4Hemocentro de São José do Rio Preto, Sáo Paulo, Brazil CYP17 gene encodes the enzyme cytochrome p450c17a, which mediates two steps in the steroid biosynthesis pathway. Steroid hormones are believed to play a key role in the etiology of prostate cancer. A polymorphic T?C transition in the 5 0 promoter region of CYP17 creates an additional Sp1-type (CCACC box) promoter site (allele A2). We have evaluated the genotypic and allelic distribution of this polymorphism among 92 prostate cancer patients in order to assess risk by comparison with a population-based series of 200 healthy individuals from Brazil. Our results provide no evidence for an association between prostate cancer risk and CYP17 T/C polymorphism. Prostate Cancer and Prostatic Diseases (2002) 5, 28-31. DOI: 10.1038/sj/pcan/4500550Keywords: CYP17 gene; T/C polymorphism; prostate cancer risk
IntroductionProstate cancer is the most common malignancy and the third most common cause of cancer mortality in Brazilian men. 1 Studies of risk factors such as occupation, diet, smoking, alcohol and sexual activity are still inconclusive, however, age, ethnicity and family history clearly affect the risk of prostate cancer. 2 -7 There is evidence to support the hypothesis of hormonal etiology of prostate cancer involving androgen action. 8 -10 Androgen is required for differentiation and growth of the prostate in utero and at puberty. 8 Testosterone, the most abundant circulating androgen is synthesized from cholesterol by a series of enzymatic reactions involving the cytochrome p450c17a. The enzyme has a bifunctional active site: the catalytic center performs the 17a-hydroxylation of pregnenolone and progesterone while the 17,20-lyase activity is responsible for the conversions of 17a-hydroxypregnenolone to dehydroepiandrosterone and 17a-hydroxyprogesterone to androstenedione, precursors of testosterone and estrogen. 11 Testosterone is converted to 5a-dihydrotestosterone (DHT) in the prostate by the enzyme 5a-reductase. DHT binds to AR (androgen receptor gene), and the DHT -AR complex transactivates a number of genes with ARresponsive elements. These events ultimately result in cell division in the prostate. 12 The CYP17 gene codes for cytochrome p450c17a enzyme, is located on chromosome 10, spans 6569 bp, and is divided into eight exons. 13 A polymorphic T?C transition in the 5 0 promoter region of CYP17 creates an additional Sp1-type (CCACC box) promoter site. 14 This base pair change also creates a recognition site for the MspA I restriction enzyme, which allows the identification of the CYP17 A2 allele. Since the number of 5 0 promoter elements correlates with promoter activity, it has been proposed that the A2 allele may lead to an increased rate of transcription, thus increasing the prostate cancer risk. 15 Recent in vitro evidence suggests that the 5 0 Sp1 type site resulting from the T to C substitution does not actually bind transcription factor Sp1, but there is still some functional evidence to indicate that this polymorphism may act as a risk facto...
A rare family of six discrete binuclear [PdCl(PEt3)2] phenylene ethynylene rods with alkoxy side chains (methoxy, ethoxy and heptoxy) have been developed, and their solid-state photoluminescence results have been presented and discussed. The shorter bridging ligands are of the general formula H-C≡C-C6H2(R)2-C≡C-H, where R = H, OCH3, OC2H5, and OC7H15, whereas the longer ones are based on H-C≡C-C6H4-C≡C-C6H2(R)2-C≡C-C6H4-C≡C-H, where R = OCH3, OC2H5. These ligands display increasing length in both the main dimension (backbone length) as well as the number of carbons in the side chains (R, alkoxide side chain) that stem from the central phenylene moiety. The X-ray crystal structures of two of the prepared complexes are reported: one corresponds to a shorter rod, 1,4-bis[trans-(PEt3)2ClPd-C≡C]-2,5-diethoxybenzene (6c), while the second one is associated with a longer rod, the binuclear complex 1,4-bis[trans-(PEt3)2ClPd-4-(-C≡C-C6H4-C≡C)]-2,5-diethoxybenzene (7c). All new compounds were characterized by NMR spectroscopy ((1)H, (13)C{(1)H} and (31)P{(1)H}) as well as ESI-MS(TOF), EA, FTIR, UV-Vis, cyclic voltammetry and solid-state photoluminescence. Our work shows the influence of the alkoxy side chains on the electronic structure of the family of binuclear Pd rods by lowering its oxidation potential. In addition to this, the increase of the length of the bridge results in a higher oxidation potential. Solid state photoluminescence results indicate that Pd complexes are characterized by a marked decrease in both the emission intensity and the fluorescence lifetime values as compared to their ligands. This behaviour could be due to some degree of ligand-to-metal charge transfer.
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