8 research outputs found

    Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy

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    Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46–72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting

    Implication of human papillomavirus-66 in vulvar carcinoma: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Vulvar cancer in older women is seldom associated with human papillomavirus infection.</p> <p>Case presentation</p> <p>We present the case of an 80-year-old Greek Caucasian woman with an undetermined obstetric and gynecologic history. The patient underwent radical vulvectomy and bilateral inguinal lymphadenectomy for a vulvar carcinoma. A human papillomavirus infection was suggested on the basis of histological and cytological examinations followed by human papillomavirus DNA typing, which revealed the presence of human papillomavirus-66.</p> <p>Conclusion</p> <p>Even though human papillomavirus-16 and human papillomavirus-18 are most frequently implicated in the pathogenesis of vulvar carcinoma, human papillomavirus-66 can also be regarded as a causative factor. Suspicious lesions should be biopsied, and in the presence of carcinoma, vulvectomy with bilateral lymphadenectomy, if necessary, must be performed. Furthermore, polymerase chain reaction assay analysis with clinical arrays in cytological samples is an accurate test for the detection of a wide range of human papillomavirus genotypes and can be used to verify the infection and specify the human papillomavirus type implicated.</p

    Energy Valorization of Fine Screenings from a Municipal Wastewater Treatment Plant

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    The aim of this paper was to evaluate the characteristics and the energy potential for the methane production of fine screenings collected from the primary stage of a municipal wastewater treatment plant, and assess the impact on the properties and the oxygen demand of the aqueous effluents downstream from the sieves. Commercial filter bags with sieve openings of 3000, 1250, 1000, and 300 &mu;m were used for the collection of screenings following a measurement of their biochemical methane potential. It was revealed that solid fractions from the sieves with a large size presented a high net methane production capacity exceeding 900 mL/g VS, but the gas production rate was rather slow, requiring a long time to reach the final value. However, cumulative solid fractions containing particles with a size larger than 300 &mu;m had a lower net methane production, about 700 mL/g VS, but with a faster rate, resulting in almost 80% of the total volume released in 30 days. Aqueous samples downstream from the sieves presented decreasing organic matter content by sieve size and reduced the requirements for aeration oxygen. The installation of fine sieves in existing municipal wastewater treatment plants, therefore, may be beneficial due to the enhancement of biogas production and a reduction in the oxygen consumption of the activated sludge process
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