Occurrence of cervical intraepithelial neoplasia in generally healthy women with exophytic vulvar condyloma acuminata.

AIM: To disclose possible association between exophytic vulvar condyloma acuminata and cervical intraepithelial neoplasia in generally healthy, sexually active women. METHODS: This retrospective study included 74 patients (study group) who were referred for laser vaporization therapy of exophytic vulvar condyloma acuminata, and 88 asymptomatic volunteers without evidence of exophytic vulvar condyloma acuminata (control group) who were referred for screening Papanicolaou (Pap) test cervical evaluation including colposcopy. The diagnosis of cervical intraepithelial neoplasia was based on Pap smear, colposcopy and/or biopsy. RESULTS: On Pap smear, atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions were found in 10 (13.5%) women with exophytic vulvar condyloma acuminata and in 2 (2.3%) asymptomatic volunteers (p < 0.05). Cervical intraepithelial neoplasia was found in 8 women with exophytic vulvar condyloma acuminata and in none of the asymptomatic volunteers (p < 0.05). CONCLUSION: An association was found between exophytic vulvar condyloma acuminata and abnormal Pap smear or positive cervical biopsy, in generally healthy women

Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events.</p> <p>Conclusion</p> <p>On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.</p

Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue.</p> <p>Methods</p> <p>H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer.</p> <p>Results</p> <p>H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth.</p> <p>Conclusion</p> <p>These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.</p

Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study

ObjectiveTo evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence.MethodsPost hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population.ResultsIn PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47–0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44–0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46–0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39–0.86) and 0.41 (0.27–0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37).ConclusionsIn this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.</p