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Biomedical subjects

P Kaskel

Publications and source records attributed to P Kaskel.

29 records · Page 2Linked to original sources

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↗

S-100 protein in peripheral blood: a marker for melanoma metastases: a prospective 2-center study of 570 patients with melanoma.

BACKGROUND: S-100 protein, commonly used in the immunohistochemical diagnosis of malignant melanoma and melanoma metastases, has recently been introduced as a tumor marker in peripheral blood. OBJECTIVE: This prospective, observational, 2-center study evaluates S-100 in peripheral blood of patients with melanoma as a marker for metastasis. METHODS: With application of an immunoluminometric assay, S-100 levels in 1396 samples of 570 patients with melanoma and 53 control subjects were measured in a blinded manner. RESULTS: The cut-off level for patients with melanoma without medical history of metastases versus patients with newly occurring lymph node, visceral, and/or brain metastases was 0.114 microg/L, with a sensitivity of 94% (95% confidence interval, 86.4%-98.5%) and a specificity of 91% (95% confidence interval, 87.7%-93.6%). False-negative results included patients with unknown primary melanoma and those with amelanotic melanoma metastases. CONCLUSION: The data suggest that S-100 in the peripheral blood of patients with melanoma could serve as a marker indicating new melanoma metastases and could help to monitor the course of the disease.

Adolescent↗

Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: a genetic model of meningioma progression.

To investigate chromosomal events that underlie formation and progression of meningiomas, we have examined a set of 18 benign (WHO grade I), 15 atypical (grade II), and 13 anaplastic/malignant (grade III) meningiomas for loss of heterozygosity (LOH) on chromosomes 1p, 6p, 9q, 10q, and 14q. Frequent loss of loci on these chromosomes was seen in grade II and grade III tumors, specifically, 14q (II and III, 47 and 55%), 1p (40 and 70%), and 10q (27 and 40%). In contrast, LOH for these loci was infrequent in benign meningiomas, specifically, 14q (0%), 1p (11%), and 10q (12%). The smallest common regions of deletion that could be defined were 14q24-q32, 1p32-pter, and 10q24-qter. These observations indicate the likely presence of tumor suppressor genes in these regions that are involved in the development of WHO grade II and grade III meningiomas. Because LOH for loci on chromosomes 1p and 10q was found in tumors of all grades and because the frequency of LOH in all three regions increased with tumor grade, these results would support a model for the formation of aggressive meningiomas through tumor progression.

Adult↗

Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma.

Loss of heterozygosity (LOH) in specific chromosomal regions, which are likely to harbor tumor suppressor genes, has been associated with human gliomas. In this study we have analyzed astrocytic and oligodendroglial tumors for LOH on chromosomes 1 and 19. By microsatellite analysis LOH was found on chromosome arm 1p in 6/15 oligodendrogliomas WHO grade II and III, 12/25 oligoastrocytomas WHO grade II and III, 6/79 glioblastomas WHO grade IV, 5/44 astrocytomas WHO grade II and III and 0/23 pilocytic astrocytomas WHO grade I. The high incidence of LOH on chromosome arm 1p in oligodendrogliomas and oligoastrocytomas indicates that a putative tumor suppressor gene in this region is involved in the formation of gliomas with oligodendroglial features. Furthermore, the frequent involvement of chromosome arm 1p in oligodendrogliomas and oligoastrocytomas, but not in astrocytomas, suggests that genetically oligoastrocytoma is more similar to oligodendroglioma than to astrocytoma. In order to support this hypothesis, oligodendroglial and astrocytic areas in three mixed oligoastrocytomas were examined differentially for LOH 1p and for LOH 19q, the second genetic region believed to be affected in these tumors. All three tumors had LOH of 1p and LOH of 19q in both areas of oligodendroglial and of astrocytic differentiation. These findings show that the astrocytic and oligodendroglial portions of oligoastrocytoma share molecular genetic features and probably are of monoclonal origin.

Alleles↗

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↗

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↗