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Vaccinia necrosum complicating immunoblastic sarcoma.

A 59-year-old man is presented who had immunoblastic lymphadenopathy which evolved over a three-year period into immunoblastic sarcoma. His course was complicated by vaccinia necrosum, which necessitated prolonged therapy with Marboran and vaccinia-immune globulin. The persistence of virus was documented at autopsy by positive viral culture and ultra-structural examination. This case illustrates the potential hazards of administration of live viral vaccines to an immune compromised host presumed to be in remission and suggests that the continued activity of viral infection may signal the unsuspected persistence of underlying disease.

Adult↗

Oncostatic activity of a thiazolidinedione derivative on human androgen-dependent prostate cancer cells.

Thiazolidinedione derivatives with potent antiarthritic activity, such as CGP 52608, have been suggested to exert their biological effects through the activation of the orphan nuclear receptor RORalpha. Since response elements for this receptor are present in the promoter region of cell cycle-related genes (i.e., p21(WAF1/CIP1) and cyclin A), we reasoned that CGP 52608 might affect cell proliferation, cell cycle progression and the expression of cell cycle-related genes. This hypothesis has been verified in the human androgen-dependent prostate cancer cell line LNCaP. We found that the treatment of LNCaP cells with CGP 52608 brings about a significant and dose-dependent decrease of cell proliferation. Thiazolidinedione affected cell cycle distribution, inducing an accumulation of the cells in the G0/G1 phase and a decrease in the S phase. This effect was accompanied by an increased expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and a decreased expression of cyclin A. These data indicate that, in human androgen-dependent LNCaP prostate cancer cells, the thiazolidinedione derivative CGP 52608 exerts a strong cytostatic activity, by reducing cell proliferation and by affecting cell cycle distribution through the modulation of the expression of cell cycle-related genes. These biological actions of CGP 52608 might be mediated by the activation of the orphan nuclear RORalpha receptor, which is expressed in LNCaP cells.

Androgens↗

DNA interstrand cross-linking efficiency and cytotoxic activity of novel cadmium(II)-thiocarbodiazone complexes.

We have prepared mono- and binuclear complexes of Zn(II) and Cd(II) with bis(2-pyridyl aldehyde) thiocarbodiazone (H(2)L(1)) and bis(methyl 3-pyridyl ketone) thiocarbodiazone (H(2)L(2)). Cytotoxicity data against the ovarian tumor cell line A2780cisR (acquired resistance to cisplatin) indicate that the mononuclear complex Cd/H(2)L(2) (1) and the binuclear complex Cd(2)/H(2)L(1) (4) are able to circumvent cisplatin resistance and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of glutathione. Moreover, DNA binding studies show that complexes 1 and 4 have higher efficiency than cisplatin at forming DNA interstrand cross-links in both naked pBR322 plasmid and A2780cisR cellular DNA. Interestingly, the thiocarbodiazone ligands alone do not show the biological properties of complexes 1 and 4. Altogether these results suggest that DNA interstrand cross-link formation by compounds 1 and 4 might be related with their cytotoxic activity in cisplatin-resistant cells. We think that compounds 1 and 4 may represent a novel structural lead for the development of cadmium cytotoxic agents capable of improving antitumor activity in cisplatin-resistant tumors.

Antineoplastic Agents↗

Syntheses and in vitro antimicrobial evaluation of some benzimidazol-2-ylmethylthioureas, benzimidazol-2-ylacetylthiosemicarbazides and products of their condensation with monochloroacetic acid.

N-Benzimidazol-2-ylacetyl-N'-[alkyl- and arylthio (carbamoyl)]hydrazines and N-benzimidazol-2-ylmethyl-N'-alkyl- and -arylthioureas were subjected to condensation with monochloroacetic acid to afford N-benzimidazol-2-ylacetyl-N'-2,3, 4,5-tetrahydro-4-oxo-3-alkyl- and -arylthiazol-2-ylidenehydrazines and 3-benzimidazol-2-ylmethyl-2-alkyl- and arylimino-2,3-dihydrothiazol-4-(5H)ones, respectively. In preliminary antimicrobial testing, some compounds turned out to have significant activity against Staphylococcus aureus.

Anti-Bacterial Agents↗