A Phase II study of 13-cis-retinoic acid in patients with advanced renal cell carcinoma

Berg, William J.; Schwartz, Lawrence H.; Amsterdam, Alison; Mazumdar, Madhu; Vlamis, Vaia; Law, Teresa Murray; Nanus, David M.; Motzer, Robert J.

doi:10.1023/a:1005902022076

Cited by 31 publications

(6 citation statements)

References 6 publications

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“…RAR-b 2 expression is frequently and progressively lost in premalignant and malignant tissues of different human cancers (see review in Xu and Lotan, 1999). Induction of RAR-b 2 in vivo has been used as a biomarker in several clinical chemoprevention trials by researchers at our institution and by other groups (Lotan et al, 1995Ayoub et al, 1999;Berg et al, 1999;Xu et al, 1999a;Kurie et al, 2000Kurie et al, , 2003Lam et al, 2003;Alberts et al, 2004). Taken together, all these data support that RAR-b 2 plays important roles in suppressing human cancer development.…”

Section: Introductionsupporting

confidence: 60%

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

et al. 2005

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Benzo [a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke and environmental pollution) has been shown to suppress retinoic acid receptor-beta2 (RAR-b 2 ) and induce cyclooxygenase-2 (COX-2) expression. Restoration of RAR-b 2 inhibited growth and colony formation of esophageal cancer cells, which was correlated with COX-2 suppression. In this study, we investigated the molecular mechanisms for RAR-b 2 -mediated suppression of COX-2 expression using BPDE as a tool. We found that BPDE-induced COX-2 expression was through inhibition of RAR-b 2 and consequently, induction of epidermal growth factor receptor (EGFR), extracellular signal-regulated protein kinases 1/2 (Erk1/2) phosphorylation, and c-Jun expression. Esophageal cancer cells that do not express RAR-b 2 did not respond to BPDE for induction of COX-2. BPDE was also unable to induce COX-2 expression after RAR-b 2 expression was manipulated in these esophageal cancer cells. Furthermore, BPDE induced time-dependent methylation of RAR-b 2 gene promoter in esophageal cancer cells. Transfection of RAR-b 2 expression vector into esophageal cancer cells suppressed expression of EGFR, Erk1/2 phosphorylation, c-Jun, and COX-2. In addition, co-treatment of RAR-b 2 -positive cells with BPDE and the MEK1/2 inhibitor U0126 caused little change in c-Jun and COX-2 expression. This study demonstrated that BPDE-suppressed expression of RAR-b 2 results in COX-2 induction and restoration of RAR-b 2 expression reduces COX-2 protein in esophageal cancer cells, thereby further supporting our previous finding that RAR-b 2 plays an important role in suppressing esophageal carcinogenesis.

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Section: Introductionsupporting

confidence: 60%

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

et al. 2005

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“…RA is a diffusible factor derived from vitamin A that has been used for the treatment of a number of cancers. However, some renal malignancies have shown resistance to this therapy [101, 102]. Data from RCC cell lines suggest that this retinoid-resistance is due to loss of RARβ2 expression [103].…”

Section: Hdac Inhibitors and Renal Carcinomamentioning

confidence: 99%

HDAC inhibitors in kidney development and disease

et al. 2012

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The discovery that histone deacetylase inhibitors (HDACis) can attenuate acute kidney injury (AKI)-mediated damage and reduce fibrosis in kidney disease models has opened the possibility of utilizing HDACis as therapeutics for renal injury. Studies to date have made it abundantly clear that HDACi treatment results in a plethora of molecular changes, which are not always linked to histone acetylation, and that there is an essential need to understand the specific target(s) of any HDACi of interest. New lines of investigation are beginning to delve more deeply into target identification of specific HDACis and to address the relative toxicity of different HDACi classes. This review will focus on the utilization of HDACis during kidney organogenesis, injury, and disease, as well as on the development of these compounds as therapeutics.

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“…Retinoids were also shown to be active in the treatment of certain malignancies such as acute promyelocytic leukemia (APL), juvenile chronic myelogenous leukemia, mycosis fungoides, Kaposi's sarcoma, and high-risk neuroblastoma, as reviewed by Cheer and Foster (2000), Reynolds and Lemons (2001), and Kitareewan et al (2003). When combined with interferon-a2A, 13-cis-retinoic acid is active in the treatment of specific epithelial malignancies that include squamous cell cancers of the skin or cervix, and advanced renal cancer (Moore et al, 1994;Berg et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Retinoids in cancer therapy and chemoprevention: promise meets resistance

2003

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Retinoids (natural and synthetic derivatives of vitamin A) signal potent differentiation and growth-suppressive effects in diverse normal, premalignant, and malignant cells. A strong rationale exists for the use of retinoids in cancer treatment and chemoprevention based on preclinical, epidemiological, and early clinical findings. Despite the success of all-trans-retinoic acid (RA)-based differentiation therapy in acute promyelocytic leukemia (APL), the broad promise of retinoids in the clinic has not yet been realized. In addition to the expected limited activity of any single therapeutic agent, translation of retinoid activities from the laboratory to the clinic has met with intrinsic or acquired retinoid resistance. Evidence suggests that solid tumors develop intrinsic resistance to retinoids during carcinogenesis. In contrast, relapse of APL is often associated with acquired resistance to retinoid maturation induction. This review discusses what is known about retinoid resistance mechanisms in cancer therapy and chemoprevention. Strategies to overcome this resistance will be discussed, including combination therapy with other differentiation-inducing, cytotoxic or chromatin-remodeling agents, as well as the use of receptor-selective and nonclassical retinoids. Opportunities exist in the post-genomic era to bypass resistance to classical retinoids by identifying target genes and associated pathways that directly mediate the antineoplastic effects of retinoids. In this regard, the retinoids are useful pharmacological tools to reveal important pathways targeted in cancer therapy and chemoprevention.

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A Phase II study of 13-cis-retinoic acid in patients with advanced renal cell carcinoma

Cited by 31 publications

References 6 publications

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

HDAC inhibitors in kidney development and disease

Retinoids in cancer therapy and chemoprevention: promise meets resistance

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