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Zhen Wu, Jing Wu, Ping Fang, Shifeng Kan
The present study investigated the effect of puerarin (Pu) on the sensitivity of HepG2 human hepatocellular carcinoma (HCC) cells to chemotherapeutic drugs to determine the possible mechanism. HepG2 cells were treated with different concentrations of Pu and cisplatin (CDDP), alone or in combination. MTT assay was used to determine the inhibitory effects of the different drugs on HepG2 cells. Cell morphology was observed by inverted microscopy. The expression of B-cell lymphoma 2 (Bcl-2) and Bax protein was measured by western blot analysis...
September 2017: Oncology Letters
Koji Harada, Tarannum Ferdous, Toyoko Harada, Takanori Takenawa, Yoshiya Ueyama
Gimeracil or 5-chloro-2,4-dihydroxypyridine (CDHP) enhances the antitumor effects of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU. CDHP, as part of a combination therapy, was also reported to exert a radiosensitizing effect. Therefore, CDHP may have underlying mechanisms of action other than DPD inhibition. The focus of the present study was to investigate the antitumor effects of CDHP and cisplatin (CDDP) combination treatment in vitro and in vivo against oral squamous cell carcinoma (OSCC) tumors...
September 2017: Oncology Letters
Feihong Chen, Gang Xu, Xiaodong Qin, Xiufeng Jin, Shaohua Gou
Two hybrids were designed and prepared by addition of a chlorambucil unit to an axial position of the Pt(IV) complex derived from DN603 or DN604 which was recently found to exhibit significant anticancer activity and low toxicity. Cytotoxicity of two compounds against two pairs of cisplatin sensitive and resistant cancer cell lines indicated that compound 5 had superior antitumor activity to cisplatin and chlorambucil via suppressing DNA damage repair to reverse drugs resistances. Mechanistic investigation suggested that the potent antitumor activity of 5 arose from its major suppression of CK2-mediated MRE11-RAD50-NBS1(MRN) complex promotion of DNA double-strand breaks (DSBs) repair...
September 15, 2017: Journal of Pharmacology and Experimental Therapeutics
Hiroshi Uchino, Junko Fujishima, Kaori Fukuoka, Teppei Iwakiri, Akira Kamikuri, Hidenori Maeda, Kazuhiro Nakama
The objective of this study was to investigate the availability of novel urinary biomarkers (BMs) such as total protein, albumin, β2-microglobulin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute nephrotoxicity in cynomolgus monkeys. Animals (total 9 males/3 groups) were administered gentamicin (GM) subcutaneously at 40 mg/kg for 7 days, cisplatin (CDDP) intravenously at 3 mg/kg once and puromycin aminonucleoside (PAN) intravenously at 20 mg/kg for 7 days...
2017: Journal of Toxicological Sciences
Martina Zduriencikova, Dana Cholujova, Jozef Duraj, Maria Mastihubova, Vladimir Mastihuba, Elena Karnisova Potocka, Eliska Galova, Andrea Sevcovicova, Martina Klapakova, Eva Horvathova
Natural products represent the source or the inspiration for the majority of the active ingredients of medicines because of their structural diversity and a wide range of biological effects. Our aims in this study were (i) to synthesize enzymatically salidroside (SAL), the most effective phenylethanoid glycoside in Rhodiola species; (ii) to examine its antioxidant capacity using cell-free assays (reducing power, DPPH radicals scavenging and Fe(2+) -chelating assays); (iii) to assess its DNA-protective potential on plasmid DNA (DNA topology assay) and in HepG2 cells (comet assay) damaged by Fe(2+) ions and hydrogen peroxide, respectively; and (iv) to investigate the effects of SAL, cisplatin (CDDP) and combined treatments of SAL + CDDP on cell viability (MTT test), level of DNA damage (comet assay), proliferation, cell cycle (flow cytometry) and the expression of signalling molecules associated with cell growth and apoptotic pathways (western immunoblotting)...
September 10, 2017: Basic & Clinical Pharmacology & Toxicology
Long Huang, Meiying Liu, Liucheng Mao, Qiang Huang, Hongye Huang, Qing Wan, Jianwen Tian, Yuanqing Wen, Xiaoyong Zhang, Yen Wei
As a new type of mesoporous silica materials with large pore diameter (pore size between 2 and 50nm) and high specific surface areas, SBA-15 has been widely explored for different applications especially in the biomedical fields. The surface modification of SBA-15 with functional polymers has demonstrated to be an effective way for improving its properties and performance. In this work, we reported the preparation of PEGylated SBA-15 polymer composites through surface-initiated chain transfer free radical polymerization for the first time...
December 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Liuxi Chen, James D Smith, Jaromir Mikl, Ryan Fryer, Frank Pack, Brad J Williams, Jonathan Phillips, Vladimir Papov
Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrate the use of label-free liquid chromatography - mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety biomarker assessments for identification of new toxicity marker candidates and for improved mechanistic understanding. Two different anti-cancer drugs doxorubicin (DOX) and cisplatin (cis-diamminedichloridoplatinum, CDDP) were chosen as the toxicants due to their different modes of nephrotoxicity...
September 8, 2017: Chemical Research in Toxicology
Yuta Ushida, Kiyoshi Hiramatsu, Satomi Saeki, Takeshi Amemiya, Hidenari Goto, Toshiyuki Arai
INTRODUCTION: Gastric cancer with paraaortic lymph node (PAN) metastasis have unfavorable prognosis. There are no evidence-based preoperative chemotherapy regimens available. CASE PRESENTATION: A 62-year-old female was diagnosed with advanced gastric cancer and PAN metastasis. We attempted S-1/CDDP chemotherapy in six coursed and total gastrectomy as well as systematic dissection of regional lymph nodes and PAN. Histologically, no cancerous cells were detected in specimens...
August 18, 2017: International Journal of Surgery Case Reports
Sudjit Luanpitpong, Paweorn Angsutararux, Parinya Samart, Nawin Chanthra, Pithi Chanvorachote, Surapol Issaragrisil
Aberrant metabolism in hexosamine biosynthetic pathway (HBP) has been observed in several cancers, affecting cellular signaling and tumor progression. However, the role of O-GlcNAcylation, a post-translational modification through HBP flux, in apoptosis remains unclear. Here, we found that hyper-O-GlcNAcylation in lung carcinoma cells by O-GlcNAcase inhibition renders the cells to apoptosis resistance to cisplatin (CDDP). Profiling of various key regulatory proteins revealed an implication of either p53 or c-Myc in the apoptosis regulation by O-GlcNAcylation, independent of p53 status...
September 6, 2017: Scientific Reports
Akimitsu Maeda, Hitoshi Ando, Takashi Ura, Kei Muro, Masahiro Aoki, Ken Saito, Eisaku Kondo, Shinji Takahashi, Yuko Ito, Yasunari Mizuno, Akio Fujimura
BACKGROUND/AIM: We investigated whether measuring the excretion of each acute kidney injury (AKI) biomarker after cisplatin (CDDP) administration is useful for predicting AKI and evaluated the most appropriate AKI marker in patients treated with CDDP. PATIENTS AND METHODS: We measured NAG, Kim-1, and NGAL in urinary samples of 40 cancer patients treated with chemotherapy on day 1 (before chemotherapy), day 2, and day 5 after treatment; serum creatinine (sCr) was compared on days 7 and 28 after CDDP administration vs...
September 2017: Anticancer Research
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Takashi Murakami, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Robert M Hoffman
BACKGROUND: Methionine dependence may be the only known general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino-γ-mercaptomethane lyase [EC]) (recombinant methioninase [rMETase]), which was subsequently tested in mouse models of various types of human tumors. The present study aimed to investigate the efficacy of rMETase on human osteosarcoma cells in vitro and in vivo. MATERIALS AND METHODS: Human osteosarcoma cell lines 143B, HOS and SOSN2 were tested in vitro for survival during a 72-h exposure to rMETase using the WST-8 assay...
September 2017: Anticancer Research
Xia Qin, Feng Qiu, Zhen Zou
Lung cancer, in particular, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related mortality. Cis-Diamminedichloroplatinum (cisplatin, CDDP) as first-line chemotherapy for NSCLC, but resistance occurs frequently. We previously reported that Tripartite motif protein 25 (TRIM25) was highly expressed in cisplatin-resistant human lung adenocarcinoma A549 cells (A549/CDDP) in comparison with its parental A549 cells. Herein, we take a further step to demonstrate the association of TRIM25 and cisplatin resistance and also the underlying mechanisms...
August 31, 2017: Biochemical and Biophysical Research Communications
Yoshitaka Saito, Keisuke Okamoto, Masaki Kobayashi, Katsuya Narumi, Ayako Furugen, Takehiro Yamada, Ken Iseki
PURPOSE: Pretreatment with magnesium (Mg) has been reported to attenuate cisplatin (CDDP)-induced nephrotoxicity (CIN). This attenuation involves modulation of the expression of renal transporters, resulting in reduced renal platinum accumulation after a single round of CDDP treatment. In this study, we investigated whether Mg co-administration ameliorates CIN after multiple doses of CDDP as effectively as after a single dose. METHODS: Rats were divided into control, Mg alone, CDDP alone, and CDDP with Mg groups...
August 29, 2017: Life Sciences
Weisha Liu, Shuyuan Wang, Shunheng Zhou, Feng Yang, Wei Jiang, Qingyuan Zhang, Lihong Wang
Cisplatin (CDDP)-based chemotherapy is a standard first-line therapy for ovarian cancer. However, drug resistance remains a major obstacle to its efficacy. Recently, increasing evidence suggested that the aberrant expression of microRNAs (miRNAs) may contribute to drug resistance. Here, we proposed a systems biology analysis strategy to identify the novel miRNAs potentially involved in CDDP resistance in human ovarian cancer cells. Firstly, we identified the candidate miRNAs associated with CDDP resistance using NCI-60 data...
September 1, 2017: Molecular BioSystems
Asuka Tada, Sachiko Horie, Shiro Mori, Tetsuya Kodama
Systemic administration of drugs into the blood circulation is a standard treatment for the prevention of metastasis. However, systemic delivery cannot maintain sufficiently high concentrations of anticancer drugs in lymphatic nodes (LNs). Here, we show that administering cisplatin (CDDP) using a lymphatic drug delivery system (LDDS) has the potential to treat false-negative metastatic LNs. We found that in MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs up to 10 mm in diameter, the accumulation of indocyanine green (ICG, which has a similar molecular weight to CDDP) in a target LN was greater for lymphatic delivery of ICG than for systemic (intravenous) administration...
August 28, 2017: Cancer Science
Long Huang, Jing Wu, Meiying Liu, Liucheng Mao, Hongye Huang, Qing Wan, Yanfeng Dai, Yuanqing Wen, Xiaoyong Zhang, Yen Wei
Mesoporous silica nanoparticles have attracted considerable research attention due to their various applications. Surface modification of these mesoporous silica nanoparticles with polymers not only can improve their water dispersity but can also endow several new functions, such as drug loading and delivery or targeting capability. In this work, we report a novel strategy for the direct surface grafting of phospholipid choline-containing copolymers onto Santa Barbara Amorphous-15 (SBA-15) through surface-initiated chain transfer free radical polymerization...
August 24, 2017: Journal of Colloid and Interface Science
Akinori Taketani, Bibin B Andriana, Hiroko Matsuyoshi, Hidetoshi Sato
A miniaturized Raman endoscope (mRE) system was employed to study the effects of anticancer treatment on colorectal tumors in a live murine model. The endoscope is narrow enough to observe the inside of the mouse colon under anesthesia. It has a channel for a ball lens mounted on a hollow fiber Raman probe (BHRP) to measure any targeted point under the visual control of the endoscope. Colorectal cancer tissue was observed to study the alterations of the tissue in response to anticancer drug treatment. Three anticancer drugs, 5-fluorouracil (5-FU), cisplatin (CDDP), and docetaxel, were employed...
August 24, 2017: Analyst
Wei Li, Hongjie Zhou, Yang Chu, Xiangyang Wang, Ruizhi Luo, Liu Yang, Navaneethakrishnan Polachi, Xiao Li, Min Chen, Luqi Huang, Xueying Yan, Zhixin Guo, He Sun
Compound Danshen Dripping Pills (CDDP), a herbal patent medicine, is widely used in China for the prevention and treatment of cardiovascular diseases. A simple, sensitive and reliable method for simultaneous determination of danshensu (DSS), protocatechuic aldehyde (PCA), and their related metabolites, 4-hydroxy-3-methyloxyphenyl lactic acid (HMLA) and protocatechuic acid (PAA) in human plasma was developed and validated based on liquid chromatography tandem mass spectrometry (LC-MS/MS). The analytes and internal standard (IS), vanillic acid (VAA), were extracted from plasma with ethyl acetate and separated on a C18 column by using the mobile phase consisted of methanol-0...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
Richard J Browning, Philip James Thomas Reardon, Maryam Parhizkar, R Barbara Pedley, Mohan Edirisinghe, Jonathan C Knowles, Eleanor Stride
Few chemotherapeutics have had such an impact on cancer management as cis-diamminedichloridoplatinum(II) (CDDP), also known as cisplatin. The first member of the platinum based drug family, CDDP's potent toxicity in disrupting DNA replication has led to its widespread use in multi-drug therapies, with particular benefit in patients with testicular cancers. However, CDDP also produces significant side effects that limit the maximum systemic dose. Various strategies have been developed to address this challenge including encapsulation within micro- or nanocarriers and the use of external stimuli such as ultrasound to promote uptake and release...
August 22, 2017: ACS Nano
Hailong Ma, Shufang Jin, Wenyi Yang, Zhuowei Tian, Shuli Liu, Yang Wang, Ge Zhou, Mei Zhao, Shalva Gvetadze, Zhiyuan Zhang, Jingzhou Hu
Objectives: IFNα can stimulate an antitumor immune response and has a direct inhibition on cancer cells. This study is to test whether IFNα can activate dormant cancer stem cell (CSC) in oral squamous cell carcinoma (OSCC) to facilitate their elimination by chemotherapy. Materials and methods: Nude mouse transplantation tumor model was established and administrated with IFNα and saline. The influence on CD44 and ALDH1A1 expression under IFNα treatment was detected by in vivo experiments. Flow cytometry, western blot, and immunofluorescence were used to detect the expression of CD44 and ALDH1A1 after INFa treatment in OSCC cell lines...
2017: Journal of Cancer
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