Ovarian cancer ascites confers platinum chemoresistance to ovarian cancer cells.

Ovarian cancer (OC), the second most common form of gynecologic malignancy, has a poor prognosis and is often discovered in the late stages. Platinum-based chemotherapy is the first line of therapy. Nevertheless, treatment OC has proven challenging due to toxicity and the development of acquired resistance to therapy. Tumor microenvironment (TME) has been associated with platinum chemoresistance. Malignant ascites has been used as OC tumor microenvironment and its ability to induce platinum chemoresistance has been investigated. Our results suggest that exposure to OC ascites induces platinum chemoresistance in 11 of 13 cases (85 %) on OC cells. In contrast, 75 % of cirrhotic ascites (3 of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL -6 and to a lesser extent HGF were enriched in OC ascites, whereas IL -22 was enriched in cirrhotic ascites. Pharmaceutical inhibitors targeting the IL -6/ JAK pathway were mildly effective in overcoming platinum chemoresistance induced by malignant ascites. In contrast, crizotinib, an HGF/c- MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemosensitivity to OC. Our results demonstrate the importance of OC ascites in supporting platinum chemoresistance and the potential of combination therapy to restore chemosensitivity of OC cells.

A New Insight on Exophytic Serous Borderline Adnexal Tumors: Specific Sonographic Features.

OBJECTIVES: To characterize and compare the sonographic features of exophytic serous borderline ovarian tumors (ESBOT) with those of high-grade serous carcinoma of the ovary (HGSC). METHODS: Seven patients with histological diagnosis of ESBOT diagnosed between 2011 and 2019 and 10 consecutive cases of HGSC detected during 2019, both depicting an exophytic growth pattern, were identified retrospectively. The sonographic imaging of the masses was reassessed and characterized according to the International Ovarian Tumor Analysis terms. RESULTS: A unilateral irregular solid adnexal mass was demonstrated in all patients with ESBOT. The mass typically wrapped an apparently normal ovary, with a clear demarcation line depicted between them and it contained tiny cystic inclusions and calcifications. On color Doppler study of all the ESBOT cases, a unique vascular pattern could be demonstrated: an intratumoral vascular bundle originating from the ovarian vessels and supplying a rich radial blood flow to the tumor periphery. These characteristic morphological and color Doppler features could not be observed in any of the HGSC cases (P < .001). In 42.8% of the patients with ESBOT, additional unilocular-solid components (ipsilateral or contralateral) could be detected, whereas all the HGSC patients presented with a multilocular-solid tumor morphology (P < .001). The interface of the external mass border with the adjacent pelvic walls was regular in all the cases with ESBOT, whereas in 80% of HGSC patients, it was irregular, suggesting invasiveness (P = .002). CONCLUSIONS: ESBOT can mimic HGSC. Our results suggest that ESBOT has specific B-mode and color Doppler features, enabling differentiation from HGSC and planning appropriate intervention.

Primary Papillary Serous Carcinoma of the Fallopian Tube Presenting as a Vaginal Mass: A Case Report and Review of the Literature.

BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.

Association between a functional dopamine D4 receptor promoter region polymorphism (-C521T) and pre-eclampsia: a family-based study.

Although many candidate genes have been studied in pre-eclampsia (PE), the important class of catecholamine receptors that contribute to sympathetic tone and blood pressure regulation has yet to be investigated. We therefore examined the dopamine D4 receptor (DRD4) gene. We performed a prospective family-based study in 50 families (patient and both her parents) who were genotyped for three DRD4 promoter regions. These single-nucleotide polymorphisms (SNPs) were tested for association using family-based association test (FBAT) that also included two quantitative measures, aspartate aminotransferase [serum glutamic oxalacetic transaminase (SGOT)] and systolic blood pressure. SNPs were assayed using a commercially available SNAPSHOT kit and PCR products were analysed in an ABI 310 DNA analyser. A significant association (preferential transmission of the T allele from a heterozygous parent to affected mother) was observed between the -C521T SNP and PE (P = 0.019). Significant association was also observed between the -521T allele and two-dimensional measures of PE : GOT (P = 0.039) and systolic blood pressure (P = 0.036). The DRD4 promoter region -C521T SNP that reduces transcriptional efficiency of this gene is suggested to contribute to developing PE. Additionally, DRD4 -521 TT homozygosity may be a marker for severe PE.