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Biomedical subjects

G Krähn

Publications and source records attributed to G Krähn.

At least 19 recordsLinked to original sources
PubMed2004

Risk and protective factors for sporadic basal cell carcinoma: results of a two-centre case-control study in southern Germany. Clinical actinic elastosis may be a protective factor.

BACKGROUND: There are very few data regarding sun exposure behaviour of patients with basal cell carcinoma (BCC) in central Europe. OBJECTIVES: A case-control study of patients with sporadic BCC was conducted to assess the risk of occupational and leisure-time sun exposure behaviour, precursor lesions for skin cancer and phenotypic factors on the development of sporadic BCC in Ulm and Dresden, Germany. METHODS: A comparison was made of 213 patients with BCC (128 from Ulm, 85 from Dresden; 103 men and 110 women; median age at diagnosis 69 years) and 411 controls (237 from Ulm, 174 from Dresden; 197 men and 214 women; median age 58 years). Crude odds ratios (ORs) and corresponding 95% confidence intervals for all of 64 possible risk factors revealed strong associations in 33 items. Selection of important risk factors was performed in a multiple logistic regression. RESULTS: For sporadic BCC, an increased risk was shown for persons with actinic cheilitis (OR 7.1), actinic keratosis (OR 2.7) and solar lentigo (OR 2.5). The only phenotypic factor indicating risk of sporadic BCC was hair colour, with a higher risk for red/fair than brown/black hair (OR 4.3). There was an increased risk for persons with BCC in first-degree relatives (OR 5.1) and those with sunburn 20 years before sporadic BCC was diagnosed (OR 3.6). Additionally, occupational ultraviolet (UV) exposure appeared to be a risk factor (OR 2.4). In contrast, clinical actinic elastosis showed a protective effect (OR 0.1). CONCLUSIONS: In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.

Adult↗
PubMed2001

Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.

In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.

Animals↗
PubMed2001

Interlaboratory evaluation of a new reverse transcriptase polymerase chain reaction-based enzyme-linked immunosorbent assay for the detection of circulating melanoma cells: a multicenter study of the Dermatologic Cooperative Oncology Group.

PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is the most frequently used laboratory method for the detection of circulating tumor cells in melanoma patients. However, previously published results showed considerable variability in the PCR positivity rates. MATERIALS AND METHODS: We designed a collaborative study to assess the sensitivity, specificity, and clinical relevance of a new standardized RT-PCR-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma cell line were prepared in a blinded fashion, and aliquots were sent to seven participating laboratories experienced in RT-PCR. RESULTS: The results demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no false-negatives and 7.4% [2 of 28] false-positives) of the assay and a satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in 17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV patients. The interlaboratory reproducibility of positive samples, however, was extremely low and indicates the presence of low amounts of target mRNA. CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and specificity for the detection of tyrosinase mRNA in peripheral blood cells. The low interlaboratory reproducibility for the detection of tumor cells in blood samples of melanoma patients, however, raises the question of relevance of this assay for clinical use.

Adult↗
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

Increased blood levels of human S100 in melanoma chick embryo xenografts' circulation.

The chorioallantoic membrane (CAM) of the fertilized egg allows grafting of human melanomas for short-term investigations and offers the opportunity to investigate the behavior of metastasizing cells and the release of S100beta into peripheral blood. Tissue from one primary melanoma as well as cutaneous and subcutaneous metastases of 10 melanoma patients with elevated levels of S100 in the peripheral blood before surgery were transplanted onto the CAM of chick embryos at day 5/6 of development. Grafts were nourished by the host blood supply 2 days after transplantation. Histologically, 3 days after grafting, metastasizing melanoma cells could be found near the vessels of the host membrane, penetrating the endothelial layer and entering the blood system. Growth conditions remained stable for 6 days after transplantation. Blood samples were taken from a larger CAM vessel before collecting the xenografts 5 days after grafting. Measurement of human S100 in peripheral blood was performed in a blinded manner. No negative control showed elevated levels of human S100 protein. Samples deriving from melanoma xenografts contained highly elevated levels of S100 protein in 80% of cases. The data strongly support the concept of graft-host interaction concerning adherence of tumors and extravasation of human melanoma cells.

Animals↗
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

Outdoor activities in childhood: a protective factor for cutaneous melanoma? Results of a case-control study in 271 matched pairs.

BACKGROUND: A matched case-control study was performed in Munich, Germany, in 1996-97 to evaluate the risk of cutaneous melanoma due to ultraviolet (UV) exposure behaviour in Southern Bavaria, Germany. OBJECTIVES: Patients with cutaneous melanoma and controls were investigated by two physicians using a standardized questionnaire to identify risk factors for the development of melanoma, such as professional and leisure sun exposure behaviour. In each person, a total body examination was performed to detect benign skin alterations, phenotypic characteristics and precursor lesions for skin cancer. PATIENTS/METHODS: A total of 271 melanoma patients and 271 controls were individually matched for residence, age and gender. A multiple conditional logistic regression analysis was performed. RESULTS: Of 56 factors, those risk factors with a strong effect on the development of melanoma were: the existence of melanoma in first degree relatives, solar lentigo, actinic keratosis, actinic cheilitis, skin phototype, immediate skin reaction to UV light at the start of the outdoor season, sunburn in childhood and sun exposure during holidays in sunny areas 20 years before melanoma was diagnosed; outdoor activities in childhood were found to be protective. CONCLUSIONS: Sunburn in childhood and increased sun exposure during annual holidays in sunny areas should be avoided. In contrast, outdoor activities in childhood, including soccer and gardening, should be encouraged because they are associated with a lower risk of melanoma formation.

Adolescent↗
PubMed2000

c-MYC and nodular malignant melanoma. A case report.

BACKGROUND: The incidence of skin cancer has been rising since the 1950s. About 75% of skin cancer-associated deaths are caused by malignant melanoma. Nodular malignant melanoma accounts for 20% of melanocytic malignant tumors and is associated with a relatively poor prognosis. Extensive research has been undertaken, but a molecular marker that can predict a more aggressive course of melanoma still has not been found. METHODS: The authors applied cytogenetic and molecular genetic techniques to a case of nodular malignant melanoma. They used comparative genomic hybridization (CGH) to identify chromosomal regions affected by genomic changes and interphase fluorescence in situ hybridization (FISH) on touch preparations of the tissue to elucidate the CGH findings further. To investigate the functionality of the affected c-MYC gene, the authors detected its transcript via reverse transcription and polymerase chain reaction. RESULTS: CGH revealed a copy number gain in the 6p and 8q24-8qter region. FISH with c-MYC and centromere eight specific probes revealed that the tumor, in contrast to unaffected skin, was characterized by a gain in copy numbers of the c-MYC gene. The c-MYC gene transcript was detected at higher levels in the tumor than in the tissue taken from the safety margin. CONCLUSIONS: The WAF1 gene located on chromosome 6p, which in this case had a copy number gain, might be involved in melanoma pathogenesis. The authors suggest that the c-MYC gene plays an important role in melanoma development and progression. The c-MYC gene seems to be affected by gaining functional copies, leading to a change in the normally regulated gene-dose effect.

Chromosomes, Human, Pair 6↗
PubMed2000

[Cutaneous radiation syndrome: clinical features, diagnosis and therapy].

Accidental exposure to ionizing radiation may occur during such catastrophic events as the Chernobyl accident in 1986 or over days to weeks as in Goiania in 1987 and in the military camp during the training of soldiers in Lilo/Georgia in 1997, as well as in medical institutions. The cutaneous symptoms after radiation exposure are based on a combination of inflammatory processes and alteration of cellular proliferation as a result of a specific pattern of transcriptionally activated proinflammatory cytokines and growth factors. They follow a time course consisting of prodromal erythema, latency period, acute stage, chronic stage and late stage. The entire complex is referred to as cutaneous radiation syndrome. The time course depends on several factors such as the radiation dose, radiation quality, individual radiation sensitivity, the extent of contamination and absorption and amount of skin exposed. For the diagnosis of the cutaneous radiation syndrome the following procedures are used: 7.5 MHz to 20 MHz-B-scan sonography, thermography, capillary microscopy, profilometry, nuclear magnetic resonance imaging, bone scintigraphy and histology. Based on the results of experimental and clinical research, today treatment may include topical or systemic corticosteroids, gamma-interferon, pentoxifylline, vitamin E and superoxide dismutase. The treatment depends on the stage of the cutaneous radiation syndrome. Due to the complexity of the clinical manifestations of radiation disease, most patients require interdisciplinary treatment in specialized centres. Dermatologists are essential partners in the life-long follow-up and therapy of such patients.

Adrenal Cortex Hormones↗
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

Lymph node dissection in cutaneous melanoma: surgical and oncological implications.

The concept of Sentinel Lymph Node Dissection (SLND) has strongly influenced the surgical approach towards primary melanoma in the last decade. Initiated by the disappointing results of elective lymph node dissection (ELND) in this malignancy, the concept of analyzing the first draining lymph node (Sentinel) of a regional basin was developed as a diagnostic means to avoid unnecessary ELND in case of negative SLNs. According to recent standards detection of the SLN should be performed by a triple approach: injection of 90 nm Technetium and patent blue in the periphery of the primary melanoma, and intraoperative tracing of radioactivity with the aid of a hand-held gamma probe. Histopathological examination of alternating series sections of the whole lymph node appears to be the best analytic approach. Molecular biologic procedures such as tyrosinase RT-PCR are time-consuming to perform and produce contradictory results. SLND for cutaneous melanoma is an interdisciplinary diagnostic approach involving surgery, dermatology, pathology, and nuclear medicine. In spite of a variety of published promising results derived from clinical trials ranging from a few dozens to several hundred included patients the diagnostic and prognostic value of SLND remains to be confirmed by ongoing controlled prospective clinical trials. At this stage, SLND can by no means be considered a therapeutic procedure. These aspects have to be kept in mind when informed consent is obtained from patients as well as in the individual determination of the risk-benefit ratio.

Clinical Trials as Topic↗
PubMed2000

Trauma and melanoma formation: a true association?

BACKGROUND: Little is known about the role of mechanical trauma in the pathogenesis of malignant melanoma. In individual patients, traumatic events have been discussed as a causative factor for the induction of melanoma and diagnosis of melanoma following trauma may raise medico-legal questions. OBJECTIVES: To evaluate the relationship between traumatic single or recurrent events and melanoma characteristics. METHODS: Retrospective questionnaire in 369 melanoma patients. RESULTS: A large number of patients (337 of 369; 91.3%) denied an association between a possible traumatic event and melanoma formation. Thirty-two of 369 patients (8.7%) considered an association of trauma and melanoma formation likely. Of these 32 patients, 22 patients (13 men, nine women) reported a single event, and 10 patients (four men, six women) a persisting irritation. An irritation of a pre-existing melanocytic naevus was reported by two patients with histologically confirmed melanoma on acquired or congenital naevus. CONCLUSIONS: As most of the patients who mentioned a trauma in this study suffered from acral melanoma, or melanoma located on the extremities, a history of trauma should be expected more frequently at these body sites. A review of epidemiological, clinical and scientific research indicates that there seems to be no evidence for single or persistent traumatic events as a causative factor for melanoma formation.

Adolescent↗
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

Interferon gamma in survivors of the Chernobyl power plant accident: new therapeutic option for radiation-induced fibrosis.

BACKGROUND: One of the remarkable clinical consequences of the Chernobyl accident was skin involvement, leading to extensive cutaneous fibrosis. Apart from surgery, no established treatment is available. METHODS: A group of survivors, working in or present at the accident site on April 26, 1986, and a few days thereafter, were examined, treated, and followed-up in 6-month intervals from September 1991 to November 1995. Eight individuals were identified as suffering from excessive cutaneous fibrosis. Skin thickness was measured with high-frequency (20 MHz) ultrasound in a clinically well-defined target skin lesion, in addition to histologic confirmation of radiation fibrosis. Interferon gamma was scheduled for all patients on a low-dose regimen (3 x 50 microg/week s.c.). In 2 patients, interferon was discontinued after the first injection, due to withdrawal of consent. In 6 patients, interferon was continued for 30 months, with 1 injection weekly for a further 6 months. Treatment was discontinued in November 1994. Four patients in the treated group and 1 of the 2 patients treated only once ("untreated patients") were reexamined 1 year later. RESULTS: In all individuals treated for 36 months, a significant (p < 0.005) reduction of radiation fibrosis could be determined, in contrast to a significant (p < 0.005) increase in the 2 untreated patients. Follow-up 1 year after discontinuation of the interferon treatment demonstrated significant (p < 0.005) recurrence of fibrosis. CONCLUSION: Low-dose interferon appears to be a safe and effective treatment of cutaneous radiation fibrosis following accidental exposure to high doses of ionizing radiation. Long-term supportive therapy may be required.

Adult↗