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https://www.readbyqxmd.com/read/29345908/a-small-molecule-inhibitor-of-human-dna-polymerase-eta-potentiates-the-effects-of-cisplatin-in-tumor-cells
#1
Maroof K Zafar, Leena Maddukuri, Amit Ketkar, Narsimha Penthala, Megan R Reed, Sarah D Eddy, Peter A Crooks, Robert L Eoff
Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC50 value of 8 μM and exhibited five- to ten-fold specificity for hpol η over replicative pols...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29344124/molecular-biological-characterization-and-drug-sensitivity-of-chidamide-resistant-non-small-cell-lung-cancer-cells
#2
Song'e Luo, Kai Ma, Hongxia Zhu, Shuren Wang, Mei Liu, Weina Zhang, Shufang Liang, Ningzhi Xu
Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical trials for various types of hematological and solid tumors. Although acquired resistance is common in chemotherapy, the mechanism of resistance to chidamide is poorly characterized. The goal of the present study was to explore, in detail, the mechanism for the induced resistance to chidamide, and investigate a potential cross-resistance to other chemotherapeutic drugs. A549 cells were exposed to gradually increasing chidamide concentrations to establish a chidamide-resistant non-small cell lung cancer cell line (A549-CHI-R)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343747/computational-trans-omics-approach-characterised-methylomic-and-transcriptomic-involvements-and-identified-novel-therapeutic-targets-for-chemoresistance-in-gastrointestinal-cancer-stem-cells
#3
Masamitsu Konno, Hidetoshi Matsui, Jun Koseki, Ayumu Asai, Yoshihiro Kano, Koichi Kawamoto, Naohiro Nishida, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
We investigated the relationship between methylomic [5-methylation on deoxycytosine to form 5-methylcytosine (5mC)] and transcriptomic information in response to chemotherapeutic 5-fluorouracil (5-FU) exposure and cisplatin (CDDP) administration using the ornithine decarboxylase (ODC) degron-positive cancer stem cell model of gastrointestinal tumour. The quantification of 5mC methylation revealed various alterations in the size distribution and intensity of genomic loci for each patient. To summarise these alterations, we transformed all large volume data into a smooth function and treated the area as a representative value of 5mC methylation...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29340120/effect-of-short-hydration-on-cisplatin-induced-nephrotoxicity-in-cancer-patients-a-retrospective-study
#4
Farzaneh Ashrafi, Zeinab Ebrahimi, Mehdi Nematbakhsh
Background: The aim of this study was to evaluate the protective role of short hydration against nephrotoxicity induced by cisplatin (CDDP). Materials and Methods: Twenty-two patients (13 men and 9 women) under CDDP therapy were enrolled in this retrospective study between 2009 and 2014. The CDDP was given in 500 ml of isotonic solution, and before and after CDDP administration, the patients received 10mEq potassium chloride15% and 1gr magnesium sulfate in 1000 ml isotonic saline. Renal parameters were evaluated on the first day of each cycle of CDDP therapy...
October 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/29340044/cepharanthine-hydrochloride-reverses-the-mdr1-p-glycoprotein-mediated-esophageal-squamous-cell-carcinoma-cell-cisplatin-resistance-through-jnk-and-p53-signals
#5
Pengjun Zhou, Rong Zhang, Ying Wang, Dandan Xu, Li Zhang, Jinhong Qin, Guifeng Su, Yue Feng, Hongce Chen, Siyuan You, Wen Rui, Huizhong Liu, Suhong Chen, Hongyuan Chen, Yifei Wang
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29332411/%C3%AE-1-integrin-mediated-multicellular-resistance-in-hepatocellular-carcinoma-through-activation-of-the-fak-akt-pathway
#6
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/29328398/synergistic-antitumor-effect-of-brusatol-combined-with-cisplatin-on-colorectal-cancer-cells
#7
Hai-Ming Chen, Zheng-Quan Lai, Hui-Jun Liao, Jian-Hui Xie, Yan-Fang Xian, Yun-Long Chen, Siu-Po Ip, Zhi-Xiu Lin, Zi-Ren Su
Colorectal cancer (CRC) is a common and life‑threatening type of malignant cancer, which is associated with a high mortality rate. Cisplatin (CDDP) is a commonly used chemotherapy drug with significant side effects. Brusatol (BR) is one of the principal chemical compounds isolated from the Chinese herb Bruceae Fructus, which has been reported to markedly inhibit the proliferation of numerous cancer cell lines. The present study aimed to investigate the possible synergistic anticancer effects of CDDP combined with BR on CT‑26 cells, and to evaluate the underlying mechanisms of action...
January 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29301138/the-effect-of-cisplatin-on-blood-ammonia-elevation-by-alanyl-glutamine-supplementation
#8
Yoko Obayashi, Kenta Kajiwara, Eiji Nakamura
BACKGROUND: Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. METHODS: To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1-4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters...
January 4, 2018: Pharmacology
https://www.readbyqxmd.com/read/29299162/foxo3-induces-ubiquitylation-of-akt-through-mul1-regulation
#9
Sun-Yong Kim, Hyo Jeong Kim, Hyung Kwon Byeon, Dae Ho Kim, Chul-Ho Kim
AKT (also known as protein kinase B, PKB) plays an important role in cell survival or tumor progression. For these reasons, AKT is an emerging target for cancer therapeutics. Previously our studies showed that mitochondrial E3 ubiquitin protein ligase 1 (MUL1, also known as MULAN/GIDE/MAPL) is suppressed in head and neck cancer (HNC) and acts as negative regulator against AKT. However, the MUL1 regulatory mechanisms remain largely unknown. Here we report that cisplatin (CDDP) induces thyroid cancer cell death through MUL1-AKT axis...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287202/microrna-381-suppresses-the-growth-and-increases-cisplatin-sensitivity-in-non-small-cell-lung-cancer-cells-through-inhibition-of-nuclear-factor-%C3%AE%C2%BAb-signaling
#10
Ri-Sheng Huang, Yuan-Liang Zheng, Jun Zhao, Xu Chun
microRNA (miR)-381 is downregulated and exhibits anti-invasive activity in non-small cell lung cancer (NSCLC). In this study, we investigated the role of miR-381 in proliferation, tumorigenesis, and cisplatin resistance of NSCLC cells. The effects of miR-381 overexpression on proliferation, tumorigenesis, cell cycle progression, and cisplatin sensitivity were examined. Overexpression of miR-381 significantly inhibited cell proliferation and colony formation in vitro and tumorigenesis in vivo. Ectopic expression of miR-381 arrested NSCLC cells at G0/G1 phase, which was accompanied by increased expression of p21 and p27 and decreased expression of cyclin D1 and CDK4...
December 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29285367/clinical-study-on-collagen-gel-droplet-embedded-culture-drug-sensitivity-test-for-multidrug-combination-chemotherapy-and-super-selective-intra-arterial-infusion-chemoradiotherapy-in-oral-squamous-cell-carcinoma
#11
Kaname Sakuma, Ryuki Tamura, Shintaro Hanyu, Haruka Takahashi, Hideaki Sato, Takahiro Oneyama, Akira Yamaguchi, Akira Tanaka
Using trace three-dimensional culture, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) can be tested even in cases with a small number of cells, including oral squamous cell carcinoma (OSCC), and evaluation of the antitumor effect with a drug concentration close to the in vivo level is possible. The present report aimed to evaluate the utility of the CD-DST in the assessment of the in vitro efficacy of single-agent and multidrug combination chemotherapy for OSCC in comparison with the clinical response rates and to examine the possible clinical application of CD-DST for such cases...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29285357/utility-of-chemoradioselection-for-the-optimization-of-treatment-intensity-in-advanced-hypopharyngeal-and-laryngeal-carcinoma
#12
Muneyuki Masuda, Takahiro Wakasaki, Satoshi Toh, Yoshinori Uchida, Hidefumi Rikimaru, Naonobu Kunitake, Yuichiro Higaki
Definitive concomitant chemoradiotherapy (CRT) with high-dose cis-platinum (CDDP) is a current standard protocol for advanced laryngeal and hypopharyngeal cancer sparing surgery for salvage. However, this modality is associated with limited feasibility and frequent sever toxicities. In the present study, a 'chemoradioselection' protocol with minimal toxicity was developed using initial response to CRT as a biomarker for patient selection. Between 2000, March and 2012, September 123 patients with stage III (44), IV (79) laryngeal (64) and hypopharyngeal carcinoma (59) excluding T4 cases were enrolled to this protocol...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29277774/combination-of-osthole-and-cisplatin-against-rhabdomyosarcoma-te671-cells-yielded-additive-pharmacologic-interaction-by-means-of-isobolographic-analysis
#13
Agata Jarząb, Jarogniew Łuszczki, Małgorzata Guz, Krystyna Skalicka-Woźniak, Marta Hałasa, Jolanta Smok-Kalwat, Krzysztof Polberg, Andrzej Stepulak
BACKGROUND/AIM: Osthole is a simple coumarin that has been found to have anticancer, anti-inflammatory, antiviral, anticoagulant, anticonvulsant and antiallergic activities. The aim of this study was to analyze the combined anti-proliferative effect of cisplatin (CDDP) and osthole on a rhabdomyosarcoma cell line, and assess the pharmacology of drug-drug interaction between these drugs using isobolographic analysis. MATERIALS AND METHODS: The anticancer actions of osthole in combination with CDDP were evaluated using the tetrazolium dye-based MTT cell proliferation assay...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29273566/nutritional-shortage-augments-cisplatin-effects-on-murine-melanoma-cells
#14
F Antunes, G J Pereira, M G Jasiuliones, C Bincoletto, S S Smaili
Melanoma incidence increases every year worldwide and is responsible for 80% of skin cancer deaths. Due to its metastatic potential and resistance to almost any treatments such as chemo, radio, immune and target-therapy, the patients still have a poor prognosis, especially at metastatic stage. Considering that, it is crucial to find new therapeutic approaches to overcome melanoma resistance. Here we investigated the effect of cisplatin (CDDP), one of the chemotherapeutic agents used for melanoma treatment, in association with nutritional deprivation in murine melanoma cell lines...
December 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29245943/saikosaponin-d-a-calcium-mobilizing-agent-sensitizes-chemoresistant-ovarian-cancer-cells-to-cisplatin-induced-apoptosis-by-facilitating-mitochondrial-fission-and-g2-m-arrest
#15
Hideaki Tsuyoshi, Vincent Kam Wai Wong, Yu Han, Makoto Orisaka, Yoshio Yoshida, Benjamin K Tsang
Cisplatin (CDDP) and its derivatives are first line anti-cancer drugs for ovarian cancer (OVCA). However, chemoresistance due to high incidence of p53 mutations leads to poor clinical prognosis. Saikosaponin-d (Ssd), a saponin from a herbal plant extract, has been shown to induce cell death and sensitize chemoresistant cells to chemotherapeutic agents. Here, we demonstrated that Ssd sensitized chemoresistant OVCA cells with either p53-wt, -mutant and -null to CDDP. The action of Ssd appears to be through induction of mitochondrial fragmentation and G2/M arrest...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228308/rxr%C3%AE-enriched-cancer-stem-cell-like-properties-triggered-by-cddp-in-head-and-neck-squamous-cell-carcinoma-hnscc
#16
Pan Jiang, Chaoqi Xu, Ming Zhou, Huaqun Zhou, Weida Dong, Xiaoyue Wu, Aochang Chen, Qing Feng
Retinoid X receptor-α (RXRα) is a kind of nuclear receptor and is a target of cancer prevention and treatment in various types of cancers. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism how RXRα regulates CSCs remains unknown. In the present study, we found that RXRα was up-regulated in head and neck squamous cell carcinoma (HNSCC) tissues and the enriched HNSCC cancer stem cells. Over-expression of RXRα was able to expand the CSC-like properties in HNSCC cells, while knockdown of RXRα could repress the stemness respectively...
December 6, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29209208/the-clinical-pharmacokinetics-and-pharmacodynamics-of-warfarin-when-combined-with-compound-danshen-a-case-study-for-combined-treatment-of-coronary-heart-diseases-with-atrial-fibrillation
#17
Chunxiao Lv, Changxiao Liu, Zhuhua Yao, Xiumei Gao, Lanjun Sun, Jia Liu, Haibo Song, Ziqiang Li, Xi Du, Jinxia Sun, Yanfen Li, Kui Ye, Ruihua Wang, Yuhong Huang
Warfarin is used as anticoagulant and Compound Danshen prescription (CDP) is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs) with atrial fibrillation (AF). Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP) on the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of warfarin was investigated in patients. The dose and blood concentrations of warfarin, the four indicators of blood coagulation, prothrombin time, activated partial thromboplatin time, thrombin time, fibrinogen, and international normalized ratio value were compared when with and without CDDP treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29207183/src-homology-phosphotyrosyl-phosphatase-2-mediates-cisplatin-related-drug-resistance-by-inhibiting-apoptosis-and-activating-the-ras-pi3k-akt1-survivin-pathway-in-lung-cancer-cells
#18
Chunlan Tang, Hu Luo, Dan Luo, Heping Yang, Xiangdong Zhou
Cisplatin resistance is a major cause of chemotherapeutic failure in lung cancer patients. Unraveling the molecular mechanisms underlying cisplatin (CDDP) resistance is important in lung cancer therapeutics. To explore the role of Src homology phosphotyrosyl phosphatase 2 (SHP2) in the development of cisplatin resistance in lung cancer and the underlying mechanism, we established stable SHP2‑overexpressing H446‑SHP2-OE cells and SHP2‑knockdown H446/CDDP‑SHP2-shRNA cells derived from H446 and H446/CDDP (cisplatin-resistant) parental lung cancer cells...
November 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29204983/phyllanthus-emblica-linn-fruit-extract-potentiates-the-anticancer-efficacy-of-mitomycin-c-and-cisplatin-and-reduces-their-genotoxicity-to-normal-cells-in-vitro
#19
Xi-Han Guo, Juan Ni, Jing-Lun Xue, Xu Wang
OBJECTIVE: Fruit of Phyllanthus emblica Linn. (PE) is widely consumed as a functional food and used as a folk medicine due to its remarkable nutritional and pharmacological effects. Mitomycin C (MMC) and cisplatin (cDDP) are the most widely used forms of chemotherapeutic drug, but their clinical use is limited by their genotoxicity to normal cells. We aimed to determine whether PE has potential to reduce the genotoxicity, while improving the anticancer effect, of MMC and cDDP. METHODS: Cell proliferation was evaluated using the trypan blue exclusion assay and colony-forming assay...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29190391/radiotherapy-for-locally-advanced-resectable-t3-t4-laryngeal-cancer-does-laryngeal-preservation-strategy-compromise-survival
#20
Hideya Yamazaki, Gen Suzuki, Satoaki Nakamura, Shigeru Hirano, Ken Yoshida, Koji Konishi, Teruki Teshima, Kazuhiko Ogawa
With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT...
November 28, 2017: Journal of Radiation Research
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