Resorcinarene 1b forms a hexameric assembly in water-saturated CDCl(3) that encapsulates one tetraalkylammonium salt (2(+)Br(-)). The remaining space is occupied by coencapsulated solvent molecules. A maximum of three and minimum of one CHCl(3) molecule were found inside of capsules with tetrapropyl- and tetraheptylammonium bromide, respectively. The encapsulation of the salt is endothermic and entropically favored by the liberation of the solvent molecules. The stabilities of the encapsulation complexes and the rates of guest exchange decrease for larger cations. The higher activation barriers for in/out exchange of the larger guests suggest tight conformational restraints in the transition state. It is likely that complete dissociation of one resorcinarene molecule is necessary for the exchange of the alkylammonium salts.

Calix[4]resorcinarene-based cavitands with a bowl-shaped aromatic cavity are widely used as scaffolds for covalently bound and self-assembled capsules. There are two main categories of calix[4]resorcinarene-based cavitands that are tetrafunctionalized at the upper (wider) rim: one category includes derivatives that have functionalized bridges between pairs of hydroxy groups of the calix[4]resorcinarene, and the second category includes derivatives with functional groups at the 2-position on the resorcinol ring and the methylene bridge between pairs of hydroxy groups. This review describes capsular self-assemblies of the latter type of methylene-bridge cavitands, which are formed through hydrogen bonds, metal-coordination bonds, and dynamic covalent bonds.

The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylationspecific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RAR␤2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O 6 -methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RAR␤2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RAR␤2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RAR␤2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancerrelated genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RAR␤2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.

SUMMARY:The retinoic acid receptor (RAR) ␤ gene is a putative tumor suppressor gene on chromosome 3p24, where a high incidence of loss of heterozygosity is detected in many types of tumors. Retinoic acid suppresses cancer cell growth through binding to RARs, especially RAR␤, indicating a critical role in mediating anticancer effects. Selective loss or down-regulation of RAR␤ mRNA and protein has been reported in prostate cancers (PCas), although the mechanisms remain unclear. We investigated the role of epigenetic modification in RAR␤2 gene silencing. Aberrant methylation was detected in 11 of 14 (79%) primary PCas, 9 of 10 (90%) hormone-refractory PCas, and 2 of 4 (50%) PCa cell lines, but not in any normal prostate samples. Chromatin immunoprecipitation assay showed that all RAR␤2-negative cells (LNCaP, PC3, and DU145) were hypoacetylated at both histones H3 and H4. After exposure to 5-aza-2'-deoxycytidine treatment, Trichostatin A and all-trans retinoic acid induced partial demethylation, increased accumulation of acetylated histones, and markedly restored the expression of RAR␤2 in RAR␤2-negative cells. These data suggest that the RAR␤2 gene may be one of the frequently silenced genes by epigenetic modifications in PCa. (Lab Invest 2001, 81:1049 -1057.

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