Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma

Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches

Mesothelial cells in tissue repair and fibrosis

Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis. In addition to secreting proinflammatory mediators and contributing to both coagulation and fibrinolysis, mesothelial cells undergo mesothelial-to-mesenchymal transition, a process analogous to epithelial-to-mesenchymal transition, and become fibrogenic cells. Fibrogenic mesothelial cells have now been identified in tissues where they have not previously been thought to occur, such as within the parenchyma of the fibrotic lung. These findings show a direct role for mesothelial cells in fibrogenesis and open therapeutic strategies to prevent or reverse the fibrotic process

Body Image and Sexuality in Indonesian Adults with a Disorder of Sex Development (DSD)

In Indonesia, disorders of sex development (DSDs) are not well recognized and medical care for affected individuals is scarce. Consequently, many patients live with ambiguous genitalia and appearance. We compared reported outcomes on body image, sexual functioning, and sexual orientation of 39 adults with DSDs (aged 18 to 41) and 39 healthy controls matched for gender, age, and residential setting (urban, suburban, rural). Differences in gender and treatment status (treated or untreated) were also explored. On body image, adults with DSDs reported dissat-isfaction with sex-related body parts. Compared to the matched controls, women with DSDs reported greater sexual distress, and men with DSDs reported lower erectile and ejaculation fre-quencies, and more dissatisfaction with sexual life but not with sexual desire and activities. Men with DSDs who had undergone genital surgery reported higher erectile and ejaculation frequen-cies than untreated men. More women than men in the DSDs group reported a nonexclusive heterosexual orientation. DSDs and infertility had a great impact on sexuality. Fear of ostra-cism complicated DSD acceptance. Findings were compared to those of Western studies. Based on these results, education about DSDs and their psychosexual consequences may help reduce the sexual distress and problems in adults with DSDs and improve quality of life

Gender Development in Indonesian Children, Adolescents, and Adults with Disorders of Sex Development

Abstract In most Western countries, clinical management of disorders of sex development (DSD), including ambiguous gen-italia, begins at diagnosis soon after birth. For many Indonesian patients born with ambiguous genitalia, limited medical treat-ment is available. Consequently, affected individuals are raised with ambiguous genitalia and atypical secondary sex character-istics. We investigated gender identity and gender role behavior in 118 Indonesian subjects (77 males, 41 females) with different types of DSD in comparison with 118 healthy controls matched forgender,age,andresidentialsetting(rural,suburban,orurban).In Study 1, we report on methodological aspects of the investigation, including scale adaptation, pilot testing, and determining reliability and validity of measures. In Study 2, we report on gender devel-opment in 60 children (42 boys, 18 girls), 24 adolescents (15 boys, 9 girls), and 34 adults (19 men, 15 women) with DSD. The majority of participants with DSD never received any medical or surgical treatmentpriortothisstudy.Weobservedagenderchangeinallage groups, with the greatest incidence in adults. Among patients who changed, most changed from female to male, possessed a 46,XY karyotype, and had experienced significant masculinization during life. Gender identity confusion and cross-gender behavior was more frequently observed in children with DSD raised as girls compared to boys. Puberty and associated masculinization were related to gender problems in individuals with 46,XY DSD raised female. An integrated clinical and psychological follow-up on gender outcome is necessary prior to puberty and adulthood