FGFR2 Abnormalities Underlie a Spectrum of Bone, Skin, and Cancer Pathologies.
J Invest Dermatol. 2009 Apr 23; Katoh MFibroblast growth factor receptor (FGFR)2 is regulated on the basis of the balance of FGFs, heparan-sulfate proteoglycans, FGFR2 isoforms, endogenous inhibitors, and microRNAs. FGFR2 signals cross-talk with hedgehog, bone morphogenetic protein, and other regulatory networks. Some cases of congenital skeletal disorders with an FGFR2 mutation show skin phenotypes, including acne, cutis gyrata, and acanthosis nigricans. Gain-of-function mutations or variations of human FGFR2 occur in estrogen receptor-positive breast cancer, diffuse-type gastric cancer, and endometrial uterine cancer. Oral administration of AZD2171 or Ki23057 inhibits in vivo proliferation of cancer cells with aberrant FGFR2 activation in rodent therapeutic models. However, loss-of-function mutations of FGFR2 are reported in human melanoma. Conditional Fgfr2b knockout in the rodent epidermis leads to increased macrophage infiltration to the dermis and adipose tissue, epidermal thickening accompanied by basal-layer dysplasia and parakeratosis, and the promotion of chemically induced squamous-cell carcinoma. Dysregulation of FGFR2 results in a spectrum of bone and skin pathologies and several types of cancer.Journal of Investigative Dermatology advance online publication, 23 April 2009; doi:10.1038/jid.2009.97.
Photodynamic therapy: off-label and alternative use in dermatological practice.
Photodiagnosis Photodyn Ther. 2008 Jun; 5(2): 134-8Buggiani G, Troiano M, Rossi R, Lotti TPhotodynamic therapy (PDT) is a treatment technique that permits the clearance of different skin lesions with high success rates in many dermatological diseases. Worldwide recognized uses for PDT in dermatology include non-melanoma skin cancer, actinic keratoses, acne vulgaris, photorejuvenation, and hidradenitis suppurativa. In the European Union, and in the USA, its indication is for the treatment of nonhyperkeratotic actinic keratoses (AKs) of the face and scalp, for basal cell carcinoma and for Bowen's disease. However, due to its intriguing mechanism of action, many dermatologists have begun to look at the use of PDT in photorejuvenation, acne vulgaris and hidradenitis suppurativa. Moreover, clinicians have to learn how to maximize this kind of therapy to treat other dermatologic entities, and many anecdotic reports can already be found in the literature. This paper aims to briefly but critically review these reports to give the dermatologist a useful guide to what could be the future experiences in PDT and how to target their efforts in clinics and research.
Smoking is associated with increased free testosterone and fasting insulin levels in women with polycystic ovary syndrome, resulting in aggravated insulin resistance.
Fertil Steril. 2009 Apr 24; Cupisti S, Häberle L, Dittrich R, Oppelt PG, Reissmann C, Kronawitter D, Beckmann MW, Mueller AOBJECTIVE: To evaluate the impact of smoking on endocrine, metabolic, and clinical parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Cohort analysis. SETTING: University hospital. PATIENT(S): 346 women with PCOS, including 98 smokers and 248 nonsmokers. INTERVENTION(S): Screening panel, including physical examination, weight and height measurement, and ultrasound examination of the ovaries, and hormone and insulin measurements. MAIN OUTCOME MEASURE(S): Clinical, metabolic, and endocrine parameters, oral glucose tolerance test, calculation of insulin resistance indexes. RESULT(S): In women with PCOS, smoking was associated with statistically significantly increased levels of fasting insulin and calculated free testosterone (cFT) and with a raised free androgen index (FAI) score, which resulted in aggravated scores on the homeostatic model for assessment of insulin resistance (HOMA-IR). However, no differences were observed between the smoking and nonsmoking groups with regard to the clinical parameters for hirsutism, acne, ovulatory function (classified as eumenorrhea, oligomenorrhea, and amenorrhea), or polycystic ovaries using the ultrasound criteria recommended according to the Rotterdam definition. CONCLUSION(S): In women with PCOS, smoking is associated with increased free testosterone and fasting insulin levels, resulting in aggravated insulin resistance. However, there were no differences between smokers and nonsmokers when clinical parameters were compared.
