Pleiotropic functions of Rho GTPase signaling: a Trojan horse or Achilles' heel for breast cancer treatment?

Rho GTPase signaling is altered in human breast tumors, and elevated expression and activation of Rho GTPases correlate with tumor progression, metastasis, and poor prognosis. Here we review the evidence that Rho signaling functions as a key regulator of cell cycle, mitosis, apoptosis, and invasion during breast cancer growth and progression and discuss whether these pleiotropic actions enhance or limit the targetability of this network. We propose that depending on the stage and subtype of breast cancer, targeting Rho signaling may have chemopreventative, anti-tumor, and anti-metastatic efficacy. An understanding of how Rho signaling is perturbed in specific stages and subtypes of breast cancer and how it functions in the context of the complex in vivo environment during the stochastic process of tumor formation and progression are necessary in order to effectively target this signaling network for breast cancer treatment.

Narrowband ultraviolet B (UVB) phototherapy in children.

BACKGROUND: While narrowband ultraviolet B (UVB) phototherapy is a well-established treatment for a range of skin conditions in adults, there is little in the literature about its use in children and data regarding its long-term carcinogenic potential are lacking. AIM: We undertook a retrospective review of the use of narrowband UVB phototherapy in a paediatric population attending two Glasgow Hospitals. METHODS: Phototherapy case notes for all children aged 16 years and under at time of treatment were reviewed at two hospital sites between 1996 and 2002. RESULTS: In total, 77 children had been treated (median age 12 years, range 4-16). The conditions treated most frequently were psoriasis (45%) and atopic eczema (32%). Other dermatoses treated included alopecia areata, acne, hydroa vacciniforme and polymorphic light eruption. Treatment courses for atopic conditions were longer than those required for psoriatic conditions: median number of treatments 24 for atopic eczema (range 3-46), and 17.5 for psoriasis (range 9-35). By the end of treatment, 68% of the atopic patients and 63% of the patients with psoriasis had cleared. The adverse event profile was similar to that in adults, with erythema, herpes simplex reactivation and PLE all recorded. Anxiety was a problem for five patients. CONCLUSION: We conclude that narrowband UVB phototherapy is a useful and well-tolerated treatment for children with severe or intractable inflammatory skin disease, but concerns remain regarding long-term side-effects.

Nodular presentation of eosinophilic cellulitis (Wells' syndrome).

Eosinophilic cellulitis is a rare condition of unknown aetiology. The classical presentation is of a tender or mildly pruritic cellulitis-like eruption, that has typical histology characterized by tissue eosinophilia, oedema and "flame" figures. Other reported clinical presentations include papular and nodular eruptions. It may be recurrent, and preceded at a variable time by a pruritic papular eruption. We describe a patient with the rare nodular variant of eosinophilic cellulitis affecting the palms of the hands, which occurred 2 years after a nonspecific pruritic papular eruption, without an obvious precipitant and in the absence of the more typical cellulitis-like plaques.

Nail dystrophy due to lichen sclerosus?

Lichen sclerosus (LS) affects anogenital skin alone in 80% of cases. When extragenital disease occurs, it usually affects the trunk, neck, axillae and wrist flexures. Nail involvement with LS is rare. In contrast, lichen planus (LP) commonly affects extragenital skin. Mucosal lesions occur in 50% of cases, affecting the mouth and genitalia. Nail disease in LP is common, and, if severe, can lead to destruction of the nail bed. LS and LP can coexist. We report two cases of LS with nail involvement. In the Case 1 disease was confined to the nail, and nail biopsy confirmed LS. In the Case 2, the nail changes formed part of the widespread genital and extragenital LS, confirmed histologically. We review existing literature on nail disease in LS and discuss the possible aetiology of the nail changes.

Long-term patient satisfaction with cosmetic outcome of minor cutaneous surgery.

We evaluated our patients' own assessment of the cosmetic outcome of minor dermatological surgery procedures. A postal questionnaire was sent to patients who had undergone surgery between 12 and 18 months previously. Patient satisfaction was correlated with variables, including age, sex, lesion size and site, indication for excision, histological diagnosis and operator. Two hundred and seven excisional procedures were identified in 193 patients. Seventy-nine per cent of the questionnaires (163/207) were returned. Seventy per cent of patients reported that the scar was invisible or better than expected and 9% rated it to be worse than expected. Ninety per cent of patients said they would undergo the procedure again. Patient dissatisfaction was associated significantly and independently with excisions from the back, younger age and benign histology.

Cutaneous manifestations of fucosidosis.

Angiokeratoma corporis diffusum (ACD) is still often thought to be synonymous with Anderson-Fabry disease, a deficiency of alpha-galactosidase. It is important, however, to consider other possible enzyme deficiencies in patients with ACD. We report an 8-year-old boy with neurodevelopmental delay who was diagnosed as having fucosidosis following recognition of ACD in the dermatology department. Other cutaneous features in this patient included distal transverse purple nail bands, acrocyanosis and a naevus anaemicus. Histology and electron microscopy of skin papules was consistent with angiokeratoma. Skeletal survey demonstrated dysostosis multiplex. The diagnosis was confirmed by leucocyte oligosaccharide enzyme analysis. There are only three previous reports of fucosidosis in the U.K.

Interactions with the pharmaceutical industry: a survey of family medicine residents in Ontario.

OBJECTIVE: To determine the attitudes, knowledge and practices of family medicine residents relating to the pharmaceutical industry and to assess the effectiveness of existing guidelines on appropriate interactions with the pharmaceutical industry. DESIGN: Survey by mailed questionnaire. SETTING: Ontario. PARTICIPANTS: All 262 second-year family medicine residents in Ontario (seven centres); 226 (86.3%) responded. RESULTS: Fifty-two (23.0%) of the residents who responded stated that they had read the CMA policy statement on appropriate interactions between physicians and the pharmaceutical industry. A total of 124 (54.9%) stated that they would attend a private dinner paid for by a pharmaceutical representative; the proportion was not significantly reduced among those who had read the CMA guidelines, which prohibit the acceptance of personal gifts. In all, 186 (82.3%) reported that they would like the opportunity to interact with pharmaceutical representatives in an educational setting, even though several programs now discourage these interactions. Approximately three quarters (172/226 [76.1%]) of the residents indicated that they plan to see pharmaceutical representatives in their future practice. Residents at Centre 2 were significantly more critical of the pharmaceutical industry than those from the other centres. Overall, being aware of, and familiar with, departmental policy or CMA policy on interactions with the pharmaceutical industry did not affect the residents' attitudes or intended future practices. CONCLUSION: The presence of guidelines concerning physicians' interactions with the pharmaceutical industry does not appear to have a significant impact on family medicine residents in Ontario.

Assessment of an anti-T-cell receptor variable region antibody panel in cutaneous T-cell lymphoma.

Using a panel of seven commercially available monoclonal antibodies directed against specific sites of the T-cell receptor variable region, we have studied the staining patterns in 15 biopsies from 11 patients with cutaneous T-cell lymphoma (CTCL), and in five patients with benign lymphocytic infiltrates. Eight of the 11 patients with CTCL showed staining of the majority of lymphocytes with either V beta 8 alone (n = 3), V beta 12 alone (n = 2) or with both V beta 8 and V beta 12 (n = 3). None of the biopsies from patients with benign dermatoses showed staining of the majority of lymphocytes with any of the antibodies.

Naevi in schoolchildren in Scotland and Australia.

To test the hypothesis that children living in subtropical and tropical environments have more naevi than those of similar ethnicity living in temperature countries, a comparative study of melanocytic naevi in 111 schoolchildren from Brisbane, Australia, and 222 from Glasgow, Scotland, was carried out. All children were aged 13-15 years, of European ancestry, and had spent most of their lives at latitudes of less than 30 degrees S (Australia) or greater than 30 degrees N (Scotland). Using an identical protocol, all naevi of 2 mm or more in diameter occurring on the right arm were counted by either a highly experienced research nurse in Brisbane, or a dermatologist in Glasgow. Hair and eye colour, and facial freckling, were assessed by the examiner, and axillary skin colour of children in both cities was measured using the same reflectance spectrophotometer. Children in Brisbane had significantly more naevi than those in Glasgow (P < 0.05), after adjusting for complexion variables. The difference in the geometric mean number of naevi on the arm was much greater among boys (7.7 vs. 4.4, in Brisbane and Glasgow, respectively) than among girls (7.3 vs. 6.7). This has parallels with the sex differences in melanoma at later ages in the two countries. Besides country of residence, freckles and innate skin colour were the most significant predictors of large numbers of naevi, whereas red hair had a significant protective effect. Overall, these data on prevalence of naevi in children from contrasting environments provide some evidence in support of the theory that naevus development is related to the level of sun exposure in childhood and adolescence.