BackgroundThere is an urgent need for more novel and efficacious therapeutic agents and strategies for the treatment of ovarian cancer - one of the most formidable female malignancies. These approaches should be based on comprehensive understanding of the pathobiology of this cancer and focused on decreasing its recurrence and metastasis. The aim of this study was to evaluate the efficacy of five-year maintenance therapy with indole-3-carbinol (I3C) as well as I3C and epigallocatechin-3-gallate (EGCG) conducted before, during, and after combined treatment compared with combined treatment alone in advanced ovarian cancer.MethodsPatients with stage III-IV serous ovarian cancer were assigned to receive combined treatment plus I3C (arm 1), combined treatment plus I3C and EGCG (arm 2), combined treatment plus I3C and EGCG plus long-term platinum-taxane chemotherapy (arm 3), combined treatment alone without neoadjuvant platinum-taxane chemotherapy (control arm 4), and combined treatment alone (control arm 5). Combined treatment included neoadjuvant platinum-taxane chemotherapy, surgery, and adjuvant platinum-taxane chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and rate of patients with recurrent ovarian cancer with ascites after combined treatment.ResultsAfter five years of follow-up, maintenance therapy dramatically prolonged PFS and OS compared to control. Median OS was 60.0 months (95% CI: 58.0–60.0 months) in arm 1, 60.0 months (95% CI: 60.0–60.0 months) in arms 2 and 3 while 46.0 months (95% СI: 28.0–60.0 months) in arm 4, and 44.0 months (95% СI: 33.0–58.0 months) in arm 5. Median PFS was 39.5 months (95% СI: 28.0–49.0 months) in arm 1, 42.5 months (95% СI: 38.0–49.0 months) in arm 2, 48.5 months (95% СI: 39.0–53.0 months) in arm 3, 24.5 months (95% СI: 14.0–34.0 months) in arm 4, 22.0 months (95% СI: 15.0–26.0 months) in arm 5. The rate of patients with recurrent ovarian cancer with ascites after combined treatment was significantly less in maintenance therapy arms compared to control.ConclusionsLong-term usage of I3C and EGCG may represent a new promising way of maintenance therapy in advanced ovarian cancer patients, which achieved better treatment outcomes.Trial registrationRetrospectively registered with ANZCTR number: ACTRN12616000394448. Date of registration: 24/03/2016.

Ovarian cancer is known to be the most lethal malignancy among all gynecological cancers affecting a large number of women worldwide. The treatment of ovarian cancer is challenging due to the high recurrence rate of the disease and is further complicated by acquired chemoresistance. Most ovarian cancer deaths are the result of the metastatic spread of drug-resistant cells. The theory of cancer stem cells (CSC) suggests that both tumor initiation and progression are driven by a population of undifferentiated capable of self-renewal, tumor initiation and development of chemoresistance. The CD117 mast/stem cell growth factor receptor (KIT) is the most commonly used marker for ovarian CSCs. Here, we analyze the correlation between CD117 expression and histological tumor type in ovarian cancer cell lines (SK-OV-3 and MES-OV) and in small/medium extracellular vesicles (EVs) isolated from the urine of ovarian cancer patients. We have demonstrated that the abundance of CD117 on cells and EVs is correlated with tumor grade and therapy resistance status. Moreover, using small EVs isolated from ovarian cancer ascites, it was shown that recurrent disease is characterized by a much higher abundance of CD117 on EVs than primary tumor.

The aim of the study was to evaluate the five-year survival rate in patients with stage ib2–iiib cervical cancer treated with neoadjuvant chemotherapy and radical surgery.Material and Methods. Long-term treatment outcomes were studied in 173 patients with histologically-verified stage ib2–iiib cervical squamous cell carcinoma. The patients underwent neoadjuvant chemotherapy using intravenous infusion of cytostatic drugs (n=106) and intra-arterial infusion of cytostatic drugs in combination with embolization of tumor-feeding arteries (n=67). Patients with resectable tumors underwent radical surgery. Disease-free survival was assessed.Results. The median follow-up time was 66 months, and the maximum follow-up period was 144 months. 160 (92.5 %) patients underwent radical surgery after chemotherapy. 55 (34.4 %) patients did not receive adjuvant radiation therapy. The five-year disease-free survival rate was 79.6 %.Conclusion. For the group of patients with locally advanced cervical cancer, who achieved respectability following neoadjuvant chemotherapy, radical surgery could be performed. Chemotherapy followed by radical surgery can improve disease-free survival rates in patients with stage ib2–iiib cervical cancer.

Cancer-associated fibroblasts (CAFs) have long been known as one of the most important players in tumor initiation and progression. Even so, there is an incomplete understanding of the identification of CAFs among tumor microenvironment cells as the list of CAF marker genes varies greatly in the literature, therefore it is imperative to find a better way to identify reliable markers of CAFs. To this end, we summarized a large number of single-cell RNA-sequencing data of multiple tumor types and corresponding normal tissues. As a result, for 9 different types of cancer, we identified CAF-specific gene expression signatures and found 10 protein markers that showed strongly positive staining of tumor stroma according to the analysis of IHC images from the Human Protein Atlas database. Our results give an insight into selecting the most appropriate combination of cancer-associated fibroblast markers. Furthermore, comparison of different approaches for studying differences between cancer-associated and normal fibroblasts (NFs) illustrates the superiority of transcriptome analysis of fibroblasts obtained from fresh tissue samples. Using single-cell RNA sequencing data, we identified common differences in gene expression patterns between normal and cancer-associated fibroblasts, which do not depend on the type of tumor.

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