Prognostic factors value of germline and somatic brca in patients undergoing surgery for recurrent ovarian cancer with liver metastases.

OBJECTIVE: To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. METHODS: Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors of post-HR progression free survival (PHR-PFS) were assessed by univariate analyses using Cox-proportional hazard regression models. RESULTS: Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr post-HR overall survival was 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to 15.2% in wild type ones (p value: 0.001). CONCLUSIONS: Our clinical analyses suggest that in ROC patients with liver disease the assessment of germline and somatic BRCA mutational status can help to select patients elegible for SCS.

Protective mechanisms of purified polyphenols from pinecones of Pinus koraiensis on spleen tissues in tumor-bearing S180 mice in vivo.

The previous study evaluated the antitumor activity and the underlying mechanism of the purified polyphenols from pinecones of Pinus koraiensis (PPP-40) using a tumor-bearing S180 mice model. This study was designed to evaluate the protective effects of PPP-40 on spleen tissues of S180 mice in vivo. Pretreatment with PPP-40 (150 mg per kg BW per D) could significantly inhibit tumor growth, enhance spleen index and prevent the decline of haematological parameters of S180 mice induced by the tumor microenvironment. Moreover, the treatment with PPP-40 was shown to significantly inhibit splenocyte apoptosis by TUNEL staining and flow cytometry, characterized by the inhibition of splenocyte cycle (G0/G1) arrest, increase in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD3+CD4+ and CD3+CD8+ T cells), as well as the production of T cell-related cytokines (IL-2, IL-12, and TNF-α) in splenocytes exposed to the tumor microenvironment. These effects were associated with a decrease in oxidative stress, as evidenced by the changes in the SOD, GSH-Px, GSH and MDA levels of liver and spleen tissues of S180 mice. Furthermore, the protective effect of PPP-40 on spleen tissues was deeply analyzed by detecting apoptosis-related proteins using immunohistochemistry staining. The results indicated that the protective multi-mechanisms of action also were associated with the inhibition of apoptosis through down-regulation protein expressions of Bax, caspase-9, caspase-8 caspase-3, Fas and up-regulation of the expressions of Bcl-2. These results suggested that PPP-40 is a natural antitumor agent and possesses strong immunomodulatory activities by protecting the spleen tissues of tumor-bearing S180 mice.