLG were investigated using different spectroscopic methods of fluorescence and circular dichroism (CD) in combination with a molecular docking at two temperatures of 25 and 37 °C...
January 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29338309/oral-microbiota-reduce-wound-healing-capacity-of-epithelial-monolayers-irrespective-of-the-presence-of-5-fluorouracil
#8
Eline Vanlancker, Barbara Vanhoecke, Tom Sieprath, Janie Bourgeois, Annelore Beterams, Barbara De Moerloose, Winnok H De Vos, Tom Van de Wiele
Oral mucositis is still one of the most painful side effects of chemotherapeutic treatment and a mounting body of evidence suggests a key role for the oral microbiome in mucositis development. However, the underlying mechanisms remain elusive. In this work, we have investigated the interactions between the host, the microbiome, and chemotherapeutic treatments in more detail. The effect of 5-fluorouracil, commonly inducing mucositis, was assessed on a co-culture model that consists of an epithelial cell layer and a biofilm derived from oral microbiota from different types of samples (saliva, buccal swabs and tongue swabs) and donors (healthy individuals and patients suffering from mucositis)...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29337259/mathematical-modeling-of-tumor-induced-immunosuppression-by-myeloid-derived-suppressor-cells-implications-for-therapeutic-targeting-strategies
#9
Seyed Peyman Shariatpanahi, Seyed Pooya Shariatpanahi, Keivan Madjidzadeh, Moustapha Hassan, Manuchehr Abedi-Valugerdi
Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs...
January 11, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29333068/nab-paclitaxel-as-second-line-treatment-in-advanced-gastric-cancer-a-multicenter-phase-ii-study-of-the-hellenic-oncology-research-group
#10
Panagiotis Katsaounis, Athanasios Kotsakis, Nikolaos Kentepozidis, Aris Polyzos, Marios Bakogeorgos, Filippos Koinis, Lambros Vamvakas, Nikolaos Vardakis, Kostas Kalbakis, Ioannis Boukovinas, Ioannis I Varthalitis, Efthimios Prinarakis, Vassilis Georgoulias, John Souglakos
Background: This study evaluated the safety and efficacy of nab-paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma. Methods: Thirty-nine pretreated patients [33 with taxane-based regimens (docetaxel, cisplatin, and fluorouracil)] and 6 with combination of fluoropyrimidines plus cisplatin with locally advanced inoperable and metastatic gastric and gastroesophageal junction adenocarcinoma were treated with weekly nab-paclitaxel (150 mg/m2 d1, d8, d15 in cycles of 28 days)...
January 2018: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/29332468/local-radiotherapy-affects-drug-pharmacokinetics-exploration-of-a-neglected-but-significant-uncertainty-of-cancer-therapy
#11
Yu-Jen Chen, Tung-Hu Tsai, Li-Ying Wang, Chen-Hsi Hsieh
PURPOSE: Concurrent chemoradiation therapy is the mainstay of treatment for many types of malignancies. However, concurrent chemoradiation therapy is associated with a greater number of systemic adverse effects than radiotherapy or chemotherapy alone. SUMMARY: Pharmacokinetics is the study of a drug and/or its metabolite kinetics in the body, including absorption, distribution, metabolism, and elimination. The incidences of adverse effects are markedly higher in patients who receive concurrent chemoradiation therapy than in those who receive either radiotherapy or chemotherapy alone...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29332411/%C3%AE-1-integrin-mediated-multicellular-resistance-in-hepatocellular-carcinoma-through-activation-of-the-fak-akt-pathway
#12
Tao Tian, Chun-Li Li, Xiao Fu, Shu-Hong Wang, Jun Lu, Hui Guo, Yu Yao, Ke-Jun Nan, Yu-Juan Yang
Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29331856/schizandrin-a-enhances-chemosensitivity-of-colon-carcinoma-cells-to-5-fluorouracil-through-up-regulation-of-mir-195
#13
Dongfang Kong, Deyong Zhang, Xianqun Chu, Jing Wang
Nowadays 5-fluorouracil (5-FU)-based adjuvant chemotherapy is widely used for treating colon carcinoma. However, 5-FU resistance in the treatment of colon carcinoma has become more common and thereby new therapeutic strategies and new adjuvant drugs still need to be explored. Two 5-FU-resistant colon cancer cell lines, HCT116 and SW480, were used to investigate the effects of Schizandrin A (SchA), 5-FU, or their combination on cell viability and apoptosis. Besides, the role of miR-195 was studied to further clarify the specific function of SchA...
January 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29331415/nogo-b-receptor-promotes-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer-cells-through-the-ras-erk-snail1-pathway
#14
Donghua Wu, Baofeng Zhao, Xiaoyu Qi, Fang Peng, Hailu Fu, Xinming Chi, Qing Robert Miao, Shujuan Shao
Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane translocation and activation of Ras in breast cancer cells and enhances the chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the role of NgBR in lung cancer has not yet been elucidated. In the present study, we found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells in vivo...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330682/life-threatening-reaction-with-topical-5-fluorouracil
#15
Patrick Kishi, Cynthia J Price
A 67-year-old man developed a suspected adverse drug reaction during treatment with topical 5-fluorouracil (5-FU) for multiple actinic keratosis of the face, neck, and forearms. The man received topical 5-FU at a dosage of 0.5% for the actinic keratoses. After 1 week, he developed extreme lethargy, fatigue, fever, and mouth erosions. Several days later, and after discontinuation of 5-FU, painful mucositis and systemic side effects occurred, meeting criteria for hospitalization because of dehydration and a 6...
January 12, 2018: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29328475/heat-shock-protein-27-knockdown-using-nucleotide%C3%A2-based-therapies-enhances-sensitivity-to-5-fu-chemotherapy-in-sw480-human-colon-cancer-cells
#16
Takehiro Shimada, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Kohei Shigeta, Takashi Ishida, Yusuke Asada, Hirofumi Suzumura, Kaoru Koishikawa, Shingo Akimoto, Yuko Kitagawa
Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327356/gene-specific-variant-classifier-dpyd-varifier-to-identify-deleterious-alleles-of-dihydropyrimidine-dehydrogenase
#17
Shikshya Shrestha, Cheng Zhang, Calvin R Jerde, Qian Nie, Hu Li, Steven M Offer, Robert B Diasio
Deleterious variants in dihydropyrimidine dehydrogenase (DPD, DPYD gene) can be highly predictive of clinical toxicity to the widely prescribed chemotherapeutic 5-fluorouracil (5-FU). However, there is very limited data pertaining to the functional consequences of the >450 reported non-synonymous DPYD variants. We developed a DPYD-specific variant classifier (DPYD-Varifier) using machine learning and in vitro functional data for 156 missense DPYD variants. The developed model showed 85% accuracy and outperformed other in silico prediction tools...
January 12, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29327075/phase-ii-study-of-sorafenib-combined-with-concurrent-hepatic-arterial-infusion-of-oxaliplatin-5-fluorouracil-and-leucovorin-for-unresectable-hepatocellular-carcinoma-with-major-portal-vein-thrombosis
#18
Min-Ke He, Ru-Hai Zou, Qi-Jiong Li, Zhong-Guo Zhou, Jing-Xian Shen, Yong-Fa Zhang, Zi-Shan Yu, Li Xu, Ming Shi
BACKGROUND: Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results...
January 11, 2018: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/29322431/daylight-photodynamic-therapy-versus-5-fluorouracil-for-the-treatment-of-actinic-keratosis-a-case-series
#19
Gaston Nestor Galimberti
INTRODUCTION: The incidence of actinic keratosis (AK) continues to increase worldwide. Currently available options for the treatment of AK include topical 5-fluorouracil (5-FU) and daylight-mediated photodynamic therapy (DL-PDT). This split-face pilot study compared DL-PDT using 16% methyl aminolevulinate (MAL) cream versus 5-FU cream in patients with AK on the face/scalp. METHODS: Five male subjects (mean age 70 years) with grade I-III AK on the face/scalp were enrolled...
January 10, 2018: Dermatology and Therapy
https://www.readbyqxmd.com/read/29322091/a-retroviral-replicating-vector-encoding-cytosine-deaminase-and-5-fc-induces-immune-memory-in-metastatic-colorectal-cancer-models
#20
Kader Yagiz, Maria E Rodriguez-Aguirre, Fernando Lopez Espinoza, Tiffany T Montellano, Daniel Mendoza, Leah A Mitchell, Carlos E Ibanez, Noriyuki Kasahara, Harry E Gruber, Douglas J Jolly, Joan M Robbins
Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local production of 5-fluorouracil (5-FU). In brain tumor models, this treatment induces systemic anti-tumor immune responses and long-term immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compared to historic controls...
March 30, 2018: Molecular Therapy Oncolytics
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