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Biomedical subjects

G Bartolini

Publications and source records attributed to G Bartolini.

65 records · Page 4Linked to original sources

Effects of streptozotocin in the WDHA syndrome not amenable to radical surgery.

Two cases of Verner-Morrison syndrome due to pancreatic carcinoma were treated H. h streptozotocin (STZ) according to the schedule suggested by the Division of Cancer Treatment of the National Cancer Institute. In both patients the drug caused a remission of the WDHA syndrome: therefore, this finding seems to recommend such treatment when the syndrome is not amenable to radical surgery. Renal toxicity is, however, an important limitation. It occurs mostly when STZ is administered by iv infusion. In one of the patients, after a serious impairment of renal function caused by STZ, prednisone controlled the syndrome for a long period of time.

Female↗

Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line.

OBJECTIVE: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. MATERIALS AND METHODS: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as BCL-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. RESULTS: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of BCL-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-gamma more than RAR-alpha. CONCLUSION: The findings indicate that IIF transcriptionally activates RXR-gamma preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60.

Animals↗

Effect of a new derivative of retinoic acid on proliferation and differentiation in human neuroblastoma cells.

Neuroblastoma, a tumor originating from the sympathetic nervous system, is the most common extracranial malignant solid tumor of childhood. Human neuroblastoma cells may differentiate in vitro under treatment with a variety of biological agents and drugs. Among these, retinoic acid (RA) is quite potent and its effectiveness as a therapeutic agent is now being evaluated in clinical trials. As its pleiotropic biological activities may produce side-effects limiting clinical use, it is important to find new compounds that present the same effectiveness together with few side-effects. In this study we have explored the action of IIF, (pat. WIPO W0 00/17143) a new derivative of RA, as a differentiation inducer in the human neuroblastoma cell line TS12. In the same cell line, we have also compared the effect of IIF with that of all trans RA (ATRA) and of 9 cis RA (9cRA), with respect to morphological and biochemical differentiation and growth inhibition. Treatment with IIF resulted in a strong inhibition of proliferation and in a marked induction of neuronal differentiation as revealed by neurite extension, increase of actylcholinesterase (AchE) specific activity and tyrosine hydroxylase (TH) expression. The results demonstrate the effectiveness of this new retinoid as a differentiation inducer on neuroblastoma cells TS12. Furthermore, the differentiation-promoter and antimitotic activities of IIF were on the whole more pronounced than those of ATRA and 9cRA. Therefore our study suggests the evaluation of the new retinoid IIF as a therapeutic approach in the treatment of neuroblastoma.

Alitretinoin↗

Retinoids and cancer: antitumor effect of ATRA and of a new derivative of retinoic acid, IIF, on colon carcinoma cell lines CaCo-2 and HT-29.

Vitamin A and its metabolic forms, like all-trans retinoic acid (ATRA), are used with promising results in the treatment of many tumors. Two major problems in the clinical use of retinoids are that the doses needed for successful treatment are often toxic, leading to "hypervitaminosis A syndrome" and that patients often develop drug resistance. In order to find compounds that can overcome these problems, many new derivatives of retinoids have been synthesized and tested. Here we present a study on the effect of a new derivative of retinoic acid, IIF (pat. WIPO W0 00/17143), on growth and differentiation of two colon carcinomna cell lines, CaCo-2 and HT-29, with different degrees of tumorigenicity, the second one being more undifferentiated. The effect of IIF was compared with that of ATRA, whose antitumoral action on colon cancer cells and other tumoral cells is widely described in the literature. Besides exerting a strong antiproliferative effect, even higher than that of ATRA, IIF induced cellular differentiation, as demonstrated by the appearance of morphological (domes and microvilli formation) and biochemical (alkaline phosphatase induction) markers. Therefore, these findings indicate the new retinoid IIF as a possible candidate in the treatment of colon cancer.

Antineoplastic Agents↗

A search for multidrug resistance modulators: the effects of retinoids in human colon carcinoma cells.

The development of multidrug resistance (MDR) is one of the major causes of failure in cancer therapy. The use of cell lines with acquired resistance to anticancer agents represents a very good tool for investigation into the possibility of reversal of MDR. In this study the ability of all-trans-retinoic acid (RA) and its derivative 6-OH-11-O-hydroxyphenanthrene (IIF; pat. WIPO W000 /117143) as antitumor agents was investigated in the human colon carcinoma cell line LoVo and in the counterpart resistant derivative LoVo/MDR cell line. Cell proliferation was measured by MTT assay, apoptosis was evaluated using DNA fragmentation and Annexin V detection assay. Retinoids suppressed cell proliferation in a time- and dose-dependent manner. Interestingly, IIF was significantly more effective than RA, particularly on LoVo/MDR cells. RA and IIF induced apoptosis in both cell lines, with IIF effect significantly higher than that of RA. Furthermore, on the basis that MDR phenotype is often caused by drug efflux due to overexpression of the membrane P-glycoprotein (P-gp), it was demonstrated that RA and IIF reduced P-gp synthesis in LoVo/MDR cells. Our results suggest that IIF could be a powerful tool in the development of colon carcinoma treatments, even when tumor cells present an MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prostaglandins and cyclic nucleotides as effectors in non-lymphocyte mediated surveillance processes ( short review).

This paper reviews the evidence pointing to a role of prostaglandins and cyclic AMP in the regulation of surveillance processes against transformed cells carried out by activated monocytes macrophages and natural killer (NK) cells. Specific topics of discussion include: (a) the regulation of monocyte/macrophage system and NK cells by prostaglandins and cyclic AMP; and (b) the possible immunomodulatory role of thromboxanes generated by activated monocytes and macrophages. Also the role of cyclic AMP dependent and independent protein kinases as well as their link with oncogenes is briefly reviewed.

Cell Division↗

Effects fo streptozotocin in the WDHA syndrome not amenable to radical surgery.

Two cases of Verner-MOrrison syndrome due to pancreatic carcinoma were treated H. h streptozotocin (STZ) according to the schedule suggested by the Division of Cancer Treatment of the National Cancer Institute. In both patients the drug caused a remission of the WDHA syndrome: therefore, this finding seems to recommend such treatment when the syndrome is not amenable to radical surgery. Renal toxicity is, however, an important limitation. It occurs mostly when STZ is administered by iv infusion. In one of the patients, after a serious impairment of renal function caused by STZ, prednisone controlled the syndrome for a long period of time.

Acute Kidney Injury↗