Search PubMed⌕ Search

Biomedical subjects

W Tilgen

Publications and source records attributed to W Tilgen.

At least 19 recordsLinked to original sources
PubMed2006

Clusterin and DNA repair: a new function in cancer for a key player in apoptosis and cell cycle control.

The glycoprotein clusterin (CLU), has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. Both forms are implicated in various cell functions, including DNA repair, cell cycle regulation, and apoptotic cell death. CLU expression has been associated with tumorigenesis and the progression of various malignancies. In response to DNA damage, cell survival can be enhanced by activation of DNA repair mechanisms, while simultaneously stimulating energy-expensive cell cycle checkpoints that delay the cell cycle progression to allow more time for DNA repair. This review summarizes our current understanding of the role of clusterin in DNA repair, apoptosis, and cell cycle control and the relevance.

Apoptosis↗
PubMed2006

[Therapy of malignant melanoma. First-, second- and pathogenesis-oriented third-line therapies].

The incidence of malignant melanoma is steadily increasing worldwide. The most crucial requirement to cure the disease is early detection of thin primary tumors. At the stage of distant metastases, the treatment options are predominantly palliative. Resection of localized metastases is currently the most effective approach. Dacarbazine is considered as standard chemotherapy for inoperable metastatic disease showing remission rates of 5-20% without any noteworthy effect on overall survival. Quite recently, a large spectrum of innovative treatment approaches have been developed from an increasing insight into tumor biology. Along with improved vaccination strategies, targeted therapies have attracted the most attention in the treatment of advanced melanoma. Those anti-proliferative, anti-angiogenic and proapoptotic agents are directed against pathogenetically important pathways of the tumor cell. First clinical experiences are encouraging, but results from controlled trials have to be awaited.

Adjuvants, Immunologic↗
PubMed2006

Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer.

Clusterin (CLU) has been implicated in various cell functions involved in carcinogenesis and tumour progression. There are two known CLU protein isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is proapoptotic, and a secretory form (sCLU) is prosurvival. CLU expression has been associated with tumorigenesis of various malignancies, including tumours of prostate, colon, and breast. Furthermore, CLU expression is modulated by many factors that are believed to regulate tumour growth and/or apoptosis, including 1,25-dihydroxyvitamin D3, transforming growth factor beta-1, ultraviolet radiation, and IR. sCLU upregulation appears to be a general molecular stress response. Presently, preliminary results indicate that therapeutic modalities targeting CLU may be effective in cancer treatment. However, such strategies should make sure that nCLU is not eliminated or reduced. This review summarizes our present understanding of the importance of CLU in various physiological functions including tumour growth, and discusses its relevance to future cancer therapy.

Apoptosis↗
PubMed2006

Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study.

BACKGROUND: Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial. PATIENTS AND METHODS: Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety. RESULTS: Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%). CONCLUSIONS: Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases.

Adult↗
PubMed2005

[Generalized hyperpigmentation and malignant acanthosis nigricans. A case of a patient with hereditary hemochromatosis and gastric cancer].

A 56-year-old previously healthy man developed hyperpigmentation of the entire skin over the previous 6 months without any other signs of further impairment. Additionally, we found accentuated skin lines of the neck and intertriginous sites as well as cutaneous papillomatosis. Histological examinations, laboratory tests and technical diagnostics revealed the existence of both hereditary hemochromatosis and adenocarcinoma of the stomach. Simultaneous manifestation of hyperpigmentation as a result of hemochromatosis as well as malignant acanthosis nigricans as a paraneoplastic symptom in gastric cancer is very rare.

Acanthosis Nigricans↗
PubMed2005

[Established and current procedures in wound healing].

Most chronic wounds are caused by arterial or venous vascular disease. Wound care is an interdisciplinary task and economic challenge. Numerous new wound dressings and treatment methods have been introduced recently. Basic research has enhanced our understanding of stimulation and inhibition of wound healing. Well-constructed clinical studies have shown some traditional approaches to be effective and others, less so. Successful wound healing requires treatment of the underlying disease as well as correction of local factors that may delay healing. The choice of dressings must be based on continuous re-assessment of the wound. Modern approaches for the most common types of chronic wounds, as well as options such as vacuum treatment and tissue-engineered skin are presented along with information on latest rules for reimbursement for wound care in Germany.

Bandages↗
PubMed2005

Incidence of antiretinal antibodies in melanoma: screening of 77 serum samples from 51 patients with American Joint Committee on Cancer stage I-IV.

BACKGROUND: Patients with melanoma-associated retinopathy (MAR) experience different visual symptoms caused by the production of antitumoral antibodies that cross-react with retinal epitopes. Immunofluorescence assays of serum from patients with MAR on sectioned monkey or human retina characteristically reveal antibody activity located within the inner nuclear layer, with a focus of activity upon the membranes of bipolar cells. OBJECTIVES: We inquired into the association with disease of this serological abnormality by evaluating sera from patients with melanoma with no MAR-like signs or symptoms. METHODS: Groups of patients were selected with different stages of melanoma (American Joint Committee on Cancer stages I-IV). Seventy-seven serum samples from 51 patients with melanoma were examined by indirect immunohistochemical assay on sections of human retina. RESULTS: Of the 77 serum samples, 53 were found to contain antibodies reactive with various components of retina. Eight were from 17 sera from patients in stage I or II, 14 were from 23 sera from patients in stage III, and 31 were from 37 sera from patients in stage IV. Statistical analysis revealed a correlation between antibody activity and the stage of disease, with a higher percentage of antibody activity in advanced stages (P = 0.002). CONCLUSIONS: The presence of antiretinal antibodies in patients with melanoma without ocular symptoms appears to be more common than previously suspected. Antibody activity similar to that ascribed to the MAR syndrome appears in some patients with melanoma who have no MAR-like retinopathy. Follow-up studies will determine if patients with antiretinal antibodies go on to develop MAR and if staining intensity and staining patterns change over the course of the disease.

Adult↗
PubMed2004

[Complete remission of cutaneous satellite and in-transit metastases. After intralesional therapy with interleukin-2 in 2 patients with malignant melanoma].

Multiple cutaneous satellite and in-transit metastases of melanoma without involvement of lymph nodes or other organs are a challenge especially when they occur in elderly inoperable patients with multiple internal diseases. In this particular situation, intralesional application of interleukin-2 may represent an effective alternative to systemic chemo- or immunotherapy as it can be performed on an out-patient basis and has few side effects. We treated two elderly female patients with multiple cutaneous metastases of malignant melanoma with intra- and perilesional application of interleukin-2 (3 x 6-12 Mio IE) over 12 weeks and achieved a complete remission of these metastases. In follow-up biopsies, no viable tumor cells were found. Despite a slight burning at the injection side and a transient local inflammatory reaction, the therapy was well tolerated in both cases after premedication with paracetamol 500 mg orally and pretreatment of the injection site with a cream containing lidocaine and prilocaine. No systemic side effects were observed.

Aged↗
PubMed2004

[Vacuum assisted wound closure after excision of a high risk melanoma heel wound - using the v.a.C. heel-dressing].

Vacuum-assisted wound closure is established in acute wound treatment and assists granulation tissue as well as promotion of graft survival in critical localisation. A new vacuum-assisted wound closure device is launched for the treatment of heel wounds (V.A.C. GranuFoam Heel Dressing). First experience with this heel contour shaped dressing is presented in a case of primary surgical care of a high risk melanoma. The initial defect after excision, measuring 8 x 6 x 3.5 cm, granulated by V.A.C. treatment in 5 weeks to skin surface niveau and was successfully covered with a full thickness skin graft. The V.A.C. Heel Dressing is easy to apply, reduces vacuum leakage und increases patients' comfort and treatment safety in comparison to "classic" vacuum dressings.

Debridement↗
PubMed2003

[Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma].

PURPOSE: The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases. PATIENTS AND METHODS: Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m(-2) on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d(-1), days 1-5, 3 consecutive weeks). RESULTS: Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test). CONCLUSION: Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗
PubMed2003

Melanoma-associated retinopathy: high frequency of subclinical findings in patients with melanoma.

BACKGROUND: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome with symptoms of night blindness, light sensations, visual loss, defect in visual fields, and reduced b-waves in the electroretinogram. Patients with MAR often suffer from a sudden onset of ocular symptoms that are believed to result from antibody production against melanoma-associated antigens that cross-react with corresponding epitopes on retinal depolarizing bipolar cells. OBJECTIVES: To correlate the frequency of subclinical symptoms suggestive of MAR in melanoma patients to different stages of disease, patient age, type and thickness of the primary tumour, form of therapy, S-100 level and tumour burden. METHODS: We analysed 28 patients with melanoma in stages I-IV (according to the American Joint Committee on Cancer tumour classification) for the presence of subclinical MAR symptoms using scotopic electroretinography, static and kinetic perimetry and nyctometry. RESULTS: Seven patients had clinical signs and symptoms consistent with MAR, 18 had some indications, while the remaining three had none. We found no correlation between clinical symptoms and stage of disease, tumour burden or S-100 level, but findings suggestive of MAR were observed more frequently in advanced stages of disease. CONCLUSIONS: Subclinical retinal involvement characteristic of MAR appears to be more common than previously suspected in patients with cutaneous malignant melanoma. Our findings in this small cohort seem to indicate that the percentage of patients with symptoms suggestive of MAR is higher in advanced stages of disease. Further clinical studies are required to evaluate if the presence of subclinical symptoms suggestive of MAR is correlated with a worse prognosis and a shortened progression-free and overall survival.

Adult↗
PubMed2003

No evidence of skin infection with Chlamydia pneumoniae in patients with cutaneous T cell lymphoma.

Recently, Chlamydia pneumoniae-specific DNA and antigens were reported in the skin of patients with Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas. In order to revalidate these data we analyzed skin sections of patients with MF for the expression of three different chlamydial antigens and C. pneumoniae DNA by immunohistochemistry and PCR according to previously described protocolls. Neither C. pneumoniae-specific DNA sequences nor antigens were detected in any of the skin biopses from 24 MF patients tested, suggesting that further studies are needed to establish any pathogenetic relevance of C. pneumoniae in MF.

Adult↗
PubMed2003

A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.

The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗