New Research Directions in DNA Repair

Chen, Clark

doi:10.5772/46014

2013

DOI: 10.5772/46014

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New Research Directions in DNA Repair

Clark Chen¹

Abstract: He completed his neurosurgery training at the Massachusetts General Hospital and subsequently completed independent fellowships in stereotactic neurosurgery and radiosurgery. Dr. Chen previously served as the director of Clinical Neuro-Oncology at the Beth Israel Deaconess Medical Center before his current role as the Director of Stereotactic and Radiosurgery and Co-Director of Surgical Neuro-Oncology at the University of California, San Diego. Dr. Chen's research is directed at identifying alterations in DNA … Show more

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Cited by 10 publications

References 57 publications

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Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1

Pinhu

et al. 2017

Oncotarget

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BackgroundThe serum microRNAs have been reported as potential biomarkers for hepatitis virus-related hepatocellular carcinoma (HCC); however, their role in aflatoxin B1 (AFB1)-related HCC to has not yet been evaluated.Materials and MethodsWe conducted a case-control study, including 366 HCC cases and 662 controls without any evidence of tumors, to identify and assess diagnostic and prognostic potential of serum microRNAs for AFB1-related HCC. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to elucidate diagnostic performance, and to compare the microRNAs with α-fetoprotein (AFP) at a cutoff of 20 ng/mL (AFP20) and 400 ng/mL (AFP400).ResultsWe found 8 differentially expressed microRNAs via the microRNA array analysis; however, only microRNA-4651 was further identified to detect AFB1-positive HCC but not AFB1-negative HCC. For AFB1-positive HCC, microRNA-4651 showed higher accuracy and sensitivity than AFP400 (AUC, 0.85 vs. 0.72; Sensitivity, 78.1% vs. 43.0%). Compared to AFP20, microRNA-4651 exhibited higher potential in identifying small-size (0.68 vs. 0.84 for AUC and 36.7% vs. 75.5% for sensitivity, respectively) and early-stage HCC (0.69 vs. 0.84 for AUC and 38.7% vs. 75.7% for sensitivity, respectively). Additionally, miR-4651 was also associated with HCC prognosis (hazard risk value, 2.67 for overall survival and 3.62 for tumor recurrence analysis).ConclusionsThese data suggest that serum microRNA-4651 may be a useful marker for HCC diagnosis and prognosis, especially AFB1-positive cases.

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Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1

Pinhu

et al. 2017

Oncotarget

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The Role of Nicotinamide in Cancer Chemoprevention and Therapy

2020

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Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.

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Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers

et al. 2021

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Gastrointestinal (GI) malignancies are a major global health burden, with high mortality rates. The identification of novel therapeutic strategies is crucial to improve treatment and survival of patients. The poly (ADP-ribose) polymerase (PARP) enzymes involved in the DNA damage response (DDR) play major roles in the development, progression and treatment response of cancer, with PARP inhibitors (PARPi) currently used in the clinic for breast, ovarian, fallopian, primary peritoneal, pancreatic and prostate cancers with deficiencies in homologous recombination (HR) DNA repair. This article examines the current evidence for the role of the DDR PARP enzymes (PARP1, 2, 3 and 4) in the development, progression and treatment response of GI cancers. Furthermore, we discuss the role of HR status as a predictive biomarker of PARPi efficacy in GI cancer patients and examine the pre-clinical and clinical evidence for PARPi and cytotoxic therapy combination strategies in GI cancer. We also include an analysis of the genomic and transcriptomic landscape of the DDR PARP genes and key HR genes (BRCA1, BRCA2, ATM, RAD51, MRE11, PALB2) in GI patient tumours (n = 1744) using publicly available datasets to identify patients that may benefit from PARPi therapeutic approaches.

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New Research Directions in DNA Repair

Cited by 10 publications

References 57 publications

Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1

Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers

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