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All-trans Retinoic Acid (all-tran + retinoic_acid)
Selected AbstractsAn efficient therapeutic approach to patients with acute promyelocytic leukemia using a combination of arsenic trioxide with low-dose all-trans retinoic acidHEMATOLOGICAL ONCOLOGY, Issue 2 2004Guanjun Wang Abstract The use of arsenic trioxide (As2O3, ATO) combined with all-trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low-dose ATRA (LD-ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD-ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD-ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side-effects have been no worse with the combined ATO/LD-ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD-ATRA regimen is superior to either regimen given alone to patients with APL. Copyright © 2004 John Wiley & Sons, Ltd. [source] PLC-,2 monitors the drug-induced release of differentiation blockade in tumoral myeloid precursorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Federica Brugnoli Abstract The differentiation therapy in treatment of acute promyelocytic leukemia (APL), based on the administration of all-trans retinoic acid (ATRA), is currently flanked with the use of As2O3, a safe and effective agent for patients showing a resistance to ATRA treatment. A synergy between ATRA and As2O3 was also reported in inducing granulocytic differentiation of APL-derived cells. We have demonstrated that phospholipase C-,2 (PLC-,2), highly expressed in neutrophils and nearly absent in tumoral promyelocytes, largely increases during ATRA treatment of APL-derived cells and strongly correlates with the responsiveness of APL patients to ATRA-based differentiating therapies. Here we report that, in APL-derived cells, low doses of As2O3 induce a slight increase of PLC-,2 together with a moderate maturation, and cooperate with ATRA to provoke a significant increase of PLC-,2 expression. Remarkably, the amounts of PLC-,2 draw a parallel with the differentiation levels reached by both ATRA-responsive and -resistant cells treated with ATRA/As2O3 combinations. PLC-,2 is not necessary for the progression of tumoral promyelocytes along the granulocytic lineage and is unable to overcome the differentiation block or to potentiate the agonist-induced maturation. On the other hand, since its expression closely correlates with the differentiation level reached by APL-derived cells induced to maturate by drugs presently employed in APL therapies, PLC-,2 represents indeed a specific marker to test the ability of differentiation agents to induce the release of the maturation blockade of tumoral myeloid precursors. J. Cell. Biochem. 98: 160,173, 2006. © 2006 Wiley-Liss, Inc. [source] Effect of all-trans retinoic acid on apoptosis and expression of regulatory genes (Bcl-2, Fas, ICE) in experimentally induced gastric epithelial cell dysplasia in ratsJOURNAL OF DIGESTIVE DISEASES, Issue 1 2001Cui Rutao OBJECTIVE: To study the mechanism and effect of all-trans retinoic acid on apoptosis and the expression of Bcl-2, Fas and ICE in experimentally induced dysplastic gastric epithelial cells. METHODS: Apoptosis and expression of Bcl-2, Fas and ICE in gastric epithelial cells was studied using the terminal dUTP nucleotide end-labeling (TUNEL) technique. The immunohistochemistry of Wistar rats enrolled in three groups was studied: group 1, blank controls; group 2, dysplasia induced by N -methyl- N -nitro- N -nitrosoguanidine (MNNG) and then treated with all-trans retinoic acid; and group 3, dysplasia induced by MNNG and treated with a placebo. RESULTS: In the three groups, the rates of dysplasia were 0, 26.7 and 73.3%; the apoptosis indices were 8.3 ± 3.1, 7.8 ± 2.6 and 2.2 ± 0.4; the expression of Bcl-2 was 13.3, 33.3 and 66.7%; and overexpression of Bcl-2 was 6.7, 6.7 and 33.3%, respectively. There were significant differences between group 2 and group 3 (P < 0.05), but no significant differences were found between group 2 and group 1 (P > 0.05). The expression rates of Fas were 46.7, 40 and 6.7%; the overexpression rates were 13.3, 26.7 and 13.3%, respectively; the expression rates of ICE were 20, 60 and 13.3%; the overexpression rates were 0, 13.3 and 6.7% in the three groups, respectively. The expression rates of Fas and ICE in group 2 were significantly different from that of group 3 (P < 0.05), but there were no significant differences in overexpression rates between group 2 and group 3. No significant differences were found either in expression or overexpression of Fas and ICE between group 2 and group 1. CONCLUSIONS: These results suggest that all-trans retinoic acid inhibits Bcl-2 expression, promotes Fas expression, enhances ICE expression and gastric mucosal epithelial cell apoptosis, and thus may reverse or inhibit the progression to cancer. [source] Secondary clonal cytogenetic abnormalities following successful treatment of acute promyelocytic leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009Crisoula Batzios To identify patients who developed secondary clonal cytogenetic aberrations (CCA) following therapy for acute promyelocytic leukemia (APL), we retrospectively analyzed cytogenetic results from 123 patients diagnosed with APL between 1995 and 2007, who had ongoing cytogenetic analysis undertaken in our laboratory. During follow-up for APL we identified 12 patients (9.8%) who developed CCA, not detected at diagnosis of APL and unrelated to their original APL karyotype. All patients had received all-trans retinoic acid (ATRA) and chemotherapy and were in complete remission for APL when secondary CCA were identified. The median latency period between diagnosis of APL and emergence of secondary CCA was 27.5 months (range: 2,54 months). To date, four patients with CCA have been diagnosed with therapy-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (t-AML), giving a median t-MDS/AML free survival of 78 months, with follow-up ranging between 20 and 136 months from APL diagnosis. Three patients have died: two patients died of t-AML and another developed relapsed APL with persistence of his secondary clone but no diagnosis of t-MDS/AML and died from transplant-related complications. Two patients are alive with t-MDS. Seven patients with CCA are alive with no morphological evidence of MDS at the time of their last known follow-up; thus median survival has not been reached. The appearance of these abnormalities in the absence of morphological evidence of MDS in the majority of patients is unusual, and highlights the importance of continued cytogenetic follow-up in these patients. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Factors affecting proliferation and differentiation of lepidopteran midgut stem cells,ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2010Marcia J. Loeb Midgut stem cells of last instar larvae and pupae of Heliothis virescens, Lymantria dispar and several other Lepidopteran species have been cultured in vitro and have been induced to proliferate using low titers of ecdysteroids and the 77-Kda peptide fragment, ,-arylphorin, isolated and identified from pupal fat body tissue. The insulin-related hormone, Bombyxin, also induced mitosis in cultured midgut stem cells; it appeared to be fast-acting and quickly inactivated, while ,-arylphorin was slower to act and had a longer lasting effect in vitro, indicating different functions for these proliferation agents. Changes in Calcium ion concentration within or outside the cells discretely affected stem cell differentiation, indicating a role for second messenger participation in peptide regulation of this process. Four different peptides (MDFs 1,4) that induced midgut stem cells to differentiate to mature midgut cell types in vitro were isolated and characterized from conditioned media and hemolymph of H. virescens and L. dispar. However, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and all-trans retinoic acid (RA) from vertebrate sources induced differentiation to non-midgut cell types as well. MDF1 was located in basal areas of columnar cells of midgut epithelium, although MDF2 was observed in all of the cytoplasm of columnar cells and in droplets of antibody positive material in the midgut lumen, suggesting a digestive function as well for this peptide. Anti-MDF-3 stained the central areas of cultured midgut columnar cells and the bases of columnar cells of midgut epithelium in vivo. Midgut secretory cells stained with anti-MDF-4; streams of MFD-4-positive material were observed extending from secretory cells facing the epithelial lumen, and as a layer on the hemolymph-facing side, suggesting an endocrine or paracrine function for this or an immunologically similar peptide. Published 2010 Wiley Periodicals, Inc. [source] Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acidCANCER, Issue 1 2005Chiara Pilatrino M.D. Abstract BACKGROUND The authors investigated the efficacy and safety of the histone deacetylase inhibitors valproic acid (VPA) and all-trans retinoic acid (ATRA) as differentiation agents in a cohort of older, poor-risk patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). METHODS Twenty older patients with recurrent or refractory AML or MDS were treated in a Phase II protocol with sequential VPA and ATRA therapy. VPA was started at a dose of 10 mg/kg per day and then escalated to achieve the serum concentration of 45,100 ,g/mL. ATRA was added at 45 mg/square meters (sm) per day when VPA reached the target serum concentration. Only patients treated continuously for , 2 months were considered evaluable. RESULTS Hematologic improvement, according to World Health Organization criteria, was observed in 6 of 20 patients enrolled in the protocol but in 6 of 11 considered evaluable. In five patients, a major platelet response was observed, achieving platelet transfusion independence. Three of these five patients also exhibited a minor erythroid response. A sixth patient showed both a minor erythroid response and a platelet response. The median duration of response was 189 days (range, 63,550 days). No significant reduction in the blast count was observed. Grade 3 neurocortical toxicity was observed in four patients. Severe bone pain was experienced by 4 patients (2 Grade 4 and 2 Grade 3) and was associated with an increase in the peripheral blast cell count. Treatment with ATRA did not modify the response observed with VPA alone. CONCLUSIONS Differentiation therapy with VPA was of clinical benefit in approximately 30% of elderly patients with AML and MDS of the refractory anemia with excess of blast type with unfavorable prognostic features. A striking platelet transfusion independence lasting several months may be obtained in some patients, reducing the burden of palliative care and improving the quality of life. Cancer 2005;. © 2005 American Cancer Society. [source] | ||||||||||