Cytotoxic and antitumor effect of fibrinogen-methotrexate conjugate

被引：33

作者：

Boratynski, J ^{[1
]}

Opolski, A ^{[1
]}

Wietrzyk, J ^{[1
]}

Górski, A ^{[1
]}

Radzikowski, C ^{[1
]}

机构：

[1] Polish Acad Sci, Ludwik Hirszfeld Inst Immunol & Expt Therapy, Dept Tumor Immunol, PL-53114 Wroclaw, Poland

来源：

CANCER LETTERS | 2000年 / 148卷 / 02期

关键词：

fibrinogen; methotrexate; conjugate; cancer; drug carriers;

D O I：

10.1016/S0304-3835(99)00334-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In this paper we describe the chemical procedure of fibrinogen-methotrexate (F-MTX) conjugate preparation and its in vitro and in vivo antitumor activity. F-MTX conjugates were synthesized in reaction of fibrinogen with MTX N-hydroxysuccynimide ester. The conjugates were not cross-linked and were soluble in water. The results of the in vitro and in vivo studies have shown: (1) a lower in vitro cytotoxicity of the F-MTX conjugate as compared with MTX alone; (2) a significantly higher in vivo antitumor activity of the F-MTX conjugate in mice with P388 leukemia as compared with MTX alone; (3) a significantly increased in vivo lethal toxicity of F-MTX as compared with MTX. The results suggest the therapeutic utility of the fibrinogen-methotrexate conjugate and the usefulness of fibrinogen as a chemotherapeutic drug carrier. However, a new effort in the preparation of F-MTX conjugate should be made to decrease its in vivo toxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：189 / 195

页数：7

共 33 条

[1] Dry reaction of proteins with carbohydrates at 120°C yields neoglycoconjugates [J].

Boratynski, J .

BIOTECHNOLOGY TECHNIQUES, 1998, 12 (09) :707-710

[2] COLORIMETRIC MICROMETHODS FOR GLUTARALDEHYDE DETERMINATION BY MEANS OF PHENOL AND SULFURIC-ACID OR PHENOL AND PERCHLORIC-ACID [J].

BORATYNSKI, J ;

ZAL, T .

ANALYTICAL BIOCHEMISTRY, 1990, 184 (02) :259-262

[3] High temperature conjugation of proteins with carbohydrates [J].

Boratynski, J ;

Roy, R .

GLYCOCONJUGATE JOURNAL, 1998, 15 (02) :131-138

[4]

BORATYNSKI J, 1983, ARCH IMMUNOL THER EX, V31, P99

[5] THE ROLE OF FIBRIN IN TUMOR-METASTASIS [J].

COSTANTINI, V ;

ZACHARSKI, LR .

CANCER AND METASTASIS REVIEWS, 1992, 11 (3-4) :283-290

[6]

DANG WB, 1994, CANCER RES, V54, P1729

[7]

DONATI MB, 1995, THROMB HAEMOSTASIS, V74, P278

[8] FIBRIN AS A COMPONENT OF THE TUMOR STROMA - ORIGINS AND BIOLOGICAL SIGNIFICANCE [J].

DVORAK, HF ;

SENGER, DR ;

DVORAK, AM .

CANCER AND METASTASIS REVIEWS, 1983, 2 (01) :41-73

[9] VASCULAR-PERMEABILITY FACTOR, FIBRIN, AND THE PATHOGENESIS OF TUMOR STROMA FORMATION [J].

DVORAK, HF ;

NAGY, JA ;

BERSE, B ;

BROWN, LF ;

YEO, KT ;

YEO, TK ;

DVORAK, AM ;

VANDEWATER, L ;

SIOUSSAT, TM ;

SENGER, DR .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1992, 667 :101-111

[10]

DYR JE, 1986, NEOPLASMA, V33, P401

← 1 2 3 4 →