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Biomedical subjects

Claus Garbe

Publications and source records attributed to Claus Garbe.

At least 37 records · Page 2Linked to original sources
PubMed2005

Interventional study in 1,232 young German children to prevent the development of melanocytic nevi failed to change sun exposure and sun protective behavior.

Sunscreens have been proposed as protective measures to inhibit the development of melanocytic nevi in childhood and to decrease the long term risk for cutaneous melanoma development. Our present study investigates the influence of sunscreen use and education on the number of incident melanocytic nevi. A total of 1,812 children in 78 public nursery schools in 2 German cities were randomized to 3 study arms: (i) parents were informed on study purpose and sun protection measures only at an initial educational meeting; (ii) parents received educational material 3 times yearly; and (iii) education and 800 ml free broad spectrum sunscreens with sun protection factor 25 provided on a yearly basis. Final assessment after 3 years follow-up included 1,232 children (68%). Changes of sun protection habits including sunscreen use were sparse, without any differences attributable to the intervention efforts. As a consequence, there were no significant differences between the 3 study arms for the main outcome measure, the number of incident melanocytic nevi. Analysis of the sunscreen use in the entire cohort irrespective of our study arms did not show any impact on incident nevus numbers in bivariate or multivariate analysis. In conclusion, intervention with educational letters and free sunscreens seemingly had no additional effect on sun-protection for German children. High prevalence of sunscreen use at study commencement, social desirability, and inadequate application of sunscreens might have partially covered their effect.

Child↗
PubMed2005

The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma.

Malignant melanoma is a highly aggressive tumor of the pigment-producing cells in the skin with a rapidly increasing incidence and a poor prognosis for patients with advanced disease that is resistant to current therapeutic concepts. Therefore, the development of novel strategies for treating melanoma are of utmost importance. In melanoma, both the Ras-Raf-MEK-ERK (MAPK) and the PI3K-AKT (AKT) signaling pathways are constitutively activated through multiple mechanisms, and thus exert several key functions in melanoma development and progression. Conversely, several molecules known to play key roles in melanoma development and progression such as the adhesion molecules E-/N-cadherin, MelCAM and alphavbeta3 integrin are regulated by these pathways and/or activate the same. The results of the research to date indicate that in melanoma both the MAPK and the AKT signaling pathways may represent promising therapeutic targets.

Apoptosis↗
PubMed2005

Production and characterization of amplified tumor-derived cRNA libraries to be used as vaccines against metastatic melanomas.

BACKGROUND: Anti-tumor vaccines targeting the entire tumor antigen repertoire represent an attractive immunotherapeutic approach. In the context of a phase I/II clinical trial, we vaccinated metastatic melanoma patients with autologous amplified tumor mRNA. In order to provide the large quantities of mRNA needed for each patient, the Stratagene Creator SMART cDNA library construction method was modified and applied to produce libraries derived from the tumors of 15 patients. The quality of those mRNA library vaccines was evaluated through sequencing and microarray analysis. RESULTS: Random analysis of bacterial clones of the library showed a rate of 95% of recombinant plasmids among which a minimum of 51% of the clones contained a full-Open Reading Frame. In addition, despite a biased amplification toward small abundant transcripts compared to large rare fragments, we could document a relatively conserved gene expression profile between the total RNA of the tumor of origin and the corresponding in vitro transcribed complementary RNA (cRNA). Finally, listing the 30 most abundant transcripts of patient MEL02's library, a large number of tumor associated antigens (TAAs) either patient specific or shared by several melanomas were found. CONCLUSION: Our results show that unlimited amounts of cRNA representing tumor's transcriptome could be obtained and that this cRNA was a reliable source of a large variety of tumor antigens.

Journal Article↗
PubMed2005

Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo.

Antimicrobial peptides are an integral part of the epithelial innate defense system. Dermcidin (DCD) is a recently discovered antimicrobial peptide with a broad spectrum of activity. It is constitutively expressed in human eccrine sweat glands and secreted into sweat. Patients with atopic dermatitis (AD) have recurrent bacterial or viral skin infections and pronounced colonization with Staphylococcus aureus. We hypothesized that patients with AD have a reduced amount of DCD peptides in sweat contributing to the compromised constitutive innate skin defense. Therefore, we performed semiquantitative and quantitative analyses of DCD peptides in sweat of AD patients and healthy subjects using surface-enhanced laser desorption ionization time-of-flight mass spectrometry and ELISA. The data indicate that the amount of several DCD-derived peptides in sweat of patients with AD is significantly reduced. Furthermore, compared with atopic patients without previous infectious complications, AD patients with a history of bacterial and viral skin infections were found to have significantly less DCD-1 and DCD-1L in their sweat. To analyze whether the reduced amount of DCD in sweat of AD patients correlates with a decreased innate defense, we determined the antimicrobial activity of sweat in vivo. We showed that in healthy subjects, sweating leads to a reduction of viable bacteria on the skin surface, but this does not occur in patients with AD. These data indicate that reduced expression of DCD in sweat of patients with AD may contribute to the high susceptibility of these patients to skin infections and altered skin colonization.

Adult↗
PubMed2005

Risk factors of incident melanocytic nevi: a longitudinal study in a cohort of 1,232 young German children.

The number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic-moderate and intermittent-high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3-year follow-up was conducted in 1,232 young children 2-7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun-protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers' (p < 0.001) and fathers' (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent-high sun exposure during holidays (p < 0.001) and chronic-moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic-moderate or intermittent-high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts.

Child↗
PubMed2005

Effect of sunscreen and clothing on the number of melanocytic nevi in 1,812 German children attending day care.

The number of melanocytic nevi is the most important risk factor for cutaneous melanoma. This 1998 cross-sectional study of 1,812 children aged 2-7 years from 78 day-care centers in Germany analyzed the protective effect of sunscreen and clothing on the number of melanocytic nevi. Total body nevi were counted, and pigmentary features were assessed. Parents underwent a standardized interview concerning their children's sun exposure and sun-protective behavior. Almost 95% of the children had used sunscreen previously. Children who used sunscreen and wore more clothing spent significantly longer periods on holidays in sunny climates (p < 0.001 and p = 0.006, respectively) and had a higher outdoor activity score at home (p < 0.001 and p = 0.012, respectively). Multivariate analysis adjusted for confounders showed no significant protective effects of applying sunscreen. Examination of the potential protective effect of clothing revealed an inverse dose-response correlation between the number of clothes worn at the beach or outdoor swimming pool and the number of melanocytic nevi (p < 0.001, adjusted for confounding). Randomized controlled trials are needed to confirm these results. Meanwhile, public education should aim to protect children primarily by sun avoidance and protective clothing, while sunscreen should also be used.

Chi-Square Distribution↗
PubMed2005

Development of prognostic factors and survival in cutaneous melanoma over 25 years: An analysis of the Central Malignant Melanoma Registry of the German Dermatological Society.

BACKGROUND: Recent studies revealed that incidence rates of cutaneous melanoma (CM) were leveling off predominantly among younger people and patterns suggested birth-cohort effects. The current study analyzed the development of prognostic factors and survival in incident CM over 25 years. METHODS: All 45,483 patients with incident CM diagnosed between 1976 and 2000 recorded by the German Central Malignant Melanoma Registry were considered. Linear and logistic regression analyses were used to judge time trends. Trends of survival rates were tested with the multivariate Cox model. RESULTS: Median tumor thickness decreased from 1.81 mm in 1976 to 0.53 mm in 2000 (P < 0.0001). The percentages of in situ and level II CM increased, respectively (P < 0.0001). The percentage of ulcerated CM decreased (P < 0.0001). The percentage of superficial spreading melanoma increased, whereas the percentage of nodular melanoma decreased (P < 0.0001). These time trends were all significant in the strata of gender, however, male patients presented in general with more advanced disease. Between 1976 and 2000, the average patient got older (P < 0.0001). The percentage of patients diagnosed with the primary tumor alone increased (P < 0.0001). Across the 25 years of observation, adjusted survival rates did not increase for females (P = 0.1561) but they increased for males (P < 0.0001). CONCLUSIONS: The data demonstrated a strong trend towards prognostically more favorable CM most likely due to earlier diagnosis. Men and older people should be the focus of health promotion activities as they presented with more advanced disease.

Adult↗
PubMed2005

Imiquimod in the treatment of extensive recurrent lentigo maligna.

We report the case of a 70-year-old white male with an extensive recurrence of lentigo maligna in a skin-transplanted region. He was treated with imiquimod 5% cream topically applied 5 times a week for a total duration of 9 months. Clinically and histologically, a complete clearing of the lesion was observed after treatment. Topical treatment with imiquimod seems to be effective and safe in lentigo maligna.

Administration, Cutaneous↗
PubMed2005

[Experiences with the new American Joint Committee on Cancer (AJCC) classification of cutaneous melanoma].

A new AJCC/UICC staging classification of malignant melanoma was published in 2001 and has been in use since then. Compared to the TNM classification used for the previous 15 years, the new classification contains fundamental changes. The classification of the primary tumor is now based on newly defined classes for Breslow's tumor thickness (0 - 1.0 mm; 1.01 - 2.0 mm, 2.01 - 4.0 mm; > 4.0 mm). Histopathologically diagnosed ulceration is the second prognostic factor in primary melanoma and its presence leads to upstaging into the next higher T category. Clark level of invasion is now only relevant for tumors up to 1 mm thick; levels IV and V are also reasons for upstaging. Classification of regional lymph node metastasis distinguishes between microscopic metastasis only as detected with sentinel lymph node biopsy and clinically detectable macroscopic metastasis. Additionally, the number of metastatic nodes and the presence of satellite and in-transit metastasis are prognostic factors for classification of regional lymph node metastasis. In distant metastasis, the kind of organ involvement has a role for classification (only skin and lymph nodes vs. lung vs. other organs) and an elevated LDH value leads to upstaging. A critical analysis of data of the German Central Malignant Melanoma Registry did not confirm the strong role of histopathological ulceration of the primary tumor in all T- and N-stages. Furthermore, there is an inconsistency of the classification as stage IIC displays a significantly worse prognosis as compared to stage IIIA. In spite of these drawbacks the new staging classification should used particularly in clinical trials in order to make data internationally comparable.

Germany↗
PubMed2005

Multicenter evaluation of the analytical and clinical performance of the Elecsys S100 immunoassay in patients with malignant melanoma.

The aim of this multicenter study was to evaluate the technical and clinical performance of the Elecsys S100 electrochemiluminescence immunoassay and to assess its utility as a tumor marker in patients with malignant melanoma. Imprecision studies yielded within-run coefficients of variation (CVs) of 0.7-2.0% and between-day CVs of 1.0-6.4%. Serum samples that were distributed to 11 participating laboratories for a comparability analysis resulted in excellent recoveries of 93-105% related to the median for all laboratories. The functional sensitivity of the assay was determined to be below 0.02 microg/L. The lot-to-lot reproducibility of Elecsys S100 was tested by analyzing 110 sera with three different reagent lots on an E2010 analyzer. This lot-to-lot comparison showed excellent correlation, with a coefficient of 0.99. A 95th percentile cut-off value of 0.10 microg/L was calculated from values measured in 206 healthy individuals. Using this cut-off value, sensitivity of 41% was found, with positive and negative predictive values of 0.50 and 0.91, respectively. Method comparison with the Sangtec 100 luminescence immunoassay, run on two different analyzers, showed correlation with coefficients ranging from 0.76 to 0.95. A comparison of S100 values obtained with both tests showed identical patterns in 68 serial samples from 15 patients with malignant melanoma during follow-up. These findings indicate that serial measurements with the Elecsys S100 assay are useful for the follow-up and monitoring of therapy in patients with malignant melanoma.

Adult↗
PubMed2004

Impact of ulceration in stages I to III cutaneous melanoma as staged by the American Joint Committee on Cancer Staging System: an analysis of the German Central Malignant Melanoma Registry.

PURPOSE: In 2001, the new American Joint Committee on Cancer classification of cutaneous melanoma (CM) introduced ulceration of the primary melanoma as a new key parameter being represented in respective subcategories of the tumor (T) classification. The present study was performed to validate the prognostic significance of ulceration in relation to T thickness and clinical stages of CM (stages I to III). PATIENTS AND METHODS: Patients (N = 15,158) with incident invasive primary nonmetastatic CM and follow-up data recorded between 1976 and 2000 by the German Central Malignant Melanoma Registry were investigated using survival analysis to evaluate prognostic factors such as T thickness, level of invasion, body site, histologic subtype, ulceration, regression, age, and sex. RESULTS: Comparisons of survival probabilities according to the Kaplan-Meier method between ulcerated and nonulcerated CM were not statistically significant for subgroups with T thickness < or = 1 mm and more than 4.00 mm (P = .2601 and P = .0699, respectively) but were significant for T thickness of 1.01 to 2.00 mm and 2.01 to 4.00 mm (P < .0001 for both). This result was confirmed in the multivariate analysis. For stage III CM, the impact of ulceration on overall survival was statistically significant in the bivariate Cox model (P = .0111) but not in the multivariate Cox model (P = .0522). CONCLUSION: Whereas ulceration seems to have a negative impact on the prognosis of patients with stages T2 and T3, a potential influence for patients with stages T1 and T4 could not be established. If factors of the primary CM were to be taken into consideration to judge prognosis of stage III CM, T thickness but not ulceration should be the focus.

Female↗
PubMed2004

Prognostic factors of thin cutaneous melanoma: an analysis of the central malignant melanoma registry of the german dermatological society.

PURPOSE: The increasing number of thin cutaneous melanomas (CM) with tumor thickness up to 1 mm demands a detailed analysis of prognostic factors for the classification and grading of these tumors. The aim of the present study was to identify prognostic factors in thin CM. PATIENTS AND METHODS: A series of 12,728 patients with thin incident primary invasive CM and follow-up data recorded between 1976 and 2000 by the German-based Central Malignant Melanoma Registry was analyzed using the multivariate Cox proportional hazard model to evaluate prognostic factors, and classification and regression trees analysis (CART) to define prognostic groups. RESULTS: Multivariate analysis found tumor thickness, sex, age, body site, and histopathologic subtype to be significant prognostic factors of thin CM. Ulceration and regression did not affect prognosis significantly. Prognostic classification based on the results of CART analysis resulted in three groups defined by tumor thickness, age, and sex. Ten-year survival rates of these groups varied between 91.8% and 98.1%, with improved classification as compared with subgroups by tumor thickness alone. CONCLUSION: Classification by tumor thickness identified prognostic subgroups with highest significance in thin CM, and the classification was improved by the introduction of age and sex. However, neither ulceration nor the level of invasion included in the new American Joint Committee on Cancer TNM system classification, revealed statistical significance as prognostic factors in thin CM.

Adult↗
PubMed2004

The natural course of cutaneous melanoma.

The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies.

Humans↗