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PARP inhibitor

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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212547/resveratrol-induces-cell-cycle-arrest-and-apoptosis-with-docetaxel-in-prostate-cancer-cells-via-a-p53-p21waf1-cip1-and-p27kip1-pathway
#2
Santosh Kumar Singh, Saswati Banerjee, Edward P Acosta, James W Lillard, Rajesh Singh
Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212373/poly-adp-ribose-polymerase-1-mrna-levels-strongly-correlate-with-the-prognosis-of-myelodysplastic-syndromes
#3
P Diamantopoulos, K Zervakis, P Zervakis, M Sofotasiou, T Vassilakopoulos, I Kotsianidis, A Symeonidis, V Pappa, A Galanopoulos, E Solomou, E Kodandreopoulou, V Papadopoulou, P Korkolopoulou, M Mantzourani, G Kyriakakis, N-A Viniou
Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28208611/betulinic-acid-mediated-apoptosis-in-human-prostate-cancer-cells-involves-p53-and-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathways
#4
Eswar Shankar, Ailin Zhang, Daniel Franco, Sanjay Gupta
Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network in primary prostate cancer specimens and in metastatic tumors. Betulinic acid (BA), is a triterpenoid that has been reported to be an effective inducer of apoptosis through modification of several signaling pathways...
February 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28207569/poly-adp-ribose-polymerase-inhibition-suppresses-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#5
Ling-Yi Xiao, Wai-Ming Kan
Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib...
March 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28205193/new-therapeutic-strategies-for-triple-negative-breast-cancer
#6
REVIEW
Borbála Székely, Andrea L M Silber, Lajos Pusztai
Relatively few clinically important therapeutic advances have occurred in the treatment of triple-negative breast cancer (TNBC) since the introduction of taxanes as adjuvant therapy over 20 years ago. However, this is rapidly changing due to a variety of conceptually important clinical trials and emerging new options such as immune checkpoint inhibitors and antibody-drug conjugates. Evidence also increasingly supports that platinum drugs and inhibitors of poly (ADP-ribose) polymerase, or PARP, are particularly effective in the treatment of germline BRCA-mutant cancers, including TNBC...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28197640/sb-t-121205-a-next-generation-taxane-enhances-apoptosis-and-inhibits-migration-invasion-in-mcf-7-ptx-cells
#7
Xiaowei Zheng, Changwei Wang, Yuanming Xing, Siying Chen, Ti Meng, Haisheng You, Iwao Ojima, Yalin Dong
Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. the aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms...
February 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28188923/arsenic-sulfide-induces-apoptosis-and-autophagy-through-the-activation-of-ros-jnk-and-suppression-of-akt-mtor-signaling-pathways-in-osteosarcoma
#8
Gangyang Wang, Tao Zhang, Wei Sun, Hongsheng Wang, Fei Yin, Zhuoying Wang, Dongqing Zuo, Mengxiong Sun, Zifei Zhou, Binhui Lin, Jing Xu, Yingqi Hua, Haoqing Li, Zhengdong Cai
Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25-30 years. Arsenic sulfide (As2S2), the main active ingredient of the traditional Chinese medicine realgar, has been proved to have antitumor efficacy in several tumor types including acute promyelocytic leukemia, gastric cancer and colon cancer. Here, we investigated the efficacy and mechanism of As2S2 in osteosarcoma both in vitro and in vivo. In this study, we demonstrated that As2S2 potently suppressed cell proliferation by inducing G2/M phase arrest in various osteosarcoma cell lines...
February 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28186131/recq1-helicase-is-involved-in-replication-stress-survival-and-drug-resistance-in-multiple-myeloma
#9
E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here, we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28182994/atm-deficient-colorectal-cancer-cells-are-sensitive-to-the-parp-inhibitor-olaparib
#10
Chen Wang, Nicholas Jette, Daniel Moussienko, D Gwyn Bebb, Susan P Lees-Miller
The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors...
February 6, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28178193/cearoin-induces-autophagy-erk-activation-and-apoptosis-via-ros-generation-in-sh-sy5y-neuroblastoma-cells
#11
Tonking Bastola, Ren-Bo An, Youn-Chul Kim, Jaehyo Kim, Jungwon Seo
Neuroblastomas are the most common solid extracranial tumors in childhood. We investigated the anticancer effect of cearoin isolated from Dalbergia odorifera in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with various doses of cearoin. The viability was measured by MTT assay. DCFDA fluorescence assay and Griess assay were used for the measurement of intracellular reactive oxygen species (ROS) and nitric oxide (NO), respectively. Western blot analysis was performed to clarify the molecular pathway involved...
February 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28177757/microrna-181-inhibits-proliferation-and-promotes-apoptosis-of-chondrocytes-in-osteoarthritis-by-targeting-pten
#12
Xiao-Feng Wu, Zi-Hui Zhou, Jian Zou
OBJECTIVE: To investigate the effects of microRNA-181 (miR-181) on proliferation and apoptosis of chondrocytes in osteoarthritis (OA) by targeting PTEN. METHODS: The chondrocytes in logarithmic growth phase were selected and divided into 6 groups: the normal, blank, negative control, miR-181 mimics, miR-181 inhibitors and miR-181 inhibitors + PTEN-siRNA groups. RT-qPCR was used to detect the expressions of miR-181 and PTEN mRNA. MTT assay and flow cytometry were performed to detect cell proliferation and apoptosis...
January 25, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28177128/the-sgk1-inhibitor-si113-induces-autophagy-apoptosis-and-endoplasmic-reticulum-stress-in-endometrial-cancer-cells
#13
Domenico Conza, Paola Mirra, Gaetano Calì, Teresa Tortora, Luigi Insabato, Francesca Fiory, Silvia Schenone, Rosario Amato, Francesco Beguinot, Nicola Perrotti, Luca Ulianich
Endometrial cancer is often characterized by PI3K/AKT pathway deregulation. Recently it has been suggested that SGK1, a serine/threonine protein kinase that shares structural and functional similarities with the AKT family, might play a role in cancer, since its expression and/or activity has been found to be deregulated in different human tumors. However, the role of SGK1 in endometrial cancer has been poorly investigated. Here we show that SGK1 expression is increased in tissue specimens from neoplastic endometrium...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28176879/parp-inhibitor-increases-chemosensitivity-by-upregulating-mir-664b-5p-in-brca1-mutated-triple-negative-breast-cancer
#14
Wei Song, Lin Tang, Yumei Xu, Jing Xu, Wenwen Zhang, Hui Xie, Shui Wang, Xiaoxiang Guan
Emerging evidence has shown that adding poly(ADP-ribose) polymerase (PARP) inhibitors to chemotherapy regimens is superior to the control regimens alone in BRCA1-mutated triple-negative breast cancer (TNBC) patients, but their underlying mechanisms have not been fully elucidated. In this study, using miRNA microarray analysis of two BRCA1-mutated TNBC cell lines, we found that miR-664b-5p expression was increased after adding a PARP inhibitor, olaparib, to a carboplatin (CBP) plus gemcitabine (GEM) therapy regimen...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176296/brca1-and-brca2-mutations-in-ovarian-cancer-patients-from-china-ethnic-related-mutations-in-brca1-associated-with-an-increased-risk-of-ovarian-cancer
#15
Tingyan Shi, Pan Wang, Caixia Xie, Sheng Yin, Di Shi, Congchong Wei, Wenbin Tang, Rong Jiang, Xi Cheng, Qingyi Wei, Qing Wang, Rongyu Zang
BRCA1/2 are cancer predisposition genes involved in hereditary breast and ovarian cancer (HBOC). Mutation carriers display an increased sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP). Despite a number of small-size hospital-based studies being previously reported, there is not yet, to our knowledge, precise data of BRCA1/2 mutations among Chinese ovarian cancer patients. We performed a multicenter cohort study including 916 unselected consecutive epithelial ovarian cancer (EOC) patients from eastern China, to screen for BRCA1/2 mutations using the next-generation sequencing approach...
February 8, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28174179/s100b-impairs-glycolysis-via-enhanced-poly-adp-ribosyl-ation-of-glyceraldehyde-3-phosphate-dehydrogenase-in-rodent-muscle-cells
#16
Kaori Hosokawa, Yoji Hamada, Atsushi Fujiya, Masatoshi Murase, Ryuya Maekawa, Yasuhiro Niwa, Takako Izumoto, Yusuke Seino, Shin Tsunekawa, Hiroshi Arima
S100 calcium-binding protein B (S100B), a multifunctional macromolecule mainly expressed in nerve tissues and adipocytes, has been suggested to contribute to the pathogenesis of obesity. To clarify the role of S100B in insulin action and glucose metabolism in peripheral tissues, we investigated the effect of S100B on glycolysis in myoblast and myotube cells. Rat myoblast L6 cells were treated with recombinant mouse S100B to examine glucose consumption, lactate production, glycogen accumulation, glycolytic metabolites and enzyme activity, insulin signaling, and poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)...
February 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28173629/enhanced-dependency-of-kras-mutant-colorectal-cancer-cells-on-rad51-dependent-homologous-recombination-repair-identified-from-genetic-interactions-in-saccharomyces-cerevisiae
#17
Murugan Kalimutho, Amanda L Bain, Bipasha Mukherjee, Purba Nag, Devathri M Nanayakkara, Sarah K Harten, Janelle L Harris, Goutham Narayanan Subramanian, Debottam Sinha, Senji Shirasawa, Sriganesh Srihari, Sandeep Burma, Kum Kum Khanna
Activating KRAS mutations drive colorectal cancer tumorigenesis and influence response to anti-EGFR targeted therapy. Despite recent advances in understanding Ras signaling biology and the revolution in therapies for melanoma using BRAF inhibitors, no targeted agents have been effective in KRAS mutant cancers, mainly due to activation of compensatory pathways. Here, by leveraging the largest synthetic lethal genetic interactome in yeast, we identify that KRAS-mutated colorectal cancer cells have augmented homologous recombination repair (HRR) signaling...
February 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28171799/synergistic-antitumor-effect-of-histone-deacetylase-inhibitor-and-doxorubicin-in-peripheral-t-cell-lymphoma
#18
Huilai Zhang, Ling Dong, Qingqing Chen, Lingzhe Kong, Bin Meng, Huaqing Wang, Kai Fu, Xi Wang, Qiang Pan-Hammarström, Ping Wang, Xianhuo Wang
Chidamide (CS055) is a new and highly selective histone deacetylase inhibitor displaying significant single-agent activity in peripheral T-cell lymphoma (PTCL). But there is little known the synergistic effect between CS055 and chemotherapy. The purpose of this study is to explore the synergistic effect and molecular mechanisms of CS055 combination with Doxorubicin in PTCL cells. We found that CS055 showed dose- and time-dependent inhibition effects on PTCL cell. Meanwhile, the synergistic effect was significantly observed after combination treatment with lower drug-concentration of CS055 and Doxorubicin...
January 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28167507/parp-inhibitor-upregulates-pd-l1-expression-and-enhances-cancer-associated-immunosuppression
#19
Shiping Jiao, Weiya Xia, Hirohito Yamaguchi, Yongkun Wei, Mei-Kuang Chen, Jung-Mao Hsu, Jennifer L Hsu, Wen-Hsuan Yu, Yi Du, Heng-Huan Lee, Chia-Wei Li, Chao-Kai Chou, Seung-Oe Lim, Shih-Shin Chang, Jennifer K Litton, Banu Arun, Gabriel N Hortobagyi, Mien-Chie Hung
PURPOSE: To explore whether a crosstalk exists between PARP inhibition and PD-L1/ PD-1 immune checkpoint axis, and determine if blockade of PD-L1/ PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression. EXPERIMENTAL DESIGN: Breast cancer cell lines, xenograft tumors and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, immunohistochemistry and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation...
February 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28159921/curcumin-blocks-autophagy-and-activates-apoptosis-of-malignant-mesothelioma-cell-lines-and-increases-the-survival-of-mice-intraperitoneally-transplanted-with-a-malignant-mesothelioma-cell-line
#20
Laura Masuelli, Monica Benvenuto, Enrica Di Stefano, Rosanna Mattera, Massimo Fantini, Giuseppina De Feudis, Enrico De Smaele, Ilaria Tresoldi, Maria Gabriella Giganti, Andrea Modesti, Roberto Bei
Malignant mesothelioma (MM) is a primary tumor arising from the serous membranes. The resistance of MM patients to conventional therapies, and the poor patients' survival, encouraged the identification of molecular targets for MM treatment. Curcumin (CUR) is a "multifunctional drug". We explored the in vitro effects of CUR on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, autophagy of human (MM-B1, H-Meso-1, MM-F1), and mouse (#40a) MM cells. In addition, we evaluated the in vivo anti-tumor activities of CUR in C57BL/6 mice intraperitoneally transplanted with #40a cells forming ascites...
30, 2017: Oncotarget
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