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Biomedical subjects

M Volkenandt

Publications and source records attributed to M Volkenandt.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Psychiatric side effects during adjuvant therapy with interferon-alphain patients with malignant melanoma. Clinical evaluation as well as diagnostic and therapeutic possibilities].

Interferon-alpha (IFN-alpha) is of high interest in the adjuvant treatment of malignant melanoma. During long term treatment, psychiatric side effects play an important role and not infrequently lead to reduction or discontinuation of therapy. Most common are sleeping disturbance, agitation, weariness, sleepiness, irritability, social withdrawal and depression, which most often develop during the first three months of the therapy. Also more severe side effects may occur, like delirium, organic depression, psychotic episodes and organic personality change, which in some patients may even lead to suicidal thoughts or suicide attempts, which is illustrated in two case reports. Therapeutic intervention depend to the severity of side effects. Moderate depressive syndromes may successfully be treated by antidepressive drugs like serotonin reuptake inhibitors (SSRI), which may even allow continuation of IFN-alpha therapy. In patients with severe depression or organic personality changes with increased risk of suicide, immideate discontinuation of IFN-alpha therapy is mandatory and treatment in a psychiatric hospital must be considered.

Adult↗
PubMed1999

Tumor markers in peripheral blood of patients with malignant melanoma: multimarker RT-PCR versus a luminoimmunometric assay for S-100.

The identification of circulating tumor cells in the peripheral blood of patients with malignant melanoma by detection of melanoma associated protein transcripts using the reverse transcriptase polymerase chain reaction (RT-PCR) technique has been introduced as a noninvasive and sensitive technique for early detection of tumor progression and metastatic disease. An alternative approach is the analysis of S-100 protein in the serum of melanoma patients by a luminoimmunometric assay (LIA). In this study, the sensitivities of RT-PCR and LIA were compared. Seventy-seven blood samples of 59 melanoma patients were analyzed for tyrosinase, Melan-A/MART-1, MAGE-3, gp100, and p97 expression by multimarker RT-PCR; 540 serum samples of 352 melanoma patients were analyzed for S-100 protein concentration by LIA. In stage III 23.8% and in stage IV 37.5% of the samples were positive for at least one marker in multimarker RT-PCR, versus 8.1% and 48.1% of elevated S-100 levels analyzed by LIA, respectively. In a direct comparison, 31 identical samples were analyzed by multimarker RT-PCR and by S-100 LIA. In stage III 18.2% and in stage IV 45% of the samples were positive by multimarker RT-PCR versus 45.5% and 80% by S-100 LIA, respectively. S-100 LIA was more sensitive in detection of metastatic disease in melanoma patients than multimarker RT-PCR and should be evaluated in further studies. RT-PCR might be more useful in the analysis of micrometastases in anatomic compartments other than peripheral blood.

Biomarkers, Tumor↗
PubMed1999

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↗
PubMed1999

[Adjuvant therapy of malignant melanoma].

The goal of adjuvant therapy after routine surgery of malignant melanoma is the effective suppression of progression of disease caused by clinically inapparent micrometastases. While individual small and mostly retrospective clinical studies comparing adjuvant chemotherapy with untreated historical controls suggested a possible benefit for treated patients, large and multicenter prospective, randomized studies failed to clearly demonstrate a benefit for treated patients in regard to improvement of disease free or overall survival. Therefore, adjuvant chemotherapy can no longer be recommended for patients with malignant melanoma outside of controlled clinical studies. Current promising candidates for successful adjuvant therapy of patients with malignant melanoma are recombinant biological response modifiers, in particular interferons. Three randomized studies consistently reported a benefit in regard to relapse free survival for patients treated with interferon-alpha compared to untreated controls. However, the impact, on extension of overall survival ('cure') remains unclear. Furthermore, to date, no definitive data on the optimal dose and duration of interferon-alpha-therapy are available. Thus, patients with high risk of tumor progression should be enrolled in national and international prospective, randomized clinical trials, which may lead to valid data and clear recommendations about optimal adjuvant therapy.

Chemotherapy, Adjuvant↗
PubMed1999

In vivo selective expansion of a tumour-specific cytotoxic T-cell clone derived from peripheral blood of a melanoma patient after vaccination with gene-modified autologous tumour cells.

Melanoma-specific cytotoxic T lymphocytes (CTL) can be generated from peripheral blood lymphocytes (PBL) by mixed lymphocyte-tumour cell cultures. Analysis of CTL precursor frequencies in peripheral blood of melanoma patients is generally used for immunomonitoring purposes to evaluate vaccination efficacy. At present, it is unclear whether PBL-derived CTL generated in vitro are indicative of an anti-tumour immune response in vivo. Three tumour-specific human leucocyte antigen (HLA)-B/C-restricted CTL clones were derived from peripheral blood of a melanoma patient immunized with interleukin-7 (IL-7) gene-modified tumour cells. CTL clones differing in their T-cell receptor-gamma (TCRgamma) rearrangement produced interferon-gamma, IL-4 and/or IL-10. On the basis of their unique TCRgamma gene rearrangements clone-specific primers were generated for detection of clone-specific DNA by polymerase chain reaction. One CTL clone (E5) of the three was found to be selectively expanded in one of seven metastases obtained at autopsy, as determined by Southern blot hybridization. However, the presence of E5 in only one of seven metastases at death indicates that the in vivo accumulation of the specific CTL clone was not sufficient to contain tumour progression. Nevertheless, our data support the proposition that analysis of anti-tumour activity of PBL-derived CTLs may reflect an anti-tumour immune response in vivo.

Blotting, Southern↗
PubMed1999

[Clinical and epidemiological data of patients with malignant melanoma from the Munich Tumor Center 1977-1997].

Since 1997, data of patients with malignant melanomas have been systematically documented in the tumor registry of the Tumor Center Munich. Analysis of data of 8071 patients revealed that tumor thickness has steadily declined over the years. While in 1977 the median tumor thickness was 1.45 mm, it is now 0.75 mm. This has been followed by a significant improvement in overall survival. Males and older patients tend to have thicker melanomas than females and younger patients. There has been a relative increase of melanomas of the trunk. At diagnosis, 95% of patients had local disease. Of these patients, 18.3% developed metastastes. At least two-thirds of these patients had progression at the primary tumor site or the regional lymph nodes, both of which can be assessed by clinical or ultrasound examinations. Overall survival of patients with thin melanomas is excellent and does not differ substantially from the overall survival of the general population comparable in sex and age.

Adult↗
PubMed1998

Recombinant adeno-associated virus for the generation of autologous, gene-modified tumor vaccines: evidence for a high transduction efficiency into primary epithelial cancer cells.

To explore the potential of recombinant vectors based on recombinant adeno-associated virus (rAAV) for cancer vaccination, we investigated the transduction efficiency of rAAV into cancer cells ex vivo. Infection of human epithelial cancer cell lines with rAAV carrying reporter genes encoding beta-galactosidase (rAAV/LacZ) or luciferase (rAAV/Luc) resulted in high levels of reporter gene expression (>90% positive cells). In marked contrast, rAAV poorly transduced all murine tumor cell lines, as well as human hematopoietic cell lines. Either irradiation or adenovirus infection of tumor cells prior to rAAV infection induced a 10- to 100-fold increase of reporter gene expression. To determine the transduction efficiency of rAAV into primary cancer cells, freshly isolated, irradiated tumor cells from malignant melanoma and ovarian carcinoma patients were infected with rAAV/Luc, resulting in up to 6.9-fold higher levels of gene expression than in a HeLa tumor cell line. Time course experiments with freshly isolated tumor cells infected with rAAV/Luc showed maximal levels of luciferase expression between days 3 and 9 posttransduction. Simultaneous infection of primary tumor cells with up to three rAAV vectors containing genes encoding the immunostimulatory proteins B7-2 (CD86), p35 subunit of IL-12, and p40 subunit of IL-12 resulted in high expression of B7-2 in more than 90% of the tumor cells and in the secretion of high levels of IL-12. Taken together, our results demonstrate that rAAV efficiently transduces freshly isolated human, epithelial tumor cells and might therefore be a potent tool to produce improved, gene-modified cancer vaccines.

Antigens, CD↗
PubMed1998

Low-dose UVA phototherapy for treatment of localized scleroderma.

BACKGROUND: For treatment of localized scleroderma numerous treatments, including ones with potentially hazardous side effects, are currently used with only limited success. OBJECTIVE: We attempted to determine the efficacy of low-dose UVA1 irradiation in patients with severe localized scleroderma. METHODS: Patients were irradiated with 20 J/cm2 UVA1 for 12 weeks (total number of treatments: 30; cumulative UVA1 dose: 600 J/cm2). RESULTS: Low-dose UVA1 irradiation induced significant clinical improvement (clearance of > 80% of lesions) in 18 of 20 patients. Clearance was documented by clinical score as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: Low-dose UVA1 phototherapy can be highly effective for sclerotic plaques, even in patients with advanced localized scleroderma and with lesions rapidly evolving despite conventional therapy.

Adolescent↗
PubMed1998

Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma.

Very rapid progression of disease with a median survival of 6-9 months is a common feature of metastatic cutaneous malignant melanoma. Nevertheless, substantial variability of survival suggests that metastatic cutaneous malignant melanoma can be divided into several biological subgroups. Pretreatment serum levels of soluble adhesion molecules and various clinical parameters in cutaneous metastatic malignant melanoma were evaluated to determine their prognostic value. In this study pretreatment serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular cell adhesion molecule 1 (sICAM-1), soluble endothelial leukocyte adhesion molecule 1 (sE-selectin) and multiple clinical factors were assessed in relation to overall survival of 97 consecutive patients with metastatic cutaneous malignant melanoma seen at our institution between May 1990 and April 1996. For statistical analysis, both univariate and multivariate Cox proportional-hazards models were used. Elevated pretreatment serum levels of sVCAM-1 (P < 0.005) and of lactate dehydrogenase (P < 0.002) were rendered statistically independent and were significantly associated with unfavourable outcome. Patients were assigned to one of three risk categories (low, intermediate and high) according to a cumulative risk score defined as the function of the sum of these two variables. There were significant differences in overall survival (P < 0.0001) between low- (n = 53, 5-year survival probability of 23.3%), intermediate- (n = 29, 5-year survival probability of 9.9%) and high-risk (n = 15) patients. Elevated pretreatment serum levels of sVCAM-1 and of lactate dehydrogenase correlate with poor outcome in metastatic cutaneous malignant melanoma. These data support risk stratification for future therapeutic trials and identify factors that need to be validated in prospective studies and may potentially influence decision-making in palliative management of patients with disseminated cutaneous malignant melanoma.

Adult↗
PubMed1997

Elevated serum levels of S100 and survival in metastatic malignant melanoma.

Current reports suggest serum S100 as a prognostic marker for disease progression in advanced malignant melanoma. In this study, we assessed serum levels of S100 and multiple clinical factors in relation to overall survival in 99 patients with metastatic malignant melanoma seen at our institution between May 1990 and April 1996. For statistical analysis, we used both univariate and multivariate Cox proportional-hazards models. Elevated serum levels of S100 correlated with poor outcome in metastatic malignant melanoma (P < 0.0001), univariate analysis). Upon multivariate analysis, however, S100 added no information to known clinical prognostic parameters.

Aged↗
PubMed1997

Detection of melanoma cells in peripheral blood stem cell harvests of patients with progressive metastatic malignant melanoma.

The detection of melanocyte-specific messenger RNA in patients with malignant melanoma suggests the potential contamination of peripheral blood stem cell (PBSC) harvests by neoplastic cells. In this study, the melanocyte-specific transcripts of tyrosinase and Melan-A/MART-1 were used to detect neoplastic cells in PBSC harvests of nine metastatic malignant melanoma patients. Only one patient's PBSC harvest tested positive for tyrosinase. All harvests were negative for Melan-A/MART-1. Our results suggest that contamination of PBSC harvests with neoplastic cells may not contribute to disease progression following high-dose chemotherapy in advanced malignant melanoma.

Adult↗