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Maria Antonietta Gambacorta, Antonino De Paoli, Marco Lupattelli, Giuditta Chiloiro, Angela Pia Solazzo, Brunella Barbaro, Sergio Alfieri, Fabio Maria Vecchio, Jacopo Lenkowicz, Francesco Navarria, Elisa Palazzari, Giulio Bertola, Alessandro Frattegiani, Bruce Minsky, Vincenzo Valentini
Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned...
March 2018: Clinical and Translational Radiation Oncology
Parisa Zargar, Esmaeel Ghani, Farideh Jalali Mashayekhi, Amin Ramezani, Ebrahim Eftekhar
5-Fluorouracil (5-FU)-based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5-FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5-FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5-FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay...
June 2018: Oncology Letters
Chuan Chen, Tongdan Xue, Peng Fan, Linlin Meng, Jingjing Wei, Duqiang Luo
Fumosorinone (Fumos) isolated from entomogenous fungi Isaria fumosorosea exhibited selective inhibition of Src homology phosphotyrosine phosphatase 2 inhibitor (Shp2) in our previous study. The purpose of the present study was to investigate the effects of Fumos on cell cycle arrest, tumor cell migration and the in vitro antiproliferative activity of Fumos alone or in combination with the commonly used cytotoxic drugs 5-fluoracil (5-FU) and p38 inhibitor SB203580. Fumos exhibited cytotoxicity against selected human cancel lines, including HeLa, MDA-MB-231 and MDA-MB-453 cell lines...
June 2018: Oncology Letters
Sen Lu, Caizhao Lin, Xiaobin Cheng, Hanju Hua, Tao Xiang, Yu Huang, Xi Huang
It has previously been reported that cardamonin is able to regulate glycometabolism and vasodilation whilst also exhibiting anti-inflammatory and antitumor properties. The antitumor effect of cardamonin is multifaceted, and so it is necessary to investigate the antitumor mechanisms of cardamonin at the molecular level. Cardamonin alters chemotherapy-resistant colon cancer cell growth; however, the underlying mechanism is unknown. The present study was conducted to investigate the effect of cardamonin on chemotherapy-resistant colon cancer cells and the possible mechanisms of action...
June 2018: Oncology Letters
Giancarlo Meloni, Massimo Milani
Plantar warts account for 30% of all cutaneous warts. These lesions could be very painful, especially if the lesion is located over pressure sites such as the metatarsal head. Plantar wart treatment remains a challenging therapeutic problem. A 67-year-old immunocompetent nonsmoking man presented with a large mosaic plantar wart on his right foot. The lesion had been present for 5 years. Several cryotherapy sessions (a total of 6 procedures) had been performed with no success. The lesion was therefore treated with a 5-fluorouracil (5-FU) regimen and then with a topical combination of 5-FU and salicylic acid, but also these approaches failed...
May 2018: Case Reports in Dermatology
Elizabeth M La, Emily Nash Smyth, Sandra E Talbird, Li Li, James A Kaye, Aimee Bence Lin, Lee Bowman
This study evaluated the patterns of care and health care resource use (HCRU) in patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) who received ≥3 lines of systemic therapy in the United Kingdom (UK). Oncologists (n = 40) abstracted medical records for patients with metastatic SCCHN who initiated third-line systemic therapy during 1 January 2011-30 August 2014 (n = 220). Patient characteristics, treatment patterns and SCCHN-related HCRU were summarised descriptively for the metastatic period; exploratory multivariable regression analyses were conducted on select HCRU outcomes...
June 21, 2018: European Journal of Cancer Care
Erika Durinikova, Jana Plava, Silvia Tyciakova, Pavel Skvara, Andrea Vojs Stanova, Zuzana Kozovska, Lucia Kucerova, Miroslava Matuskova
Gene-directed enzyme/prodrug therapy (GDEPT) mediated by mesenchymal stromal cells (MSC) was already approved for clinical study on a progressive disease refractory to standard therapy. In this work, we examined the effect of several GDEPT approaches on chemoresistant cells. First, we derived 5-fluorouracil (5-FU)-resistant variant of human colorectal adenocarcinoma cells HT-29 designated HT-29/EGFP/FUR. Our data show that the upregulation of thymidylate synthase (TS) and downregulation of thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) contributed to the 5-FU resistance in cancer cells...
June 21, 2018: Cancer Gene Therapy
Xiao-Xin Chen, Kar Ho Lam, Yibin Feng, Kai Xu, Stephen C W Sze, Chi Wai Tang, George P H Leung, Calvin Kai-Fai Lee, Jun Shi, Zhijun Yang, Sheng-Tao Li, Zhang-Jin Zhang, Yanbo Zhang
Worldwide, colorectal cancer (CRC) is a deleterious disease causing millions of death annually. 5-Fluorouracil (5-FU) is a first-line chemotherapy for CRC, but chemoresistance and gastrointestinal mucositis limit its efficacy. Polyphenol-rich foods are increasingly popular due to their potential beneficial role in cancer. Ellagitannins is a group of phenolic compounds commonly found in pomegranate, strawberries, raspberries, etc. The objective of this study was to explore whether ellagitannins from pomegranate (PETs) could ameliorate 5-FU-induced intestinal mucositis and enhance its efficacy against CRC...
June 19, 2018: Journal of Agricultural and Food Chemistry
Pimradasiri Srijiwangsa, Saranyoo Ponnikorn, Kesara Na-Bangchang
BACKGROUND: Cholangiocarcinoma (CCA), an epithelial malignancy of the biliary tree, is one of the aggressive cancers with poor prognosis and unsatisfactory response to chemotherapy with acquired resistance. NAD(P)H-quinone oxidoreductase 1 (NQO1), an antioxidant/detoxifying enzyme, plays important roles in chemo-resistance and proliferation in several cancer cells. The study aimed to investigate the inhibitory effect of β-eudesmol on NQO1 enhanced chemotherapeutic effects of 5-fluorouracil (5-FU) and doxorubicin (DOX) in the high NQO1-expressing human CCA cell line, NQO1-KKU-100...
June 19, 2018: BMC Pharmacology & Toxicology
Rolando A G Garcia, Joel A Saydoff, Michael K Bamat, Reid W von Borstel
Uridine triacetate has been shown to be an effective antidote against mortality and toxicity caused by either overdoses or exaggerated susceptibility to the widely used anticancer agents 5-fluorouracil (5-FU) and capecitabine. However, a direct assessment of efficacy based on when emergency treatment was initiated was not clinically feasible. In this study we used mouse models of 5-FU overdose and of dihydropyrimidine dehydrogenase (DPD) deficiency to compare the efficacy of uridine triacetate in reducing toxicity and mortality when treatment was initiated at time points from 4 to 144 h after administration of 5-FU...
June 13, 2018: Toxicology and Applied Pharmacology
Emma B Holliday, Scott C Lester, W Scott Harmsen, Cathy Eng, Michael G Haddock, Sunil Krishnan, Prajnan Das, Christopher L Hallemeier
PURPOSE: To report cancer control rates and adverse events (AEs) of curative-intent, extended-field chemoradiation therapy administered to patients with squamous cell carcinoma (SCC) of the anal canal presenting with distant metastasis limited to the para-aortic (PA) lymph nodes. METHODS: This was a retrospective review of patients with SCC of the anal canal metastatic to the PA lymph nodes at initial diagnosis who were treated with curative-intent, extended-field chemoradiation therapy between September 2002 and February 2016 at two tertiary care centers...
May 5, 2018: International Journal of Radiation Oncology, Biology, Physics
Gertraud Stocker, Ulrich T Hacker, Frédéric Fiteni, Jestinah John Mahachie, Arnaud D Roth, Eric Van Cutsem, Marc Peeters, Florian Lordick, Murielle Mauer
BACKGROUND: Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. METHODS: Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m2 ), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i...
June 12, 2018: European Journal of Cancer
Z Kozovska, A Patsalias, V Bajzik, E Durinikova, L Demkova, S Jargasova, B Smolkova, J Plava, L Kucerova, M Matuskova
BACKGROUND: Recent evidence in cancer research, developed the notion that malignant tumors consist of different subpopulations of cells, one of them, known as cancer stem cells, being attributed many important properties such as enhanced tumorigenicity, proliferation potential and profound multidrug resistance to chemotherapy. Several key stem cells markers were identified in colon cancer. In our study we focused on the aldehyde dehydrogenase type 1 (ALDH1) expression in colon cancer-derived cell lines HT-29/eGFP, HCT-116/eGFP and LS-180/eGFP, and its role in the chemoresistance and tumorigenic potential...
June 15, 2018: BMC Cancer
June Lee, Jong-Su Kang, Le Ba Nam, Ok-Kyung Yoo, Young-Sam Keum
NF-E2-related factor 2 (NRF2) regulates transcription of phase II cytoprotective enzymes to protect normal cells against oxidative stress. However, a high level of NRF2 offers a growth advantage, chemoresistance, and radioresistance in cancer. In the present study, we have identified convallatoxin as a novel inhibitor of NRF2/ARE suppression of NRF2 by convallatoxin was not transcriptionally mediated, but regulated at the level of proteolysis. Convallatoxin activated GSK-3β and suppression of NRF2 by convallatoxin required the Neh6 domain...
June 14, 2018: Free Radical Research
Alessio Cortellini, Katia Cannita, Alessandro Parisi, Olga Venditti, Paola Lanfiuti Baldi, Berardo De Berardis, Roberto Vicentini, Vincenzo Vicentini, Lucilla Verna, Giampiero Porzio, Corrado Ficorella
To date, there is no consensus regarding first‑line chemotherapy for patients with HER2‑negative, locally advanced/metastatic gastric cancer (a/m GC). In the present study we reported a retrospective case‑series of patients treated with a weekly regimen containing timed‑flat infusion of 5‑fluorouracil (TFI/5‑FU), docetaxel and oxaliplatin. From June 2007 to July 2017, 32 consecutive a/m GC patients were treated with first‑line standard (st) or modulated (mod) 'FD/FOx' regimen: Weekly 12 h (from 10...
June 6, 2018: Oncology Reports
Ya-Min Cheng, Po-Lin Lin, De-Wei Wu, Lee Wang, Chi-Chou Huang, Huei Lee
Nuclear Nrf2 (nNrf2) binding to the antioxidant response element may promote chemoresistance in colorectal cancer. However, the shuttling of Nrf2 between cytoplasm and nucleus in colon cancer cells has revealed the possibility that cytoplasmic location of Nrf2 (cNrf2) may play a specific role in chemoresistance. Transfection of a nuclear location sequence (NLS)-wild-type or NLS-mutated Nrf2 expression vector into a stable shNrf2 HCT116 clone using the MTT assay to examine whether chemoresistance induced by cNrf2 may be greater than nNrf2...
May 29, 2018: Oncotarget
Yueh-Ming Lin, Chih-I Chen, Yi-Ping Hsiang, Yung-Chia Hsu, Kung-Chuan Cheng, Pei-Hsuan Chien, Hsiao-Lin Pan, Chien-Chang Lu, Yun-Ju Chen
Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear...
June 14, 2018: International Journal of Molecular Sciences
Huayi Li, Xingwen Wang, Cheng Zhang, Yiwei Cheng, Miao Yu, Kunming Zhao, Wenjie Ge, Anyong Cai, Yao Zhang, Fengtong Han, Ying Hu
Renal cell carcinoma (RCC) is highly resistant to chemotherapies. The lack of efficacious treatment for metastatic RCC has led to a poor 5-year survival rate. Here, we found that Apoptosis-stimulating protein of p53-2(ASPP2) was frequently decreased in primary RCC tissues in comparison with non-tumoural kidney controls. Decreased ASPP2 was correlated with high grades and poor outcomes of RCC. Further studies revealed that ASPP2 downregulation promoted EMT and increased resistance to 5-Fluorouracil (5-FU)-induced apoptosis...
June 8, 2018: Cancer Letters
Aung Win Tin, Eleanor Smith, Rebecca Hepworth, Julie Walker, David Wilson, Nick Wadd
INTRODUCTION: Perioperative epirubicin, cisplatin and 5-FU or capecitabine (ECF/X) chemotherapy is recognised as a standard of care for patients with resectable gastroesophageal adenocarcinoma; however, there is limited evidence regarding its use in older patients. The aims of this study were to assess the effectiveness and tolerability of perioperative ECX chemotherapy in patients aged ≥70 years-old (group 1) compared with a younger population (group 2), and to assess differences in the histology of these groups...
June 5, 2018: Journal of Geriatric Oncology
Matthias F Froelich, Volker Heinemann, Wieland H Sommer, Julian W Holch, Franziska Schoeppe, Nina Hesse, Alena B Baumann, Wolfgang G Kunz, Maximilian F Reiser, Jens Ricke, Melvin D'Anastasi, Sebastian Stintzing, Dominik P Modest, Philipp M Kazmierczak, Felix O Hofmann
OBJECTIVES: To assess the prognostic value of pre-therapeutic computed tomography (CT) attenuation of liver metastases for overall survival (OS) in metastatic colorectal cancer (mCRC). METHODS: In the open-label, randomised, prospective phase-III FIRE-3 trial, patients with histologically confirmed mCRC received fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) with either cetuximab or bevacizumab. Participating patients gave written informed consent prior to study entry...
June 7, 2018: European Radiology
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