S_mmmmary Nitric oxide (NO) is generated by a family of isoenzymes (NO synthases)

As well as having anti-tumour activity in animal models. TNF alpha has been implicated in the promotion of tumour invasion and metastasis. Expression and localization of TNF alpha mRNA and protein has been investigated in a series of benign and malignant breast tissues. TNF alpha mRNA was expressed in a minority of cells (< 0.5%) in 4/11 cases of benign breast tissue and in a higher proportion of invasive carcinomas (43/49 cases). Expression of TNF alpha mRNA was focal and confined to the tumour stroma. The presence of TNF alpha was confirmed by immunohistochemistry and again was predominantly stromal. Expression of mRNA and protein localized to infiltrating macrophages defined by the antibody EBM/11 in adjacent sections and using 2-colour immunofluorescence. Although the average number of macrophages per high-power field did not vary among invasive carcinomas of different histological type or grade, the number of cells expressing TNF alpha increased with increasing tumour grade. Immunodetectable p75 TNF receptor and to a lesser extent p55 receptor was present on cells of the mononuclear infiltrate and on the endothelium of invasive carcinomas, but not on the tumour cells themselves.

Interleukin-2 (IL-2) treatment induces other cytokines such as tumour necrosis factor (TNF) TNF may mediate some of the anti-tumour activity of IL-2, but conversely, may contribute to its dose limiting toxicities. Cleaved extracellular domains of the p55 and the p75 TNF receptors (sTNF-R1 and R2) bind to and inhibit the biological activity of TNF in vitro, but may also act as carrier molecules. We have assayed TNF and sTNFR-1 and 2 in the plasma of advanced cancer patients, before and during treatment with IL-2. Plasma levels of TNF in 22 patients were not significantly different from 25 normal controls, but levels of sTNFR-1 and sTNFR-2 were higher (P < 0.001). Levels of TNF and both its soluble receptors were significantly increased in 13 patients receiving IL-2 therapy. Maximum induced levels of sTNFR-1 and sTNFR-2 correlated closely with maximum induced levels of TNF (P < 0.001), but peak levels of sTNFR-1 and two were achieved 24-48 h after peak TNF. Levels of TNF and sTNF-Rs did not correlate with toxicity. Treatment with IL-2 leads not only to induction of TNF but also soluble binding proteins at levels which may modulate its biological activity.

The effects of certain substituents and solvents on the circular dichroism (CD) spectra are reported for a number of guanine nucleoside derivatives from 320 to 200 nm. Both theoretical and empirical analyses of the data suggest that the anti conformation predominates in aqueous solution, but that the syn conformation is preferred in alcoholic solvents, at low pH in water, and when the heterocycle carries a large substituent on carbon 8 of the imidazole ring. Theoretical optical calculations based on the bond-bond coupled oscillator theory are included to check the validity of the theory with experimental data. The interaction of guanine nucleoside derivatives with actinomycin is also reported and the data suggest that the anti conformation is necessary for complex formation.A fundamental aspect of the conformational analyses of nucleic acids and their fragments concerns the allowed conformational states of the individual nucleotide or nucleoside monomers.In particular the relative position of the sugar and the base about the glycosidic bond, as described by the torsion angle, <£CN, has received a great deal of attention.1-4 Steric considerations lead to two extreme conformations as demonstrated by 1 and 5 in Figure 1, which are designated anti and syn, respectively. Crystallographic studies have pointed to the almost exclusive presence of the anti conformation.5 A number of exceptions, however, are known: deoxyguanosine, which is syn in a mixed crystal with 5-bromodeoxycytidine;6 3',5' cyclic AMP, which can exist simultaneously in the anti and syn conformations in the same crystal structure;7 8bromoguanosine;8 8-bromoadenosine;8 and 3'-0-acetyladenosine.9 Several independent calculations using (1) A.

Multiple white lines are present in the fingernails of a patient undergoing anthracycline chemotherapy for metastatic carcinoma of the breast. The spacing of the lines coincides with the three-week intervals between cycles of chemotherapy. The cause of the lines is unclear, but they may be a consequence of abnormal keratinocyte maturation.