ALL-TRANS-RETINOIC ACID-INDUCED GROWTH SUPPRESSION OF BLASTEMAL WILMS' TUMOR

1996 ◽  
Vol 16 (5) ◽  
pp. 777-789
Author(s):  
Timothy Vincent
Keyword(s):  
Retinoic Acid ◽  
Wilms Tumor ◽  
Growth Suppression ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-Trans-Retinoic ACID-Induced Growth Suppression of Blastemal Wilms' Tumor

1996 ◽  
Vol 16 (5) ◽  
pp. 777-790 ◽  
Author(s):  
Timothy Vincent ◽  
Gian Re ◽  
Debra Hazen-Martin ◽  
Betty Tarnowski ◽  
Mark Willingham ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Wilms Tumor ◽  
Growth Suppression ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-Trans-Retinoic ACID-Induced Growth Suppression of Blastemal Wilms’ Tumor

1996 ◽  
Vol 16 (5) ◽  
pp. 777-790
Author(s):  
Timothy S. Vincent ◽  
Gian G. Re ◽  
Debra J. Hazen-Martin ◽  
Betty I. Tarnowski ◽  
Mark C. Willingham ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Wilms Tumor ◽  
Growth Suppression ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

ALL-TRANS-RETINOIC ACID-INDUCED GROWTH SUPPRESSION OF BLASTEMAL WILMS' TUMOR

1996 ◽  
Vol 16 (5) ◽  
pp. 777-789 ◽  
Author(s):  
Timothy S. Vincent ◽  
Gian G. Re ◽  
Debra J. Hazen-Martin ◽  
Betty I. Tarnowski ◽  
Mark C. Willingham ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Wilms Tumor ◽  
Growth Suppression ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Expression of the Wilms’ Tumor 1 (WT1) Gene Renders Acute Promyelocytic Leukemia Cells Resistant to All-Trans-Retinoic-Acid-Induced Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4385-4385
Author(s):  
Aschwin L. Menke ◽  
Ruth H.J.N. Knops ◽  
Jurgen A.F. Marteijn ◽  
Willemijn Wissink ◽  
Josie Smeets ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Wilms Tumor ◽  
Promyelocytic Leukemia ◽  
Induced Differentiation ◽  
Expression Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Wilms Tumor 1

Abstract Acute myeloid leukemia is characterized by the uncontrolled proliferation of immature cells that have lost their ability to differentiate. In the case of acute promyelocytic leukemia (AML-M3), the cells can be forced to differentiate by pharmacological dosages of all-trans retinoic acid (ATRA), a phenomenon that is successfully used in the treatment of APL patients. About 70% of the patients, suffering from PML-RARa -positive acute promyelocytic leukemia, can be cured with a combination of ATRA and anthracycline - based chemotherapy. However, relapse remains a major problem. The molecular mechanisms by which the retinoic acid receptors mediate their biological functions have been studied extensively and although various retinoic acid-responsive genes have been identified, the target genes that are crucially involved in leukemogenesis are unknown. The Wilms’ Tumor 1 gene, has been implicated in the development of leukemia. WT1 overexpression can be detected in most acute leukemias and is particularly highly expressed in APL cells. Several groups have found an inverse correlation between the expression levels of WT1 and the overall survival of leukemia patients. The underlying mechanism, however, remains to be elucidated. We have shown that the Wilms’ Tumor 1 (WT1) is strongly downregulated in APL cells, during ATRA-induced differentiation. Using a newly developed realtime RT-PCR method we have found that the expression levels of all four major WT1 isoforms are downregulated. To study the biological activity of each WT1-isoform, we have retrovirally transduced the APL cell line NB4, with the 4 major WT1 isoforms and analyzed the effect on ATRA-induced differentiation. Using flowcytometry and NBT staining, we show that ectopic expression of the different WT1-isoform inhibited ATRA-induced differentiation and subsequently, the apoptosis of APL cells, albeit with different potential. WT1-transduced cells survived pharmacological dosages of ATRA for more than 14 days and in some cases even continued to grow. These data indicate that downregulation of WT1 is essential for ATRA-induced differentiation of APL cells and provide an explanation why AML patients with high WT1 expression levels have worse overall survival in comparison to patients with low WT1 expression levels.

Rhabdomyomatous differentiation in primary Wilms tumor and hepatic metastases after chemotherapy and all-trans-retinoic acid in combination with interferon-α

2011 ◽  
Vol 57 (4) ◽  
pp. 698-699
Author(s):  
Yu-Hua Chao ◽  
Han-Ping Wu ◽  
I-Ping Chiang ◽  
Ching-Tien Peng ◽  
Yung-Li Yang ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Wilms Tumor ◽  
Hepatic Metastases ◽  
Interferon Α ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Oncogene ◽  
2005 ◽  
Vol 24 (33) ◽  
pp. 5246-5251 ◽  
Author(s):  
Birgit Zirn ◽  
Birgit Samans ◽  
Christian Spangenberg ◽  
Norbert Graf ◽  
Martin Eilers ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Tumor Cells ◽  
Acid Treatment ◽  
Wilms Tumor ◽  
Retinoic Acid Treatment ◽  
Trans Retinoic Acid ◽  
Expression Of Genes ◽  
All Trans Retinoic Acid

Phase I trial and pharmacokinetic study of all-trans-retinoic acid administered on an intermittent schedule in combination with interferon-alpha2a in pediatric patients with refractory cancer.

1997 ◽  
Vol 15 (11) ◽  
pp. 3330-3337 ◽  
Author(s):  
P C Adamson ◽  
G Reaman ◽  
J Z Finklestein ◽  
J Feusner ◽  
S L Berg ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Phase Ii ◽  
Drug Exposure ◽  
Wilms Tumor ◽  
Objective Response ◽  
Plasma Concentrations ◽  
Intermittent Schedule ◽  
Time Curve ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

PURPOSE To determine the maximum-tolerated dose (MTD) of all-trans-retinoic acid (ATRA) administered on an intermittent oral schedule with interferon-alpha2a (IFN-alpha2a) in children with refractory cancer, and whether the marked reduction in plasma ATRA concentrations observed with chronic daily oral dosing could be circumvented with an intermittent dosing schedule. PATIENTS AND METHODS Thirty-three children with refractory cancer (stratified by age, < or = 12 and > 12 years) were treated with ATRA 3 consecutive days per week and IFN-alpha2a 3 x 10(6) U/m2 5 consecutive days per week, both repeated weekly. The starting dose of ATRA was 60 mg/m2/d divided into three doses, with planned escalations to 90 and 120 mg/m2/d. Because severe headaches have been noted to occur on the initial day of ATRA administration, only two of three doses of ATRA were administered on day 1 of each week. RESULTS Pseudotumor cerebri or dose-limiting headache was observed in two of five patients older than 12 years treated at the 120-mg/m2/d dose level and in one of six < or = 12 years at the 90-mg/m2/d level. Other non-dose-limiting toxicities of ATRA included reversible elevations in hepatic transaminases and triglycerides, dry skin, cheilitis, and nausea/vomiting. One child with recurrent neuroblastoma had an objective response of 6 months' duration, and one with recurrent Wilms' tumor had histologic maturation of multiple tumors. This intermittent schedule allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. Following 30-mg/m2 doses, the ATRA area under the concentration-time curve (AUC) decreased from 96 +/- 14 micromol/L/min on day 1 to 26 +/- 24 micromol/L/min by day 3 of drug administration, but on day 1 of the fourth consecutive week of therapy, the AUC averaged 110 +/- 16 micromol/L/min. The recommended pediatric phase II dose of ATRA administered on this schedule is 90 mg/m2/d. CONCLUSION An intermittent schedule of ATRA administration appears to circumvent the low plasma drug exposure that is a result of the sustained upregulation of metabolism when this drug is administered on a chronic daily schedule. Based on the results of this trial, a phase II trial of ATRA/IFN-alpha2a in neuroblastoma and Wilms' tumor using this schedule is in progress.

scholarly journals Expression profile of Wilms Tumor 1 (WT1) isoforms in undifferentiated and all-trans retinoic acid differentiated neuroblastoma cells

2016 ◽  
Vol 7 (1-2) ◽  
pp. 47-58 ◽  
Author(s):  
Grazia Maugeri ◽  
Agata Grazia D’Amico ◽  
Daniela Maria Rasà ◽  
Rita Reitano ◽  
Salvatore Saccone ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Expression Profile ◽  
Wilms Tumor ◽  
Neuroblastoma Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Wilms Tumor 1
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