Biomedical subjects

Selma Ugurel

Publications and source records attributed to Selma Ugurel.

22 records · Page 2Linked to original sources

PubMed2003

Chemosensitivity testing in malignant melanoma.

The prognosis of patients with metastatic melanoma remains poor. In patients with distant metastases only low response rates between 10% and 15% have been achieved by the most effective cytostatics in single-agent therapy leading to a mean 5-year survival rate of less than 5%. More aggressive treatment regimens using multidrug chemotherapy yielded response rates of up to 40% but failed to show a significant benefit in overall survival compared to single-agent therapy. However, complete remissions of metastatic lesions after multidrug cytostatic regimens have been reported in some cases of melanoma patients. To evaluate an in vitro test system providing information on the drug sensitivity profile of melanoma cells, we examined tumor tissue specimens from 31 metastatic melanoma patients with an ATP-based chemosensitivity assay (ATP-TCA) testing eight anticancer drugs alone or in different combinations. Chemosensitivity was assessed using a luciferin-luciferase- based luminescence assay providing individual chemosensitivity indices for each test drug. We found a heterogeneous chemosensitivity in the melanoma tissue samples tested. The highest sensitivity was detected for the combination of treosulfan and gemcitabine, with 76% of the tissue samples revealing high sensitivity and 10% resistance, followed by the combination of paclitaxel and doxorubicine (66%/0%), gemcitabine and cisplatin (55%/21%),and paclitaxel and cisplatin (46%/8%). Our data indicate that the ATP-TCA can be used to select patients who might benefit from an individually adapted cytostatic therapy. On the basis of these results a multicenter trial has recently been initiated to evaluate the feasibility and predictive value of an ATP-TCA directed chemotherapy in metastatic melanoma patients.

Adenosine Triphosphate↗

PubMed2003

Treosulfan and gemcitabine in metastatic uveal melanoma patients: results of a multicenter feasibility study.

No effective treatment currently exists for metastatic uveal melanoma. However, recent results obtained by an ATP-based tumor chemosensitivity assay have shown consistent activity of treosulfan+gemcitabine in up to 80% of tumor specimens tested. In this study we describe the first clinical results observed with this drug combination at different European centers in patients with metastatic uveal melanoma. Clinical case series of patients with metastatic uveal melanoma were treated with treosulfan+gemcitabine at seven different centers. Fourteen patients, 13 previously untreated and one pretreated with chemoimmunotherapy, were included in the study. Patients received treosulfan+gemcitabine in four different dose regimens. The response rates, progression-free and overall survival, and toxicity were evaluated. The analysis of 14 patients revealed one complete response, three partial responses and a stable disease in eight cases. The objective response rate was 28.6%, the median overall survival was 61 weeks [95% confidence interval (CI) 54-133 weeks], the progression-free survival was 28.5 weeks (95% CI 13-62 weeks) and the 1-year survival rate was 80%. The drugs were well tolerated. The most common side-effects were leuko- and thrombocytopenia. These preliminary results suggest potential therapeutic benefit of treosulfan+gemcitabine treatment in metastatic uveal melanoma and warrant further controlled studies.

Aged↗

PubMed2002

Soluble HLA-DR is a potent predictive indicator of disease progression in serum from early-stage melanoma patients.

Despite numerous therapeutic options, the prognosis of malignant melanoma, once metastasized, is still poor. Thus, the search for reliable methods to identify patients with high risk of disease progression as early as possible is of major importance. In our study, we analyzed the predictive value of soluble HLA-DR (sHLA-DR) in comparison to S100-beta in serum from 183 melanoma patients of different stages of disease and with or without current therapy using immunosorbent assays. sHLA-DR serum levels of 121 healthy individuals served as controls. We found significantly (p < 0.0005) reduced sHLA-DR serum levels in melanoma patients (0.70 +/- 0.08 SEM microg/ml) compared to controls (1.49 +/- 0.10 SEM microg/ml). Reduced sHLA-DR and increased S100-beta levels were associated with advanced disease stages and tumor load. S100-beta was increased under cytostatic therapy (p < 0.0005), whereas sHLA-DR was not influenced by therapy modalities. Univariate analysis showed an association of sHLA-DR < 0.3 microg/ml and S100-beta > 0.12 microg/l with poor overall (p = 0.021 and p = 0.0009) and progression-free survival (p < 0.0005 and p = 0.0025). Multivariate analysis revealed disease stage (p = 0.0093) and tumor burden (p < 0.0005) as independent predictive factors for overall survival, and sHLA-DR (p = 0.0007) and tumor burden (p = 0.0015) for progression-free survival. In contrast to S100-beta, sHLA-DR serum concentrations < 0.3 microg/ml were strongly associated (p = 0.0001) with poor progression-free survival in a subgroup of 60 nonmetastasized patients. In conclusion, our results suggest sHLA-DR as a potent prognostic serum marker in melanoma patients superior to S100-beta in helping to identify early-stage patients at high risk of disease progression.

Disease Progression↗

PubMedDate not supplied

Jo-1 positive paraneoplastic systemic sclerosis in a patient with metastatic melanoma.

A link between systemic sclerosis (SSc) and malignancy is suggested by epidemiological evidence, but the underlying mechanism connecting both diseases has been a source of ongoing controversy. Here, we describe the first case of paraneoplastic SSc secondary to a primarily diagnosed melanoma. Two months after diagnosis of metastatic melanoma, a 40-year-old female presented with high serum titers of antinuclear antibodies (ANA), but no symptoms of autoimmune disease. Five months later, the onset of Raynaud's phenomenon together with highly positive Jo-1 antibodies was observed. The following clinical course of scleroderma was correlated to melanoma remission and progression. Finally, the patient developed severe pulmonary fibrosis, massive pleural effusion, severe thoracic scleroderma and necrosis of the fingertips, simultaneously with a progression of melanoma to disseminated lymph node metastases and a small brain metastasis. This rare case of SSc concurrent with melanoma suggests that besides other possible mechanisms, paraneoplastic etiology can be responsible for the association between SSc and cancer.

Adult↗