A multicenter Phase II study of the intravenous administration of liposomal tretinoin in patients with acquired immunodeficiency syndrome‐associated Kaposi's sarcoma

Bernstein, Zale P.; Chanan‐Khan, Asher; Miller, Carolyn; Northfelt, Donald W.; López-Berestein, Gabriel; Gill, Parkash S.

doi:10.1002/cncr.11009

Cited by 17 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experimental studies report growth-inhibitory effects on osteosarcoma [47], rhabdomyosarcoma [40], and AIDS-associated Kaposi sarcoma [15]. Approximately 30% of patients with AIDSassociated Kaposi sarcoma have a substantial clinical response to ATRA treatment [8], and one case report suggested ATRA treatment combined with interferon-a was effective against inoperable metastatic osteosarcoma [48]. Our data demonstrate SS cell lines were far more sensitive to treatment with ATRA than the other types of tumors analyzed, and NMS-2, a cell line derived from MPNST, which in clinical practice is resistant to all chemotherapeutic treatments, also showed marked sensitivity to treatment with ATRA.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application

Ishibe

Nakayama

Aoyama

et al. 2008

Clin Orthop Relat Res

View full text Add to dashboard Cite

Synovial sarcoma is a rare sarcoma of unknown histologic origin. We previously reported the gene expression profile of synovial sarcoma was closely related to that of malignant peripheral nerve sheath tumors, and the fibroblast growth factor (FGF) signal was one of the main growth signals in synovial sarcoma. Here we further demonstrate the neural origin of synovial sarcoma using primary tumors and cell lines. The expression of neural tissuerelated genes was confirmed in synovial sarcoma tumor tissues, but the expression of some genes was absent in synovial sarcoma cell lines. Treatment of synovial sarcoma cell lines with BMP4 or FGF2 enhanced or restored the expression of neural tissue-related genes and induced a neuron-like morphology with positive Tuj-1 expression. Treatment with all-trans-retinoic acid also induced the expression of neural tissue-related genes in association with growth inhibition, which was not observed in other cell lines except a malignant peripheral nerve sheath tumor cell line. A growth-inhibitory effect of all-trans-retinoic acid was also observed for xenografted tumors in athymic mice. The simultaneous treatment with FGF signal inhibitors enhanced the growth-inhibitory effect of all-trans-retinoic acid, suggesting the combination of growth signaling inhibition and differentiation induction could be a potential molecular target for treating synovial sarcoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application

Ishibe

Nakayama

Aoyama

et al. 2008

Clin Orthop Relat Res

View full text Add to dashboard Cite

show abstract

“…A multicenter trial was conducted to determine the efficacy and toxicity of escalating dosages of IV liposomal tretinoin (alltrans-retinoic acid) administered once or three times weekly in patients with AIDS-related KS. 343 A 3 times per week dosing schedule was noted to be more effective compared with a once-a-week schedule without any significant difference in toxicity.…”

Section: Retinoidsmentioning

confidence: 96%

Kaposi sarcoma: A continuing conundrum

Schwartz

Micali

Nasca

et al. 2008

Journal of the American Academy of Dermatology

203

212

View full text Add to dashboard Cite

“…This study suggested that coadministration of PXR ligands can increase ATRA metabolism through activation of the PXR-CYP3A pathway, which might be a mechanism for some form of ATRA resistance. Other PXR target transporters might also be involved.All-trans retinoic acid (ATRA) is currently used as a chemotherapeutic agent against acute promyelocytic leukemia (APL), breast cancer, Kaposi's sarcoma, and glioma (Muindi et al, 1992b;Defer et al, 1997;Toma et al, 2000;Bernstein et al, 2002). ATRA modulates the transcription of a set of genes associated with cellular apoptosis, growth, and differentiation by binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs).…”

mentioning

confidence: 99%

Role of Pregnane X Receptor in Control of All-TransRetinoic Acid (ATRA) Metabolism and Its Potential Contribution to ATRA Resistance

Wang

Ma²,

Krausz³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Although all-trans-retinoic acid (ATRA) is an effective treatment for acute promyelocytic leukemia and several solid tumors, its use is limited by resistance due to increased metabolism. The most studied mechanism for ATRA resistance is the autoinduced metabolism regulated by the retinoic acid receptor-CYP26 pathway. However, treatment of cancer is usually not done with a single antineoplastic agent, but with a variety of combined chemotherapy regimens, including several anticancer drugs, and other concomitantly administered supportive drugs. Pregnane X receptor (PXR), an orphan nuclear receptor that functions as a ligandactivated transcription factor, serves as an important xenobiotic sensor regulating metabolism and elimination. Many prescription drugs are PXR ligands, which can activate PXR target genes, including phase I enzyme, phase II enzyme, and transporter genes. The present study was designed to examine the role of PXR in ATRA metabolism. Due to the marked species differences in response to PXR ligands, Pxr-null, wild-type, and PXR-humanized transgenic mouse models were used. In addition to pregnenolone 16␣-carbonitrile, several clinically relevant PXR ligands (rifampicin and dexamethasone) all increased ATRA metabolism both in vitro and in vivo, which was PXR-dependent, and upregulation of Cyp3a was the major contributor. Furthermore, induction of the Mdr1a, Mrp3, and Oatp2 genes was also observed. This study suggested that coadministration of PXR ligands can increase ATRA metabolism through activation of the PXR-CYP3A pathway, which might be a mechanism for some form of ATRA resistance. Other PXR target transporters might also be involved.All-trans retinoic acid (ATRA) is currently used as a chemotherapeutic agent against acute promyelocytic leukemia (APL), breast cancer, Kaposi's sarcoma, and glioma (Muindi et al., 1992b;Defer et al., 1997;Toma et al., 2000;Bernstein et al., 2002). ATRA modulates the transcription of a set of genes associated with cellular apoptosis, growth, and differentiation by binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Incorporation of ATRA into the treatment of APL was the most significant step forward over the past 25 years, resulting in very high rates of complete remission and cure. Unfortunately, despite the general efficacy of ATRA-based therapy, a major drawback to its clinical application is the prompt development of resistance.Several mechanisms have been proposed to explain the involved ATRA resistance arising during cancer therapy, including increased metabolism, sequestration by cellular retinoic acid-binding proteins, decreased uptake by P-glycoprotein (Pgp), and mutations in the ligand-binding domain of promyelocytic leukemia protein-RAR␣ fusion protein, most of which, however, were not well elucidated and still remain controversial when comparing in vitro data with in vivo data (Gallagher, 2002). The only well recognized mechanism is the clear relationship between induction of ATRA metabolism and progressive clinical resista...

show abstract

A multicenter Phase II study of the intravenous administration of liposomal tretinoin in patients with acquired immunodeficiency syndrome‐associated Kaposi's sarcoma

Cited by 17 publications

References 31 publications

Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application

Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application

Kaposi sarcoma: A continuing conundrum

Role of Pregnane X Receptor in Control of All-TransRetinoic Acid (ATRA) Metabolism and Its Potential Contribution to ATRA Resistance

Contact Info

Product

Resources

About