Characterisation of human kallikrein 6 protease M expression in ovarian cancer

Kallikrein 6 (hK6, also known as protease M/zyme/neurosin) is a member of the human kallikrein gene family. We have previously cloned the cDNA for this gene by differential display and shown the overexpression of the mRNA in breast and ovarian primary tumour tissues and cell lines. To thoroughly characterise the expression of this kallikrein in ovarian cancer, we have developed a novel monoclonal antibody specific to hK6 and employed it in immunohistochemistry with a wide range of ovarian tumour samples. The expression was found elevated in 67 of 80 cases of ovarian tumour samples and there was a significant difference in the expression levels between normal and benign ovarian tissues and the borderline and invasive tumours (P<0.001). There was no difference of expression level between different subtypes of tumours. More significantly, high level of kallikrein 6 expression was found in many early-stage and low-grade tumours, and elevated hK6 proteins were found in benign epithelia coexisting with borderline and invasive tissues, suggesting that overexpression of hK6 is an early phenomenon in the development of ovarian cancer. Quantitative real-time reverse transcription-polymerase chain reactions also showed elevated kallikrein 6 mRNA expression in ovarian tumours. Genomic Southern analysis of 19 ovarian tumour samples suggested that gene amplification is one mechanism for the overexpression of hK6 in ovarian cancer.

Personality disorders in the community: Results from the Australian National Survey of Mental Health and Well-Being Part III - Relationships between specific type of personality disorder, Axis 1 mental disorders and physical conditions with disability and health consultations

Background The aims of this study were threefold. First, to ascertain whether personality disorder (PD) was a significant predictor of disability (as measured in a variety of ways) over and above that contributed by Axis I mental disorders and physical conditions. Second, whether the number of PD diagnoses given to an individual resulted in increasing severity of disability, and third, whether PD was a significant predictor of health and mental health consultations with GPs, psychiatrists, and psychologists, respectively, over the last 12 months. Method Data were obtained from the National Survey of Mental Health and Wellbeing, conducted between May and August 1997. A stratified random sample of households was generated, from which all those aged 18 and over were considered potential interviewees. There were 10 641 respondents to the survey, and this represented a response rate of 78%. Each interviewee was asked questions indexing specific ICD-10 PD criteria. Results Five measures of disability were examined. It was found that PD was a significant predictor of disability once Axis I and physical conditions were taken into account for four of the five disability measures. For three of the dichotomously-scored disability measures, odds ratios ranged from 1.88 to 6.32 for PD, whilst for the dimensionally-scored Mental Summary Subscale of the SF-12, a beta weight of -0.17 was recorded for PD. As regards number of PDs having a quasi-linear relationship to disability, there was some indication of this on the SF-12 Mental Summary Subscale and the two role functioning measures, and less so on the other two measures. As regards mental consultations, PD was a predictor of visits to GPs, psychiatrists and psychologists, over and above Axis I disorders and physical conditions. Conclusion The study reports findings from a nationwide survey conducted within Australia and as such the data are less influenced by the selection and setting bias inherent in other germane studies. However, it does support previous findings that PD is a significant predictor of disability and mental health consultations independent of Axis I disorders and physical conditions.

Height, age at menarche, and risk of epithelial ovarian cancer

Objective: We hypothesized that the hormonal changes of adolescence influence ovarian cancer risk particularly in younger women. We investigated this possibility by examining the relationship between ovarian cancer and adult height and age at menarche as both factors reflect pubertal hormonal levels. Methods: Participants were a population-based sample of women with incident ovarian cancer (n = 794) and control women randomly selected from the Australian Electoral Roll (n = 855). The women provided comprehensive reproductive and lifestyle data during a standard interview. Results: Although neither height nor age at menarche was significantly related to the risk of ovarian cancer overall, increasing height was associated with increasing risk of the subgroup of mucinous borderline ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for women 175 cm compared with women < 160 cm, P-trend = 0.02). Similarly, later age at menarche was associated with increasing risk of mucinous borderline cancers (odds ratio, 3.8; 95% confidence interval, 1.3-11.4 for those with age at menarche >= 44 years compared with those < 12 years, P-trend = 0.003). Women with mucinous borderline cancers were significantly younger than the women diagnosed with invasive cancers (mean 44 versus 57 years; P < 0.0001). Conclusions: Development of mucinous borderline ovarian cancers, predominantly diagnosed in women ages under 50 years, seems to be associated with age at menarche and attained adult height. These results are consistent with our original hypothesis that pubertal levels of reproductive hormones and insulin-like growth factor-I influence ovarian cancer risk in younger women.

Connective tissue panniculitis in a child with vitiligo and Hashimoto's thyroiditis

A 9-year-old girl presented with a 6-month history of inflamed tender nodules in the pretibial area. These eventually healed leaving depressed areas of atrophy and loss of subcutaneous tissue. Histology showed a predominantly lymphocytic lobular panniculitis, consistent with connective tissue panniculitis. Investigations revealed an elevated thyroid stimulating hormone, elevated thyroid antiperoxidase antibody and a weakly positive antinuclear antibody (titre 1 in 40). She was commenced on hydroxychloroquine 300 mg daily, which resulted in resolution of the pannictulitis. She developed focal Vitiligo oil the thighs. This gradually improved with 0.1% mometasone furoate ointment. The hydroxychloroquine dose was tapered to 200 mg daily after 12 months, then to 100 mg daily after 18 months therapy. Her thyroid autoantibody levels continued to rise and the hydroxychloroquine was increased again to 300 mg daily. She became borderline hyothyroid. Hashimoto's thyroiditis was diagnosed. Thyroxine was instituted with a resultant improvement in her thyroid blood tests. The lipoatrophy has not developed further during 2-year follow up.

Selenium binding protein 1 in ovarian cancer

Selenium binding protein I (SELENBP1) was identified to be the most significantly down-regulated protein in ovarian cancer cells by a membrane proteome profiling analysis. SELENBP1 expression levels in 4 normal ovaries, 8 benign ovarian tumors, 12 borderline ovarian tumors and 141 invasive ovarian cancers were analyzed with immunohistochemical assay. SELENBP1 expression was reduced in 87% cases of invasive ovarian cancer (122/141) and was significantly reduced in borderline tumors and invasive cancers (p < 0.001). Cox multivariate analysis within the 141 invasive cancer tissues showed that SELENBP1 expression score was a potential prognostic indicator for unfavorable prognosis of ovarian cancer (hazard ratio [HR], 2.18; 95% CI = L22-190; p = 0.009). Selenium can disrupt the androgen pathway, which has been implicated in modulating SELENBP1 expression. We investigated the effects of selenium and androgen on normal human ovarian surrace epithelial (HOSE) cells and cancer cells. Interestingly, SELENBP1 mRNA and protein levels were reduced by androgen and elevated by selenium treatment in the normal HOSE cells, whereas reversed responses were observed in the ovarian cancer cell lines. These results suggest that changes of SELENBP1 expression in malignant ovarian cancer are an indicator of aberration of selenium/androgen pathways and may reveal prognostic information of ovarian cancer. (c) 2005 Wiley-Liss, Inc.

Evidence for microsatellite instability in bilateral breast carcinomas

The molecular pathogenesis of various categories of breast cancer (BC) has been well described, but surprisingly few reports have appeared on analysis of somatic mutations in bilateral BC. We have performed a polymerase chain reaction (PCR)-driven investigation of chromosomal regions showing common loss of heterozygosity (LOH) in 23 cases (46 rumors) from patients diagnosed with bilateral BC, LOH was observed in 15/46 (33%) informative tumors for chromosome 1p, 5/32 (16%) for 5q, 12/44 (27%) for 11q, 15/40 (38%) for 13q and 4/24 (17%) for 17p. These values are within the range of interlaboratory variations reported fur unilateral BC, There was no strong evidence for concordance of LOH within the same patient for any of the chromosomal loci tested. Atypical for breast carcinomas, 7/46 (15%) turners accumulated a high frequency (ranging from 11 to 29%) of shortened dinucleotide CA repeats, implying microsatellite instability (MI). Further analysis with the highly informative BAT-26 marker allowed for the classification of two of these tumors as having a replication error positive (RER+/MSI-H) phenotype, whereas the remaining five carcinomas harbored so-called borderline MI. Thus an involvement of both RER+ and borderline MI appears to be a distinct feature of bilateral breast carcinomas compared to unilateral lesions. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.