ABSTRACT
Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Mycosis Fungoides/drug therapy , Retinoids/therapeutic use , Sezary Syndrome/drug therapy , Skin Neoplasms/drug therapy , Tetrahydronaphthalenes/therapeutic use , Administration, Cutaneous , Administration, Oral , Adult , Aged , Aged, 80 and over , Anticarcinogenic Agents/administration & dosage , Anticarcinogenic Agents/adverse effects , Bexarotene , Female , Humans , Hyperlipidemias/chemically induced , Hypothyroidism/chemically induced , Male , Middle Aged , Mycosis Fungoides/mortality , Peptic Ulcer Hemorrhage/chemically induced , Poland/epidemiology , Retinoids/administration & dosage , Retinoids/adverse effects , Retrospective Studies , Sezary Syndrome/mortality , Skin Neoplasms/mortality , Stomach Ulcer/chemically induced , Tetrahydronaphthalenes/administration & dosage , Tetrahydronaphthalenes/adverse effects , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: Treatment of T cell cutaneous lymphoma( CTCL) is a controversial subject and the effectiveness of treatment is still low. AIM: Report of single center experience of management CTCL after progression after first line treatment. MATERIAL AND METHODS: We present 41 patients with CTCL, 29 received interferon α2b in first line, and 12 of them received second line therapy. RESULTS: Overall response rate for second line therapy was 60%. CONCLUSIONS: Results of the follow-up of patients with mycosis fungoides after interferon α2b treatment failure with the literature review and discussion.
ABSTRACT
Jurkat human lymphoblastoid cells were incubated in increasing concentrations of doxorubicin (0.05, 0.1 and 0.15 µM) to induce cell death, and their expression of cyclin A, B1 and D1 was evaluated by flow cytometry (cell cycle progression, Annexin V assay, percentages and levels of each of the cyclins), transmission electron microscopy (ultrastructure) and confocal fluorescence microscopy (expression and intracellular localization of cyclins). After low-dose doxorubicin treatment, Jurkat cells responded mainly by G2/M arrest, which was related to increased cyclin B1, A and D1 levels, a low level of apoptosis and/or mitotic catastrophe. The influence of doxorubicin on levels and/or localization of selected cyclins was confirmed, which may in turn contribute to the G2/M arrest induced by the drug.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Cell Cycle Checkpoints/drug effects , Cyclin A/genetics , Cyclin B1/genetics , Cyclin D1/genetics , Doxorubicin/pharmacology , Gene Expression Regulation, Leukemic/drug effects , Cell Death/drug effects , Cyclin A/analysis , Cyclin B1/analysis , Cyclin D1/analysis , Humans , Jurkat Cells , Leukemia, T-Cell/drug therapy , Leukemia, T-Cell/geneticsABSTRACT
Cutaneous T-cell lymphomas (CTCLs) are slowly progressive diseases with a poor prognosis. There are no specific prognostic factors in development of cutaneous lymphomas. SATB1 protein controls expression of many genes, including the cellular cycle and apoptosis. The subject of our study was the expression of SATB1 protein in the skin sample in patients with mycosis fungoides and Sezary syndrome and its correlation with clinical course. Immunohistochemical reaction with SATB1 antibody was observed in 29 cases of mycosis fungoides of different stages (15 patients) and two cases of Sezary syndrome. SATB1 expression was observed in 22 cases of mycosis fungoides, 7 of which were in the patch stage, 11 were in the plaque stage and 4 were in the tumor stage. SATB1 expression was not found in 2 cases of the patch stage, 4 cases of the plaque stage and one case of the tumor stage. Negative reaction was confirmed in both cases of the Sezary syndrome. There were no changes in SATB1 expression during progression of the disease. A group of patients with the positive reaction of the SATB1 is characterized by a noticeably longer time to progression between the stages. The SATB1 expression seems to be a potential prognosis factor confirming the inner heterogeneous features of CTCLs.
Subject(s)
Biomarkers, Tumor/analysis , Lymphoma, T-Cell, Cutaneous/metabolism , Matrix Attachment Region Binding Proteins/biosynthesis , Skin Neoplasms/metabolism , Disease Progression , Female , Humans , Lymphoma, T-Cell, Cutaneous/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Skin Neoplasms/pathologyABSTRACT
Here we present a case report of a patient with mycosis fungoides (MF). A short overview of the currently used clinical algorithm and diagnostic methods is presented. The authors also provide a comparison of other T-cell skin lymphomas. The currently recommended disease staging is given.
Subject(s)
Mycosis Fungoides , Skin Neoplasms , Algorithms , Humans , Lymphoma, T-Cell, CutaneousABSTRACT
The purpose of this study was to evaluate the level of mitotic cyclin B1 in the context of senescence and cell death in A549 non-small cell lung carcinoma cells. This was performed through analysis of the cell cycle, the percentage of SA-ß-galactosidase-positive, as well as TUNEL-positive cells. Morphological alterations were studied using a transmission electron microscope. Changes in the intracellular level and the presence of cyclin B1 in the nucleus and cytoplasm areas were detected by flow cytometry and confocal fluorescence microscopy, respectively. In the cells exposed to various concentrations of doxorubicin, different kinds of cell death and senescent phenotype were observed. Alterations in the cell cycle and increased polyploidy may be indicative of mitotic catastrophe execution. Changes in cyclin B1 may also be strictly related to its different regulation at mitotic catastrophe and senescence programs.