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Biomedical subjects

P Rocchi

Publications and source records attributed to P Rocchi.

At least 55 records · Page 3Linked to original sources
PubMedDate not supplied

Retinoic acid modulates stem cell factor secretion by human neuroblastoma cell lines.

The hemopoietin stem cell factor (SCF) and its receptor c-kit are expressed in some tumoral cells, including neuroblastoma (NB) cells. We have investigated the effect of retinoic acid (RA), one of the most active differentiating agents on human NB cells, on the SCF production by human neuroblastoma cell lines. SCF concentration was determined by immunoenzymatic assay in the supernatants of seven neuroblastoma cell lines. All cell lines except one showed detectable amounts of SCF in the supernatant in basal culture conditions. A progressive increase pattern of the SCF concentration over time, was common to all SCF secreting cell lines, both unstimulated and RA-stimulated. Moreover, after 48 and 72 hours-exposure to RA, SCF concentrations were higher than in the untreated controls (p < 0.01). Membrane SCF mRNA isoform was also detected by reverse-transcription polymerase chain reaction. These effects demonstrated that RA, besides inducing neuronal differentiation, enhanced SCF production in neuroblastoma cell lines.

Antineoplastic Agents↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Neuronal cell differentiation of human neuroblastoma cells by inducing agents in combination.

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.

Acetylcholinesterase↗
PubMedDate not supplied

Effectiveness of differentiation inducers in combination on human neuroblastoma cells in vitro.

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.

Acetylcholinesterase↗
PubMedDate not supplied

Different responsiveness of normal and leukemic hemopoietic cells to esorubicin.

The effect of different Esorubicin concentrations (10(-7) M to 10(-10) M) has been tested on the in vitro growth of human normal hemopoietic progenitor cells and of three leukemic cell lines (K562, U 937, HL60). The highest drug concentration completely abolished both normal and leukemic proliferation. Lower doses of Esorubicin failed to induce any morphological or phenotypic differentiation of leukemic cell lines. A 24h pretreatment of the cells with 10(-9) M Esorubicin enhanced the in vitro proliferation of normal early myeloid progenitor cells, whereas it did not affect leukemic, myelomonocytic cell proliferation.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Epirubicin-induced differentiation of human neuroblastoma cells in vitro.

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.

Acetylcholinesterase↗
PubMedDate not supplied

The in vitro effect of epirubicin on human normal and leukemic hemopoietic cells.

Epirubicin, at concentrations ranging between 10(-7) and 10(-13) M, was assayed in semisolid cultures of human normal hemopoietic cells and in liquid cultures of 5 different human leukemic cell lines. The growth of all normal hemopoietic progenitor cells was inhibited by the higher drug concentrations; at the lowest concentration, only CFU-E and 7th-day CFU-GM were not inhibited. On the other hand, leukemic cells were sensible only to the higher concentration of epirubicin, which, nevertheless, was not fully inhibitory. Leukemic cell differentiation was not promoted by the drug, as evidenced by a panel of monoclonal antibodies, by cytochemistry and by functional tests. These results suggest a marked in vitro myelotoxicity of epirubicin, that does not appear to be compensated by a powerful control of leukemic cell proliferation.

Antibodies, Monoclonal↗