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https://www.readbyqxmd.com/read/28229968/cytotoxic-and-toxicogenomic-effects-of-silibinin-in-bladder-cancer-cells-with-different-tp53-status
#1
Daiane Teixeira DE Oliveira, Andre Luiz Ventura Savio, Joao Paulo DE Castro Marcondes, Tatiane Martins Barros, Ludmila Correia Barbosa, Daisy Maria Favero Salvadori, Glenda Nicioli DA Silva
Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229963/constitutively-activated-erk-sensitizes-cancer-cells-to-doxorubicin-involvement-of-p53-egfr-erk-pathway
#2
Ratna Kumari, Surbhi Chouhan, Snahlata Singh, Rishi Raj Chhipa, Amrendra Kumar Ajay, Manoj Kumar Bhat
The tumour suppressor gene p53 is mutated in approximately 50% of the human cancers. p53 is involved in genotoxic stress-induced cellular responses. The role of EGFR and ERK in DNA-damage-induced apoptosis is well known. We investigated the involvement of activation of ERK signalling as a consequence of non-functional p53, in sensitivity of cells to doxorubicin. We performed cell survival assays in cancer cell lines with varying p53 status: MCF-7 (wild-type p53, WTp53), MDA MB-468 (mutant p53, MUTp53), H1299 (absence of p53, NULLp53) and an isogenic cell line MCF-7As (WTp53 abrogated)...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#3
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28229171/potential-biomarkers-associated-with-oxidative-stress-for-risk-assessment-of-colorectal-cancer
#4
REVIEW
Paramita Mandal
Cells are continuously threatened by the damage caused by reactive oxygen/nitrogen species (ROS/RNS), which are produced during physiological oxygen metabolism. In our review, we will summarize the latest reports on the role of oxidative stress and oxidative stress-induced signaling pathways in the etiology of colorectal cancer. The differences in ROS generation may influence the levels of oxidized proteins, lipids, and DNA damage, thus contributing to the higher susceptibility of colon. Reactive species (RS) of various types are formed and are powerful oxidizing agents, capable of damaging DNA and other biomolecules...
February 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28228262/targeting-dna-damage-response-in-prostate-cancer-by-inhibiting-androgen-receptor-cdc6-atr-chk1-signaling
#5
Styliani Karanika, Theodoros Karantanos, Likun Li, Jianxiang Wang, Sanghee Park, Guang Yang, Xuemei Zuo, Jian H Song, Sankar N Maity, Ganiraju C Manyam, Bradley Broom, Ana M Aparicio, Gary E Gallick, Patricia Troncoso, Paul G Corn, Nora Navone, Wei Zhang, Shuhua Li, Timothy C Thompson
Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226775/evaluation-of-multidrug-cancer-chronotherapy-based-on-cell-cycle-model-under-influences-of-circadian-clock
#6
Hiroshi Inokawa, Norihiro Katayama, Mitsuyuki Nakao, Hiroshi Inokawa, Norihiro Katayama, Mitsuyuki Nakao, Mitsuyuki Nakao, Hiroshi Inokawa, Norihiro Katayama
The intracellular circadian clock mechanisms are known to affect various substantial cellular machinery such as cell cycle progression, inflammatory response, apoptosis, and DNA repair. Cancer growth in various tissues is still under circadian control, which may be at least partly underlain by the survived connections between the intracellular machinery and the clock. Considering such findings, chronotherapy has been applied to cancer treatments, in which anti-cancer drugs are administered in scheduled circadian times so as to resolve the trade-off between damages against the normal and cancer cells...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225881/zinc-and-metalloproteinases-2-and-9-what-is-their-relation-with-breast-cancer
#7
Aldenora Oliveira do Nascimento Holanda, Ana Raquel Soares de Oliveira, Kyria Jayanne Clímaco Cruz, Juliana Soares Severo, Jennifer Beatriz Silva Morais, Benedito Borges da Silva, Dilina do Nascimento Marreiro
Zinc is the catalytic component of proteins that regulate responses to DNA damage, intracellular signaling enzymes, and matrix metalloproteinases, which are important proteins in carcinogenesis. The objective of this review is to bring current information on the participation of zinc and matrix metalloproteinases types 2 and 9 in mechanisms involved in the pathogenesis of breast cancer. We conducted a literature review, in consultation with the PubMed, Lilacs, and Scielo databases. The zinc and cysteine residues are structural elements shared by all members of the family of matrix metalloproteinases, and these proteins appear to be involved in the propagation of various types of neoplasms, including breast cancer...
January 1, 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28225650/nicaraven-a-potential-radioprotective-agent-has-very-limited-effects-on-the-survival-of-cancer-cells-and-the-growth-of-established-tumors
#8
Chen Yan, Lan Luo, Yoshishige Urata, Shinji Goto, Chang-Ying Guo, Tao-Sheng Li
Radiotherapy is one of the major treatment modalities for the management of various cancers, however, it is limited by the severe side effects and complications experienced by some patients. Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been shown to protect normal tissues from radiation-induced injury. We investigated the role of nicaraven in cancer cells and tumor growth. While nicaraven did not significantly change the colony-forming abilities and DNA damage levels in several cancer cell lines after irradiation, it significantly protected mouse bone marrow-derived hematopoietic stem cells from radiation injury...
February 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28222669/downregulated-xpa-promotes-carcinogenesis-of-bladder-cancer-via-impairment-of-dna-repair
#9
Yi Zhi, Huixiang Ji, Jinhong Pan, Peng He, Xiaozhou Zhou, Heng Zhang, Zhansong Zhou, Zhiwen Chen
Bladder cancer is the most common malignant tumor of urinary system, largely resulting from failure of repair of DNA damage to the environmental insults. The function of XPA in nucleotide excision repair pathway has been well documented. However, participation of XPA in the repair of DNA double-strand break remains unknown. Here, we reported that bladder cancer expressed low XPA levels compared to adjacent non-tumor bladder tissue, and this phenotype was closely associated with chromosomal aberrations. Moreover, downregulated XPA appeared to increase incidence of chromosome aberration...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28220800/bladder-cancer-mutations-in-dna-damage-repair-pathways-confer-platinum-sensitivity
#10
Peter Sidaway
No abstract text is available yet for this article.
February 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28219770/silencing-of-the-mrna-binding-protein-hur-increases-the-sensitivity-of-colorectal-cancer-cells-to-ionizing-radiation-through-upregulation-of-caspase-2
#11
Amel Badawi, Stephanie Hehlgans, Josef Pfeilschifter, Franz Rödel, Wolfgang Eberhardt
Increased abundance of the mRNA-binding protein human antigen R (HuR) is a characteristic feature of many cancers and frequently associated with a high grade malignancy and therapy resistance. HuR elicits a broad cell survival program mainly by stabilizing or increasing the translation of mRNAs coding for anti-apoptotic effector proteins. Conversally, we previously identified the pro-apoptotic caspase-2 as a novel HuR target which is mainly regulated at the level of translation. In this study, we investigated whether siRNA-mediated HuR knockdown interferes with cell survival and radiation sensitivity by monitoring apoptosis, DNA repair and three-dimensional (3D) clonogenic survival...
February 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28218735/aurora-kinase-a-regulates-survivin-stability-through-targeting-fbxl7-in-gastric-cancer-drug-resistance-and-prognosis
#12
M Kamran, Z-J Long, D Xu, S-S Lv, B Liu, C-L Wang, J Xu, E W-F Lam, Q Liu
Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies. However, little is known about its role in gastric cancer prognosis and genotoxic resistance. Here we found that AURKA was highly overexpressed in gastric cancer and inversely correlated with disease prognosis. Overexpression of AURKA exacerbated gastric cancer drug resistance through upregulating the expression of the anti-apoptotic protein Survivin...
February 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28218725/treating-cancer-by-targeting-telomeres-and-telomerase
#13
REVIEW
Marko Ivancich, Zachary Schrank, Luke Wojdyla, Brandon Leviskas, Adijan Kuckovic, Ankita Sanjali, Neelu Puri
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells...
February 19, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28218043/uhrf1-the-key-regulator-of-epigenetics-and-molecular-target-for-cancer-therapeutics
#14
Harsimran Sidhu, Neena Capalash
UHRF1 is a master regulator of epigenome as it coordinates DNA methylation and histone modifications. Compelling evidence suggests a strong link between UHRF1 overexpression and tumorigenesis, substantiating its ability to act as a potential biomarker for cancer diagnosis and prognosis. UHRF1 also mediates repair of damaged DNA that makes cancer cells resistant toward cytocidal drugs. Hence, understanding the molecular mechanism of UHRF1 regulation would help in developing cancer therapeutics. Natural compounds have shown applicability to downregulate UHRF1 leading to growth arrest and apoptosis in cancer cells...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28216890/evaluate-the-antigenotoxicity-and-anticancer-role-of-%C3%AE-sitosterol-by-determining-oxidative-dna-damage-and-the-expression-of-phosphorylated-mitogen-activated-protein-kinases-c-fos-c-jun-and-endothelial-growth-factor-receptor
#15
Ramalingam Sharmila, Ganapathy Sindhu
BACKGROUND: Plant sterols are the major source of micronutrients and have not shown any obvious side effects in human. β-sitosterol is one of the most prevalent phytosterols which have been recorded in ancient medicinal history for its use in the treatment of many chronic diseases, especially cancer. The modulations of mitogen-activated protein kinases' (MAPKs') play a crucial role in the development of human renal cell carcinoma. OBJECTIVE: The aim of the current study is to evaluate the antigenotoxic and anticancer role of β-sitosterol against renal carcinogen...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216286/rnf8-identified-as-a-co-activator-of-estrogen-receptor-%C3%AE-promotes-cell-growth-in-breast-cancer
#16
Shengli Wang, Hao Luo, Chunyu Wang, Hongmiao Sun, Ge Sun, Ning Sun, Kai Zeng, Huijuan Song, Renlong Zou, Tingting Zhou, Rijiao Cong, Wei Liu, Lei Yang, Da Li, Xin Zhou, Xinping Zhong, Lin Lin, Jiao Jiao, Guangqi Yan, Xue Wang, Xiaojie Min, Liu Cao, Yue Zhao
The ring finger protein 8 (RNF8), a key component of protein complex crucial for DNA-damage response, consists of a forkhead-associated (FHA) domain and a really interesting new gene (RING) domain that enables it to function as an E3 ubiquitin ligase. However, the biological functions of RNF8 in estrogen receptor α (ERα)-positive breast cancer and underlying mechanisms have not been fully defined. Here, we have explored RNF8 as an associated partner of ERα in breast cancer cells, and co-activates ERα-mediated transactivation...
February 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28215644/from-molecular-insight-to-therapeutic-strategy-the-holistic-approach-for-treating-triple-negative-breast-cancer
#17
REVIEW
Rittwika Bhattacharya, Koyel Banerjee, Nupur Mukherjee, Minakshi Sen, Ashis Mukhopadhyay
Aim of the present study was to analyze the molecular pathogenesis of TNBC, therapeutic practice, challenges, and future goals in treatment strategies. Based on the alterations of distinct pathways, Lehmann's subgroups of TNBCs were further categorized. Those with defective DNA damage repair and replication pathways, viz. Basal Like 1 & 2 (BL1, BL2) were found susceptible to DNA intercalating drugs while those with upregulated cell signalling & motility (mesenchymal (M), mesemchymal stem like (MSL)), cell survival (BL2, M, MSL), angiogenesis (BL2, MSL), T cell signalling (Immunomodulatory/IM) pathways required targeted therapies...
January 19, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214334/autophagy-impairment-by-helicobacter-pylori-induced-methylation-silencing-of-map1lc3av1-promotes-gastric-carcinogenesis
#18
Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Satoshi Yamashita, Takao Maekita, Toshikazu Ushijima, Yoshiaki Tabuchi, Toshiro Sugiyama
Helicobacter pylori (H. pylori) infection induces methylation silencing of tumor suppressor genes causing gastric carcinogenesis. Impairment of autophagy induces DNA damage leading to genetic instability and carcinogenesis. We aimed to identify whether H. pylori infection induced methylation silencing of host autophagy-related (Atg) genes, impairing autophagy and enhancing gastric carcinogenesis. Gastric mucosae were obtained from 41 gastric cancer patients and 11 healthy volunteers (8 H. pylori-uninfected and 3 H...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#19
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28213517/the-p53-binding-protein-1-tudor-interacting-repair-regulator-complex-participates-in-the-dna-damage-response
#20
Aili Zhang, Bo Peng, Ping Huang, Junjie Chen, Zihua Gong
The 53BP1-dependent end-joining pathway plays a critical role in DSB repair and is uniquely responsible for cellular sensitivity to PARPi in BRCA1-deficient cancers. We and others have investigated the downstream effectors of 53BP1, including replication timing regulatory factor 1 (RIF1) and Pax transactivation domain-interacting protein (PTIP), in the past few years to elucidate how loss of the 53BP1-dependent repair pathway results in PARPi resistance in BRCA1 patients. However, questions regarding the upstream regulation of the 53BP1 pathway remain unanswered...
February 17, 2017: Journal of Biological Chemistry
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