Clinical Prevention of Recurrence of Colorectal Adenomas by the Combination of Difluoromethylornithine and Sulindac: An Important Milestone

Sporn, Michael B.; Hong, Waun Ki

doi:10.1158/1940-6207.capr-08-0049

Cited by 32 publications

(15 citation statements)

References 18 publications

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“…56 The combination approach would also minimize the toxicities of the individual drugs by allowing them to be used at lower doses while achieving a significant therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer

Krishnan

Srinivas

Feldman

2009

Dermato-Endocrinology

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“…56 The combination approach would also minimize the toxicities of the individual drugs by allowing them to be used at lower doses while achieving a significant therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer

Krishnan

Srinivas

Feldman

2009

Dermato-Endocrinology

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“…Preclinical (Torrance et al 2000) and clinical studies (Meyskens et al 2008) on colon and other cancers have successfully used the strategy of combining low doses of two active drugs to achieve a more effective chemoprevention and therapeutic outcome compared to the individual agents (Sporn & Hong 2008). The combination approach would also minimize the toxicities of the individual drugs by allowing them to be used at lower doses while achieving a significant therapeutic effect.…”

Section: Clinical Studies Of Calcitriol In Pcamentioning

confidence: 99%

Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment

Krishnan¹,

Feldman²

2010

Endocrine-Related Cancer

127

118

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Calcitriol, the hormonally active form of vitamin D, exerts multiple anti-proliferative and pro-differentiating actions including cell cycle arrest and induction of apoptosis in many malignant cells, and the hormone is currently being evaluated in clinical trials as an anti-cancer agent. Recent research reveals that calcitriol also exhibits multiple anti-inflammatory effects. First, calcitriol inhibits the synthesis and biological actions of pro-inflammatory prostaglandins (PGs) by three mechanisms: i) suppression of the expression of cyclooxygenase-2, the enzyme that synthesizes PGs; ii) up-regulation of the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme that inactivates PGs; and iii) down-regulation of the expression of PG receptors that are essential for PG signaling. The combination of calcitriol and nonsteroidal anti-inflammatory drugs results in a synergistic inhibition of the growth of prostate cancer (PCa) cells and offers a potential therapeutic strategy for PCa. Second, calcitriol increases the expression of mitogenactivated protein kinase phosphatase 5 in prostate cells resulting in the subsequent inhibition of p38 stress kinase signaling and the attenuation of the production of pro-inflammatory cytokines. Third, calcitriol also exerts anti-inflammatory activity in PCa through the inhibition of nuclear factor-kB signaling that results in potent anti-inflammatory and anti-angiogenic effects. Other important direct effects of calcitriol as well as the consequences of its anti-inflammatory effects include the inhibition of tumor angiogenesis, invasion, and metastasis. We hypothesize that these anti-inflammatory actions, in addition to the other known anti-cancer effects of calcitriol, play an important role in its potential use as a therapeutic agent for PCa. Calcitriol or its analogs may have utility as chemopreventive agents and should be evaluated in clinical trials in PCa patients with early or precancerous disease.

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“…This drug combination strategy has the advantage of limiting the toxicity associated with the individual drugs while obtaining additive and potentially synergistic therapeutic effects. Preclinical [301] and clinical studies [302] in colon and other cancers have successfully employed the strategy of combining low doses of two active drugs to achieve a more effective chemoprevention and therapeutic outcome compared to the individual agents [303]. Investigators have been studying the anti-proliferative effect of calcitriol in PCa in combination with other agents [45,304,305].…”

Section: Calcitriol In Combination With Other Agentsmentioning

confidence: 99%

Vitamin D and Prostate Cancer

Krishnan¹,

Feldman²

2011

Vitamin D

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Clinical Prevention of Recurrence of Colorectal Adenomas by the Combination of Difluoromethylornithine and Sulindac: An Important Milestone

Cited by 32 publications

References 18 publications

Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer

Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer

Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment

Vitamin D and Prostate Cancer

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