RKIP Inhibition in cervical cancer Is associated with higher tumor aggressive behavior and resistance to cisplatin therapy

Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (,15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.This work was partially supported by the Portuguese Fundacao para a Ciencia e Tecnologia (grant PTDC/SAU-TOX/114549/2009). Olga Martinho and Sara Granja were recipients of PhD fellowships (SFRH/BD/36463/2007 and SFRH/BD/51062/2010, respectively), and Filipe Pinto and Vera Miranda-Goncalves were recipients of research fellowships (UMINHO/BI/016/2011 and SFRH/BI/33503/2008, respectively), both from FCT, Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study

A systematic review and meta-analysis of thermal coagulation compared with cryotherapy to treat precancerous cervical lesions in low- and middle-income countries

Background: Thermal coagulation is gaining popularity for treating cervical intraepithelial neoplasia (CIN) in screening programs in low- and middle-income countries (LMICs) due to unavailability of cryotherapy. Objectives: Assess the effectiveness of thermal coagulation for treatment of CIN lesions compared with cryotherapy, with a focus on LMICs. Search strategy: Papers were identified from previous reviews and electronic literature search in February 2018 with publication date after 2010. Selection criteria: Publications with original data evaluating cryotherapy or thermal coagulation with proportion of cure as outcome, assessed by colposcopy, biopsy, cytology, and/or visual inspection with acetic acid (VIA), and minimum 6 months follow-up. Data collection and analysis: Pooled proportions of cure are presented stratified per treatment modality, type of lesion, and region. Main results: Pooled cure proportions for cryotherapy and thermal coagulation, respectively, were 93.8% (95% CI, 88.5–97.7) and 91.4% (95% CI, 84.9–96.4) for CIN 1; 82.6% (95% CI, 77.4–87.3) and 91.6% (95% CI, 88.2–94.5) for CIN 2–3; and 92.8% (95% CI, 85.6–97.7) and 90.1% (95% CI, 87.0–92.8) for VIA-positive lesions. For thermal coagulation of CIN 2–3 lesions in LMICs 82.4% (95% CI, 75.4–88.6). Conclusions: Both cryotherapy and thermal coagulation are effective treatment modalities for CIN lesions in LMICs.Medical Instruments & Bio-Inspired Technolog