The prognosis for patients with metastasized prostate cancer is still poor, despite conventional aggressive therapeutic modalities. Several in vitro studies together with animal models and epidemiological studies have indicated that phytochemicals can be antitumorigenic and may be protective against human cancers. However, the potential antitumor effects of genistein isoflavone, a widely studied nutrient phytochemical, have been equivocal. In this study, we investigated the effects of genistein-selenium (Gn-Se) combination on chemosensitivity and matrix metalloproteinase-2 (MMP-2) expression levels in PC3 (hormone-independent) and LNCaP (hormone-dependent) prostate cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium staining and ATP bioassay showed that genistein, selenium, and Gn-Se combination significantly inhibited growth of LNCaP and PC3 cells in a dose- and time-dependent manner, independent of hormonal status, and with no significant differences in chemosensitivity between LNCaP and PC3. Gn-Se combination induced significantly the greatest growth inhibition in both cell lines. Growth inhibition was through apoptosis induction. The treatment-induced apoptotic cascades are caspase-dependent, with evidence of an alternative non-caspase pathway(s). Treatment also induced a dose- and time-dependent decrease in MMP-2 expression levels in PC3 and LNCaP with no significant differences between the two cells. Gn-Se combination induced the greatest depression in MMP-2. Overall, none of the treatment modalities had any significant inhibitory effect in normal prostate epithelial cells. The data obtained from the present study indicate that Gn-Se combination may have chemopreventive value and/or may be adjuvant to standard therapy for prostate tumors independent of hormonal status. MMP-2 expression in cancer cells has been associated with active invasion and metastasis.

We are developing a laser-based technique for the rapid sequencing of large DNA fragments (several kb in size) at a rate of 100 to 1000 bases per second. Our approach relies on fluorescent labeling of the bases in a single fragment of DNA, attachment of this labeled DNA fragment to a support, movement of the supported DNA into a flowing sample stream, sequential cleavage of the end nucleotide from the DNA fragment with an exonuclease, and detection of the individual fluorescently labeled bases by laser-induced fluorescence.

The 2'-deoxy and ara derivatives of 1-beta-(D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) were synthesized by improved routes and tested for their inhibitory properties against cytidine deaminase. It was shown that the K(i)'s of both compounds were comparable to that of the parent zebularine in inhibition studies with purified enzyme. In contrast to zebularine, 2'-deoxy and ara zebularine showed only nominal cytotoxicity against MOLT-4 and L1210 cells in vitro. A model compound for the inhibition of deoxycytidylate deaminase, 2'-deoxyzebularine 5'-monophosphate (6), was also prepared.

The 9,10- and 11,12-allenic retinoids, 5a and 6a, respectively, were synthesized in high yield and specificity by t-butylation of the propargylic benzoates 9b and 12b, respectively. Thermal isomerization of the allenes afforded the 11-cis, the 11,13-dicis and the 9,11,13-tricis isomers of the 9-t-butyl retinol 3 and the 11,13-dicis isomer of the 13-t-butyl retinol 4.

Hexamethylenebis[acetamide] (HMBA) is an agent in clinical trial that induces differentiation of certain types of tumor cells to nonmalignant phenotypes. In an attempt to discover a more potent compound, a number of bis-functionalized amides, imides, and hydrazine derivatives of HMBA were prepared and evaluated in vitro with the HL-60 human promyelocytic leukemia cell line. Among the compounds evaluated, the 5,5-dimethylhydantoin derivative is almost 10 times more potent than HMBA in inducing differentiation. The bis-imide, diacetyl-HMBA, is both more potent and effective than its parent compound. Six of the 16 compounds evaluated cause at least 20% differentiation. An inverse relationship between the degree of differentiation and the percentage of viable cells is described for HMBA and its analogues.

AbstractLewis acid‐catalyzed or high‐pressure Diels‐Alder reaction of the pyrone sulfoxide (I) with the vinyl (thio)ethers (II) gives the bicyclic adducts (III).

Spiromustine is a hydantoin-containing nitrogen mustard currently in Phase I clinical trial. Since the in vitro plasma half-life of this compound (6.4 min, 37 degrees C, pH 7.4) appeared to be influenced by the hydantoin ring, analogues containing 2-5 methylene spacer groups between this ring and the nitrogen mustard moiety were prepared and evaluated for hydrolytic stability and antitumor activity. Stability correlated with structure and pKa values. The proximity of the hydantoin ring to the mustard function was a stabilizing factor. Activity against murine P-388 leukemia was demonstrated and a gradual decrease in this activity was observed as the hydrolytic instability increased. A relationship between analogue structure and a mass spectral rearrangement ion was identified.

AbstractUsing a vitamin D‐related steroidal CD fragment as a stereochemical probe, the effect of various factors on the stereochemical course of the organocopper induced conversion of propargylic esters to allenes has been studied. In all cases, an anti mode of attack by the organocopper species was found to be preferred. The effectiveness of Gilman‐type reagents (R2CuLi) versus that of the Lipshutz‐type higher‐order mixed cuprate systems (R2CuCNLi2) in promoting the reaction was also studied.

AbstractDie Synthese der dem Vitamin D3 analogen Desoxysulfinylhydroxyvitamine (X) wird beschrieben.

Metallation (n-Buli, t-BuOK, THF) followed by quenching (DCl, D2O) of (S)-allenes 4a-c occurs primarily with retention of configuration, whereas that of (R)-allenes 4d-e occurs mainly with inversion; the allenes 4 were prepared from related propargyl alcohols (5, 7-9,)

The reactions of (CH3)2CuLi with various C-8 epimeric propargylic esters derived from Grundmann's ketone, a C/D steroid fragment originating from vitamin D3, lead to the corresponding allenes, the stereochemistry of which indicate a preferred anti 1,3-substitution.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on vitamin D (calciferol) and its analogs. 24. Heterocalciferols: novel 3-thia and 3-sulfinyl analogs of 1.alpha.-hydroxyvitamin D3Alberto Haces and William H. OkamuraCite this: J. Am. Chem. Soc. 1982, 104, 22, 6105–6109Publication Date (Print):November 1, 1982Publication History Published online1 May 2002Published inissue 1 November 1982https://pubs.acs.org/doi/10.1021/ja00386a043https://doi.org/10.1021/ja00386a043research-articleACS PublicationsRequest reuse permissionsArticle Views80Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts