Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cervical cancer remains persistently the second most common malignancies among women worldwide, responsible for 500,000 new cases annually. Only in Brazil, the estimate is for 18,430 new cases in 2011. Several types of molecular markers have been studied in carcinogenesis including proteins associated with apoptosis such as BAG-1 and PARP-1. This study aims to demonstrate the expression of BAG-1 and PARP-1 in patients with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs) and invasive squamous cell carcinomas (SCCs) of the uterine cervix and to verify a possible association with HPV infection. Fifty samples of LSILs, 50 samples of HSILs and 50 samples of invasive SCCs of the uterine cervix were analyzed by immunohistochemistry for BAG-1 and PARP-1 expression. PCR was performed to detect and type HPV DNA. BAG-1 expression levels were significantly different between LSILs and HSILs (p = 0,014) and between LSILs and SCCs (p = 0,014). In regards to PARP-1 expression, we found significant differences between the expression levels in HSILs and SCCs (p = 0,022). No association was found between BAG-1 expression and the presence of HPV. However, a significant association was found between PARP-1 expression and HPV positivity in the HSILs group (p = 0,021). In conclusion our research suggests that BAG-1 expression could contribute to the differentiation between LSIL and HSIL/SCC whereas PARP-1 could be useful to the differentiation between HSIL HPV-related and SCC. Further studies are needed to clarify the molecular aspects of the relationship between PARP-1 expression and HPV infection, with potential applications for cervical cancer prediction.
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PMID:Expression of BAG-1 and PARP-1 in precursor lesions and invasive cervical cancer associated with human papillomavirus (HPV). 2245 10

Pharmacologic inhibitors of poly(ADP-ribose) polymerase (PARP) putatively enhance radiation toxicity in cancer cells. Although there is considerable information on the molecular interactions of PARP and BRCA1- and BRCA2-deficient cancers, very little is known of the PARP inhibition effect upon cancers proficient in DNA double-strand break repair after ionizing radiation or after stalled replication forks. In this work, we investigate whether PARP inhibition by ABT-888 (veliparib) augments death-provoking effects of ionizing radiation, or of the topoisomerase I poison topotecan, within uterine cervix cancers cells harboring an unfettered, overactive ribonucleotide reductase facilitating DNA double-strand break repair and contrast these findings with ovarian cancer cells whose regulation of ribonucleotide reductase is relatively intact. Cell lethality of a radiation-ABT-888 combination is radiation and drug dose dependent. Data particularly highlight an enhanced topotecan-ABT-888 cytotoxicity, and corresponds to an increased number of unrepaired DNA double-strand breaks. Overall, our findings support enhanced radiochemotherapy toxicity in cancers proficient in DNA double-strand break repair when PARP is inhibited by ABT-888.
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PMID:Inhibition of Poly(ADP-Ribose) Polymerase Enhances Radiochemosensitivity in Cancers Proficient in DNA Double-Strand Break Repair. 2339 7

The clinical application of carbon ions generated by the heavy ion medical accelerator in Chiba (HIMAC) reached its 20th anniversary in 2014. More than 9,000 cancer patients have been treated at the National Institute of Radiological Sciences (NIRS). Carbon-ion radiotherapy has been applied for treating various types of tumors that were considered difficult to control with existing modalities. Our experience to date has indicated that carbon-ion radiotherapy is advantageous for head and neck cancer, non-small cell lung cancer, pancreatic cancer, prostate cancer, bone/soft tissue sarcomas of the pelvis, uterine cervix adenocarcinomas, and other cancers. However, some cancer types (such as those in close proximity to radiosensitive normal organs) require additional treatments to sensitize the target cancer because of limitation of the irradiation dose. Furthermore, systemic combined therapy is also utilized to suppress possible metastasis. Currently, some anticancer agents are utilized with carbon-ion radiotherapy, including dacarbazine, nimustine hydrochloride, vincristine (DAV), gemcitabine, cisplatin, and 5-fluorouracil. Interesting reagents such as PARP and HSP90 inhibitors have been proposed as cancer cell- specific sensitizers for carbon-ion irradiation during basic biological studies, especially those from the Research Project with Heavy Ions at NIRS-HIMAC. In our laboratory, we have focused our studies on the suppression of metastasis. We have proposed the concurrent use of reagents to inhibit the invasive potential of cancer cells under carbon-ion irradiation. Recently, we have also shown that combining carbon-ion radiotherapy with the local injection of dendritic cells inhibits lung metastases in an in vivo murine model.
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PMID:[Treatment with carbon-ion radiotherapy and its combinations -- basic biological studies and investigations at the National Institute of Radiological Sciences]. 2574 34