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Pawel Domagala, Jolanta Hybiak, Janusz Rys, Tomasz Byrski, Cezary Cybulski, Jan Lubinski
Pathologic complete response (pCR) after neoadjuvant chemotherapy is considered a suitable surrogate marker of treatment efficacy in patients with triple-negative breast cancers (TNBCs). However, the molecular mechanisms underlying pCR as a result of such treatment remain obscure. Using real-time PCR arrays we compared the expression levels of 120 genes involved in the main mechanisms of DNA repair in 43 pretreatment biopsies of BRCA1-associated TNBCs exhibiting pCR and no pathological complete response (non-pCR) after neoadjuvant chemotherapy with cisplatin...
September 8, 2016: Oncotarget
Howard Lopes Ribeiro, Allan Rodrigo Soares Maia, Marília Braga Costa, Izabelle Rocha Farias, Daniela de Paula Borges, Roberta Taiane Germano de Oliveira, Juliana Cordeiro de Sousa, Silvia Maria Meira Magalhães, Ronald Feitosa Pinheiro
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell (HSC) malignances characterized by peripheral cytopenias and predisposition to acute myeloid leukemia transformation. Several studies show that the MDS pathogenesis is a complex and heterogeneous process that involves multiple steps through a sequence of genetic lesions in the DNA which lead to functional changes in the cell and the emergence and subsequent evolution of pre-malignant clone. Double strand breaks (DSB) lesions are the most severe type of DNA damage in HSCs, which, if not properly repaired, might contribute to the development of chromosomal abnormalities, which in turn may lead to leukemia development...
September 2016: Leukemia Research
Helen E Gruber, Frank E Riley, Gretchen L Hoelscher, Jane A Ingram, Letitia Bullock, Edward N Hanley
Back pain and intervertebral disc degeneration have growing socioeconomic/health care impacts. Increasing research efforts address use of stem and progenitor cell-based replacement therapies to repopulate and regenerate the disc. Data presented here on the innate human annulus progenitor cells: (i) assessed osteogenic, chondrogenic and adipogenic potentials of cultured human annulus cells; and (ii) defined progenitor-cell related gene expression patterns. Verification of the presence of progenitor cells within primary human disc tissue also used immunohistochemical identification of cell surface markers and microarray analyses...
August 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Joshua M Gilmore, Mihaela E Sardiu, Brad D Groppe, Janet L Thornton, Xingyu Liu, Gerald Dayebgadoh, Charles A Banks, Brian D Slaughter, Jay R Unruh, Jerry L Workman, Laurence Florens, Michael P Washburn
Proteins that respond to DNA damage play critical roles in normal and diseased states in human biology. Studies have suggested that the S. cerevisiae protein CMR1/YDL156w is associated with histones and is possibly associated with DNA repair and replication processes. Through a quantitative proteomic analysis of affinity purifications here we show that the human homologue of this protein, WDR76, shares multiple protein associations with the histones H2A, H2B, and H4. Furthermore, our quantitative proteomic analysis of WDR76 associated proteins demonstrated links to proteins in the DNA damage response like PARP1 and XRCC5 and heterochromatin related proteins like CBX1, CBX3, and CBX5...
2016: PloS One
Jian Cui, Jiangtao Luo, Yeong C Kim, Carrie Snyder, Dina Becirovic, Bradley Downs, Henry Lynch, San Ming Wang
Ku80 is a subunit of the Ku heterodimer that binds to DNA double-strand break ends as part of the non-homologous end joining (NHEJ) pathway. Ku80 is also involved in homologous recombination (HR) via its interaction with BRCA1. Ku80 is encoded by the XRCC5 gene that contains a variable number tandem repeat (VNTR) insertion in its promoter region. Different VNTR genotypes can alter XRCC5 expression and affect Ku80 production, thereby affecting NHEJ and HR pathways. VNTR polymorphism is associated with multiple types of sporadic cancer...
2016: Frontiers in Oncology
Kamalesh Dattaram Mumbrekar, Hassan Venkatesh Goutham, Bejadi Manjunath Vadhiraja, Satish Rao Bola Sadashiva
BACKGROUND: A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it. METHODS: By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity...
April 2016: DNA Repair
Ya-Wen Cheng, Frank Cheau-Feng Lin, Chih-Yi Chen, Nan-Yung Hsu
Most studies of lung tumorigenesis have focused on smokers rather than nonsmokers. In this study, we used human papillomavirus (HPV)-positive and HPV-negative lung cancer cells to test the hypothesis that HPV infection synergistically increases DNA damage induced by exposure to the carcinogen benzo[a]pyrene (B[a]P), and contributes to lung tumorigenesis in nonsmokers. DNA adduct levels induced by B[a]P in HPV-positive cells were significantly higher than in HPV-negative cells. The DNA adduct formation was dependent on HPV E6 oncoprotein expression...
April 12, 2016: Oncotarget
Na Wang, Hanna Kjellin, Anastasios Sofiadis, Omid Fotouhi, C Christofer Juhlin, Martin Bäckdahl, Jan Zedenius, Dawei Xu, Janne Lehtiö, Catharina Larsson
Medullary thyroid carcinomas (MTCs) exhibit telomerase activation in strong association with shorter patient survival. To understand the background of telomerase activation we quantified TERT copy numbers and TERT promoter methylation in 42 MTCs and normal thyroid references. Gain of TERT was demonstrated by quantitative PCR in 5/39 sporadic MTC. Increased methylation index (MetI) for CpG methylation at the TERT promoter was found in sporadic MTCs (P < 0.0001) and in MEN 2 associated MTCs (P = 0.011) vs...
April 19, 2016: Oncotarget
Matthew M Makowski, Esther Willems, Pascal W T C Jansen, Michiel Vermeulen
In recent years, cross-linking mass spectrometry has proven to be a robust and effective method of interrogating macromolecular protein complex topologies at peptide resolution. Traditionally, cross-linking mass spectrometry workflows have utilized homogenous complexes obtained through time-limiting reconstitution, tandem affinity purification, and conventional chromatography workflows. Here, we present cross-linking immunoprecipitation-MS (xIP-MS), a simple, rapid, and efficient method for structurally probing chromatin-associated protein complexes using small volumes of mammalian whole cell lysates, single affinity purification, and on-bead cross-linking followed by LC-MS/MS analysis...
March 2016: Molecular & Cellular Proteomics: MCP
Chengcheng Zhou, Hailiang Tang, Jian Yu, Dongxiao Zhuang, Haishi Zhang
UNLABELLED: To investigate the blood-based DNA methylation of repair genes including LIG4, XRCC4, XRCC5, XRCC6 and XRCC7 that involved in non-homologous end-joining (NEHJ) DNA repair pathway in patients with glioma. Blood samples were obtained from 114 glioma patients, 96 normal controls, and 81 glioma patients after radiotherapy and chemotherapy. Blood-based DNA methylation of the five NHEJ repair genes was assayed by methylation-specific polymerase chain reaction (MSP). The DNA methylation level of XRCC5 and XRCC7 in glioma group are significantly higher than those of normal group (P<0...
2015: International Journal of Clinical and Experimental Pathology
Juan Chen, Lin Wu, Ying Wang, Jiye Yin, Xiangping Li, Zhan Wang, Huihua Li, Ting Zou, Chenyue Qian, Chuntian Li, Wei Zhang, Honghao Zhou, Zhaoqian Liu
Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY...
February 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Tianbo Jin, Yuan Wang, Gang Li, Shuli Du, Hua Yang, Tingting Geng, Peng Hou, Yongkuan Gong
BACKGROUND: Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. MATERIALS AND METHODS: We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ(2) test and genetic model analysis...
2015: American Journal of Cancer Research
Wei Wang, Yongju Lu, Paul M Stemmer, Xiangmin Zhang, Yongyi Bi, Zhengping Yi, Fei Chen
To investigate how mineral dust-induced gene (mdig, also named as mina53, MINA, or NO52) promotes carcinogenesis through inducing active chromatin, we performed proteomics analyses for the interacting proteins that were co-immunoprecipitated by anti-mdig antibody from either the lung cancer cell line A549 cells or the human bronchial epithelial cell line BEAS-2B cells. On SDS-PAGE gels, three to five unique protein bands were consistently observed in the complexes pulled-down by mdig antibody, but not the control IgG...
September 29, 2015: Oncotarget
Carmen Muñoz, Miguel Caballero, Sofia Hakim, Eugenia Verger, Juan Jose Grau
Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1, and XRCC5)...
August 2016: European Archives of Oto-rhino-laryngology
Helena C Reinardy, Andrea G Bodnar
The ability to protect the genome from harmful DNA damage is critical for maintaining genome stability and protecting against disease, including cancer. Many echinoderms, including sea urchins, are noted for the lack of neoplastic disease, but there are few studies investigating susceptibility to DNA damage and capacity for DNA repair in these animals. In this study, DNA damage was induced in adult sea urchin coelomocytes and larvae by exposure to a variety of genotoxicants [UV-C (0-3000 J/m(2)), hydrogen peroxide (0-10mM), bleomycin (0-300 µM) and methylmethanesulfonate (MMS, 0-30 mM)] and the capacity for repair was measured over a 24-h period of recovery...
November 2015: Mutagenesis
Dong Wang, Jianming Qiu, Guangen Yang, Yihuan Song, Qun Deng, Xiufeng Zhang
OBJECTIVE: To elucidate the mechanism of curcumin in radiotherapy sensitization for colorectal cancer cells. METHODS: Colorectal cancer HT-29 cells were cultured and treated with radiation and curcumin. MTT method was used to detect the cell growth inhibition. Then the high-throughput microarray was used to detect the differences in gene expression levels for each test group to identify differentially expressed genes, and each differential gene was validated by Western blotting...
June 2015: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Michael J Worley, Shubai Liu, Yuanyuan Hua, Jamie Sui-Lam Kwok, Anicka Samuel, Lei Hou, Melina Shoni, Shi Lu, Evelien M Sandberg, Anna Keryan, Di Wu, Shu-Kay Ng, Winston P Kuo, Carlos E Parra-Herran, Stephen K W Tsui, William Welch, Christopher Crum, Ross S Berkowitz, Shu-Wing Ng
BACKGROUND: Endometriosis is frequently associated with and thought of having propensity to develop into ovarian clear cell carcinoma (OCCC), although the molecular transformation mechanism is not completely understood. METHODS: We employed immunohistochemical (IHC) staining for marker expression along the potential progression continuum. Expression profiling of microdissected endometriotic and OCCC cells from patient-matched formalin-fixed, paraffin-embedded samples was performed to explore the carcinogenic pathways...
September 2015: European Journal of Cancer
Lu Dai, Yueyu Cao, Yihan Chen, Johnan A R Kaleeba, Jovanny Zabaleta, Zhiqiang Qin
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of primary effusion lymphoma (PEL), a rapidly progressing malignancy mostly arising in HIV-infected patients. Even under conventional chemotherapy, PEL continues to portend nearly 100% mortality within several months, which urgently requires novel therapeutic strategies. We have previously demonstrated that targeting xCT, an amino acid transporter for cystine/glutamate exchange, induces significant PEL cell apoptosis through regulation of multiple host and viral factors...
May 20, 2015: Oncotarget
Rebecca Cook, Georgia Zoumpoulidou, Maciej T Luczynski, Simone Rieger, Jayne Moquet, Victoria J Spanswick, John A Hartley, Kai Rothkamm, Paul H Huang, Sibylle Mittnacht
Deficiencies in DNA double-strand break (DSB) repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1) is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ). Support of cNHEJ involves a mechanism independent of RB1's cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ...
March 31, 2015: Cell Reports
Danial Jahantigh, Saeedeh Salimi, Mahdieh Mousavi, Maryam Moossavi, Milad Mohammadoo-Khorasani, Mehrnaz Narooei-nejad, Mahnaz Sandoughi
DNA repair is reduced in patients suffering from systemic lupus erythematosus (SLE), and it can induce the production of autoreactive antibodies due to the accumulation of DNA damage and nucleoprotein that produce immunogenic antigens. The accumulations of anti-Ku and DNA-PKcs antibodies, which are involved in nonhomologous DNA end joining pathway, have been detected in SLE patients. The present study was designed to evaluate the association of XRCC5, XRCC6, and XRCC7 polymorphisms with SLE susceptibility. Polymerase chain reaction (PCR) was performed to genotype 163 SLE patients and 180 healthy controls for the XRCC5 variable number of tandem repeat (VNTR) polymorphism...
May 2015: DNA and Cell Biology
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