Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors.

OBJECTIVE: Hpr6 (heme-1 domain protein/human progesterone receptor) is one of a family of proteins that are implicated in progesterone metabolism, resistance to genotoxic agents and steroid biosynthesis. Because these processes are frequently misregulated in tumors, we have examined the expression of Hpr6 in a group of clinical tumor samples and cancer cell lines. METHODS: Hpr6 expression was analyzed by Western blot in extracts from breast, cervix, colon and thyroid cell lines and in nonmalignant and adjacent tumor tissue from breast, colon and thyroid. Hpr6 localization was determined by immunofluorescence. RESULTS: Hpr6 expression is significantly elevated in breast tumors in comparison with matched nonmalignant tissue and demonstrated limited overexpression in colon and thyroid tumors. Hpr6 is strongly expressed in a panel of tumor cell lines originating from breast, thyroid and colon. Hpr6 localizes to the perinuclear region of the cell, consistent with a role in cell detoxification, signaling and/or sterol synthesis. CONCLUSIONS: Hpr6 homologues regulate cytochrome P450 proteins implicated in hormone, steroid and xenobiotic chemical metabolism. These are the first studies linking Hpr6 expression to cancer progression and cellular survival. Our results suggest that Hpr6 is an important marker for cancer progression and a potential anticancer therapeutic target.     

N-Alkyl-2-Quinolonopyrones Demonstrate Antimicrobial Activity against ESKAPE Pathogens Including Staphylococcus aureus

Antibiotic resistance has grown significantly in the last three decades, while research and development of new antibiotic classes has languished. Therefore, new chemical frameworks for the control of microbial behavior are urgently required. This study presents a novel suite of compounds, based on a tricyclic 4-hydroxy-2H-pyrano[3,2-c]quinoline-2,5(6H)-dione core, with significant antibiotic activity against the ESKAPE pathogens Staphylococcus aureus and Enterococcus faecalis and the “accidental pathogen” Staphylococcus epidermidis. A potent analogue with an N-heptyl-9-t-Bu substitution pattern emerged as a hit with MIC levels ≤2 μg/mL across four strains of MRSA. In addition, the same compound proved highly potent against Enterococcus spp. (0.25 μg/mL).     

Age at sexual initiation and number of sexual partners in the female Spanish population Results from the AFRODITA survey

Objectives

The AFRODITA study was designed to describe patterns relating to the number of lifetime sexual partners (SP) and age at first sexual intercourse (AFSI) by geographic region in a representative sample of Spanish women.

Study design

A representative sample of the female Spanish population was obtained using the Access Panel Technique. Postal questionnaires were sent to 11,086 women aged 18–70 years. Data were collected on AFSI, number of sexual partners, contraceptive methods, cervical cancer screening and socio-demographic characteristics.

Results

The average AFSI was 20.9 years. AFSI below the age of 19 years was reported by 30.8% of the women. Among sexually active women, 70.6% reported being monogamous and 6.4% reported ≥5 lifetime sexual partners. Younger age at interview was strongly related to earlier AFSI and to higher number of lifetime sexual partners. Women younger than 25 were 39 times more likely to have an AFSI before age 18 than women over age 55. The percentage of women aged less than 25 reporting two or more sexual partners was four times higher than that of women 56 and older. In the multivariate analysis, having two or more sexual partners was independently associated with young age, early AFSI, having ever used oral contraceptives, living in an urban area, having had a screening Pap test in the last 3 years, having a sexually transmitted infection and nuliparity.

Conclusions

This study confirms important changes in the sexual behaviour of Spanish women. Younger cohorts show a younger age at sexual initiation and higher number of sexual partners. These are key factors that may induce changes in the human papillomavirus (HPV) prevalence and the cervical cancer incidence in Spain.     

Success of targeted transperineal biopsy in patients on surveillance for grade group 1 prostate cancer

IntroductionWe aimed to determine the minimum cross-sectional ellipsoid area on magnetic resonance (MR) of intraprostatic nodules that best predicts for subsequent targeted biopsies revealing ≥ grade group (GG) 2 disease.MethodsForty-six patients previously diagnosed with GG 1 prostate adenocarcinoma who received cognitively fused, MR-guided, transperineal targeted biopsies in addition to six random biopsies were included in this analysis. A Youden cutpoint analysis was used to determine the ellipsoid area in the axial plane best predicting for ≥GG 2 disease within the targeted biopsy cores and logistic regression used to assess the result.ResultsMedian time from MR imaging to targeted biopsy was 2.4 (1.4–5.5) months. Forty of 46 (87%) patients had one nodule and 6/46 (13%) had two separate nodules on MR that received targeted biopsy. Of the 52 nodules, five (10%), 33 (63%), and 14 (27%) were Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4, and 5, respectively. Thirteen (25%), six (12%), and 33 (64%) were in the anterior, medial, and posterior regions of the prostate, respectively. Median area was 0.72 (0.49–1.29) cm² (average diameter 9.5 mm). Fifteen of 46 (33%) patients had ≥1 random biopsy and 20/52 (38%) nodules had ≥1 targeted biopsy revealing ≥GG 2 disease. The optimal area cutpoint was ≥0.7 cm², with an area under the curve of 0.671 (0.510–0.832). On logistic regression, area ≥0.7 cm² was solely predictive of targeted biopsy revealing ≥GG 2 disease (odds ratio 6.5, 1.3–32.4, p=0.022).ConclusionsNodule area ≥0.7 cm² may predict for transperineal-based targeted biopsies being positive for ≥GG 2 disease when 1–2 cores are taken.     

Radiation treatment of bladder squamous cell carcinoma in a patient with spina bifida: A case report

Bladder cancer is the sixth most common cancer in Canada. While most patients present with transitional cell carcinoma, few present with squamous cell carcinoma (SCC). Risk factors for SCC include a history of chronic urinary tract infection, urothelial inflammation and indwelling catheters. We present the management of a patient with locally advanced SCC of the bladder.