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Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 5, 2016: Scientific Reports
Ying Zhu, Kan Zhai, Juntao Ke, Jiaoyuan Li, Yajie Gong, Yang Yang, Jianbo Tian, Yi Zhang, Danyi Zou, Xiating Peng, Jing Gong, Rong Zhong, Kun Huang, Jiang Chang, Xiaoping Miao
Pancreatic cancer is a highly lethal disease with limited prognostic marker. BRAC1 and BRCA2 are two classic tumor suppressor genes which play an important role in DNA repair. Somatic mutations and germline genetic variants on BRCA1/2 have been found associated with the tumorigenesis of pancreatic cancer. However, the correlations between BRCA1/2 polymorphism and pancreatic cancer prognosis remained unknown. In this study, we genotyped three tag missense variants on BRCA1/2 in 603 sporadic pancreatic cancer patients in a Chinese population...
May 30, 2017: Oncotarget
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
Joonyoung Her, Nam Soo Lee, Yonghwan Kim, Hongtae Kim
Sustaining genomic integrity is essential for preventing onset of cancers. Therefore, human cells evolve to have refined biological pathways to defend genetic materials from various genomic insults. DNA damage response and DNA repair pathways essential for genome maintenance are accomplished by cooperative executions of multiple factors including breast cancer type 1 susceptibility protein (BRCA1). BRCA1 is initially identified as an altered gene in the hereditary breast cancer patients. Since then, tremendous efforts to understand the functions of BRAC1 reveal that BRCA1 is found in distinct complexes, including BRCA1-A, BRCA1-B, BRCA1-C, and the BRCA1/PALB2/BRCA2 complex, and plays diverse roles in a context-dependent manner...
July 2016: Acta Biochimica et Biophysica Sinica
Foteini Anifantaki, Ioannis Boutas, Theodoros Kalampokas, Emmanouil Kalampokas, Chrisostomos Sofoudis, Nikolaos Salakos
BACKGROUND: Endometriosis is a common, estrogen-dependent, gynecological disease, which is defined as the presence of endometrial tissue outside the uterine cavity. Current data have associated endometriosis with specific malignancies, including ovarian and breast cancer. PURPOSE: The purpose of our study is to summarize and present published literature providing evidence regarding the possible relationship between endometriosis and breast cancer. METHODS: Pubmed and Scopus databases were searched systematically for studies that sought to identify a potential association of endometriosis and breast cancer...
January 2016: Archives of Gynecology and Obstetrics
Javed Hussain Choudhury, Sankar Kumar Ghosh
BACKGROUND: Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC). Consumption of tobacco (smoking/chewing) and human papilloma virus (HPV) are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci) in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status...
2015: PloS One
Lauren M Dembeck, Wen Huang, Michael M Magwire, Faye Lawrence, Richard F Lyman, Trudy F C Mackay
Pigmentation varies within and between species and is often adaptive. The amount of pigmentation on the abdomen of Drosophila melanogaster is a relatively simple morphological trait, which serves as a model for mapping the genetic basis of variation in complex phenotypes. Here, we assessed natural variation in female abdominal pigmentation in 175 sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel, derived from the Raleigh, NC population. We quantified the proportion of melanization on the two most posterior abdominal segments, tergites 5 and 6 (T5, T6)...
May 2015: PLoS Genetics
Vijayakumar Govindaraj, Rajani Keralapura Basavaraju, Addicam Jagannadha Rao
Oocytes present at birth undergo a progressive process of apoptosis in humans and other mammals as they age. Accepted opinion is that no fresh oocytes are produced other than those present at the time of birth. Studies have shown that DNA repair genes in oocytes of mice and women decline with age, and lack of these genes show higher DNA breaks and increased oocyte death rates. In contrast to the ethical problems associated with monitoring the changes in DNA double-strand breaks in oocytes from young and old humans, it is relatively easy to carry out such a study using a rodent model...
March 2015: Reproductive Biomedicine Online
Y Han, D P Yu, S J Zhou, X Y Song, Y S Li, N Xiao, Z D Liu, X J Sun, Q Y Zhao, S K Liu
More than 40 oncogenes associated with non-small cell lung cancer (NSCLC) have been identified with varied gene expression. The correlations between specific clinical characteristics and oncogene expression in NSCLC patients were examined. From October 2011 to September 2012, a total of 60 patients with NSCLC (male:female, 34:24; mean age, 59.5 ± 10.6 years; age range, 31-81 years) were diagnosed and evaluated for treatment with radical resection at a single facility. Eligible patients exhibiting tumor node metastasis (TNM) stage I-III NSCLC confirmed by post-surgical pathology were included...
2014: Genetics and Molecular Research: GMR
Natalie Enkin, Fuan Wang, Etery Sharon, H Bauke Albada, Itamar Willner
Luminescent nucleic acid-stabilized Ag nanoclusters (Ag NCs) are applied for the optical detection of DNA and for the multiplexed analysis of genes. Two different sensing modules including Ag NCs as luminescence labels are described. One sensing module involves the assembly of a three-component sensing module composed of a nucleic acid-stabilized Ag NC and a quencher-modified nucleic acid hybridized with a nucleic acid scaffold that is complementary to the target DNA. The luminescence of the Ag NCs is quenched in the sensing module nanostructure...
November 25, 2014: ACS Nano
Yanfang Guan, Hong Hu, Yin Peng, Yuhua Gong, Yuting Yi, Libin Shao, Tengfei Liu, Gairui Li, Rongjiao Wang, Pingping Dai, Yves-Jean Bignon, Zhe Xiao, Ling Yang, Feng Mu, Liang Xiao, Zeming Xie, Wenhui Yan, Nan Xu, Dongxian Zhou, Xin Yi
Hereditary cancers occur because of inherited gene mutations. Genetic testing has been approved to provide information for risk assessment and rationale for appropriate intervention. Testing methods currently available for clinical use have some limitations, including sensitivity and testing throughput, etc. Next generation sequencing (NGS) has been rapidly evolving to increase testing sensitivity and throughput. It can be potentially used to identify inherited mutation in clinical diagnostic setting. Here we develop an effective method employing target enrichment and NGS platform to detect common as well as rare mutations for all common hereditary cancers in a single assay...
March 2015: Familial Cancer
Lauris Gastaud, Esma Saâda-Bouzid, Valérie Le Morvan, Philippe Pourquier, Antoine Ianessi, Juliette Thariat, Antoine Italiano, Antoine Thyss
BACKGROUND: Treatment of osteosarcoma of the extremities consists of surgical resection preceded and followed by chemotherapy, including high-dose methotrexate or adriamycin-based protocols. When distant relapse occurs, therapeutic options are scarce. Trabectedin, a DNA-binding agent, is indicated for the treatment of patients with advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide. In this indication, the 6-month progression-free survival is about 35-40%. Recent reports showed that some specific single nucleotide polymorphisms (SNPs) from DNA repair genes could be associated with sensitivity to trabectedin in soft tissue sarcomas...
2013: Onkologie
Shaik Mohammad Naushad, Cheruku Apoorva Reddy, Konda Kumaraswami, Shree Divyya, Srigiridhar Kotamraju, Suryanarayana Raju Gottumukkala, Raghunadha Rao Digumarti, Vijay Kumar Kutala
Our recent study showing association of hyperhomocysteinemia and hypomethioninemia in breast cancer and other studies indicating association of hyperhomocysteinemia with metastasis and development of drug resistance in breast cancer cells treated with homocysteine lead us to hypothesize that homocysteine might modulate the expression of certain tumor suppressors, i.e., RASSF1, RARβ1, CNND1, BRCA1, and p21, and might influence prognostic markers such as BNIP3 by inducing epigenetic alteration. To demonstrate this hypothesis, we have treated MCF-7 and MDA-MB-231 cells with different doses of homocysteine and observed dose-dependent inhibition of BRCA1 and RASSF1, respectively...
March 2014: Cell Biochemistry and Biophysics
Yu-Jun He, Rui-Huan Liu, Cheng-Qing Ning, Nie-Fang Yu
The poly(ADP-ribose) polymerases (PARPs) is an important group of enzymes in DNA repair pathways, especially the base excision repair (BER) for DNA single-strand breaks (SSBs) repair. Inhibition of PARP in DNA repair-defective tumors (like those with BRAC1/2 mutations) can lead to cell death and genomic instability, what is so called "synthetic lethality". Currently, PARP inhibitors combined with cytotoxic chemotherapeutic agents in the treatment of BRCA-1/2 deficient cancers are in the clinical development...
May 2013: Yao Xue Xue Bao, Acta Pharmaceutica Sinica
Clare Dyer
No abstract text is available yet for this article.
2012: BMJ: British Medical Journal
Pu Jiang, Weidong Zang, Lishan Wang, Ying Xu, Yang Liu, Shi-Xiong Deng
Intraductal papillary mucinous neoplasm (IPMN) is a type of tumor that grows within the pancreatic ducts. It is a progress from hyperplasia to intraductal adenoma (IPMA), to noninvasive carcinoma, and ultimately to invasive carcinoma (IPMC). The objective of this study was to explore the molecular mechanism of the progression from IPMA to IPMC. By using the GSE19650 affymetrix microarray data accessible from Gene Expression Omnibus (GEO) database, we first identified the differentially expressed genes (DEGs) between IPMA and IPMC, followed by the protein-protein interaction and single-nucleotide polymorphism (SNP) analysis of the DEGs...
January 15, 2013: Gene
Namhyun Choi, Kangsun Lee, Dong Woo Lim, Eun Kyu Lee, Soo-Ik Chang, Kwang W Oh, Jaebum Choo
We report the development of a programmable surface-enhanced Raman scattering (SERS)-based micro-network gradient platform to simultaneously detect two different types of DNA oligomer mixtures. The utility of this platform was demonstrated by quantitative analysis of two breast cancer-related (BRCA1) DNA oligomer mixtures. To generate on-demand concentration gradients, the microfluidic circuit was designed using an electric-hydraulic analogy. Then a multi-gradient microfluidic channel was fabricated based on the theoretical design of the concentration control module...
December 21, 2012: Lab on a Chip
Zahra Madjd, Babak Ramezani, Saadat Molanae, Mohsen Asadi-Lari
BACKGROUND: Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. METHODS: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status...
2012: Asian Pacific Journal of Cancer Prevention: APJCP
Chara Papadaki, Maria Sfakianaki, Georgios Ioannidis, Eleni Lagoudaki, Maria Trypaki, Kostas Tryfonidis, Dimitris Mavroudis, Efstathios Stathopoulos, Vassilis Georgoulias, John Souglakos
INTRODUCTION: The potential predictive role of BRCA1 and ERCC1 expression levels in patients with metastatic non-small cell lung cancer (NSCLC) receiving second-line platinum-based chemotherapy was investigated. METHODS: Real-time quantitative polymerase chain reaction after reverse transcription was used to assess the expression levels of BRCA1 and ERCC1 in 100 microdissected primary tumors from platinum-naive NSCLC patients treated with platinum-based chemotherapy in the second-line setting...
April 2012: Journal of Thoracic Oncology
Joel G Turner, Jana Dawson, Daniel M Sullivan
The intracellular location of a protein is crucial to its normal functioning in a cell. Cancer cells utilize the normal processes of nuclear-cytoplasmic transport through the nuclear pore complex of a cell to effectively evade anti-neoplastic mechanisms. CRM1-mediated export is increased in various cancers. Proteins that are exported in cancer include tumor-suppressive proteins such as retinoblastoma, APC, p53, BRAC1, FOXO proteins, INI1/hSNF5, galectin-3, Bok, nucleophosmin, RASSF2, Merlin, p21(CIP), p27(KIP1), N-WASP/FAK, estradiol receptor and Tob, drug targets topoisomerase I and IIα and BCR-ABL, and the molecular chaperone protein Hsp90...
April 15, 2012: Biochemical Pharmacology
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