The availability of lectin-resistant cell lines with altered carbohydrate moieties in cell surface glycoproteins and glycolipids has greatly facilitated study of the involvement of cellular glycoconjugates in tumor growth and metastasis. We present here a new animal model for metastasis study based on mouse Lewis lung carcinoma LL2 in vitro cell line. From this line, five lectin-resistant variant sublines were selected with the following lectins: wheat germ agglutinin (WGAR), Ricinus communis agglutinin II (RCA IIR) and Aleuria aurantia agglutinin (AAAR). The correlation of the lectin resistance with their in vitro and in vivo growth properties, and especially lung colonizing ability, were investigated. Three WGAR variants with well-preserved tumorigenicity revealed reduced metastatic ability, both spontaneous, after subcutaneous (s.c.) administration and experimental, after intravenous (i.v.) administration. The RCA IIR variant also possessed reduced spontaneous and experimental metastatic ability, but exhibited higher growth rate of local s.c. tumors. The AAAR variant possessed reduced spontaneous metastatic ability but its ability to colonize the lungs after i.v. administration was five-fold higher than that of the parent LL2 line, whereas its tumorigenicity remained unchanged. The relative differences among WGAR variants and parent LL2 line, concerning their experimental metastatic ability, remained similar in cyclophosphamide-modified mice to those in normal recipients.

Animals↗

PubMedDate not supplied

The hemostatic system and angiogenesis in malignancy.

Coagulopathy and angiogenesis are among the most consistent host responses associated with cancer. These two respective processes, hitherto viewed as distinct, may in fact be functionally inseparable as blood coagulation and fibrinolysis, in their own right, influence tumor angiogenesis and thereby contribute to malignant growth. In addition, tumor angiogenesis appears to be controlled through both standard and non-standard functions of such elements of the hemostatic system as tissue factor, thrombin, fibrin, plasminogen activators, plasminogen, and platelets. "Cryptic" domains can be released from hemostatic proteins through proteolytic cleavage, and act systemically as angiogenesis inhibitors (e.g., angiostatin, antiangiogenic antithrombin III aaATIII). Various components of the hemostatic system either promote or inhibit angiogenesis and likely act by changing the net angiogenic balance. However, their complex influences are far from being fully understood. Targeted pharmacological and/or genetic inhibition of pro-angiogenic activities of the hemostatic system and exploitation of endogenous angiogenesis inhibitors of the angiostatin and aaATIII variety are under study as prospective anti-cancer treatments.

Animals↗

PubMedDate not supplied

A study of local anaesthetics. Part 148. Influence of auxiliary substances on the surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII.

The influence of auxiliary substances of the polyol group (glycerol, propylene glycol, sorbitol) and of their concentration (5, 10, 15 and 20% by weight) upon surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII, viz., N-[2-(2-propoxyphenylcarbamoyloxy)-ethyl] piperidinium chloride was studied. The substances were applied as hydrogel humectants. It was found that their influence on the surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII depended on the type as well as concentration of the auxiliary substance. From the viewpoints of use in formulations of the drug form, sorbitol used at 5 and 10% concentrations represented the optimum.

Anesthetics, Local↗