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Biomedical subjects

U Leiter

Publications and source records attributed to U Leiter.

16 recordsLinked to original sources
PubMed2001

Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases.

Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 alpha-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266-4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma.

Adolescent↗
PubMed2001

Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer.

The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), HER2, HER3 and HER4 are involved in the pathogenesis of multiple human malignant neoplasias. However, their role in the carcinogenesis of basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) remains to be elucidated. In order to further define the role of these RTKs, 56 human skin tissue samples of normal skin, BCC and SCC were studied by conventional and differential and quantitative reverse transcriptase-polymerase chain reaction (rtPCR). EGFR and HER3 were predominantly expressed in the BCCs and SCCs, while HER2 was ubiquitously expressed. HER4 was not expressed in any sample. Since in vitro studies have provided compelling evidence that heterodimer formation of these receptors are associated with different signal transduction processes, coexpression patterns might be decisive for the induction and maintenance of a malignant phenotype. These results confirm this concept: isolated HER2 expression and EGFR/HER2 were predominantly found in normal skin, while HER2/HER3 and the triple expression of EGFR/HER2/HER3 were seen more frequently in the BCCs and SCCs compared with normal skin (50% and 40% compared with 26%, respectively). The activation of HER3, in addition to EGFR and HER2, might therefore be associated with the malignant phenotype. However, due to the small numbers in this study, further confirmation of the patterns is needed.

Biopsy↗
PubMed2001

UVB-induced decrease of p16/CDKN2A expression in skin cancer patients.

The lack of p16 expression has been shown in cultured melanoma cells, however contradictory evidence for p16 expression in melanoma tissues exist. Ultraviolet (UV) C and UVB have been shown to affect p16 expression, which impairs cell cycle regulation in vitro and in vivo. In this study, p16/CDKN2A gene expression was determined by reverse transcription polymerase chain reaction in seven skin cancer patients, in one dysplastic nevus patient and in seven healthy individuals, prior to UVB exposure and at various times after application of one minimal erythema dose (MED). Five of the seven skin cancer patients showed a down-regulation of p16/CDKN2A expression after UVB exposure, while controls remained unaltered. The UVB-induced decline of p16/CDKN2A in skin cancer patients might offer new insights into photocarcinogenesis. The putative sequence of events could start with a down-regulation of p16/CDKN2A expression, which would lead to impaired cell cycle regulation. Altered expression patterns of p16/CDKN2A following UVB exposure could be of value for identifying people with an increased risk of UV-induced skin cancer.

Adolescent↗
PubMed2001

The PUVA-turban as a new option of applying a dilute psoralen solution selectively to the scalp of patients with alopecia areata.

BACKGROUND: Alopecia areata is a burden for many patients and often resistant, even to extensive therapy. Orally administered PUVA therapy has been shown among numerous systemic and topical treatment modalities to be a therapeutic alternative. However, the clinical use of oral PUVA is often limited by systemic side effects. Bath-PUVA therapy offers an alternative solution because of the negligible systemic absorption of psoralen with this technique. Through use of a "PUVA-turban" it is now possible to administer a dilute bathwater solution containing 8-methoxypsoralen (8-MOP) to the scalp. OBJECTIVE: The purpose of this study was to determine whether PUVA turban therapy is effective in treating alopecia areata in different clinical stages. METHODS: We treated 9 patients with severe, rapidly progressing, treatment-resistant alopecia areata with PUVA-turban treatment as a modification of bath-PUVA therapy. At each treatment session a cotton towel was soaked with a 0.0001% 8-MOP solution (1 mg/L) at 37 degrees C, wrung gently to remove excess water, and wrapped around the patient's head in a turban fashion for 20 minutes. This was directly followed by UVA radiation. Treatment sessions were initially performed 3 to 4 times per week. RESULTS: The cumulative UVA doses given over treatment periods of up to 24 weeks were 60.9 to 178.2 J/cm(2), with single doses ranging from 0.3 to 8.0 J/cm(2). After up to 10 weeks of treatment, hair regrowth could be noticed in 6 of 9 patients. Two patients did not respond to the treatment, and one patient showed only vellus hair regrowth. CONCLUSION: PUVA-turban therapy can be considered a useful method of administering a dilute psoralen solution selectively to the scalp of patients. It has been shown to be a well-tolerated and, in some patients, efficient therapeutic alternative in the treatment of alopecia areata.

Administration, Topical↗
PubMed2000

Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma.

Apoptosis is an important cofactor in the pathogenesis of a plethora of malignancies. However, little is known about modulation of the expression of bcl gene family in melanocytic tumors. To determine the role of bcl-2, bcl-x and bax in melanocytic tumors we investigated the differential expression of these genes via RT-PCR in tissue samples from human benign nevi, primary melanomas and melanoma metastases in comparison with normal skin. Bcl-2 was strongly expressed in 14/16 metastases (87.5%), whereas only 7/13 primary melanomas (53%), 7/15 nevi (46%) and 7/16 normal tissue samples (43%) showed expression of bcl-2 (P < 0.05). There was a strong indication of a correlation between tumor thickness and bcl-2 expression in nodular malignant melanomas. Expression of bcl-x was found in 16/16 melanoma metastases (100%), 11/13 primary melanomas (84%), 12/15 nevi (80%) and 10/16 normal tissue samples (62%) (P < 0.05). Bcl-xL expression increased from primary melanoma to melanoma metastases, whereas bcl-xS showed a decreasing expression level during melanoma progression. No differences in bax expression were seen between melanoma metastases, primary melanoma, nevi and normal tissue. Immunohistochemical investigations of another 53 tissue samples showed similar results. Our results strongly indicate that bcl-2 and bcl-xL gene expression increases with progression of malignant melanoma. Bcl-2 and bcl-xL expression could reflect an increased malignant potential caused by an inhibition of apoptosis and growth advantage for metastatic melanoma cells.

Apoptosis↗
PubMed2000

Quantitation of herpes simplex DNA in blood during aciclovir therapy with competitive PCR ELISA.

BACKGROUND: Monitoring viral load in blood has already been introduced into clinical routine for human immunodeficiency virus and hepatitis C virus. OBJECTIVE: This study was conducted to monitor the decline of herpes simplex (HSV) viral load in the blood of a patient with gingivostomatitis herpetica prior and during acyclovir therapy. METHODS: Analysis was done by quantitative PCR ELISA using an internal quantitation standard. RESULTS: Copy numbers were 66/microl blood prior to therapy, 60 during oral medication with valaciclovir, 97 and 72 copies/microl blood during the first 2 days of intravenous acyclovir therapy, followed by a sharp decline to 8 and 9 copies on days 3 and 4. During the following days, HSV was no longer detectable. CONCLUSION: As this quantitative approach can be easily adjusted to any other PCR, it provides a reliable, easy-to-apply method for monitoring therapy, also during new antiviral clinical trials.

Acyclovir↗
PubMed1999

Mycophenolate mofetil: a new therapeutic option in the treatment of blistering autoimmune diseases.

BACKGROUND: Mycophenolate mofetil (MMF), an ester of mycophenolic acid (MPA), was approved by the Food and Drug Administration in 1995 and is currently primarily indicated for the prophylaxis of rejection in renal transplant patients. The drug seems also to be of value in the treatment of psoriasis and rheumatic arthritis. Recently there have been 6 reported cases of successful treatment of blistering autoimmune diseases with MMF in combination with high dose prednisone therapy. OBJECTIVE: On the basis of these reports we administered this new treatment regimen to several patients with blistering autoimmune diseases. Besides using a combination of MMF and high-dose prednisone we wanted to evaluate whether MMF monotherapy is also effective in the treatment of blistering autoimmune diseases. METHODS: We administered MMF to 5 patients who had severe pemphigus vulgaris or bullous pemphigoid. Two patients received MMF in combination with high-dose prednisone therapy and 3 patients received MMF monotherapy. To our knowledge, this is the first report of successful treatment of pemphigus vulgaris and bullous pemphigoid with MMF monotherapy. RESULTS: All patients were completely free of symptoms within 8 to 11 weeks of therapy. Patients who had received MMF monotherapy responded as well to treatment as those who received a combination of MMF and high-dose prednisone. CONCLUSION: Our experiences strongly suggest that MMF monotherapy may be effective for patients even with severe pemphigus vulgaris and bullous pemphigoid. In addition, MMF monotherapy, at least over the short term, offers the advantage of fewer side effects in comparison to immunosuppressive combination therapy and was well tolerated by our patients.

Aged↗
PubMedDate not supplied

Soluble p185/her2 and S100 in yolk sac blood from human melanoma metastases xenotransplanted to chick embryo chorioallantoic membrane.

BACKGROUND: The chorionallantoic membrane (CAM) of the chick embryo has been used as an experimental model for studying tumor invasion and metastasis of human malignant melanoma. In search for a model to show graft-host-interactions in vivo, tumor markers in peripheral blood of the host were investigated. MATERIALS AND METHODS: Before collecting melanoma metastasis xenografts, blood samples were taken from CAM and a control group. S100 and sp185/her2 in peripheral blood were evaluated in a blinded manner. RESULTS: 23/28 samples deriving from successfully performed human melanoma metastasis CAM xenografts were positive for S100 versus 2/22 samples for sp185/her2. CONCLUSION: Regarding melanoma, in this model sp185/her2 gave no additional information. S100 levels corresponded to clinical and immunohistological findings concerning adherence of tumors and extravasation of human melanoma cells. Based on these data S100 levels in the peripheral blood could help to determine the effect of exogenous stimuli such as radiation and therapeutic agents on metastatisation of the xenografts.

Animals↗
PubMedDate not supplied

S100 beta is a more reliable tumor marker in peripheral blood for patients with newly occurred melanoma metastases compared with MIA, albumin and lactate-dehydrogenase.

Lactate-dehydroxynase (LDH) has been described as a leading blood parameter in patients with melanoma metastases. However, recent data indicates that levels of S100 as well as melanoma inhibiting activity (MIA) in peripheral blood, correlate with melanoma progression. The aim of this study was to evaluate tumor markers S100, MIA, LDH and albumin in peripheral blood of 373 melanoma patients. 284 patients presented with in-situ or UICC stage I/II, and 89 with stage III/IV (54 tumor-free, 29 with newly occurred metastases). For newly occurred metastases, sensitivity was highest for S100 in peripheral blood (0.86), followed by MIA (0.80), LDH (0.48), and albumin (0.15). Specificity for albumin (0.99) and LDH (0.98) was higher than for S100 (0.91) and MIA (0.62). This data indicate that S100 in peripheral blood as compared to MIA, LDH and albumin appears to be the most appropriate tumor marker for newly occurred melanoma metastases.

Albumins↗