Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-i, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial

Torrisi, Rosalba; Mezzetti, Maura; Johansson, Harriet; Barreca, Antonina; Pigatto, Francesca; Robertson, Chris; DeCensi, Andrea

doi:10.1002/1097-0215(20000815)87:4<601::aid-ijc22>3.0.co;2-w

Cited by 20 publications

(15 citation statements)

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“…But more other unknown factors which may play key roles in autocrine mechanisms of TCCs need to be further characterized. The previous studies carried out have identified the high expression level of IGF-1R in bladder tumor tissue [6], [19]. Some of the present study yielded the following conclusions: (1) The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cells, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; (2) bladder cancer cells responded far better to growth stimulation by IGF-1 than did normal urothelial cells; (3) growth of bladder cancer cells was significantly inhibited by the addition of antisense ODN specific for IGF-1R cDNA.…”

Section: Discussionmentioning

confidence: 99%

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Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Sun

Shu

2001

Cell Res

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A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

“…The insulin-like growth factor system is widely involved in human carcinogenesis [6]. The type 1 insulin-like growth factor receptor (IGF-1R) is a transmembrane protein tyrosine kinase which mediated the biological effects of IGF-1 and most of the actions of IGF-2 [7].…”

Section: Introductionmentioning

confidence: 99%

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Sun

Shu

2001

Cell Res

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“…The greatest effect was observed on free PSA, where the control group exhibited an 8% reduction, whereas the 4-HPR group showed a 12% increase (P = 0.108). As previously reported (38), treatment with 4-HPR resulted in a statistically significant reduction of IGF-I. In the present analysis, also the IGF-I/IGFBP-3 ratio was reduced compared with the control group (P = 0.005), whereas it had no effect on IGFBP-3 levels (P = 0.559).…”

Section: Resultsmentioning

confidence: 99%

“…As previously reported by us (38), treatment with 4-HPR was associated with a significant down-regulation of circulating IGF-I. No substantial change in PSA forms and IGFBP-3 was observed during 4-HPR treatment.…”

Section: Discussionmentioning

confidence: 99%

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Effect of the Synthetic Retinoid Fenretinide on Circulating Free Prostate-Specific Antigen, Insulin-Like Growth Factor-I, and Insulin-Like Growth Factor Binding Protein-3 Levels in Men with Superficial Bladder Cancer

Serrano¹,

Baglietto²,

Johansson³

et al. 2005

Clinical Cancer Research

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Purpose: Fenretinide (4-HPR) is a synthetic retinoid that has shown a preventive activity in prostate cancer animal models.Experimental Design: We measured the changes in total and free prostate-specific antigen (PSA) and its association with insulin-like growth factor I (IGF-I) and IGFBP-3 levels after 1 year of treatment in 24 subjects given 4-HPR and 24 control subjects enrolled in a randomized bladder cancer prevention trial.Results: No significant effect of 4-HPR was observed on total and free fraction of PSA levels. The median percentage [95 confidence interval (95% CI)] change for % free PSA and total PSA in the 4-HPR and the control group were, respectively, 7.6 (95% CI, À À4.0 to 69.3) versus 5.1 (95% CI, À À21.4 to 59.8) and À À7.8 (95% CI, À À18.2 to 52.5) versus À À12.3 (95% CI, À À44.6 to 9.6). However, in patients ages <60 years, there was a trend to an increase of total free PSA and % free PSA after treatment with 4-HPR that was different from a trend to a decrease in the control group (P = 0.002 and 0.052, respectively). The interaction between age and treatment was statistically significant on free PSA (P = 0.001). A similar pattern was noted with smoking status (P = 0.011 for the interaction on free PSA). No association was observed between PSA levels and IGF-I or IGFBP-3 levels. Conclusions:We conclude that 4-HPR has no significant effect on circulating PSA, but it increases significantly free PSA levels in subjects younger than 60 years and in nonsmokers. These effects might support an activity in prostate cancer prevention but further studies are required.

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Retinoids

Dawson¹

2010

Burger's Medicinal Chemistry and Drug Discovery

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Retinoid drugs find major applications in the topical treatment of cutaneous proliferative disorders such as acne, psoriasis, and photoaging and cutaneous cancers such as cutaneous T‐cell lymphoma (CTCL) and Kaposi's sarcoma. Oral retinoids are successfully used to treat nodular/cystic acne, systemic CTCL, and acute promyelocytic leukemia. This overview of available retinoid drugs and those in the preclinical or clinical pipeline covers their development, indications, clinical trial results, adverse effects, and pharmacology/metabolism. Retinoids have been described historically and functionally in the context of interaction with their nuclear receptors—retinoic acid receptors (RARs) and retinoid X receptors (RXRs)—in inducing gene transcription. RAR‐selective retinoids or their prodrugs include first‐generation all‐ trans ‐retinoic acid (tretinoin) and its 13‐ cis isomer (isotretinoin), and second‐generation acitretin and its ethyl ester (etretinate), both having an aromatic 2,3,6‐trimethyl‐4‐methoxyphenyl terminus. Third‐generation more aromatic analogs include ethyl ester tazarotene (Tazorac®) and adapalene (Differin®), both selective for RAR subtypes β and γ, and RARα‐selective pipeline candidates Am80 and NRX 195183, which are in clinical trials. RAR and RXR transcriptional panagonist 9‐ cis ‐retinoic acid is next and is followed by RXR‐selective bexarotene (Targretin™) and two RXR‐selective clinical trial candidates, 9cUAB and NRX 194204. The fourth generation includes three compounds that may have applications in the treatment or prevention of cancer. While originally considered as retinoids, such as N ‐(4‐hydroxyphenyl) retinamide, or as retinoid‐related or derived, such as ST1926 (AHPC) and SHetA2, they subsequently were found to function independently of the RARs and RXRs in inhibiting cancer cell proliferation and inducing apoptosis.

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Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-i, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial

Cited by 20 publications

References 23 publications

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Effect of the Synthetic Retinoid Fenretinide on Circulating Free Prostate-Specific Antigen, Insulin-Like Growth Factor-I, and Insulin-Like Growth Factor Binding Protein-3 Levels in Men with Superficial Bladder Cancer

Retinoids

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