Imre Veres

Activation of Notch1 signaling is required for β-catenin–mediated human primary melanoma progression

Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by beta-catenin, which was upregulated following Notch1 activation. Inhibiting beta-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a beta-catenin-dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma.

Correlation among metallothionein expression, intratumoural macrophage infiltration and the risk of metastasis in human cutaneous malignant melanoma

Background  The formation of metastases and the efficacy of systemic therapies in cutaneous malignant melanoma (CMM) depend on the characteristics of the tumour cells and the host immune response. Aberrant expression of metallothionein (MT) has been observed in several types of cancers with poor prognoses.

Sebocytes differentially express and secrete adipokines.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte‐associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol‐binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease‐affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll‐like receptor (TLR)2 and 4 activators], or by 13‐cis retinoic acid (13CRA; also known as isotretinoin), a key anti‐acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines.

Cutaneous cryptococcosis mimicking basal cell carcinoma in a patient with Sézary syndrome

Cryptococcosis is an opportunistic yeast infection that is the most common systemic fiangal infection in immunocompromised patients. Skin involvement is a feature in 10-20% of cases of disseminated cryptococcal infection (1). We report here a case of a 63-year-old woman with Sézary syndrome (T4, N3, MO, Bl) with an ulcerated preauricular tumour that developed during photopheresis with a combination of methotrexate and steroid treatment. We highlight the importance of differential diagnosis of cryptococcosis in the case of any atypical or non-healing lesions observed in an immunosuppressed patient.

Sporotrichoid Cutaneous Mycobacterium Tuberculosis Infection in a Child

Eva Remenyik, Bela Nagy, Maria Kiss, Imre Veres, Monika Sapy, Iren Horkay, Iren Erdei and Janos Hunyadi Departments of Dermatology and, Pediatrics, University of Debrecen, Medical and Health Science Center, University of Debrecen, Nagyerdei korut 98, HU-4012 Debrecen, Hungary and Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. E-mail: remenyik@jaguar.dote.hu Accepted December 22, 2004.

Nijmegen breakage syndrome complicated with primary cutaneous tuberculosis

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosomal instability syndrome characterized by severe immunodeficiency, growth retardation, microcephaly, a distinct facial appearance, and a high predisposition to lymphoid malignancy. We report a 7-year-old white girl with NBS associated with cutaneous tuberculosis. The patient presented with multiple red-brown, centrally scaring plaques on the leg and had neither pulmonary nor systemic manifestation of tuberculosis. Polymerase chain reaction testing using Mycobacterium genus- and Mycobacterium tuberculosis species-specific primers confirmed the clinical diagnosis of cutaneous tuberculosis. This is the first report describing the simultaneous presentation of NBS and cutaneous tuberculosis.

Muir-Torre syndrome : A case of two brothers

Introduction Patient 1 (56 y.o. younger brother of two) first presented with tiny skin tumors at the age of 49 years. Excisions revealed two basal cell cancers, one squamous cell cancer and two sebaceous adenomas. The possibility of Muir–Torre syndrome (MTS) was raised. Tumor search revealed elevated serum prostate-specific-enolase. Prostate biopsy proved prostate cancer, and prostatectomy was performed. His relatives were examined as well. Both of his sisters had gynecologic tumors removed previously, and none had suspicious lesions on their skin. Their mother died of gynecologic cancer. The elder brother (Patient 2, 58 years old) had hemicolectomy at the age of 51 years owing to adenocarcinoma. At first examination we found tumors on his back and face. Histopathology confirmed sebaceous hyperplasia, sebaceous carcinoma and two basal cell carcinomas. During follow up of the male siblings further skin excisions resulted in various histological diagnoses (see Table 1). Sebaceous adenomas appeared as skin-colored papules with central depression (Fig. 1a). Orthokeratotic, dilated follicles with numerous nucleoli and lack of sebum were well-separated from intact areas (Fig. 2a). Non-differentiated germinative cells of the significantly thickened basal layer showed mild atypia, but no divisions, indicating a poorly differentiated but predominantly benign tumor. Sebaceous epitheliomas were clinically shiny, scaly hyperaemic tumors (Fig. 1b). Histology showed irregular lobular pattern, scattered non-differentiated clear cells with cytological atypia (> 50% of cells were basaloid cell type) (Fig. 2b). This entity could be distinguished from sebaceous adenoma by the level of sebaceous gland differentiation. Sebaceous carcinomas were poorly demarcated, asymmetrical, sometimes ulcerated, solid tumors with irregular border (Fig. 1c). Histology showed ulcerations and deep penetrating tumor cell nests obliterating the normal structure of a sebaceous gland (Fig. 2c). Higher magnification revealed immature, pleiomorphic dividing cells (Fig. 2d). According to our department’s protocol, patients are checked regularly at 6-month intervals.