Synergy between Paclitaxel and Anti-Cancer Peptide PNC-27 in the Treatment of Ovarian Cancer.

OBJECTIVES: Paclitaxel is widely used in the treatment of gynecologic malignancies. It targets tumor cells in the M phase of the cell cycle. Cells in other phases survive the insult and repopulate the tumor. PNC-27 is a peptide synthesized of amino acids of the p53-MDM-2 binding domain. It kills various cancer cell lines in a dose-dependent manner. The goal of this study is to assess ovarian cancer cells' sensitivity to PNC-27 after surviving exposure to paclitaxel and to investigate the potential for synergy between PNC-27 and paclitaxel in the treatment of ovarian cancer. METHODS: The impact of exposure to paclitaxel on the surface expression of MDM-2 was assessed with the use of flow cytometry. For measurement of cytotoxicity in vitro, ID8 cells were exposed to paclitaxel for 12 hours in various concentrations. At 12 hours, the drug containing media was removed and the cells were cultured in media containing various concentrations of PNC-27 for 24 hours. Viability was assessed with the use of an MTT assay. Survival fractions were plotted against drug concentrations and the data were fit to logistic dose-response curves. Isoeffective combinations were used to create isobolograms. The combined treatment with weekly paclitaxel and PNC-27 was tested in an intraperitoneal mouse model of ovarian cancer (ID8). RESULTS: Exposure to paclitaxel rendered incomplete time-dependent killing, while PNC-27 mediated comprehensive, dose-dependent killing of ID8 cells. The cytotoxic effect of PNC-27 was dependent on its binding to MDM-2. Blocking MDM-2 inhibited the killing by PNC-27. ID8 cells surviving paclitaxel demonstrated increased expression of MDM-2 and increased susceptibility to PNC-27. Isobologram for dose combinations that were isoeffective indicates synergistic effect between the 2 agents (Combination index <1). In an in vivo model of ovarian cancer (ID8), the addition of PNC-27 to weekly paclitaxel administration significantly reduces tumor growth. CONCLUSIONS: These data demonstrate synergism between PNC-27 and paclitaxel. PNC-27 could target cells surviving paclitaxel and improve its antitumor effect.

Extent of lymph node dissection and overall survival in patients with uterine carcinosarcoma, papillary serous and endometrioid adenocarcinoma: A retrospective cohort study.

OBJECTIVE: To evaluate the interaction between extent of lymph node dissection (LND) and overall survival (OS) in patients with various histologic types of uterine cancer. METHODS: We retrospectively identified 834 patients who had primary surgery in our institution for uterine carcinosarcoma (CS), papillary serous (UPSC) and endometrioid adenocarcinoma between 1984 and 2009. Stage, grade, total lymph node count (LNC), positive LNC, adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared with the log rank test and Cox regression analysis. RESULTS: Our cohort included 158 patients with CS, 115 patients with UPSC and 561 patients with endometrioid adenocarcinoma. Of the cohort, 38% of the patients had Stage III or IV disease. LND was performed in 73% of patients with CS, 68% of patients with UPSC and 79% of patients with endometrioid adenocarcinoma. LND was performed in 82% of Stage I-II and in 68% of Stage III-IV cases. The median total LNC was 13 (range 1-75) and there was no significant difference in the total LNC between the different histologies. Median OS was 21 months for CS, 18 months for UPSC and 200 months for patients with endometrioid adenocarcinoma. A positive association between the total and positive LNC was present in all three histologic types (Spearman coefficient, p < 0.001). The cohort was divided in quartiles based on the total LNC and a Kaplan-Meier survival analysis was performed. A continuum of improved OS was noted in correlation with increased LNC. OS was 27 months for the group with 0 nodes, 112 months for the group with 1-8 nodes, 117 months for the group with 9-16 nodes and 196 months for the group with >17 nodes. Doubling the total LNC was associated with 28% risk of death reduction (HR 0.724, CI 0.66-0.794, p < 0.001) for the first year and 14% risk reduction (HR 0.858, CI 0.761-0.967, p = 0.012) for the second year. CONCLUSIONS: In our cohort, the performance of LND is associated with improved OS. This effect appears to be uniform across pathology types. The extent of the LND is inversely correlated with the risk of death for the first 2 years.

Sonographic and magnetic resonance imaging findings of pelvic abscess following uterine perforation sustained during office endometrial sampling.

Pipelle endometrial sampling, an outpatient, office-based procedure, provides comparative successful endometrial sampling in comparison with other techniques including conventional dilatation and curettage. We present an unusual occurrence in which office Pipelle endometrial sampling in a perimenopausal patient was complicated 10 days later by lower abdominal pain and intermittent fever. Sonography depicted findings consistent with a large pelvic abscess overriding the uterine fundus. Sonography and magnetic resonance imaging confirmed the presence of the unusual pelvic abscess and, in addition, noted findings consistent with perforation of the uterus during endometrial sampling.

Transvaginal sonography of postabortal (Redo) syndrome.

Acute hematometra, also termed the postabortal syndrome or redo syndrome, is a rare immediate complication of suction curettage characterized by severe lower abdominal cramping in association with an enlarged and markedly tender uterus. We describe the transvaginal sonographic features of this syndrome.

Sonographic Findings of Medullary Thyroid Carcinoma Leading to Diagnosis of Multiple Endocrine Neoplasia Type 2a during Pregnancy.

Multiple endocrine neoplasia (MEN) type 2a (Sipple's syndrome) is characterized by medullary thyroid carcinoma and pheochromocytoma, and in a smaller percentage of cases, multiglandular parathyroid hyperplasia. This autosomal-dominant syndrome is due to a mutation in the rearranged during transfection (RET) proto-oncogene located on chromosome 10cen-10q11.2 and rarely complicates pregnancy. We present an unusual case in a patient with an enlarged thyroid with sonographic findings characteristic of thyroid cancer, which led to diagnosis and subsequent management of RET proto-oncogene-positive MEN type 2a complicating pregnancy.