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Biomedical subjects

C Garbe

Publications and source records attributed to C Garbe.

At least 145 records · Page 8Linked to original sources
PubMed1995

Kaposi's sarcoma: a reevaluation.

Kaposi's sarcoma (KS) is a multicentric neoplasia of microvascular origin arising during development of immunodeficiency in human immunodeficiency virus (HIV)-infected individuals. More than 130 patients with HIV-associated KS (98% male homosexuals; median age, 35 years) have been diagnosed at the Department of Dermatology, University Medical Center Steglitz, Berlin, during the years 1982-1992. Mucocutaneous and visceral involvement was a common finding in patients with HIV-associated KS, increasing from 39% at the first visit to 65% at the last observation. In 90% of the patients significant immunosuppression was found (75% had a CD4+ count < 200/mm3) at the time of first diagnosis. However, immunosuppression was not a prerequisite for the development of KS, since the tumor had been diagnosed before severe immunosuppression was present in about 10% of the patients. Significant prognostic predictors for the final outcome were: (a) the degree of immunosuppression, (b) the presence of mucosal and visceral manifestation, and (c) the past history of opportunistic infections. The median survival time was 28 months in KS patients with more than 300 CD4+ lymphocytes (n = 18), but only 14 months in immunosuppressed (less than 300 CD4+ lymphocytes) individuals with KS (n = 70). The median survival time in the entire group evaluated (n = 89 patients) was 17 months after first diagnosis. In 71 HIV-infected individuals who died at the Berlin Department during the last 8 years, disseminated KS was the major direct or indirect cause of death (49% of cases). Therapeutic benefit for KS patients was observed after long-term administration of recombinant interferon alpha (rIFN-alpha; 9-18 million IU s.c. every 2 days) alone or combined with antiretroviral drugs such as zidovudine over several months. Prolongation of survival was found after such treatment modalities in 30%-40% of treated patients. Bleomycin and vincristine and other systemically used cytostatics have also been applied with moderate results. The etiology of HIV-associated KS is still unknown and coinfection with herpes simplex virus (HSV), cytomegalovirus (CMV), or human papillomavirus (HPV) as well as certain growth-stimulating cytokines (transforming growth factors, TGF; tumor necrosis factor alpha, TNF-alpha; interleukin-6, IL-6; tat; vascular endothelial growth factors, VEGF; oncostatin M) produced by HIV-infected cells may be cofactors. Overall, KS was found to be a tumor with high malignant potential, and the median survival times were short.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

[Multicentric reticulohistiocytosis and myelodysplastic syndrome].

Multicentric reticulohistiocytosis (MRH) is a rare disorder of skin and joints, and its aetiology is unknown. We describe a male patient who had first developed osteoblastic lesions of the skeleton in 1976 at the age of 59 years. Three years later, he presented with multiple papular and nodular skin lesions, predominantly on the limbs and upper trunk, and 4 years later he developed painful arthropathy. In 1988 skin examination showed multiple brownish-red papulo-nodules, some of which, at mechanically stressed areas, were ulcerated. The patient complained of pronounced arthrotic disorders with reduced joint mobility. Examination of biopsy specimens from active skin lesions demonstrated extensive numbers of macrophages with partial confluence to giant cells with typical ground-glass cytoplasm. Electron microscopy revealed phagocytosis of collagen-like-structures. Examination of bone marrow biopsy specimens revealed diffuse infiltration by histiocytic cells. The diagnosis made was therefore MRH. The patient was treated for several years with different therapeutic regimens, including azathioprin, dapsone, prednisolon, chlorambucil and cyclophosphamide, and complete remission of skin lesions and of bone marrow infiltration was observed. However, a myelodysplastic syndrome with refractory anaemia and ring sideroblasts developed, which is generally understood to be a preleukaemic condition. Myelodysplastic syndromes commonly develop between 3 and 10 years after the start of a therapy with antineoplastic agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Position and recommendations of the Malignant Melanoma Committee of the German Society of Dermatology on diagnosis, treatment and after-care of malignant melanoma of the skin. Status 1993/94].

The Melanoma Committee of the German Dermatological Society has prepared this position paper on prognostic factors, classification and clinical staging of cutaneous malignant melanoma and has recommended guidelines for diagnosis, treatment and follow-up. The aim is to achieve a consensus procedure for dealing with this tumour.

Aftercare↗
PubMed1994

[Long-wave ultraviolet radiation (UVA) and skin cancer].

Ultraviolet light is frequently used for cosmetic tanning of the skin. UV light is known to be carcinogenic, but this is attributed predominantly to short-wavelength UV radiation (UVB). However, new data indicate a carcinogenic role for long wavelength ultraviolet light (UVA) also. In vitro studies have demonstrated DNA-damaging effects of UVA. In animals squamous cell carcinomas and melanomas were induced by UVA alone or in combination with UVB. Reference to a possible carcinogenicity of UVA may also be derived from the therapeutic application of UVA together with psoralens (PUVA). In addition, recent epidemiological studies have associated the use of sunbeds with the development of malignant melanoma. In conclusion, the carcinogenicity of UVA in humans cannot be ruled out, but requires further validation. Long and repeated UVA exposure should be discouraged, because of the far-reaching risks involved.

Animals↗
PubMed1994

[HIV-associated dermatoses and their prevalence in 456 HIV-infected patients. Relation to immune status and its importance as a diagnostic marker].

Some 456 patients with HIV-associated skin disorders were documented in the HIV follow-up clinics at the Department of Dermatology, University Medical Center Steglitz, Berlin, during the years 1982-1992. Males comprised 91% of the patients. The most important risk groups for HIV infection were homosexual and bisexual men (77.9%) and individuals with intravenous drug abuse (12.7%). The most frequent dermatological diagnoses were oral candidosis (44.5%), seborrhoeic dermatitis (38.6%), folliculitis (32.9%) and Kaposi's sarcoma (23.5%). Altogether, 138 of the patients died during the time of observation. The most frequent cause of death was disseminated Kaposi's sarcoma (26.8%). A significant proportion of the patients developed skin diseases before significant reduction of the circulating CD4+ lymphocytes. In a still satisfactory immune situation, predominantly infections of the skin with dermatophytes (tinea), human papilloma viruses (warts) and bacteria (pyodermas) were observed. A considerable number of the HIV patients who developed zoster were also still in a favourable immune status; another 50% of these cases, however, developed the disease with reduced CD4+ lymphocyte count (< 300/microliters). Skin manifestations that tended to occur later in the course of HIV infection were oral candidosis, oral hairy leukoplakia, herpes genitoanalis, mollusca contagiosa and Kaposi's sarcoma, in spite of their early appearance in some cases. In the large majority of these patients the immunological parameters were already clearly reduced. Fungal, bacterial and viral infections of the skin, especially with extended skin involvement, may manifest themselves during the early phases of HIV infection. The number and severity of the skin manifestations increase with progressing immunosuppression, and treatment is often a difficult challenge for the dermatologist.

AIDS-Related Opportunistic Infections↗
PubMed1994

Expression of interleukin 10 in human melanoma.

The expression of interleukin 10 (IL-10) mRNA in human malignant melanoma was investigated by reverse transcriptase polymerase chain reaction analysis. Selective expression of IL-10 mRNA in tissues of primary melanomas and melanoma metastases was found in comparison with normal skin. In addition, strong expression of IL-10 mRNA and of biologically active IL-10 was detected in 3 out of 13 melanoma cell lines. Normal melanocytes consistently expressed low levels of IL-10 mRNA but did not produce detectable IL-10 protein, nor did keratinocytes or fibroblasts. The production of biologically active IL-10 by melanoma cell lines suggests that IL-10 mRNA in melanoma lesions may derive at least in part from the tumour cells themselves. Tumour-infiltrating cells, however, could also be a source of IL-10 in melanoma tissues. The presence of IL-10 in melanoma lesions may contribute to the postulated 'paralysis' of an anti-melanoma immune response.

Gene Expression↗
PubMed1994

Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society.

Different pigmentary characteristics as well as different parameters of sun exposure have previously been identified as risk factors for developing cutaneous melanoma. The aim of the present study was to identify significant risk factors, determine the related magnitude of their estimated relative risks, and define criteria for the detection of persons at risk. Five hundred thirteen melanoma patients and 498 controls matched for age and sex underwent a whole-body examination for the number and type of melanocytic lesions and were interviewed on ultraviolet exposure and other potential risk factors. The total number of common melanocytic nevi on all body sites represented the most important risk factor in multiple logistic regression analysis with a relative risk of 7.6 for subjects with more than 100 versus no more than 10 melanocytic nevi. Other significant independent risk factors were the number of atypical melanocytic nevi (relative risk, 6.1 for at least 5 melanocytic nevi versus none), the number of actinic lentigines (relative risk, 3.5 for many versus none), hair color, skin type, and reported melanocytic nevus growth. No single parameter of sun exposure was significantly related to melanoma risk in the multivariate analysis. Groups with an estimated relative risk between 1 and 121.0 were distinguished by considering common and atypical melanocytic nevi as well as actinic lentigines as the decisive criteria. In conclusion, even without any information on the case history, whole-body examination and diagnosis of pigmented lesions was found to be an effective strategy for identifying persons at risk of developing melanoma. Furthermore, clinical recognition of at least 5 atypical melanocytic nevi without histologic examination is a key for identifying subjects at high risk.

Adult↗
PubMed1994

Associated factors in the prevalence of more than 50 common melanocytic nevi, atypical melanocytic nevi, and actinic lentigines: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society.

Several case-control studies identified common and atypical melanocytic nevi as major risk indicators for the development of cutaneous melanoma. The present investigation was planned to detect factors associated with the prevalence of these melanoma risk markers. Whole-body examination findings and interview data of 513 melanoma patients and 498 age- and sex-matched control subjects were analyzed. Existence of more than 50 common melanocytic nevi and the presence of atypical melanocytic nevi were significantly related to age and gender, with significantly elevated relative risk for their prevalence before the age of 60 and in males. Additionally, sunburns before the age of 20 were significantly associated with both more than 50 common melanocytic nevi (relative risk = 1.7) and the presence of atypical melanocytic nevi (relative risk = 1.5). Actinic lentigines were found more frequently with increasing age, and the presence of actinic lentigines was significantly related to a tendency of freckling in adolescence (relative risk = 2.0) and to two or more sunburns after the age of 20 (relative risk = 1.6). In conclusion, sunburns before the age of 20 contribute to the development of multiple melanocytic nevi and atypical melanocytic nevi. In adulthood, this type of sun exposure is associated with the development of actinic lentigines. The relative risk of developing cutaneous melanoma increases in association with the development of these benign melanocytic lesions.

Adolescent↗
PubMed1994

P53 mutation and c-fos overexpression are associated with detection of the antigen VLA-2 in human melanoma cell lines.

In this study, we examined the expression of c-fos, c-myc, mutant c-Ha-ras and mutant p53 proteins in three normal human melanocyte cell lines and the following 12 melanoma cell lines: M5, Mewo, A375, Bro, Mel 2a, O-Mel II, IgR 39, SkMel-13, -19, -28 Mel-57 and NKI-4, using an immunohistochemical assay (APAAP). An effort was made to correlate oncogene expression with growth parameters, differentiation antigens (HMB-45, vla-2, k.1.2.58, HLA-DR, HLA-I), and pigmentation. All melanocyte cell lines were negative for the oncogenes examined, whereas six of the melanoma cell lines were found also positive (three for c-fos, two for c-myc, one for c-Ha-ras, and four for p53). Three melanoma cell lines expressed one oncogene and three the combination c-fos/p53. These three melanoma cell lines were positive for the "late" tumor progression marker A. 1.43 (vla-2 adhesion molecule) and negative for the differentiation marker k. 1. 2. 58. Positivity for A. 1. 43 combined with negative staining for k. 1. 2. 58 was found in six out of the 12 cell lines. The observed oncogene expression correlated neither with growth parameters nor melanin content. The present findings revealed a coexpression of mutant p53 and c-fos proteins being associated with a highly malignant phenotype in melanoma cell lines. Further studies are necessary to clarify the significance of the above findings.

Biomarkers, Tumor↗
PubMed1994

Dose comparison of tropisetron (Navoban) 5 mg and 10 mg orally in the prophylaxis of dacarbazine-induced nausea and emesis.

In this double-blind, randomized trial performed at five study centers, the prophylactic, antiemetic effect of two different dosages of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) was investigated in dacarbazine-treated patients with melanoma. Patients received tropisetron 5 mg or 10 mg orally (as one capsule) once daily (minimum 3 days) on each day of chemotherapy. No significant differences were found in the effects of tropisetron 5 mg and 10 mg. During the first 24 hours, total control of vomiting was seen in 93% and 98% of patients receiving tropisetron 5 mg and 10 mg, respectively. Total control of nausea was achieved in 84% and 80% of patients receiving tropisetron at these dosages. Over days 2 to 7 of chemotherapy, total control of vomiting and nausea remained high. Patients reported that quality of life remained good throughout chemotherapy, as did mood; only a small decrease in food intake occurred. Tropisetron was well tolerated. Constipation was the most common adverse event, occurring in 13% of patients. Headache (4%), diarrhea (4%), and anorexia (2%) also were observed.

Administration, Oral↗
PubMed1993

12-O-tetradecanoylphorbol-13-acetate not only modulates proliferation rates, but also alters antigen expression and LAK-cell susceptibility of normal human melanocytes in vitro.

For serial cultivation of normal human melanocytes media supplemented with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) are largely employed. By using a culture medium that permits cultivation of melanocytes without TPA, the effects of TPA on melanocyte proliferation, phenotype, and susceptibility to lymphokine-activated killer cells were studied. Addition of 50 ng/ml TPA to the medium induced rapid dendrite formation and increased the cell proliferation rate by 16-63% in mitogen-rich media (four of seven cultures, p < 0.01), and by 237% in mitogen-reduced media (p < 0.001). Furthermore, several phenotypic changes indicating early stages of melanocyte transformation were induced by 50 ng/ml TPA. These included increased expression of melanoma progression-associated antigens such as A.1.43 and A.10.33, upregulation of nerve-growth factor receptor as well as of the melanocyte-activation marker HMB-45 and of histocompatibility class I antigens. In contrast, the expression of the differentiation marker K.1.2 and of intercellular adhesion molecule-1 was decreased in TPA-treated cultures. Most of these changes persisted even after removal of TPA from the culture medium (> or = 2 weeks). Staurosporine, a protein kinase C inhibitor, modulated melanocyte-antigen expression similar to TPA, suggesting that protein kinase C downmodulation rather than activation by TPA is involved. In addition to the antigenic alterations, the susceptibility of TPA-treated melanocytes to lymphokine-activated killer cell cytotoxicity decreased by 40% (p < 0.01), possibly due to their altered surface antigen expression. The presented data reveal that the tumor promoter TPA hitherto used as a supplement of melanocyte culture media induces profound phenotypic and functional changes of the cultured cells, indicating incipient transformation of normal human melanocytes in vitro.

Alkaloids↗
PubMed1993

Effects of interferons and cytokines on melanoma cells.

This review summarizes recent information on the effects of immunomodulatory cytokines on human melanoma cells. The action of interferon (IFN)-alpha, -beta, and -gamma has been extensively examined in melanoma and melanocyte cultures in vitro, and increasing information on the action of other cytokines is now available. All IFNs revealed a dose-dependent antiproliferative effect on melanoma cells with the highest growth inhibition caused by IFN-beta. Proliferation was also inhibited by interleukin (IL) 1-alpha and -beta, and tumor necrosis factor (TNF)-alpha. For IL-4, both growth-stimulatory and -inhibitory properties have been reported. Cellular differentiation in terms of melanin synthesis, formation of dendritelike structures, and antigenic changes was not affected by IFN-alpha or -beta. IFN-gamma, however, induced a more dedifferentiated and biologically more aggressive phenotype of melanoma cells. Histocompatibility antigen (HLA) class I molecules were found upregulated by all IFNs and by TNF-alpha, associated with a marked increase of melanoma cell lysis by tumor infiltrating lymphocytes in vitro. HLA class II molecules were de novo expressed or enhanced by IFN-gamma and TNF-alpha. The adhesion molecules ICAM-1, LFA-3, and VLA-2 were upregulated by IFN-gamma, TNF-alpha, and IL-1-beta, whereas melanoma-associated antigens were hardly affected by cytokines. It seems that both antiproliferative and immunomodulatory effects may contribute to the antitumoral activity of cytokines in vivo. In vivo application of cytokines as well as combinations with cytotoxic drugs, therefore, may be promising for future treatment strategies.

Animals↗
PubMed1993

Chemotherapy and chemoimmunotherapy in disseminated malignant melanoma.

Treatment of metastatic melanoma with cytotoxic drugs is still associated with low response rates and high toxicity. The most effective single agents in metastatic melanoma produce response rates between 15 and 20%. Combined schedules based on dacarbazine (DTIC), carmustine (BCNU), cisplatin and vinca alkaloids produced objective response rates between 25% and more than 40%; adverse effects, however, were severe and prolongation of survival remains uncertain. Cytokines were therefore introduced as melanoma treatment, with initial high expectations. Interferon (IFN)-alpha as a single treatment produced an overall response rate of 10-15% in melanoma patients. Clinical and experimental results suggest that the antitumour activity of IFN is mainly related to its antiproliferative effect; immunomodulatory effects were not substantiated in clinical investigations. Adoptive immunotherapy of metastatic melanoma has been established by use of lymphokine-activated killer (LAK) cells plus interleukin-2 (IL-2) or high dose IL-2 alone. Clinical trials of adoptive immunotherapy showed objective response rates of 20-25% in disseminated melanoma, and response rates could be further improved by the combination of IL-2 with IFN-alpha. Clinical trials with combined IFN or/and IL-2 and cytostatic drug therapy started a few years ago and have yielded promising initial results. The combination of IFN-alpha with dacarbazine was effective in over 50% of treated patients, leading to complete or partial remissions in 28% and stabilization of the disease in an additional 28% of more than 400 patients treated so far. Recently, a new generation of multidrug combinations including IFN-alpha and/or IL-2 has been initiated with overall response rates of more than 50% in several reports.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1993

Cytokines in human melanoma cells: synthesis, autocrine stimulation and regulatory functions--an overview.

Various cytokines are involved in growth regulation of human melanoma cells. Malignant melanoma cells express multiple growth factors, including basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-alpha, and melanoma growth stimulatory activity (MGSA), substances which are not expressed in normal human melanocytes. The simultaneous synthesis of growth factors and expression of their receptors by melanoma cells, leading to permanent stimulation of cell proliferation, has been clearly shown for bFGF and MGSA. This phenomenon has been designated autocrine growth stimulation. Increased or altered expression of growth factor receptors has been described for nerve growth factor (NGF) receptor, for PDGF-beta receptor and for a truncated form of epidermal growth factor (EGF) receptor encoded by the c-erb-B2 oncogene. Lymphokines are mainly involved in growth control of melanoma cells. Interferons (IFN)-alpha, -beta and -gamma, Interleukins (IL)-1 and -6 as well as tumour necrosis factor (TNF)-alpha inhibited melanoma cell proliferation, with the strongest effects displayed by IFN. TGF-beta which was found to inhibit proliferation of normal human melanocytes exhibited marginal effects on melanoma cells, or even stimulated their growth. In conclusion, a complex network of cytokines is involved in the regulation of melanoma cell growth. Further insight into these mechanisms may contribute to the finding of new strategies in melanoma therapy.

Antigens, Neoplasm↗
PubMed1993

[Pregnancy, hormone preparations and malignant melanoma].

For decades pregnancy has been regarded as an unfavourable prognostic factor in women with malignant melanoma and for many patients termination of pregnancy was recommended. Likewise, it was suspected that pregnancy during the first few years after diagnosis of the tumor would impair the prognosis and, therefore, a contraindication was established. An analysis of the data of the Central Malignant Melanoma Registry of the German Dermatological Society revealed that 1% of female melanoma patients were pregnant and 40.5% were found to be in premenopausal status. In several recent studies survival rates of melanoma patients who were pregnant and those who became pregnant after diagnosis were compared to the rates in women without pregnancies. No significant differences were found. In addition, the use of oral contraceptives and menopausal estrogens, which were formerly thought to be related to an elevated risk of developing melanoma, was shown not to affect the risk and natural course of malignant melanoma. In conclusion, the recent results of extensive investigations no longer substantiate recommendations for abortion in pregnant melanoma patients. The use of oral contraceptives and menopausal estrogens is likewise no longer contraindicated in melanoma patients. A waiting period before having children may be recommended in the first 2-3 years after diagnosis, as this is the period with the highest probability of relapse, and one can be more certain that the course will be favourable.

Adult↗