Antitumoral activity of rapamycin in renal angiomyolipoma associated with tuberous sclerosis complex.

A 19-year old patient with tuberous sclerosis presented with a renal angiomyolipoma. Because animal trials of tuberous sclerosis showed an effect of rapamycin on renal tumors, our patient was administered rapamycin for 6 months. During this time, the renal angiomyolipoma shrank significantly, regrew during an 8-month period, and decreased in size again after readministration of rapamycin.

[Longitudinal melanonychia induced by hydroxyurea therapy]. / Longitudinale Melanonychie bei Einnahme von Hydroxycarbamid.

UNLABELLED: Four case reports of patients with myeloproliferative syndrome receiving therapy with hydroxycarbamide (synonymous: hydroxyurea) and developing streaky longitudinal pigmentation appeared in fingernails and toenails several months after starting this therapy. BACKGROUND: Pigmentation of finger- and toenails presents a wide range of differential diagnostic considerations. They can be of infectious, melanocytic or exogenous origin or caused by metabolic disorders. PATIENTS AND METHODS: Three women and one man, ranging in age from 62 and 87 years, were treated with hydroxycarbamide for myeloproliferative syndrome or chronic myelogenous leukemia for five to twelve years. All four patients were Fitzpatrick skin types II. RESULTS: Several months after starting this therapy, they developed streaky longitudinal pigmentation of their fingernails and toenails. In two patients, these findings were diagnosed by chance, whereas two patients sought dermatological advice because of nail pigmentation. In two of the patients the longitudinal pigmentation disappeared a few month after discontinuation of hydroxycarbamide. The melanonychia persisted in another patient, while the fourth was lost to follow-up. CONCLUSIONS: When melanonychia is identified in hematology-oncology patients, a careful medical history should be obtained. A list of medications is crucial, since hydroxycarbamide causes nail pigmentation. In each case of nail pigmentation, an acral lentiginous melanoma must be excluded.

In vitro susceptibility testing of four antibiotics against Borrelia burgdorferi: a comparison of results for the three genospecies Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto.

MICs and minimal bactericidal concentrations (MBCs) were evaluated for the four antibiotics azithromycin, amoxicillin, ceftriaxone, and doxycycline against the three main genospecies of Borrelia burgdorferi sensu lato. In MBC testing, statistically significant differences between the genospecies could be found in 7 out of 12 comparative evaluations (P < 0.05).

Loss of expression of tuberin and hamartin in tuberous sclerosis complex-associated but not in sporadic angiofibromas.

BACKGROUND: Angiofibromas occur sporadically, and they develop in most patients with tuberous sclerosis complex (TSC), which is associated with alterations of the tumor suppressor genes TSC1 or TSC2. Loss of tuberin, the protein product of TSC2, has been shown in the interstitial fibroblast compartment of TSC-associated angiofibromas. It is unclear whether there is also a loss of hamartin, the product of TSC1 in TSC-associated and sporadic angiofibromas. METHODS: The expression of hamartin and tuberin was analyzed by immunohistochemistry in 59 TSC-associated and 12 sporadic angiofibromas using affinity-purified antibodies. RESULTS: Loss of expression of both tuberin and hamartin was detected in 14 angiofibromas, loss of only tuberin in three, and loss of only hamartin in four TSC-associated angiofibromas; but there was no loss in the sporadic angiofibromas. Only the interstitial cells, but not the vascular cells, showed a loss of expression of tuberin or hamartin. CONCLUSIONS: Loss of tuberin or hamartin occurred in a minority of the TSC-linked angiofibromas, but not in the sporadic angiofibromas. The absence of both tuberin and hamartin in some of the tumors suggests that the stability of tuberin and hamartin, which are believed to form an active complex in vivo, is negatively affected by the absence of either of the partners.

Reduction of expression of tuberin, the tuberous-sclerosis-complex-gene-2 product in tuberous sclerosis complex associated connective tissue nevi and sporadic squamous and basal cell carcinomas.

BACKGROUND: Patients affected with tuberous sclerosis complex (TSC) are prone to the development of multiple benign tumors of the skin and other organs. Tuberin, the protein product of the tuberous-sclerosis-complex-2 tumor suppressor gene (TSC2) has been shown to inhibit cell proliferation. In TSC associated kidney tumors and sporadic brain tumors the loss/reduction of tuberin has been shown. METHODS: Specimens of nine squamous cell carcinomas (SCC) and five basal cell carcinomas (BCC) from patients without TSC and six biopsies of connective tissue nevi (CTN) of patients with TSC were obtained. Specimens were analyzed by immunoblotting for the expression of tuberin. RESULTS: Absent or reduced levels of tuberin were detected in the dermal parts of three of six shagreen patches, two of five BCC, and four of nine SCC. CONCLUSIONS: In tumors/hamartomas of patients with TSC the complete loss of TSC2 and tuberin is a mechanism which could be shown for CTN, thereby excluding the possibility of haploinsufficiency of TSC2. In a substantial number of cutaneous BCC and SCC the loss or downregulation of tuberin seems to be epigenetic, as alterations of TSC2 are not known in these tumors. The absence or reduction of tuberin might contribute to their proliferation.