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Poisoning the spindle: serendipity and discovery of the anti-tumor properties of the Vinca alkaloids.

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In 1995, Canadian scientists Robert Noble and Charles Beer were inducted into the Canadian Medical Hall of Fame for their 1950s "discovery" of Vinblastine. Their "chance" finding of an anticancer drug in the leaves of the periwinkle plant (Vinca rosea, Linn.), is used to explore the historical issue

Non-antitumor vinca alkaloids reverse multidrug resistance in P388 leukemia cells in vitro.

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Twelve monomeric or dimeric alkaloids from Vinca rosea Linn., which had been reported to have little or no antitumor activity, were investigated to determine their combined effects with either vincristine or daunorubicin on in vitro cell growth of a P388 subline resistant to vincristine and

In vivo antitumor activity of a monoclonal antibody-Vinca alkaloid immunoconjugate directed against a solid tumor membrane antigen characterized by heterogeneous expression and noninternalization of antibody-antigen complexes.

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It is widely believed that antigen heterogeneity and noninternalization of antigen-antibody complexes will severely limit the antitumor activity of monoclonal antibody-drug conjugates. The B72.3 monoclonal antibody binds to a tumor-associated antigen which is heterogeneously expressed in human

In vivo antitumor activity demonstrated with squamous carcinoma reactive monoclonal antibody-Vinca immunoconjugates.

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An immunoconjugate (PF1/D-DAVLBHYD), made with the squamous carcinoma reactive monoclonal antibody PF1/D and a derivative of vinblastine, DAVLBHYD, was shown to suppress established T222 human tumor nude mouse xenografts using a multidose protocol. Treatments of xenograft-bearing mice with free

In vivo antitumor activity of a panel of four monoclonal antibody-vinca alkaloid immunoconjugates which bind to three distinct epitopes of carcinoembryonic antigen.

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A panel of four murine monoclonal antibodies apparently directed against three distinct epitopes of carcinoembryonic antigen (CEA) was conjugated via oxidized carbohydrate groups to 4-desacetylvinblastine-3-carboxyhydrazide. The resulting antibody-vinca conjugates were evaluated for antitumor

Comparative antitumour activity of vinblastine-isoleucinate and related vinca alkaloids in human tumour xenografts.

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The antitumour activity of the investigational agent vinblastine-isoleucinate (V-LEU) was compared with vintriptol, another investigational agent of the same series of vinblastine-23-oyl amino acid derivatives, and vinblastine, their clinically active parent compound, in a panel of nine human tumour

Preclinical antitumor activity of a new Vinca alkaloid derivative, S 12363.

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S 12363 is a new Vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of O4-deacetyl vinblastine. S 12363 was evaluated for cytotoxic and antitumor activity against a spectrum of murine and human tumors. This compound was, respectively, on

Characterization of the pharmacological antitumor effects of S 12363, a new vinca alkaloid.

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S 12363 is a new highly potent vinca alkaloid derivative characterized by the grafting of an a-aminophosphonate, bioisoster of the valine, at the C23 position of O4-deacetyl vinblastine. Using a cell image processor Samba 200 (System for Analytical Microscopic Biomedical Applications), we have

In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs.

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OBJECTIVE Vinflunine (20'-20'-difluoro-3',4'-dihydrovinorelbine), a novel derivative of vinorelbine characterized by marked antitumour activity in vivo in a series of experimental murine and human tumours is currently undergoing phase I evaluation. To investigate its potential for inclusion in

The effect of vinca alkaloid anticancer drug, vinorelbine, on chromatin and histone proteins in solution.

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Vinorelbine (navelbin) belongs to vinca alkaloid anticancer drugs family with a broad spectrum of selective activity against mitotic microtubules. The present study is the first report demonstrating chromatin components as a novel target for vinorelbine in hepatocytes. The interaction was carried

Identification and quantitation of antineoplastic compounds in chemotherapeutic infusion bags by use of HPTLC: application to the vinca-alkaloids.

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An instrumental quantitative high-performance thin-layer chromatographic (HPTLC) method has been developed for the determination of vinca-alkaloids (antineoplastic compounds) in chemotherapeutic infusion bags prepared in a hospital pharmacy. The method uses automated band application onto silica gel

Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D.

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The human squamous carcinoma-reactive murine monoclonal antibody PF1/D was used to derive a conjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxyhydrazide (PF1/D-DAVLBHYD). This immunoconjugate was shown to be largely aggregate free and there was no loss of immunoreactivity

Comparative pharmacokinetics of antitumor Vinca alkaloids: intravenous bolus injections of navelbine and related alkaloids to cancer patients and rats.

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The kinetics of distribution and elimination in rats of the antitumor drug navelbine and of two of its analogues, Na-formyl navelbine and deacetyl navelbine amide, have been studied by radioimmunoassay and compared with the kinetics obtained with vinblastine and vincristine. Fitting to

Antitumor activity of the new vinca-alkaloid S 12363 alone or in combination with verapamil on a human multidrug resistant renal carcinoma xenograft.

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We have established a model of human renal cell carcinoma, Kgg2, transplanted into athymic nude mice which expressed P-glycoprotein (P-gp) (detected by flow cytometry) and a high level of mRNA transcript of mdr1 gene (Northern blot analysis). We have evaluated the antitumor activity of a new highly

Antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids.

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This paper reviews manuscripts published from June 1991 to June 1992 that, in the author's opinion, have added to the understanding and clinical use of a group of commonly used antineoplastic agents. New developments highlighted include 1) clarification of the mechanism of action of the

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