Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4 þ /IL17 þ cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancerbinding protein b (C/EBPb) pathway as shown with a dominantnegative version of C/EBPb and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPb-dependent manner. Th17 cells may in turn maintain chronic inflammation within highgrade cervical lesions to further promote cancer progression.Cancer Res; 75(24); 5248-59. Ó2015 AACR.

Introduction Hysterectomy ranks among the most frequently performed gynecological surgical procedures. At the time of operation, the majority of patients are premenopausal and sexually active. Hence, detailed counseling about the effects of hysterectomy on postoperative sexuality and quality of life can be regarded as an integral part of preoperative counseling. However, available data on these subjects are limited and contradictory. Aim The aim of this study was to assess quality of life and sexuality following three common hysterectomy procedures—total laparoscopic hysterectomy (TLH), supracervical laparoscopic hysterectomy (SLH), and vaginal hysterectomy (VH)—in premenopausal patients using the European Quality of Life Five-Dimension Scale (EQ-5D) and Female Sexual Function Index (FSFI). Main Outcome Measures Preoperative and postoperative EQ-5D and FSFI scores were compared using the Wilcoxon signed-rank test. Kruskal–Wallis analysis and Mann–Whitney U-test with post hoc Bonferroni correction were used to assess differences among the three subgroups. Methods All premenopausal patients who underwent TLH, SLH, or VH without adnexectomy due to benign uterine disorders between April 2011 and June 2013 at the Department of Gynaecology and Obstetrics of Saarland University Hospital were enrolled in this observational cohort study. Sexuality and quality of life status were assessed preoperatively and 6 months postoperatively using two standardized validated questionnaires: the FSFI, a multidimensional, self-reported instrument for the assessment of female sexual function, and the EQ-5D, a standardized, validated instrument to measure an individual's health status. Results Of 402 eligible patients, 237 completed the study. Patient characteristics and preoperative FSFI and EQ-5D scores did not differ among the three hysterectomy subgroups. Postoperative FSFI and EQ-5D scores were significantly higher (P ≤ 0.01) than preoperative scores for all procedures but did not differ among the groups. Conclusions In this cohort of premenopausal women, hysterectomy without adnexectomy performed due to benign uterine pathologies had significant positive effects on postoperative sexual function and quality of life, regardless of the surgical technique used.

PBMT using a compactly designed treatment regime in combination with a cluster laser device did not significantly improve quality of life, pain scores, grip strength and limb volume over the time course.

Background. Currently the choice of breast cancer therapy is based on prognostic factors. The proliferation marker Ki-67 is used increasingly to determine the method of therapy. The current study analyses the predictive value of Ki-67 in foreseeing breast cancer patients' responses to neoadjuvant chemotherapy. Methods. This study includes patients with invasive breast cancer treated between 2008 and 2013. The clinical response was assessed by correlating Ki-67 to histological examination, mammography, and ultrasonography findings. Results. The average Ki-67 value in our patients collectively (n = 77) is 34.9 ± 24.6%. The average Ki-67 value is the highest with 37.4 ± 24.0% in patients with a pCR. The Ki-67 values do not differ significantly among the 3 groups: pCR versus partial pathological response versus stable disease/progress (P = 0.896). However, Ki-67 values of patients with luminal, Her2 enriched, and basal-like cancers differed significantly from each other. Furthermore, within the group of luminal tumors Ki-67 values of patients with versus without pCR also differed significantly. Conclusion. Our data shows that the Ki-67 value predicts the response to neoadjuvant chemotherapy as a function of the molecular subtype, reflecting the daily routine concerning Ki-67 and its impressing potential and limitation as a predictive marker for neoadjuvant chemotherapy response.

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