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https://www.readbyqxmd.com/read/28651338/evaluation-of-the-impact-of-tumor-hpv-status-on-outcome-in-patients-with-locally-advanced-unresectable-head-and-neck-squamous-cell-carcinoma-hnscc-receiving-cisplatin-5-fluorouracil-with-or-without-docetaxel-a-subset-analysis-of-eortc-24971-study
#1
A Psyrri, C Fortpied, G Koutsodontis, M Avgeris, C Kroupis, N Goutas, J Menis, L Herman, L Giurgea, E Remenar, M Degardin, I S Pateras, J A Langendijk, C van Herpen, A Awada, J R Germà-Lluch, H R Kienzer, L Licitra, J B Vermorken
Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF over PF, in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable HNSCC. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case de-intensifying induction treatment in HPV(+) pts could be considered. Methods: Pre-therapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and qPCR...
June 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28646338/chemotherapy-induced-gastrointestinal-toxicity-is-associated-with-changes-in-serum-and-urine-metabolome-and-fecal-microbiota-in-male-sprague-dawley-rats
#2
Richard A Forsgård, Vannina G Marrachelli, Katri Korpela, Rafael Frias, Maria Carmen Collado, Riitta Korpela, Daniel Monleon, Thomas Spillmann, Pia Österlund
PURPOSE: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT...
June 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28646148/mir-15b-5p-resensitizes-colon-cancer-cells-to-5-fluorouracil-by-promoting-apoptosis-via-the-nf-%C3%AE%C2%BAb-xiap-axis
#3
Ci Zhao, Qi Zhao, Chunhui Zhang, Guangyu Wang, Yuanfei Yao, Xiaoyi Huang, Fei Zhan, Yuanyuan Zhu, Jiaqi Shi, Jianan Chen, Feihu Yan, Yanqiao Zhang
Drug resistance, which is closely correlated with an imbalance in apoptosis, endows colorectal cancer (CRC) with enhanced progression capacity irrespective of the treatment with therapeutics. We report that miR-15b-5p is a tumor suppressor whose level is globally decreased in CRC cells and tissues. Over-expression of miR-15b-5p not only promoted 5-fluorouracil (5-FU)-induced cellular apoptosis but also reversed the chemoresistance of 5-FU in vitro and in vivo. As a key mediator of inflammation-induced cancer, miR-15b-5p enhances these therapeutic effects are mainly attributed to targeting of the NF-κB signaling pathway through negative regulation of NF-κB1 and one of its kinase complexes IKK-α...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#4
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#5
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Ye Zhou, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
June 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28643051/long-term-outcomes-by-a-transanal-approach-to-total-mesorectal-excision-for-rectal-cancer
#6
John H Marks, Elizabeth A Myers, Erik L Zeger, Albert S Denittis, Mounica Gummadi, Gerald J Marks
BACKGROUND: The challenge of performing a good total mesorectal excision (TME) dissection, particularly in the distal 1/3 of the rectum, has spurred interest in new techniques. Robotic surgery is advocated by some, and more recently, a "new" approach, the transanal total mesorectal excision, has been popularized to address this problem. While great interest in this technique exists, little long-term outcome data are available. We have been utilizing a transanal abdominal transanal approach to TME in order to facilitate the distal dissection, and here, we provide our long-term outcomes using this approach in the management of rectal cancer...
June 22, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28642830/a-rare-case-of-esophageal-adenocarcinoma-with-urinary-bladder-metastasis
#7
Heather Katz, Rahoma E Saad, Krista Denning, Toni O Pacioles
Metastatic esophageal adenocarcinoma to the urinary bladder is extremely rare. We describe a previously healthy 49-year-old female with recent diagnosis of adenocarcinoma of the gastroesophageal junction with metastatic disease to the liver. Biopsy was positive for human epidermal growth factor receptor 2 (HER2) by Fluorescence In Situ Hybridization (FISH). She received six cycles of Cisplatin, 5-Fluorouracil, and Herceptin and subsequently developed symptomatic anemia and hematuria. Cystoscopy with retroflexion was performed and she received a transurethral resection of bladder tumor with fulguration...
2017: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/28642038/functional-characterization-of-21-allelic-variants-of-dihydropyrimidinase
#8
Eiji Hishinuma, Fumika Akai, Yoko Narita, Masamitsu Maekawa, Hiroaki Yamaguchi, Nariyasu Mano, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Dihydropyrimidinase (DHP, EC 3.5.2.2), encoded by the gene DPYS, is the second enzyme in the catabolic pathway of pyrimidine and of fluoropyrimidine drugs such as 5-fluorouracil, which are commonly used in anticancer treatment; DHP catalyzes the hydrolytic ring opening of dihydrouracil and dihydro-5-fluorouracil. DPYS mutations are known to contribute to interindividual variations in the toxicity of fluoropyrimidine drugs, but the functional characterization of DHP allelic variants remains inadequate. In this study, in vitro analysis was performed on 22 allelic variants of DHP by transiently expressing wild-type DHP and 21 DHP variants in 293FT cells and characterizing their enzymatic activities by using dihydrouracil and dihydro-5-fluorouracil as substrates...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28640389/efficacy-and-safety-of-recombinant-human-lymphotoxin-%C3%AE-derivative-with-cisplatin-and-fluorouracil-in-patients-with-metastatic-esophageal-squamous-cell-carcinoma-a-randomized-multicenter-open-label-controlled-phase-2b-trial
#9
Feng-Hua Wang, Yun Wang, Guo-Ping Sun, Jian-Hua Chen, Ying-Cheng Lin, Wei Liu, Rong-Sheng Zheng, Jia Chen, He-Long Zhang, Hai-Tao Lan, Jun Qi, Yang-Qing Liu, Yan-Ming Deng, Heng Zhao, Jian-Ping Xiong, Qing Xu, Wen-Qi Jiang, Yu-Hong Li
BACKGROUND: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative that is missing 27 N-terminal amino acid residues. Previous studies indicated a benefit from the addition of rhLTα-Da to cisplatin-based treatment in patients with metastatic esophageal squamous cell carcinoma. The current study was conducted to evaluate the efficacy and safety of rhLTα-Da plus cisplatin and fluorouracil (PF) in patients with mESCC. METHODS: Patients from 15 centers in China were randomly assigned (1:1:1) to 3 arms (arm A, PF plus 10 μg/m(2) daily rhLTα-Da; arm B, PF plus 20 μg/m(2) daily rhLTα-Da; arm C, PF alone)...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28640255/aqp9-induced-cell-cycle-arrest-is-associated-with-ras-activation-and-improves-chemotherapy-treatment-efficacy-in-colorectal-cancer
#10
Dandan Huang, Xingzhi Feng, Yiting Liu, Yanhong Deng, Hao Chen, Daici Chen, Lekun Fang, Yue Cai, Huanliang Liu, Lei Wang, Jianping Wang, Zihuan Yang
Aquaporin-9 (AQP9) expression is associated with arsenic sensitivity in leukemia cells. However, the role of AQP9 in regulating tumor sensitivity to adjuvant chemotherapy in colorectal cancer (CRC) has not been elucidated. In this study, we demonstrated that AQP9 can serve as an independent predictive marker for adjuvant chemotherapy in CRC. Patients with high AQP9 expression had higher rate of disease-free survival (DFS) than those with low AQP9 expression. Upregulation of AQP9 was associated with enhanced chemosensitivity to 5-fluorouracil (5-FU) both in vitro and in vivo...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28640115/management-of-neovascular-glaucoma-with-intravitreal-ranibizumab-panretinal-photocoagulation-and-subsequent-5-fluorouracil-augmented-trabeculectomy-a-case-report
#11
Xinyue Zhao, Zhi Wang, Xiaobo Yang
RATIONALE: Neovascular glaucoma (NVG) is one of the most refractory types of glaucoma caused by high ischemic retinal disorders, resulting in severe visual loss. Intravitreal injections of ranibizumab have been reported to have anatomical and functional success in treating NVG. PATIENT CONCERNS-DIAGNOSES-INTERVENTIONS: We report a case with neovascular glaucoma due to central retinal vein occlusion who received combination therapy with intravitreal ranibizumab (IVR) injection, panretinal photocoagulation (PRP) and subsequent 5-fluorouracil (5-FU) augmented trabeculectomy...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639051/adjuvant-treatment-for-pancreatic-ductal-carcinoma
#12
REVIEW
T Macarulla, T Fernández, M E Gallardo, O Hernando, A M López, M Hidalgo
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a very poor prognosis. Most of the patients are diagnosed in advanced stages of the disease, and 5-year survival rates in these patients remains <10%. Surgery still remains the only radical treatment option, although only 15-20% of patients are candidates for surgical resection at the time of the diagnosis. Patients who undergo radical surgery still have a limited survival rate, being the average of 23 months. Three clinical trials have shown that adjuvant chemotherapy therapy after surgery may improve survival: CONKO-1, ESPAC-3, and ESPAC-4...
June 21, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28638476/therapeutic-inhibition-of-mir-4260-suppresses-colorectal-cancer-via-targeting-mcc-and-smad4
#13
Junjie Xiao, Dongchao Lv, Jinzhe Zhou, Yihua Bei, Ting Chen, Muren Hu, Qiulian Zhou, Siyi Fu, Qi Huang
Dysregulation of microRNAs (miRNAs, miRs) and their putative target genes have been increasingly reported to contribute to colorectal cancer. However, miRNAs that directly target the mutated in colorectal cancer (MCC) gene, a tumor suppressor which is downregulated or inactivated in colorectal cancer, remain largely unknown. By using an array-based miRNA analysis, we identified a group of miRNAs that were dysregulated in human metastatic versus non-metastatic colorectal cancer tissues. One of these miRNAs, miR-4260, was predicted to target MCC in the miRDB database...
2017: Theranostics
https://www.readbyqxmd.com/read/28637493/the-role-of-nlrp3-inflammasome-in-5-fluorouracil-resistance-of-oral-squamous-cell-carcinoma
#14
Xiaodong Feng, Qingqiong Luo, Han Zhang, Han Wang, Wantao Chen, Guangxun Meng, Fuxiang Chen
BACKGROUND: 5-Fluorouracil (5-FU) is a widely used drug for the therapy of cancer. However, the chemoresistance of tumor cells to 5-FU usually limits its clinical effectiveness. In this study, we explored the role of NLRP3 inflammasome in 5-FU resistance of oral squamous cell carcinoma (OSCC). METHODS: The mRNA and protein expression levels of NLRP3, Caspase1 and IL-1β in resected OSCC specimens or cell lines were measured respectively by quantitative real time-PCR (qRT-PCR) and western blot...
June 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28636554/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#15
Xiaoyu Wang, Chun Liu, Jiaqi Wang, Yue Fan, Zhenghua Wang, Yuanyuan Wang
Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634253/role-of-autophagy-in-tumor-necrosis-factor-%C3%AE-induced-apoptosis-of-osteoblast-cells
#16
Liwen Zheng, Wanchun Wang, Jiangdong Ni, Xinzhan Mao, Deye Song, Tang Liu, Jianwei Wei, Zhou Huaying
The aim of this study is to investigate the role of tumor necrosis factor-α (TNF-α) in apoptosis and autophagy of mouse osteoblast MC3T3-E1 cells, as well as the crosstalk between autophagy and apoptosis. Mouse osteoblast MC3T3-E1 cells were cultured in vitro and treated with 5-fluorouracil (5-FU), rapamycin, 3-methyl adenine (3-MA) and TNF-α either alone or in combination, respectively. MTT assays were used to monitor the cell viability upon different treatments. Annexin-V-FITC/propidium iodide (PI) staining was used to detect the apoptotic rate of osteoblasts...
June 20, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28633089/first-line-panitumumab-plus-folfox4-or-folfiri-in-colorectal-cancer-with-multiple-or-unresectable-liver-metastases-a-randomised-phase-ii-trial-planet-ttd
#17
Alfredo Carrato, Albert Abad, Bartomeu Massuti, Cristina Grávalos, Pilar Escudero, Federico Longo-Muñoz, José-Luis Manzano, Auxiliadora Gómez, María José Safont, Javier Gallego, Beatriz García-Paredes, Carles Pericay, Rosario Dueñas, Fernando Rivera, Ferrán Losa, Manuel Valladares-Ayerbes, Encarnación González, Enrique Aranda
BACKGROUND: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI...
June 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28632865/effect-of-first-line-chemotherapy-combined-with-cetuximab-or-bevacizumab-on-overall-survival-in-patients-with-kras-wild-type-advanced-or-metastatic-colorectal-cancer-a-randomized-clinical-trial
#18
Alan P Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Briant Fruth, Jeffrey A Meyerhardt, Deborah Schrag, Claire Greene, Bert H O'Neil, James Norman Atkins, Scott Berry, Blase N Polite, Eileen M O'Reilly, Richard M Goldberg, Howard S Hochster, Richard L Schilsky, Monica M Bertagnolli, Anthony B El-Khoueiry, Peter Watson, Al B Benson, Daniel L Mulkerin, Robert J Mayer, Charles Blanke
Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer...
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28631569/insulin-induced-enhancement-of-mcf-7-breast-cancer-cell-response-to-5-fluorouracil-and-cyclophosphamide
#19
Siddarth Agrawal, Mateusz Łuc, Piotr Ziółkowski, Anil Kumar Agrawal, Ewa Pielka, Kinga Walaszek, Krzysztof Zduniak, Marta Woźniak
The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28629331/depletion-of-p21-activated-kinase-1-up-regulates-the-immune-system-of-apc-%C3%A2-14-mice-and-inhibits-intestinal-tumorigenesis
#20
Nhi Huynh, Kai Wang, Mildred Yim, Chelsea J Dumesny, Mauro S Sandrin, Graham S Baldwin, Mehrdad Nikfarjam, Hong He
BACKGROUND: P21-activated kinase 1 (PAK1) stimulates growth and metastasis of colorectal cancer (CRC) through activation of multiple signalling pathways. Up-regulation of CRC stem cell markers by PAK1 also contributes to the resistance of CRC to 5-fluorouracil. The aim of this study was to investigate the effect of PAK1 depletion and inhibition on the immune system and on intestinal tumour formation in APC(∆14/+) mice. METHODS: The PAK1 KO APC(∆14/+) mice were generated by cross-breeding of PAK1 KO mice with APC(∆14/+) mice...
June 19, 2017: BMC Cancer
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