Differentiation Therapy of Acute Promyelocytic Leukemia with Tretinoin (All-trans-Retinoic Acid)

Warrell, Raymond P.; Frankel, Stanley R.; Miller, Wilson H.; Scheinberg, David A.; Itri, Loretta M.; Hittelman, Walter N.; Vyas, Rakesh Kumar; Andreeff, Michael; Tafuri, Agostino; Jakubowski, Ann A.; Gabrilove, Janice; Gordon, Michael; Dmitrovsky, Ethan

doi:10.1056/nejm199105163242002

Cited by 1,178 publications

(558 citation statements)

References 40 publications

Supporting

Mentioning

524

Contrasting

Unclassified

Order By: Relevance

“…The most successful clinical application of differentiation therapy has been the use of all-trans retinoic acid, a ligand for the retinoic acid receptor ␣ (RAR␣) in the standard treatments for acute promyelocytic leukemia. 11 Other nuclear receptors also may become the promising targets for novel therapeutic strategies in some malignancies. It has been investigated whether PPAR␥ might be a useful target for the treatment of tumors.…”

mentioning

confidence: 99%

Ligands for peroxisome proliferator-activated receptor ? inhibit growth of pancreatic cancers bothin vitro andin vivo

et al. 2001

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor ␥ (PPAR␥) is expressed largely in adipose tissues and plays an important role in adipocyte differentiation. Several studies have recently shown that ligands of PPAR␥ could lead to growth inhibition in some malignancies. In our study, we focused on pancreatic cancers, because the prognosis of advanced pancreatic cancer has not significantly improved due to its resistance to various chemotherapeutic regimens, so that a novel strategy should be required. We show here that PPAR␥ is expressed in 5 pancreatic cancer cell lines detected in both mRNA and protein level as well as in human primary and metastatic pancreatic carcinomas examined by immunohistochemical studies. A specific ligand of PPAR␥, troglitazone, led to G1 accumulation with the increase in p27(Kip1), but not p21(Waf1/Cip1) and inhibited cellular proliferation in a pancreatic cancer cell line, Panc-1. Peroxisome proliferator-activated receptor gamma (PPAR␥) is one of the members of the nuclear hormone receptor superfamily like receptors for steroids, thyroid hormone, vitamin D and retinoic acid. 1 Like other members of this superfamily, PPAR␥ binds to DNA response element and regulates the expression of specific target genes. 2,3 15-Deoxy⌬ 12,14 prostaglandin J 2 and various polyunsaturated fatty acids have been identified as natural receptor ligands for PPAR␥ 4 -6 and the anti-diabetic thiazolidinedione (TZD) drugs as synthetic ligands. 4,7 TZDs are a new class of oral anti-diabetic agents.PPAR␥ is predominantly expressed in adipose tissue and functions as a central regulator of adipocyte differentiation. 8 The receptor is induced very early in this process and, in the presence of ligand, causes morphological changes, lipid accumulation and the activation of fat-specific genes in adipocytes. 9 PPAR␥ gene gives rise to 2 isoforms. Forced expression of PPAR␥2 activates expression of a number of typical differentiation-linked adipocyte genes, including adipocyte P2 (aP2), adipsin, lipoprotein lipase in cultured fibroblasts. 10 The common process of cell differentiation involves the slowing or complete cessation of cell growth and is referred to as terminal differentiation. On the basis of its effects on differentiation and cell-cycle regulation, induction of terminal differentiation represents an alternative convention therapy for human malignancies that may have reduced toxicity. The most successful clinical application of differentiation therapy has been the use of all-trans retinoic acid, a ligand for the retinoic acid receptor ␣ (RAR␣) in the standard treatments for acute promyelocytic leukemia. 11 Other nuclear receptors also may become the promising targets for novel therapeutic strategies in some malignancies. It has been investigated whether PPAR␥ might be a useful target for the treatment of tumors. Several studies have shown that TZDs can lead to growth inhibition in liposarcoma, 12 breast cancer, 13,14 colon cancer, [15][16][17] prostatic cancer 18 and gastric cancer. 19 In the present study, we observe...

show abstract

mentioning

confidence: 99%

Ligands for peroxisome proliferator-activated receptor ? inhibit growth of pancreatic cancers bothin vitro andin vivo

et al. 2001

View full text Add to dashboard Cite

show abstract

“…In addition, they are also recommended for the treatment of nonnutritional disease in which a large dose has a unique effect independent of nutritive activity e.g. alcoholic neuritis and Wernicke's syndrome (thiamine), hyperlipoproteinaemias (niacin), to prevent neuropathy in those on isoniazid (pyridoxine), sideroblastic anemia (pyridoxine), infantile seborrhea (biotin) and acute promyelocytic leukaemia (all-trans-retinoic acid) [4][5][6][7].…”

Section: Role Of Vitaminsmentioning

confidence: 99%

Multivitamins : Use or Misuse?

Menon

Narula

Mathur

2008

Medical Journal Armed Forces India

View full text Add to dashboard Cite

“…As Vitamin A derivatives, retinoids are important regulators of cell reproduction, proliferation, and differentiation [2]. Tretinoin is indicated for the induction of complete remission in patients with acute promyelocytic leukemia [3][4][5]. The Food and Drug Administration (FDA) originally approved tretinoin as a topical agent for acne in 1971, and tretinoin capsules were approved in November 1995.…”

Section: Introductionmentioning

confidence: 99%

Tretinoin overdose: A first case report

et al. 2009

View full text Add to dashboard Cite

Introduction: Tretinoin (Vesanoid) is an all-trans-retinoic acid, and is related to retinol (Vitamin A). To date, there have been several case reports on overdose with its isomer isotretinoin, but none involving overdose of tretinoin. We report the first known case of a patient who ingested a massive overdose of tretinoin.Case Report: A 31-year-old man ingested 1000 mg of tretinoin (100 pills of Vesanoid 10 mg) in a suicide attempt. He developed nonbloody diarrhea, but otherwise had no complaints. Clinical examination was normal. The patient was treated with activated charcoal and was hydrated. The patient's blood results did not show any deterioration on the third consecutive day. He was discharged well on the third day, but was subsequently lost to follow-up.Discussion: Although there has been no reported experience with acute tretinoin overdose in humans, our patient took a dose approximately 3 times the recommended maximum tolerated daily dose in patients with myelodysplastic syndrome or solid tumors (195 mg/m 2 per day). Overdose with other retinoids such as isotretinoin have been associated with only minor symptoms that resolved quickly. Our patient had diarrhea, which also resolved quickly with symptomatic treatment and hydration.Conclusion: We believe this to be the first case report of an acute oral overdose of tretinoin. The patient developed diarrhea, but was otherwise asymptomatic.

show abstract

Differentiation Therapy of Acute Promyelocytic Leukemia with Tretinoin (All-trans-Retinoic Acid)

Cited by 1,178 publications

References 40 publications

Ligands for peroxisome proliferator-activated receptor ? inhibit growth of pancreatic cancers bothin vitro andin vivo

Ligands for peroxisome proliferator-activated receptor ? inhibit growth of pancreatic cancers bothin vitro andin vivo

Multivitamins : Use or Misuse?

Tretinoin overdose: A first case report

Contact Info

Product

Resources

About