Methotrexate in the treatment of mycosis fungoides - a multicenter observational study in 79 patients.

OBJECTIVE: The first report concerning methotrexate (MTX) in the treatment of Mycosis fungoides (MF) was published in 1964 by Wright. The mechanism of MTX action in the treatment of primary cutaneous T-cell lymphoma (CTCL) has been not explained in detail yet (the anti-inflammatory, immunomodulating, immunosuppressive, and cytostatic actions have been under discussion). PATIENTS AND METHODS: This is a retrospective analysis of 79 MF patients in 4 dermatology clinical centers in Poland. Data are presented in terms of the duration, use of MTX, the effectiveness of treatment with MTX in terms of time required to achieve remission, the disease stage, route of administration, age at diagnosis and the dosage. Moreover, the occurrence of side effects depending on the route of administration and duration of therapy with MTX was analyzed. RESULTS: The analysis has revealed that 56 patients (70,9%) had achieved remission on the MTX. The remission began in the 1st month of therapy in 20% of patients, lasted 4 to 6 months in 50% of cases. At least 12 months' remission was confirmed in 25% of patients (2-year-long only in 10% and 3-year-long in 5% of patients). The time to remission was related to the stage of disease at diagnosis as well as to minimal and maximal dose of MTX. The total therapeutic dose of MTX was found important for the course of the disease: higher total dose had prolonged the remission. CONCLUSIONS: Despite the common use of MTX in MF patients, relatively few clinical studies have been published. The response of MF subjects to MTX seems to depend on the stage and, more importantly, the dose of MTX treatment. Methotrexate appears to be an effective treatment at every stage of MF; however, it is not devoided of side effects such as infections and elevated level of aminotransferases, which are most common.

Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy.

BACKGROUND: Various skin diseases are commonly observed in diabetic patients. Typical biophysical properties of diabetic skin such as lower skin elasticity, decreased water content in stratum corneum, increased itching and sweating disturbances are reported. The aim of the study was to examine the distribution and intensity of skin pigmentation in diabetic patients in correlation with the metabolic control and with presence of microangiopathy. MATERIAL AND METHODS: The study was conducted on 105 patients (42 men and 63 women, median age 31), with type 1 diabetes (DM1). The control group of 53 healthy individuals (22 men and 31 women) was age- and sex-matched. Skin pigmentation was measured at 3 different locations of the body (cheek, dorsal surface of a forearm and dorsal surface of a foot) using Mexameter® MX 18. We calculated melanin index (MI) by the meter from the intensities of absorbed and reflected light at 880 nm. RESULTS: Patients with DM1 had lower MI on the foot (173.2 ± 38.8 vs. 193.4 ± 52.7, p=0.016) as compared to controls. In the univariate analysis cheek MI was negatively related to HbA1c level (ß=-4.53, p=0.01). Forearm MI was negatively associated with daily insulin dose (ß=-0.58, p=0.01), BMI (ß=-3.02, p<0.001), waist circumference (ß=-0.75, p=0.009), serum TG concentration (ß=-18.47, p<0.001) and positively with HDL cholesterol level (ß=15.76, p=0.02). Diabetic patients with hypertension had lower foot MI values (ß=-18.28, p=0.03). Lower MI was associated with the presence of diabetic neuropathy (ß=-18.67, p=0.04) and retinopathy (ß=-17.47, p=0.03). CONCLUSIONS: In conclusion, there seems to be loss of melanocytes in type 1 diabetes. The melanin content is related to glycemic control of diabetes and obesity. The lower melanin content the higher possibility of microangiopathy. This is a first report in the literature devoted to distribution of melanin in the skin of type 1 diabetic patients.

Human cancer gene therapy with cytokine gene-modified cells.

Cytokines can impede tumour growth and activate innate and adaptive immune responses, leading to elimination of cancer cells. For many years, it was believed that systemic administration of recombinant cytokines might become a standard treatment of different cancer types. However, due to a high toxicity of therapeutic doses and a low efficacy, even in combination with chemotherapy, this strategy is generally not accepted. On the other hand, cancer gene therapy approaches utilising cells modified with cytokine genes seem to represent a novel promising approach. For the last decade, numerous Phase I and II clinical trials evaluating different therapies based on cytokine gene-modified cells have been carried out. In the early studies, several strategies have been shown to improve clinical outcomes and induce strong antitumour immune responses. Recently, a few prospective, randomised, Phase III clinical trials have been initiated in order to finally determine the efficacy of particular cancer immunogene therapy strategies. This article reviews the present status and perspectives of clinical trials of cancer immunotherapies utilising cytokine gene-modified cells.

The 34th Annual Meeting of the German Society of Immunology with participation of the Polish Society of Experimental and Clinical Immunology.

The 34th Annual Meeting of the German Society of Immunology was held in Berlin on 24 - 27 September 2003. This meeting, organised for the first time in cooperation with the Polish Society for Experimental and Clinical Immunology, gathered 1200 participants, mostly from central Europe. The programme comprised > 30 symposium lectures and > 750 oral and poster presentations. The main concept of this meeting was based on the rule of ABC--Applied, Basic and Clinical immunology. The state-of-the-art lectures devoted to immuno-based therapies provided by experts in the particular fields discussed some well-known therapeutic approaches. However, several workshop presentations demonstrated novel approaches employing biological therapies. These lectures are the focus of these meeting highlights.

Genetically modified dendritic cells--a new, promising cancer treatment strategy?

Dendritic cells (DCs), the most potent antigen-presenting cells (APCs), were discovered almost 30 years ago. Due to the priming of antigen-specific immune responses mediated by CD4+ and CD8+ lymphocytes, DCs are crucial for the induction of adaptive immunity against cancer. Therefore, vaccination of cancer patients with DCs presenting tumour-associated antigens (TAAs) have been believed to be a promising anticancer strategy. Multiple clinical trials have been carried out in order to evaluate the safety and efficacy of cancer vaccines based on antigen-pulsed DCs. However, pulsing of DCs with particular peptides has several disadvantages: i) short-time duration of antigen-major histocompatability complex (MHC) complexes, ii) a requirement for matching defined peptides with MHC complexes and iii) exclusive presentation of single antigen epitopes. Application of gene transfer technologies in the field of DC-based vaccines made possible the development of novel, anticancer immunisation strategies. In several animal models, DCs modified with genes encoding TAA or immunostimulatory proteins have been shown to be effective in the induction of antitumour immune responses. Based on these encouraging results, a first clinical trial of prostate cancer patients vaccinated with gene modified DCs has recently been initiated. In this article, methods used for genetic modification of DCs and anticancer vaccination strategies based on genetically modified DCs are reviewed.