Proceedings: The role of short and long-lived radiolytic products in radiosensitization by iodinated aromatic compounds.
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Biomedical subjects
Publications and source records attributed to G Simone.
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The effect of selenourea and of colloidal selenium on dilute aqueous solutions of the enzyme yeast alcoholdehydrogenase and on suspensions of E. coli B/r has been studied. Selenourea usually appears to protect meanwhile colloidal selenium radiosensitizes. The results are considered in terms of chemical stability of selenourea and of its free radical reactivity.
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Argyrophilia and argentaffinity, as basic properties of APUD cells, were investigated in 50 normal and hyperplastic prostates, which included both autopsy and surgical specimens from patients of various ages. Normal prostates (including glands from 3 foetuses) had 62% of argyrophil-positive granules in the glandular epithelia, while only 44% of the hyperplastic glands were positive. Argentaffin-positive cells were found in 12% of the surgical hyperplastic cases. Both argyrophil and argentaffin cells were distributed in zones, often in lobule-like shapes, lying along the basal membrane. On the basis of these findings, there is a discussion on the possible roles played by the so-called APUD cells in hyperplastic and neoplastic growths of the prostate, such as carcinoid tumours (apudomas) or endocrine-associated syndromes in the course of prostatic cancer.
In order to verify whether the HER-2/neu gene is involved in the initial phases of neoplastic disease or in its progression, we evaluated the amplification and overexpression of this gene in the primary tumor and in synchronous metastatic axillary lymph nodes of 26 women with operable breast cancer. HER-2/neu was amplified in 35% and overexpressed in 33% of the primary sites; similar percentages were found in lymph nodes. The clear correlation between the two disease sites regarding gene, mRNA and protein levels, supports the hypothesis that this gene is involved in the initial and invasive phases of neoplasia. Its actual role with respect to other biological tumor characteristics during the metastatic process should be investigated further.
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The effect of sodium butyrate (NaB) on cell growth and expression of morphological and biochemical properties was examined in the human neuroblastoma cell lines AF8 and SJ-N-KP. The obtained data show that NaB induced a marked growth inhibition and morphological differentiation, while it was ineffective in inducing biochemical differentiation.
HER-2neu alterations (amplification and overexpression), proliferative activity (3H-Thymidine-Labeling Index, 3H-Tdr-LI) and tumor ploidy (flow-cytometry) were analyzed in a human breast cancer series. Overexpressed tumors showed a significantly higher median 3H-Tdr-LI than normally expressed (p = 0.04), as also did amplified/overexpressed with respect to non-amplified/normally expressed (p less than 0.04). These differences were confirmed only in N-primary tumors. In fact, high expressed cases demonstrated a median 3H-Tdr-LI of 5.5% with respect to 1.9% for low expressed cases (p = 0.04) and amplified/overexpressed had a 3H-Tdr-LI of 9% with respect to 2% for non amplified/low expressed (p = 0.009). HER-2/neu alterations were not correlated with tumor DNA content.
Recently, a method similar to ER.ICA has been proposed for the progesterone receptor (PgR) using two monoclonal antibodies, JZB39 and KD68, specific for human PgR and characterized by a molecular weight of 95 and 120 Kd, respectively. A series of 73 breast cancer patients was studied with regards to ER and PgR using both immunocytochemical (ICA) and biochemical (DCC) assays. Results showed no substantial differences between the two methods when considering common clinical-pathological parameters. Overall agreement between ICA and DCC methods was found: 79% for PgR and 78% for ER. A slight quantitative correlation was also observed between the "score values" of the ICA method and the Fmol content of ER and PgR using the Brave-Pearson test (r = 0.49 for PgR; r = 0.43 for ER). Specificity of PgR.ICA method was 77% for PgR and 72% for ER; sensitivity was 82% and 83%, respectively. The ICA method is a reliable technique to assess PgR presence as well as ER. Further studies are necessary to evaluate the prognostic role of nuclear PgR.
The antineoplastic drug 4'-iodo-4'-deoxydoxorubicin (IDX), a new halogenated anthracycline (1), was examined as a differentiation inducing agent on the human neuroblastoma cell lines TS12 and SK-N-MC. IDX induced morphological and biochemical differentiation and growth inhibition. The effect of a combined treatment of IDX with retinoic acid (RA) and with nerve growth factor (NGF) respectively was then investigated. The responses of neuroblastoma cells to IDX alone and to these combined treatments were compared, with respect to neuritic outgrowth, acetylcholinesterase activity and cellular growth. The data obtained indicate that the combination of differentiation-inducing drugs may be able to enhance the effects of the same drugs given alone.
Several AA, utilizing the biochemical method (DCC) showed the presence or absence of hormonal receptor in either synchronous or metachronous metastatic nodes (N) can reproduce the receptor assessment (AR) of the primary breast tumor (T). We evaluated the AR in T and in synchronous N, by using two morphological methods, immunocytochemical and histofluorescent, to detect the nuclear Estrogen Receptor (ER1) and cytoplasmic sites of the II type (ER2 and PgR2). We studied 50 patients who underwent radical mastectomy for breast cancer N+. In this series we founded a high correlation between AR in T and in N: 82% for ER1, 94% for ER2, and 92% for PgR2. Also we observed 4 cases (2 ER1 and 2 PgR2) which presented the receptor in N only. These data are comparable to results obtained with the DCC method and confirm the opportunity to perform also morphological techniques to evaluate AR in breast cancer to take into consideration also cellularity and tumor heterogeneity informations.
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The effects of epirubicin and retinoic acid (RA) as differentiation inducing agents on human neuroblastoma cell lines were investigated. We have compared the response of neuroblastoma cells to epirubicin alone, to RA alone and to combined treatment, with respect to neuritic processes outgrowth, acethylcholinesterase activity, growth inhibition and antigenic expression. The obtained data indicate that the combination of the two agents is able to produce a synergistic effect on differentiation and on growth inhibition.
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On the basis that inhibition of cell proliferation may play a role in the differentiation process, we have studied the effect of the antineoplastic drug epirubicin, an antibiotic of the anthracycline group, on human neuroblastoma cell lines SK-N-MC, SK-N-SH, SJ-N-KP, TS12 and AF8. Epirubicin induced morphological and biochemical differentiation in these cultured cell lines; treatment with it stimulated the outgrowth of neurites and increased acetylcholinesterase activity.