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Samer Al Hadidi, Ahmed Aburahma, Sunil Badami, Sunil Upadhaya
No abstract text is available yet for this article.
March 23, 2018: Oncology Research and Treatment
Sean W Reilly, Mehran Makvandi, Kuiying Xu, Robert H Mach
Access to211 At- and125 I-radiolabeled compounds in excellent RCCs and RCYs was achieved in just 10 min at room temperature using a Cu catalyst. The reaction conditions are applicable to a broad class of aryl and heteroaryl boronic reagents with varying steric and electronic properties as well as late-stage astatination and iodination of anticancer PARP inhibitors. This protocol eliminates the traditional need for toxic organotin reagents, elevated temperatures, and extended reaction times, providing a more practical and environmentally friendly approach to developing α-emitting radiotherapeutics...
March 21, 2018: Organic Letters
Genshen Zhong, Zhishan Xu, Ru Yang, Shenghua Zhang, Liang Li, Minna Wu, Hongtao Liu, Yongsu Zhen
Pancreatic cancer (PC) is one of the most dangerous cancers with less than 5% survival rate in 5 years. This study was to evaluate the antitumor activities of dFv-LDP-AE and dFv-R-LDP-AE, two energized fusion protein targeting gelatinases, on pancreatic cancer. The fusion protein dFv-LDP-AE consists of two tandem anti-gelatianses scFv and an enediyne antibiotic lidamycin (LDM) for receptor binding and cell killing. To improve the penetration capability, the fusion protein dFv-LDP-AE was integrated with an arginine-rich cell penetrating peptide (Arg)9 and then generated the fusion protein dFv-R-LDP-AE...
2018: Journal of Cancer
Zhiyuan Xing, Fengbo Sun, Wang He, Zhiwei Wang, Xiuqi Song, Fengjuan Zhang
Ubiquitin-specific peptidase 39 (USP39) has been reported to participate in the mitotic spindle checkpoint and the process of cytokinesis. and has been identified as a therapeutic target for various types of cancer. However, the effect of USP39 in colorectal cancer (CRC) has not been investigated. To explore the functional role of USP39 in CRC cell growth, lentivirus-mediated RNA interference was applied to inhibit USP39 expression in SW1116 and HCT116 cells. The relative USP39 mRNA and protein expression levels were significantly reduced in the USP39 knockdown cells, as verified by reverse transcription-quantitative polymerase chain reaction and western blot analysis...
April 2018: Oncology Letters
Loredana Campo, Eun-Kyoung Breuer
Studies have shown that transforming acidic coiled-coil protein 3 (TACC3), a key component of centrosome-microtubule dynamic networks, is significantly associated with various types of human cancer. We have recently reported that high levels of TACC3 are found in breast cancer, lead to the accumulation of spontaneous DNA damage due to defective DNA damage response signaling, and confer cellular sensitivity to radiation and poly(ADP-ribose) polymerase (PARP) inhibitors. Although our study suggests a potential role of TACC3 as a biomarker in breast cancer detection and prediction of therapy outcome, its role as a therapeutic target in breast cancer is not well studied...
March 16, 2018: Biochemical and Biophysical Research Communications
Heather H Cheng
An estimated one-fifth or more of metastatic castration-resistant prostate cancer (mCRPC) harbor defects in genes involved in DNA repair pathway (e.g., BRCA2, BRCA1, and others). Early evidence suggests these alterations may be predictive of therapeutic response to PARP inhibitors and platinum chemotherapy, thought to reflect principles of synthetic lethality and are currently being investigated in an increasing number of prospective clinical trials. Other studies have examined these alterations as prognostic biomarkers and in association with response to currently available treatments...
March 16, 2018: Urologic Oncology
Qun Dai, Yu-Qing Ge
Platycodin D(PD) has a significantly inhibitory effect on multiple malignant tumors, and can inhibit the proliferation of leukemia cells K562 and induce apoptosis. However, its effect in improving the sensitivity of drug-resistant cells to imatinib and their molecular mechanism remained unclear. To investigate the effect and mechanism of PD alone or combined with imatinib (IM) in inhibiting CML imatinib resistant cell line K562/R, the cell proliferation was examined by CCK8 assay to reveal the effect of PD on the inhibitory function of imatinib...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Ke-Wang Luo, Wing-Yin Lung, Chun-Xie, Xin-Le Luo, Wei-Ren Huang
Epigallocatechin-3-gallate (EGCG), the bioactive polyphenol in green tea, has been demonstrated to have various biological activities. We previously found that EGCG inhibited SW780 tumor growth by down-regulation of NF-κB and MMP-9. This study demonstrated that EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway, without modulation of NF-κB. Our results showed that treatment of EGCG resulted in significant inhibition of cell proliferation by induction of apoptosis, without obvious toxicity to normal bladder SV-HUC-1 cells...
February 23, 2018: Oncotarget
Zhenlei Li, Xiaoping Zou, Hao Zhu, Min Chen, Yan Zhao
Pancreatic cancer is an aggressive disease with a particularly poor prognosis contributing to a substantial percentage of cancer-associated mortality rates. In the present study, the combination treatment of baicalein (BAI) and gemcitabine (GEM) was investigated to examine whether it inhibited the growth of the human CFPAC-1 pancreatic cancer cell line in vitro and in vivo . The cytotoxic interactions between BAI and GEM in human pancreatic cancer cell lines were determined using MTT assays, and the effect of the two agents on apoptosis was detected using Hoechst 33258 staining and annexin V/7-AAD...
April 2018: Oncology Letters
Hui Di, Xinting Zhang, Yi Guo, Yanfang Shi, Chuan Fang, Yu Yuan, Jiwei Wang, Chao Shang, Wenzhe Guo, Chunhui Li
Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues...
April 2018: Oncology Letters
Concetta Saponaro, Sara Sergio, Antonio Coluccia, Maria De Luca, Giuseppe La Regina, Luca Mologni, Valeria Famiglini, Valentina Naccarato, Daniela Bonetti, Candice Gautier, Stefano Gianni, Daniele Vergara, Michel Salzet, Isabelle Fournier, Cecilia Bucci, Romano Silvestri, Carlo Gambacorti Passerini, Michele Maffia, Addolorata Maria Luce Coluccia
Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+ /H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity...
March 19, 2018: Oncogene
Bongkyun Park, Jeong Eun Kwon, Se Min Cho, Chang Won Kim, Da Eun Lee, Young Tae Koo, Sang Hun Lee, Hyun Myung Lee, Se Chan Kang
PURPOSE: Bisphenol A (BPA) has been regarded as a possible risk factor for reproductive health. We examined potential reproductive health benefits of Lespedeza cuneata ethanol extract (LCE). Previously, Lespedeza cuneata showed many therapeutic effects. However, the protective effect of LCE on BPA-induced testicular dysfunction and its mechanisms have not been precisely studied. METHODS: Mice were randomly divided into six groups (n = 7). Sperm counts and motility were measured by light microscope...
March 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Fei-Fei Wang, Chao Shi, Yue Yang, Yong Fang, Li Sheng, Ning Li
Gastric cancer (GC) is the fourth most common diagnosed cancer and the second leading cause of cancer death worldwide. Phellinus igniarius is a traditional medicinal mushroom used in China and other countries of East Asia for the treatment of various diseases including cancer. The aim of this study is to evaluate the antitumor activity of P. igniarius and elucidate the possible mechanism. MTT assay displayed that the total ethanol extract of P. igniarius (TPI) had antitumor activities against five human tumor cell lines of HepG-2, AGS, SGC-7901, Hela and A-549...
March 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bei Wang, Shu-Sen Zheng, Tan-Yang Zhou, Chun-Hui Nie, Da-Long Wan
Bigelovin (BigV) is a sesquiterpene lactone, isolated from Inula helianthus aquatica, which has been reported to induce apoptosis and show anti-inflammatory and anti-angiogenic activities. Nevertheless, the effects of BigV on liver cancer and the underlying mechanisms have not been investigated. In the study, we found that BigV exhibited potential anti-tumor activities against human liver cancer in vitro and in vivo. BigV reduced the cell proliferation and colony formation. BigV induced apoptosis through improving the cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1)...
March 13, 2018: Biochemical and Biophysical Research Communications
Radoslav Aleksandrov, Anton Dotchev, Ina Poser, Dragomir Krastev, Georgi Georgiev, Greta Panova, Yordan Babukov, Georgi Danovski, Teodora Dyankova, Lars Hubatsch, Aneliya Ivanova, Aleksandar Atemin, Marina N Nedelcheva-Veleva, Susanne Hasse, Mihail Sarov, Frank Buchholz, Anthony A Hyman, Stephan W Grill, Stoyno S Stoynov
A single mutagen can generate multiple different types of DNA lesions. How different repair pathways cooperate in complex DNA lesions, however, remains largely unclear. Here we measured, clustered, and modeled the kinetics of recruitment and dissociation of 70 DNA repair proteins to laser-induced DNA damage sites in HeLa cells. The precise timescale of protein recruitment reveals that error-prone translesion polymerases are considerably delayed compared to error-free polymerases. We show that this is ensured by the delayed recruitment of RAD18 to double-strand break sites...
March 15, 2018: Molecular Cell
Yanlan Li, Xiaodan Liu, Pengchao Gong, Xin Tian
Bufalin, a key active ingredient of the Chinese medicine Chan Su, inhibits breast cancer tumorigenesis in vitro and in vivo. Here we found that the pan-caspase inhibitor zVAD-fmk failed to inhibit bufalin-induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells, confirming that the cell death induced by bufalin is caspase-independent. Instead, bufalin increased the expression of the necroptosis mediators RIP1 and RIP3. Bufalin-induced cell death was prevented by small molecule inhibitors of RIP1 and poly (ADP-ribose) polymerase-1 (PARP-1) or genetic knockdown of RIP3 by shRNA transfection...
March 13, 2018: Carcinogenesis
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
Hong Qi, Aiping Li
The present study aimed to investigate the effects of JWA knockout (JWA-/- ) on malignant transformation of murine embryonic fibroblast (MEF) cells using a conditional JWA-/- mouse model. Once MEF cells were prepared, the potential role of JWA-/- on proliferation, migration, invasion and colony formation of MEF cells was investigated by cytological examination. The effects of JWA-/- on the regulation and protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins in MEF cells, including poly(ADP-ribose) polymerase-1 (PARP-1), vimentin, β-catenin and E-cadherin, were investigated using western blot analysis...
April 2018: Experimental and Therapeutic Medicine
Pingping Fang, Jill A Madden, Lisa Neums, K Ryan Moulder, M Laird Forrest, Jeremy Chien
FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in poly (ADP-ribose) polymerase (PARP) inhibitor response has not yet been studied. The present study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. Based on ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair...
March 15, 2018: Molecular Cancer Research: MCR
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