Read by QxMD icon Read


Wei Cui, Wenzhe Fan, Qun Zhang, Jia Wen, Yonghui Huang, Jianyong Yang, Jiaping Li, Yu Wang
AIMS: To compare the safety and efficacy of TACE using raltitrexed, oxaliplatin and epirubicin with 5-fluorouracil, oxaliplatin and epirubicin for patients with unresectable hepatocelluar carcinoma. RESULTS: Median overall survival (OS) was 7.4 months in the raltitrexed group [95% confidence interval (CI): 5.4, 9.4) and 5.8 months in the control group (95% CI: 5.2, 6.4; P = 0.177). The median progression-free survival (PFS) time was significantly higher in the raltitrexed group (3...
March 16, 2017: Oncotarget
Jian-Hai Guo, Hang-Yu Zhang, Song Gao, Peng-Jun Zhang, Xiao-Ting Li, Hui Chen, Xiao-Dong Wang, Xu Zhu
AIM: To evaluate the efficiency and safety of hepatic artery infusion chemotherapy (HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer (CRC) liver metastasis (CRCLM). METHODS: A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed...
February 28, 2017: World Journal of Gastroenterology: WJG
Sian Cregan, Maeve Breslin, Gerard Roche, Sigrid Wennstedt, Lauren MacDonagh, Cinaria Albadri, Yun Gao, Kenneth J O'Byrne, Sinead Cuffe, Stephen P Finn, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes...
March 2017: International Journal of Oncology
Zhe Jia, Ke Zhang, RongHai Huang, XinGang Zhou, Li Jiang
PATIENT CONCERNS: We report a rare case of pancreatic carcinosarcoma involving a 44-year-old woman. The patient complained of discomfort associated with the upper abdomen and jaundice of skin and sclera for 1 week. DIAGNOSES: After hospitalization, relevant examinations were completed. The disease was diagnosed as carcinoma of the pancreatic head. INTERVENTIONS: Whipple procedure was conducted in May 2013. Intraoperative exploration indicated 2 components of the tumor: a fish-shaped gray matter and a hard structure similar to cancellous bone...
January 2017: Medicine (Baltimore)
Paola Bertocchi, Francesca Aroldi, Tiziana Prochilo, Fausto Meriggi, Giordano Domenico Beretta, Alberto Zaniboni
INTRODUCTION: The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts)...
April 2017: Journal of Chemotherapy
Yong Mi Choi, Hyun Ku Yeo, Young Woo Park, Jae Young Lee
Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), complexes with dUMP (binary), and complexes with both dUMP and raltitrexed (ternary) were determined at 1...
2016: PloS One
Simon Dewar, Natasha Sienkiewicz, Han B Ong, Richard J Wall, David Horn, Alan H Fairlamb
The aim of this study was to identify and characterize mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. In conjunction with drug susceptibility and folate transport studies, RNAi knockdown was used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterized in whole cells...
November 18, 2016: Journal of Biological Chemistry
Paul J Sapienza, Andrew L Lee
Thymidylate synthase (TSase) is responsible for synthesizing the sole de novo source of dTMP in all organisms. TSase is a drug target, and as such, it has been well studied in terms of both structure and reaction mechanism. Cysteine 146 in Escherichia coli TSase is universally conserved because it serves as the nucleophile in the enzyme mechanism. Here we use the C146S mutation to probe the role of the sulfur atom in early events in the catalytic cycle beyond serving as the nucleophile. Surprisingly, the single-atom substitution severely decreases substrate binding affinity, and the unfavorable ΔΔG°bind is comprised of roughly equal enthalpic and entropic components at 25 °C...
October 11, 2016: Biochemistry
Vincenzo Picardi, Francesco Deodato, Alessandra Guido, Lucia Giaccherini, Gabriella Macchia, Maria A Gambacorta, Alessandra Arcelli, Andrea Farioli, Francesco Cellini, Dajana Cuicchi, Francesca DI Fabio, Gilberto Poggioli, Andrea Ardizzoni, Giovanni Frezza, Savino Cilla, Luciana Caravatta, Vincenzo Valentini, Lorenzo Fuccio, Alessio G Morganti
AIM: The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. PATIENTS AND METHODS: Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction)...
August 2016: Anticancer Research
N G Gurudatt, M Halappa Naveen, Changill Ban, Yoon-Bo Shim
Electrochemical biosensors using five anticancer drug and lipid molecules attached on the conducting polymer layer to obtain the orientation of drug molecules toward cancer cells, were evaluated as sensing materials and their performances were compared. Conjugation of the drug molecules with a lipid, phosphatidylcholine (PC) has enhanced the sensitivity towards leukemia cells and differentiates cancer cells from normal cells. The composition of each layer of sensor probe was confirmed by electrochemical and surface characterization experiments...
December 15, 2016: Biosensors & Bioelectronics
Marc W Gibson, Simon Dewar, Han B Ong, Natasha Sienkiewicz, Alan H Fairlamb
Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a chemically and genetically validated target in African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Here we report the kinetic properties and sensitivity of recombinant enzyme to a range of lipophilic and classical antifolate drugs. The purified recombinant enzyme, expressed as a fusion protein with elongation factor Ts (Tsf) in ThyA- Escherichia coli, retains DHFR activity, but lacks any TS activity...
May 2016: PLoS Neglected Tropical Diseases
Chang Zhao, Liwei Fan, Feng Qi, Shengqiu Ou, Lei Yu, Xiaoyu Yi, Bingqiang Ni, Zhiyong Zheng, Jianxun Lu, Chengwen Zhang, Changsheng Chen, Xiong Lu, Lin Cheng, Tianlian Hu, Yilong Ma
Raltitrexed has shown efficacy and safety in many tumor types; however, the clinical data on the treatment of hepatocellular carcinoma is rare. In this report, we aim to assess the efficacy and safety of raltitrexed plus oxaliplatin (OXA)-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC). Patients with uHCC were recruited from multi-centers in China and assigned randomly to raltitrexed+OXA-based (n=76), fluorouracil+OXA-based (n=76), and doxorubicin+OXA-based (n=75) TACE treatment...
August 2016: Anti-cancer Drugs
Hongwei Zhao, Yubao Zhang, Jianmin Sun, Chao Zhan, Liang Zhao
Raltitrexed (RTX) is an antimetabolite drug used as a chemotherapeutic agent for treating colorectal cancer, malignant mesothelioma, and gastric cancer. The antitumor capacity of RTX is attributed to its inhibitory activity on thymidylate synthase (TS), a key enzyme in the synthesis of DNA precursors. The current study is aimed at investigating the potential antitumor effects of RTX in liver cancer. Using the HepG2 cell line as an in vitro model of liver cancer, we evaluated the effects of RTX on cell proliferation employing both a WST-8 assay and a clone formation efficiency assay...
2016: Oncology Research
Sian Cregan, Lauran McDonagh, Yun Gao, Martin P Barr, Kenneth J O'Byrne, Stephen P Finn, Sinead Cuffe, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance...
March 2016: International Journal of Oncology
Ming-Chen Ba, Hui Long, Xiang-Liang Zhang, Yuan-Feng Gong, Yun-Qiang Tang, Yin-Bing Wu, Fei-Hong Yu, Shu-Zhong Cui
BACKGROUND: To compare the efficacy of three chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS: From January 2010 to December 2013, 38 GC patients were randomly divided into three groups and treated by laparoscopic HIPPC with one of the three following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin [trans-(±)-diaminocyclohexane oxalatoplatinum (l-OHP)], Ra with cisplatin (DDP), and Ra with mitomycin C (MMC)...
January 2016: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
Xiang-Rong Zhao, Chao Gao, Yong Zhang, Yong-Hua Yu
Retrorectal cystic hamartomas are rare congenital presacral lesions and malignancy is extremely rare. Although surgical excision is the essential for treatment, a unique feature of our case compared with previously reported tailgut cysts is that this patient's blood irregular antibodies are positive with higher operational risks.A 44-year-old woman presented to our department complaining of pelvic and perineal pain for 6 months. Computed tomography (CT) scan of the abdomen and pelvis demonstrated a well-demarcated hypodense, multilocular cystic lesion, 10 cm in size, in the presacral region of the right of the midline...
December 2015: Medicine (Baltimore)
Kelly Hew, Sue-Li Dahlroth, Saranya Veerappan, Lucy Xin Pan, Tobias Cornvik, Pär Nordlund
Varicella zoster virus (VZV) is a highly infectious human herpesvirus that is the causative agent for chicken pox and shingles. VZV encodes a functional thymidylate synthase (TS), which is the sole enzyme that produces dTMP from dUMP de novo. To study substrate binding, the complex structure of TSVZV with dUMP was determined to a resolution of 2.9 Å. In the absence of a folate co-substrate, dUMP binds in the conserved TS active site and is coordinated similarly as in the human encoded TS (TSHS) in an open conformation...
2015: PloS One
Amelia M Huehls, Catherine J Huntoon, Poorval M Joshi, Carly A Baehr, Jill M Wagner, Xiaoxiao Wang, Marietta Y Lee, Larry M Karnitz
5-Fluorouracil (5-FU) and its metabolite 5-fluorodeoxyuridine (FdUrd, floxuridine) are chemotherapy agents that are converted to 5-fluorodeoxyuridine monophosphate (FdUMP) and 5-fluorodeoxyuridine triphosphate (FdUTP). FdUMP inhibits thymidylate synthase and causes the accumulation of uracil in the genome, whereas FdUTP is incorporated by DNA polymerases as 5-FU in the genome; however, it remains unclear how either genomically incorporated U or 5-FU contributes to killing. We show that depletion of the uracil DNA glycosylase (UNG) sensitizes tumor cells to FdUrd...
January 2016: Molecular Pharmacology
Antonio Avallone, Biagio Pecori, Franco Bianco, Luigi Aloj, Fabiana Tatangelo, Carmela Romano, Vincenza Granata, Pietro Marone, Alessandra Leone, Gerardo Botti, Antonella Petrillo, Corradina Caracò, Vincenzo R Iaffaioli, Paolo Muto, Giovanni Romano, Pasquale Comella, Alfredo Budillon, Paolo Delrio
BACKGROUND: We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. PATIENTS AND METHODS: This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC...
October 6, 2015: Oncotarget
Rongbao Zhao, Michele Visentin, I David Goldman
PURPOSE: Elements in the endocytic process that are determinants of the activities of antifolates delivered by folate-receptor alpha (FRα) were explored. METHODS: Antifolate growth inhibition was assessed with a 1- or 5-day exposure in reduced folate carrier-null HeLa cell lines that express a high level of FRα in the presence or absence of the proton-coupled folate transporter (PCFT). pH-dependent rates of dissociation from FRα were also determined. RESULTS: With a 1-day drug exposure which is relevant to the pulse clinical administration of these drugs, FRα expression enhanced raltitrexed activity and modestly enhanced ZD9331 activity, but did not significantly augment the activity of pemetrexed or lomotrexol...
June 2015: Cancer Chemotherapy and Pharmacology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"