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S Spinelli

Publications and source records attributed to S Spinelli.

66 records · Page 4Linked to original sources
PubMed1992

Current approaches to new drug development in cancer chemotherapy.

This review summarizes and discusses current developments of new antitumor agents, with particular reference to mechanism of action, preclinical efficacy and interest for clinical evaluation. A progress is appreciable in the study of analogues of existing agents and in the identification of new series of cytotoxic compounds with a mechanism of action somewhat similar to that of conventional cytotoxic drugs. Advances in knowledge of tumor cell biology and biochemistry offer the prospect of identifying new targets for a selective drug action. The value of this new drug discovery approach remains to be established.

Animals↗
PubMed1992

[Why a gynecological consultation service in a hematology day hospital. Our experience].

The paper described the role of a gynaecological advisory service in an hematological day hospital. The main gynaecological problems which arose during anti-cancer and immunosuppressive therapy were classified according to patients' symptoms. The paper stresses the need for close collaboration between hematologists and gynaecologists and underlines the psychological importance of this aspect from the patient's point of view.

Adult↗
PubMed1991

The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU.

The crystal structure of the aspartyl protease encoded by the gene pol of the human immunodeficiency virus (HIV-1, isolate BRU) has been determined to 2.7 A resolution. The enzyme, expressed as an insoluble denatured polypeptide in inclusion bodies of Escherichia coli has been renatured and crystallized. It differs by several amino acid replacements from the homologous enzymes of other HIV-1 isolates. A superposition of the C alpha-backbone of the BRU protease with that of the SF2 protease gives a roots mean square positional difference of 0.45 A. Thus, neither the denaturation/renaturation process nor the amino acid replacements have a noticeable effect on the three-dimensional structure of the BRU protease or on the detailed conformation of the catalytic site, which is very similar to that of other aspartyl proteases.

Cloning, Molecular↗
PubMed1991

Synthesis and antitumor evaluations of symmetrically and unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones and 1,4-bis[(aminoalkyl)amino]-5,8-dihydroxyanthracene-9,10-diones.

The ipso bis displacements of fluoride from 1,4-difluoroanthracene-9,10-dione (3) and 1,4-difluoro-5,8-dihydroxyanthracene-9,10-dione (4) by excess of a diamine (or a monoamine) in pyridine at room temperature lead to the symmetrically substituted 1,4-bis-substituted analogues 5 and 6, respectively. The ipso monodisplacements of fluoride from 3 and 4 can be accomplished by treatment with less than 1 molar equiv of a diamine (or a monoamine) to yield 7 and 8, respectively. Treatment of 7 or 8 with a different diamine leads to the unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones 9 and 10, respectively. Many of the synthetic unsymmetrical analogues have been evaluated for their antitumor activity against L1210 in vitro and in vivo. Cross resistance of analogue 10a with mitoxantrone (2) and doxorubicin was evaluated against MDR lines in vitro against human colon carcinoma LOVO and its subline resistant to DOXO (LOVO/DOXO). Potential mechanisms for the observed cytotoxicity are presented and discussed.

Animals↗
PubMed1990

Three-dimensional structure determination of an anti-2-phenyloxazolone antibody: the role of somatic mutation and heavy/light chain pairing in the maturation of an immune response.

The three-dimensional structure of the Fab fragment of an anti-2-phenyloxazolone monoclonal antibody (NQ10/12.5) in its native and complexed forms has been determined at 2.8 and 3.0 A resolution, respectively. Identification of hapten-contacting residues has allowed us to evaluate the contribution of individual somatic point mutations to maturation of the immune response. In particular, amino acid residues 34 and 36 of the light chain, which are frequently mutated in antibodies with increased affinity for 2-phenyloxazolone, are shown to interact directly with the hapten. We propose that the strict maintenance of certain amino acid sequences at the potentially highly variable VL-JL and VH-D-JH junctions observed among anti-2-phenyloxazolone antibodies is due largely to structural constraints related to antigen recognition. Finally, the three-dimensional model of NQ10/12.5, which uses the typical light chain of primary response anti-2-phenyloxazolone antibodies but a different heavy chain, allows an understanding of how, by preserving key contact residues, a given heavy chain may be replaced by another, apparently unrelated one, without loss of hapten binding activity and why the V kappa Ox1 germline gene is so frequently selected amongst the other known members of this family.

Amino Acid Sequence↗
PubMed1990

Three-dimensional structure and antigen binding specificity of antibodies.

A number of specific Fab and Fv fragments and their complexes with antigens (avian lysozymes), haptens, and anti-idiotopic Fabs have been studied by immunochemical and crystallographic techniques. Antigen and antibody interact through closely complementary contacting surfaces, without major conformational changes. An idiotopic determinant of a monoclonal antibody is shown to include parts of most of its complementarity determining regions. The specificity of antigen recognition resides in the close complementarity of the antigenic determinant with the antibody combining site.

Animals↗
PubMedDate not supplied

Cytotoxicity evaluation of natural coptisine and synthesis of coptisine from berberine.

The crude extract (80% MeOH in water) of Chelidonii herba exhibited very interesting cytotoxicity against brine shrimp (Artemia salina Leach) nauplii and cultured human tumour cell in vitro, the colon carcinoma HT 29 (144 h treatment). Fractionation of the crude extract and bioassay-guided procedures showed that the cytotoxic and the antitumour activities were concentrated in the basic extract. On the basis of IR, MS and 1H NMR the compound responsible of the cytotoxic activity was determined to be coptisine. Cytotoxicity evaluation of coptisine was next extended to a panel of human and murine cell lines in comparison with the established antitumour drugs mitoxantrone, doxorubicin (Dx) and cisplatin (CDDP). Coptisine was cytotoxic on LoVo and HT 29 and less potent on L-1210, and it was partially crossresistant on the human tumour colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukaemia cell line resistant to CDDP, L-1210/CDDP. Coptisine alkaloid was then synthesised in gram amount from commercial berberine. A four-step synthetic route was elaborated. The overall yield was about 8-10%. The structural identity of synthetic coptisine was verified by IR and NMR methods. A comparison of the cytotoxic effects on the human tumour colon cell line LoVo and on the murine leukaemia L1210 showed, for both natural and synthetic coptisines, a comparable cytotoxic activity more evident against HT 29 cell line and LoVo cell line, while the activity was lower against the L1210 cell line.

Animals↗
PubMedDate not supplied

Bbr 2778, an aza-anthracenedione endowed with preclinical anticancer activity and lack of delayed cardiotoxicity.

With the aim to provide second-generation anthracenedione analogues endowed with reduced side effects and a wider spectrum of action than mitoxantrone and doxorubicin, a large number of new molecules bearing nitrogen atoms in the chromophore was synthesized and screened in vitro and in vivo. From this screening, BBR 2778 (6,9-bis[(2-aminoethyl)amino] benzo[g]isoquinoline-5,10-dione dimaleate) emerged as the most interesting compound. BBR 2778 was tested in vitro on several murine and human tumor cell lines and showed cytotoxic potency lower than that of mitoxantrone and doxorubicin. BBR 2778 was more cytotoxic in leukemia and lymphoma cell lines than in solid tumor cell lines. Although against in vivo models BBR 2778 was less potent than mitoxantrone and doxorubicin, its antitumor activity was equal or superior (in certain tumor models) to that of the above standard compounds. In particular, BBR 2778 was curative against L1210 murine leukemia and YC-8 murine lymphoma. Moreover, it showed an antitumor activity comparable to that of mitoxantrone and doxorubicin on solid tumors. No cardiotoxic effect of BBR 2778 in animals not pretreated with anthracyclines was observed compared to standards. In light of its spectrum of activity and marked efficacy against lymphomas and leukemias over a wide dose range, together with its lack of delayed cardiotoxicity, BBR 2778 has been entered in clinical studies.

Animals↗
PubMedDate not supplied

[Epidemiological study of Chlamydia trachomatis infection in a sample of women requesting voluntary termination of pregnancy, treated with rokitamycin].

BACKGROUND: Infection with Chlamydia trachomatis usually involves the cervix uteri, causing no symptoms, and may easily be unrecognised and untreated until troublesome symptoms arise, such as pelvic inflammatory disease, which can affect fertility and reproductive life. Therapies include the macrolide antibiotics, and in this class rokitamycin offers marked lipophilia, excellent intracellular penetration, and bactericidal activity at concentrations close to the MIC. The present study was therefore designed to establish the frequency of intracervical infection with Chlamydia trachomatis in women applying for termination of pregnancy, and to assess the efficacy and safety of this drug in this indication. METHODS: Women aged 18-40 years were admitted for termination of pregnancy, with a positive cervical swab for Chlamydia trachomatis. The study was conducted in accordance with the Declaration of Helsinki and amendments. Patients were given one oral tablet of 400 mg rokitamycin in the morning, and one in the evening, for two weeks. Treatment started ten days before the termination, within 48 h of taking the swab. Partners were to receive the same treatment. RESULTS: 292 women requiring termination of pregnancy, on average at the 9th week of pregnancy, were assessed. Of these, 24 (8.2%), mean (+/- SD) age 27.1 +/- 6.1 years, range 18-39, with a positive cervical swab for Chlamydia trachomatis, were treated with rokitamycin; 22 of their partners were treated too. Forty days after the start of treatment 22 patients (92%) gave negative results; these were all the cases whose partners had received treatment. No adverse events were reported and the acceptability of the treatment was considered good or excellent in 91% and fair in 9% of the cases. CONCLUSIONS: The findings confirm that rokitamycin is one of the most useful and effective macrolides for the treatment of infections caused by intracellular microorganisms; it is extremely well tolerated and has marked microbiological efficacy.

Abortion, Therapeutic↗