Treatment of Early Folliculotropic Mycosis Fungoides with Special Focus on Psoralen plus Ultraviolet A

Data on the treatment of early folliculotropic mycosis fungoides, a recently defined clinicopathological subgroup of folliculotropic mycosis fungoides with an indolent course, is limited. Treatment outcomes were studied in a retrospective cohort of 47 adults with early folliculotropic mycosis fungoides, with a focus on psoralen plus ultraviolet A (PUVA) monotherapy, including dosimetric data, and the findings were compared with data for PUVA in 18 adults with early-classic mycosis fungoides. PUVA was given to 27 patients with early folliculotropic mycosis fungoides: 70% achieved complete response and 26% partial response. Significantly more treatments were needed to achieve complete response in stage IB compared with stage IA. There was no significant difference in the complete response rate from classic plaque-stage disease, although the early folliculotropic mycosis fungoides group required more treatments to achieve complete response, and a higher cumulative dose of UVA. Thus, PUVA is an effective treatment for early folliculotropic mycosis fungoides. Its complete response rate might be equal to early-classic mycosis fungoides; however, a longer induction phase is needed to achieve complete response

Cutaneous B-cell neoplasms mimicking granulomatous rosacea or rhinophyma

BACKGROUND: Unlike T-cell neoplasms, B-cell lymphoproliferative disorders have a limited clinical spectrum of skin involvement. Cutaneous B-cell neoplasms mimicking rosacea or rhinophyma are rare. OBSERVATIONS: We described 12 patients with B-cell lymphoproliferative neoplasms presenting with a facial eruption clinically mimicking rosacea or rhinophyma. Eleven patients were women; ages ranged from 36 to 81 years. The clinical presentation included small papules on the nose and cheeks and around the eyes mimicking granulomatous rosacea; nodules on the nose, cheeks, chin, or forehead mimicking phymatous rosacea; or a combination of both. Three patients had preexisting erythematotelangiectatic rosacea and 1 had rhinophyma. Based on a clinicopathologic correlation and B-cell clonality analysis, the diagnosis was primary cutaneous follicular center B-cell lymphoma in 4 cases, primary cutaneous marginal zone lymphoma in 6, and skin involvement of chronic lymphocytic leukemia in 2. All patients had an indolent course as expected for their disease. CONCLUSIONS: Cutaneous involvement of B-cell neoplasms may mimic granulomatous rosacea or rhinophyma. This unusual clinical presentation is more common in women and appears in the setting of preexisting rosacea or as a new eruption. Proliferative B-cell disorders should be added to the differential diagnosis of symmetric papular or papulonodular eruptions of the face

MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma.

Neuroblastoma (NB) arises from the embryonic neural crest and is the most common extracranial solid tumor in children under 5 years of age. Reduced expression of Dicer1 has recently been shown to be in correlation with poor prognosis in NB patients. This study aimed to investigate the mechanisms that could lead to the down-regulation of Dicer1 in neuroblastoma. We used computational prediction to identify potential miRs down-regulating Dicer1 in neuroblastoma. One of the miRs that were predicted to target Dicer1 was miR-192. We measured the levels of miR-192 in 43 primary tumors using real time PCR. Following the silencing of miR-192, the levels of dicer1 cell viability, cell proliferation and migration capability were analyzed. Multivariate analysis identified miR-192 as an independent prognostic marker for relapse in neuroblastoma patients (p=0.04). We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288. An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic. Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression

Site-directed mutagenesis of miR-192 binding sites on 3' UTR of Dicer1.

<div><p>Three mutations were introduced into the three potential binding sites of miR-192 on 3' UTR of pI DICER1 using Multi Site-Drected Mutagenesis Kit .</p> <p>The nucleotides that were mutated are circled and were changed to the nucleotides in bold. </p></div

3′UTR of Dicer 1 is directly targeted by miR-192.

<div><p>The dual luciferase assay detected that Dicer1 is modulated by miR-192 in NB cell lines. The relative luciferase unit (RLU) was measured in SHEP (A) or NUB (B) cells.</p> <p>A. The dual-luciferase assay resulted in a significant reduction of RLU of WT Dicer1 (3' UTR of Dicer1 wild type) following transfection with miR-192-vec (*p=0.049).</p> <p>B. Following transfection with miR-192 mimic, WT Dicer1 RLU was significantly decreased (*p=0.0003). Following mutagenesis, cells were transfected with Dicer1 plasmid in which mutations were introduced in all three BSs of Dicer1 (MUT ALL); active BS1 (mutated at BS2+BS3)(* p=0.004); active BS2 (mutated at BS1+BS3) (* p=0.04) and active BS3 (mutated at BS1+BS2). </p> <p>Values are expressed as the mean ± SE of combined results from three independent experiments. </p></div

Kaplan Meier analysis by miR-192 expression.

<p>Kaplan Meier analysis for PFS by miR-192 expression: high and low miR-192 expression levels were determined as above or below the median expression level and were analyzed in (A) a whole cohort (n=43) and in (B) a cohort following exclusion of MYCNA (n= 36) .</p

miR-192 regulates Dicer1 protein expression.

<div><p>A. Dicer1 protein expression in NUB6 cells, as evaluated by Western blotting, after exposure to miR-192.</p> <p>B. Graphic illustration of relative Dicer1 protein levels (normalized to tubulin) in Nub6 cells following transfection with miR-192 mimic (*p=0.04) and inhibitor.</p> <p>Data are presented as means ± SE of three independent experiments.</p></div