Soft tissue sarcomas of adults: state of the translational science.

Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.     

CROHN'S DISEASE OF THE PREPUCE IN A 12-YEAR-OLD BOY: A Case Report and Review of the Literature

We report a case of Crohn's disease with involvement of the foreskin in a 12-year-old boy. One year previously, on the basis of clinical features (diarrhea with blood, perianal fissures) and histologic examination, a diagnosis of Crohn's disease was made. Subsequently, he developed phimosis and balanitis and underwent circumcision. Sections submitted from the foreskin revealed noncaseating granulomatous inflammation consistent with Crohn's disease. Crohn's disease with involvement of the genitalia is unusual. Only 26 cases including our case have been reported in the scientific literature. We have analyzed these cases with emphasis on gender, age, clinical features, duration of Crohn's disease, and probable mode of spread to the genitalia. Careful examination of sections from genital lesions, including those submitted from the foreskin, is essential to detect small isolated granulomas that may then lead to the diagnosis of inflammatory bowel disease.     

An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina

Objective Tomap potential sites of sex steroid action in the human vulva.
Methods Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stainfrozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to comparereceptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma.
Results Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hairfollicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora thanin vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginalepithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin.They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of theskin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest insuprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smoothmuscle but not in the vulva. There was no evidence of significant differences in androgen oroestrogen receptor staining in the vulva of pre- or postmenopausal women.
Conclusion The transition from vagina to vulva is marked by an increase in androgen and a decrease inoestrogen and progesterone receptors. This distribution of receptors would indicate a limited role foroestrogen creams on the vulva.     

Green tea extract modulates actin remodeling via Rho activity in an in vitro multistep carcinogenic model.

Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent.     

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer

Breast Cancer Research and Treatment - Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing...     

Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women

OBJECTIVE: To report on the natural history of high-risk human papillomavirus (HPV) infection and cervical disease in human immunodeficiency virus (HIV)-1-infected women living in Cape Town, South Africa. METHODS: This was a prospective study of 400 untreated, HIV-1-infected women who underwent high-risk HPV DNA testing, cytology, colposcopy, histology, and CD4 count testing every 6 months for 36 months. Human immunodeficiency virus viral loads and HPV type distribution were determined at entry and after 18 months. RESULTS: Sixty-eight percent of the women were high-risk HPV DNA positive at entry, 35% had a cytologic diagnosis of low-grade squamous intraepithelial lesion (LSIL), and 13% had high-grade squamous intraepithelial lesion (HSIL). There were no cancers. Abnormal cytology and high-risk HPV positivity were strongly correlated with low CD4 counts and high HIV viral loads. The most prevalent types of HPV were HPV-16, -52, -53, -35, and -18. Incident high-risk HPV infection occurred in 22%, and of those infected with high-risk HPV, 94% of infections persisted over an 18-month period, and 6% cleared their infections. Cytologic progression to SIL from normal/atypical squamous cells of undetermined significance cytology occurred in 17% of cases, but only 4% of cases of LSIL progressed to HSIL. CONCLUSION: There is a high level of high-risk HPV infection in HIV-1 infected women, but progression to HSIL over 36 months occurred in the minority of cases. We recommend an initial colposcopy for an abnormal test, and if no high-grade lesion is identified, triennial screening would be appropriate. Human papillomavirus type 16 was the commonest, and HPV-18 was the fifth commonest, suggesting that vaccination against these two types would have a significant effect. LEVEL OF EVIDENCE: II.     

Dissatisfaction with body size among low-income, postpartum black women

OBJECTIVE: To explore the body size perceptions of low-income, postpartum Black women. DESIGN: Prospective, exploratory survey using a culturally sensitive figure rating scale, to assess body size perceptions. SETTING: Four inner city clinics in Washington, DC. Participants: Low-income, postpartum Black women (N= 105). METHOD: A validated, culturally sensitive figure rating scale was used to assess perception of current, typical, healthy, and preferred body sizes of participants. Derived scores were used to assess other body image measures. MAIN OUTCOME MEASURES: Measures were mean scores of perceived sizes and derived scores representing body size satisfaction, adherence to typical size, and health ideal size. RESULTS: Over 75% of subjects exhibited dissatisfaction with current body size. The perceived size for the typical (reference) woman was larger and not representative of the perceived healthy or preferred sizes of the sample. No difference between preferred and healthy sizes was observed. CONCLUSIONS: Two thirds of the participants were dissatisfied with their current body size and over half desired weight loss. The lack of difference between preferred and healthy body sizes suggests desire for a body size that meets both cultural standards of attractiveness and personal standards of health. Nursing opportunity for engaging in anticipatory interventions is highlighted.