Rate of Appendiceal Metastasis with Non-Serous Epithelial Ovarian Cancer in Manitoba.

OBJECTIVE: This study sought to evaluate the rate of appendiceal involvement in non-serous mucinous and endometrioid-associated epithelial ovarian cancers. METHODS: The Manitoba Cancer Registry and CancerCare database were used to find all women with non-serous epithelial ovarian, fallopian tube, or primary peritoneal cancer between 1995 and 2011. All patients with an appendectomy were then identified, and their final pathology findings were reviewed. Women who did not receive treatment or lacked follow-up were excluded. RESULTS: We identified 338 patients from 1995-2011 with no prior appendectomy. Of these, 16.6% received an appendectomy, and 22.8% were clinically evaluated. Most cases within this cohort were mucinous (62%) and stage 1 (63%). Four appendiceal metastases were identified (7.2%), and one half appeared clinically normal at the time of surgery (3.6%). Within the mucinous histologic type, 32.7% of patients received an appendectomy, with a metastatic rate of 5.7%. Of the 127 endometrioid cases, only 10 patients received an appendectomy, and 2 were found to have metastases. No metastases were found in the 85 patients in the clear cell cohort, only 5 of whom received an appendectomy. CONCLUSION: Routine appendectomy or clinical assessment of the appendix is valuable for all non-serous ovarian cancers. The rate of involvement for endometriosis-associated ovarian cancers may be significantly higher than expected, and further studies need to be conducted.

Hormone Use After Nonserous Epithelial Ovarian Cancer: Overall and Disease-Free Survival.

OBJECTIVE: To evaluate whether hormone therapy (HT) after nonserous epithelial ovarian cancer is associated with a decrease in overall and disease-free survival. METHODS: We conducted a retrospective cohort study. The Manitoba Cancer Registry and Drug Programs Information Network were searched to find all women with known nonserous epithelial ovarian, fallopian tube, or primary peritoneal cancer between 1995 and 2010 who had used HT after treatment. Women who did not receive treatment or had no follow-up were excluded. RESULTS: Three hundred ninety-one patients met the inclusion criteria. Seventeen patients were excluded because the patients did not receive treatment for cancer, and 17 were excluded for lack of follow-up. A total of 94 women received HT after treatment, and 263 women did not. The average age was 57.8 years. In HT users younger than 55 years of age, disease-free survival is improved according to both the multivariable landmark analysis (n=68/145, adjusted hazard ratio 0.354, 95% confidence interval [CI] 0.17-0.74, P=.006) and the time-varying Cox regression analysis (n=42/158, adjusted hazard ratio 0.212, 95% CI 0.07-0.60, P=.004) when adjusting for International Federation of Gynecology and Obstetrics stage and need for chemotherapy. There is no statistical difference in overall survival in this age group. No associations between HT use and overall survival or disease-free survival were found among women aged 55 years and older. CONCLUSION: After treatment for nonserous epithelial ovarian cancer, hormone therapy is not associated with decreased disease-free or overall survival.

High-throughput screening identifies three inhibitor classes of the telomere resolvase from the lyme disease spirochete.

Lyme disease, the most common vector-borne zoonosis in North America, is caused by the spirochetal pathogen Borrelia burgdorferi. The telomere resolvase encoded by this organism (ResT) promotes the formation of covalently closed hairpin ends on the linear DNA molecules of B. burgdorferi through a two-step transesterification. ResT is essential for survival and is therefore an attractive target for the development of highly specific antiborrelial drugs. To identify ResT inhibitors, a novel fluorescence-based high-throughput assay was developed and used to screen a library of 27,520 small-molecule drug-like compounds. Six confirmed inhibitors of ResT, with 50% inhibitory concentrations between 2 and 10 muM, were identified. The inhibitors were characterized further and were grouped into three distinct classes based on their inhibitory features. The high-throughput screening assay developed in this paper, along with the six inhibitory compounds identified, provides a starting point for the future development of novel antiborrelial drugs as well as small-molecule inhibitors that will be helpful for the further dissection of the reaction mechanism.

Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats.

Inducers of phase II detoxifying enzymes have been studied as chemopreventive agents for a variety of cancers. Phase II detoxifying enzymes may play a significant role in preventing carcinogen-induced colon cancer at the initiation and post-initiation stage, but the contribution of NAD(P) H:quinone oxidoreductase 1 (NQO1) to this effect remains unclear. Using the carcinogen-induced colon cancer Sprague-Dawley rat model, we previously showed that oltipraz selectively induces NQO1 in the colons of these rats without inducing other phase II detoxifying enzymes. We demonstrated that selective induction of NQO1 in the rat colon prior to treatment with a carcinogen significantly inhibited the formation of aberrant crypt foci (ACF). Using the same rat model, we found that rats fed oltipraz containing diet following treatment with the colon carcinogen, azoxymethane (AOM), had 60% fewer ACF after 12 weeks compared with rats fed a control diet. In addition, rats fed oltipraz containing diet after AOM treatment developed 40% fewer colon adenomas and fewer colon tumors than rats fed a control diet. There was also a 60% increase in the percentage of apoptotic cells in ACF from oltipraz fed rats compared with ACF from control fed rats. Together, these results suggest that NQO1 can contribute to inhibition of colon carcinogenesis at the post-initiation stage. A possible mechanism for this effect may be that induction of NQO1 increases apoptosis in carcinogen initiated colonic epithelial cells that prevents these cells from progressing to a neoplastic state. Thus, NQO1 may be an important target for chemoprevention of colon cancer.