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https://www.readbyqxmd.com/read/28081275/role-of-xrcc1-gene-polymorphisms-in-non-small-cell-lung-cancer-cisplatin-based-chemotherapy-and-their-effect-on-clinical-and-pathological-characteristics
#1
H F Liu, J S Liu, J H Deng, R R Wu
Non-small cell lung cancer (NSCLC) is the most common cancer globally. The XRCC1 protein interacts with ligase and poly(ADP-ribose) polymerase to repair cisplatin-induced DNA damage. The authors of previous studies have reported XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms and advanced NSCLC prognosis, but the results are inconclusive. We investigated the association between clinical outcome and XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms in advanced NSCLC patients treated with cisplatin...
December 23, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28058814/overexpression-of-tnks1bp1-in-lung-cancers-and-its-involvement-in-homologous-recombination-pathway-of-dna-double-strand-breaks
#2
Wei Tan, Hua Guan, Lian-Hong Zou, Yu Wang, Xiao-Dan Liu, Wei-Qing Rang, Ping-Kun Zhou, Hua-Dong Pei, Cai-Gao Zhong
TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation...
January 6, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28008145/msh2-brca1-expression-as-a-dna-repair-signature-predicting-survival-in-early-stage-lung-cancer-patients-from-the-ifct-0002-phase-3-trial
#3
Guénaëlle Levallet, Fatéméh Dubois, Pierre Fouret, Martine Antoine, Solenn Brosseau, Emmanuel Bergot, Michèle Beau-Faller, Valérie Gounant, Elisabeth Brambilla, Didier Debieuvre, Olivier Molinier, Françoise Galateau-Sallé, Julien Mazieres, Elisabeth Quoix, Jean-Louis Pujol, Denis Moro-Sibilot, Alexandra Langlais, Franck Morin, Virginie Westeel, Gérard Zalcman
INTRODUCTION: DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. METHODS: We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002)...
December 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27960087/leveraging-an-nqo1-bioactivatable-drug-for-tumor-selective-use-of-poly-adp-ribose-polymerase-inhibitors
#4
Xiumei Huang, Edward A Motea, Zachary R Moore, Jun Yao, Ying Dong, Gaurab Chakrabarti, Jessica A Kilgore, Molly A Silvers, Praveen L Patidar, Agnieszka Cholka, Farjana Fattah, Yoonjeong Cha, Glenda G Anderson, Rebecca Kusko, Michael Peyton, Jingsheng Yan, Xian-Jin Xie, Venetia Sarode, Noelle S Williams, John D Minna, Muhammad Beg, David E Gerber, Erik A Bey, David A Boothman
Therapeutic drugs that block DNA repair, including poly(ADP-ribose) polymerase (PARP) inhibitors, fail due to lack of tumor-selectivity. When PARP inhibitors and β-lapachone are combined, synergistic antitumor activity results from sustained NAD(P)H levels that refuel NQO1-dependent futile redox drug recycling. Significant oxygen-consumption-rate/reactive oxygen species cause dramatic DNA lesion increases that are not repaired due to PARP inhibition. In NQO1(+) cancers, such as non-small-cell lung, pancreatic, and breast cancers, cell death mechanism switches from PARP1 hyperactivation-mediated programmed necrosis with β-lapachone monotherapy to synergistic tumor-selective, caspase-dependent apoptosis with PARP inhibitors and β-lapachone...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27923905/%C3%AE-lapachone-inhibits-lung-metastasis-of-colorectal-cancer-by-inducing-apoptosis-of-ct26-cells
#5
Ji-Ye Kee, Yo-Han Han, Jinbong Park, Dae-Seung Kim, Jeong-Geon Mun, Kwang Seok Ahn, Hyun-Jung Kim, Jae-Young Um, Seung-Heon Hong
BACKGROUND: β-Lapachone is a quinone-containing compound found in red lapacho (Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. METHODS: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38)...
December 5, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27919953/bishydroquinone-renieramycin-m-induces-apoptosis-of-human-lung-cancer-cells-through-a-mitochondria-dependent-pathway
#6
Tatchakorn Pinkhien, Arnatchai Maiuthed, Supakarn Chamni, Khanit Suwanborirux, Naoki Saito, Pithi Chanvorachote
BACKGROUND: Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells. METHODS: HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27898232/unfolded-protein-response-promotes-doxorubicin-induced-nonsmall-cell-lung-cancer-cells-apoptosis-via-the-mtor-pathway-inhibition
#7
Xiaofang Zhao, Yan Yang, Fuli Yao, Bin Xiao, Ying Cheng, Chunhong Feng, Chunyan Duan, Chunyan Zhang, Youping Liu, Hong Li, Bo Xiao, Rongyang Dai
Drug resistance is extremely common in nonsmall cell lung cancer (NSCLC) and is one of the major problems in NSCLC chemotherapy. However, the detailed mechanisms remain largely unknown. Unfolded protein response (UPR) is involved in the tumorigenesis of NSCLC. Here, the authors demonstrated that the UPR promotes poly (ADP-ribose) polymerase activation (PARP) cleavage in NSCLC cells on doxorubicin treatment, which is a hallmark of apoptosis and caspase activation. In NSCLC cells, doxorubicin treatment triggers the UPR activation, which subsequently promotes doxorubicin-mediated apoptosis...
December 2016: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27875549/the-synthetic-%C3%AE-nitrostyrene-derivative-cyt-rx20-inhibits-esophageal-tumor-growth-and-metastasis-via-pi3k-akt-and-stat3-pathways
#8
Wen-Chin Chiu, Yi-Chen Lee, Yu-Han Su, Yen-Yun Wang, Chun-Hao Tsai, Yi-An Hou, Chie-Hong Wang, Ying-Fong Huang, Chih-Jen Huang, Shah-Hwa Chou, Pei-Wen Hsieh, Shyng-Shiou F Yuan
The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers...
2016: PloS One
https://www.readbyqxmd.com/read/27871924/mir-335-regulates-the-chemo-radioresistance-of-small-cell-lung-cancer-cells-by-targeting-parp-1
#9
Yingshan Luo, Lihua Tong, Hui Meng, Weiliang Zhu, Linlang Guo, Ting Wei, Jian Zhang
The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of small cell lung cancer (SCLC) was investigated. miR-335 was significantly downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with parental cells as detected by qRT-PCR. Then, we demonstrated the negative correlation between miR-335 expression and the chemo-radiosensitivity of SCLC cells, including cell proliferation, cell clonality and cell apoptosis. In addition, miR-335 overexpression inhibited cell migration in vitro and tumor growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor growth...
February 5, 2017: Gene
https://www.readbyqxmd.com/read/27831000/targeted-therapies-for-the-treatment-of-non-small-cell-lung-cancer-monoclonal-antibodies-and-biological-inhibitors
#10
Ana P S Silva, Priscila V Coelho, Maristella Anazetti, Patricia U Simioni
The usual treatments for patients with non-small-cell lung cancer (NSCLC), such as advanced lung adenocarcinoma, are unspecific and aggressive, and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. In recent years, several clinical trials using monoclonal antibodies presented potential benefits to NSCLC, and four of them are already approved for the treatment of NSCLC, such as cetuximab, bevacizumab, nivolumab and pembrolizumab...
November 10, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27756319/depletion-of-thymopoietin-inhibits-proliferation-and-induces-cell-cycle-arrest-apoptosis-in-glioblastoma-cells
#11
Lin Zhang, Gan Wang, Shiwen Chen, Jun Ding, Shiming Ju, Heli Cao, Hengli Tian
BACKGROUND: Glioblastoma (GBM) is the most malignant nervous system tumor with an almost 100 % recurrence rate. Thymopoietin (TMPO) has been demonstrated to be upregulated in various tumors, including lung cancer, breast cancer, and so on, but its role in GBM has not been reported. This study was aimed to determine the role of TMPO in GBM. METHODS: Publicly available Oncomine dataset analysis was used to explore the expression level of TMPO in GBM specimens. Then the expression of TMPO was knocked down in GBM cells using lentiviral system, and the knockdown efficacy was further validated by real-time quantitative PCR and western blot analysis...
October 19, 2016: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27739325/a-randomized-phase-ii-study-of-veliparib-with-temozolomide-or-carboplatin-paclitaxel-versus-placebo-with-carboplatin-paclitaxel-in-brca1-2-metastatic-breast-cancer-design-and-rationale
#12
Steven J Isakoff, Shannon Puhalla, Susan M Domchek, Michael Friedlander, Bella Kaufman, Mark Robson, Melinda L Telli, Véronique Diéras, Hyo Sook Han, Judy E Garber, Eric F Johnson, David Maag, Qin Qin, Vincent L Giranda, Stacie P Shepherd
Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and breast cancer. Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation (Trial registration: EudraCT 2011-002913-12, NCT01506609)...
October 14, 2016: Future Oncology
https://www.readbyqxmd.com/read/27729209/jaceosidin-induces-apoptosis-through-bax-activation-and-down-regulation-of-mcl-1-and-c-flip-expression-in-human-renal-carcinoma-caki-cells
#13
Seon Min Woo, Taeg Kyu Kwon
Jaceosidin is a flavonoid isolated from Artemisia vestita that has been reported to possess anti-tumor and anti-proliferative activities in many cancer cells. In this study, we investigated the anti-tumor activity of jaceosodin in renal carcinoma cells. Jaceosidin induced apoptosis in multiple human renal carcinoma cells (Caki, ACHN, A498, and 786-O), lung cancer cells (A549) and glioma cells (U251MG). In contrast, jaceosidin does not induce apoptosis in normal human umbilical vein cells (EA.hy926). Apoptotic cell death was associated with the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase...
December 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27708213/resistance-to-parp-inhibitors-by-slfn11-inactivation-can-be-overcome-by-atr-inhibition
#14
Junko Murai, Ying Feng, Guoying K Yu, Yuanbin Ru, Sai-Wen Tang, Yuqiao Shen, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small cell lung cancer cell lines, and in xenograft models...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27639369/synthesis-and-apoptosis-inducing-studies-of-triazole-linked-3-benzylidene-isatin-derivatives
#15
Atulya Nagarsenkar, Lalita Guntuku, Sravanthi Devi Guggilapu, Danthi Bai K, Srinivasulu Gannoju, V G M Naidu, Nagendra Babu Bathini
In our venture towards the development of effective cytotoxic agents, a panel of triazole linked 3-benzylidene isatin hybrids were synthesized and characterized by IR, (1)H NMR, (13)C NMR and Mass spectral analysis. All the newly synthesized target compounds were assessed against DU145 (prostate), PC-3 (prostate), MDA-MB-231 (breast), BT549 (breast), A549 (lung) and HeLa (cervical) human cancer cell lines by employing MTT assay for their cytotoxic potential. Significantly, compound Z-8l was found to be most potent amongst all the tested compounds with an IC50 value of (3...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27572101/casticin-induces-dna-damage-and-inhibits-dna-repair-associated-protein-expression-in-b16f10-mouse-melanoma-cancer-cells
#16
Yung-Luen Shih, Jason Chou, Ming-Yang Yeh, Hsiao-Min Chou, Hsiu-Chen Chou, Hsu-Feng Lu, Hung-Sheng Shang, Fu-Shin Chueh, Yung-Lin Chu, Shu-Ching Hsueh, Jing-Gung Chung
Casticin, a polymethoxyflavone, has been demonstrated to possess anticancer activities, yet no study has shown in detail that casticin induces DNA damage in lung cancer cells. The purpose of this study was to investigate the possible molecular mechanisms of casticin which induce DNA damage and nuclear condensation in murine melanoma cancer B16F10 cells. In this study, by examining and capturing images using phase contrast microscopy, we found that casticin induced cell morphological changes. Moreover, it decreased the total number of viable cells which was measured by flow cytometry...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27539140/suppression-of-reactive-oxygen-species-mediated-erk-and-jnk-activation-sensitizes-dihydromyricetin-induced-mitochondrial-apoptosis-in-human-non-small-cell-lung-cancer
#17
Shang-Jyh Kao, Wei-Jiunn Lee, Jer-Hwa Chang, Jyh-Ming Chow, Chi-Li Chung, Wen-Yueh Hung, Ming-Hsien Chien
Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains a therapeutic challenge. A strategy for targeting NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. Dihydromyricetin (DHM) is the major flavonoid component derived from Ampelopsis grossedentata, which has a long history of use in medicine. Herein, the molecular mechanisms by which DHM exerts its anticancer effects against NSCLC cells were investigated...
August 19, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27498029/calotropin-from-asclepias-curasavica-induces-cell-cycle-arrest-and-apoptosis-in-cisplatin-resistant-lung-cancer-cells
#18
En-Pan Mo, Rong-Rong Zhang, Jun Xu, Huan Zhang, Xiao-Xiong Wang, Qiu-Tong Tan, Fang-Lan Liu, Ren-Wang Jiang, Shao-Hui Cai
Calotropin (M11), an active compound isolated from Asclepias curasavica L., was found to exert strong inhibitory and pro-apoptotic activity specifically against cisplatin-induced resistant non-small cell lung cancer (NSCLC) cells (A549/CDDP). Molecular mechanism study revealed that M11 induced cell cycle arrest at the G2/M phase through down-regulating cyclins, CDK1, CDK2 and up-regulating p53 and p21. Furthermore, M11 accelerated apoptosis through the mitochondrial apoptotic pathway which was accompanied by increase Bax/Bcl-2 ratio, decrease in mitochondrial membrane potential, increase in reactive oxygen species production, activations of caspases 3 and 9 as well as cleavage of poly ADP-ribose polymerase (PARP)...
September 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27488020/treatment-of-breast-cancer-2-brca2-mutant-follicular-dendritic-cell-sarcoma-with-a-poly-adp-ribose-polymerase-parp-inhibitor-a-case-report
#19
Charlotte R Lemech, Rachel Williams, Stephen R Thompson, Brian McCaughan, Melvin Chin
BACKGROUND: Follicular dendritic cell sarcoma is a rare tumour with clinical behaviour covering a spectrum from indolent to aggressive disease. Treatment recommendations are currently based on case reports and small series describing combinations of surgery, chemotherapy and radiotherapy providing the best patient outcomes. Recent knowledge on molecular aberrations in this disease have not yet impacted on therapeutic decisions. CASE PRESENTATION: We describe a case of progressive follicular dendritic cell sarcoma of the lung and pleura, treated based on knowledge of the tumour's molecular aberrations...
August 3, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/27470574/rosemary-extract-reduces-akt-mtor-p70s6k-activation-and-inhibits-proliferation-and-survival-of-a549-human-lung-cancer-cells
#20
Jessy Moore, Mark Megaly, Adam J MacNeil, Panagiota Klentrou, Evangelia Tsiani
Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Rosemary extract contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt, mammalian target of rapamycin (mTOR) and p70S6K, and the apoptotic protein poly ADP ribose polymerase (PARP) are key modulators of cancer cell growth and survival. In this study, we examined the effects of rosemary extract on proliferation, survival and apoptosis of human non-small cell lung cancer (NSCLC) cells and its influence on signaling events...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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