Synergistic inhibition of prostate cancer cell lines by a 19- nor hexafluoride vitamin D3 analogue and anti-activator protein 1 retinoid

The secosteroid hormones, all- trans- and 9- cis -retinoic acid and vitamin D3, have demonstrated significant capacity to control proliferation in itro of many solid tumour cell lines. Cooperative synergistic effects by these two ligands have been reported, and it is, therefore, possible that greater therapeutic effects could be achieved if these compounds were administered together. The role of retinoid-dependent anti-activator protein 1 (anti-AP-1) effects in controlling cancer cell proliferation appears significant. We have utilized an anti- AP-1 retinoid [2-(4,4-dimethyl-3,4-dihydro-2H-1 benzopyran-6-yl)carbonyl-2-(4-carboxyphenyl)-1,3,-dithiane; SR11238], which does not transactivate through a retinoic acid response element (RARE), and a potent vitamin D3analogue [1α,25(OH)2-16-ene-23-yne-26,27-F6-19-nor -D3, code name LH] together at low, physiologically safer doses against a panel of prostate cancer cell lines that represent progressively more transformed phenotypes. The LNCaP (least transformed) and PC-3 (intermediately transformed) cell lines were synergistically inhibited in their clonal growth by the combination of LH and SR11238, whereas SR11238 alone was essentially inactive. DU-145 cells (most transformed) were completely insensitive to these analogues. LNCaP cells, but neither PC-3 nor DU-145, underwent apoptosis in the presence of LH and SR11238. Transactivation of the human osteocalcin vitamin D response element (VDRE) by LH was not enhanced in the presence of SR11238, although the expression of E-cadherin in these cells was additively up-regulated in the presence of both compounds. These data suggest the anti-AP-1 retinoid and the vitamin D3 analogue may naturally act synergistically to control cell proliferation, a process that is interrupted during transformation, and that this combination may form the basis for treatment of some androgen-independent prostate cancer. © 1999 Cancer Research Campaig

The Relationships of Intergroup Contact to Social Identity and Political Consciousness

The impact of three forms of intergroup contact (Mexican descent, other minority, and Anglo) on the social identities and political attitudes of a national sample of native-born persons of Mexican descent was examined. Cast within Tajfel's Social Identity theory, the various social contexts were expected to predict three distinct types of ethnic identity: Cultural Ethnicity (Ingroup contact), Politicized Ethnicity (Ingroup and Minority Outgroup contact), and Assimilationist Ethnicity (Anglo contact). Contrasting political orientations were also predicted for the types of contact, with group-conscious attitudes associated with Ingroup and Minority Outgroup contacts and conservative political attitudes with A nglo contact. Support is provided for the expected relationships between Ingroup and Minority Outgroup interactions and identity and political attitudes. Anglo contact was related to conservative political attitudes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67440/2/10.1177_07399863900123001.pd

Further definition of the protein kinase C activation domain of the parathyroid hormone: J.Bone Miner.Res.

NRC publication: Ye