Abstract
Spontaneous neoplasm metastasis, a fatalist pathological feature of cancer, is a long-evolving, multi-steps process that can now only be treated or controlled by drugs or immuno-modulators. As we have previously hypothesized, each drug or immuno-modulator might act differently within various stages of a metastasis. Therefore any researches helping to determine these differences will be beneficial for updating therapeutics for metastasis. In this work, we have testified this hypothesis by using a series of well-known anti-metastatic agents – Bisdioxopiperazine compounds.
Highlights
There have been two most difficult problems in cancer biology and therapeutics, neoplasm metastasis and multi-drug-resistances (MDR)
Spontaneous neoplasm metastasis is a long pathogenesis process to deteriorate the hosts in natural conditions, at least a week-long course in mice and a month-long course in human. It encompasses at least three main different substages: (i) tumor detachment from primary location; (ii) tumor cells flow in the blood or lymphatic vessels; (iii) tumor cell attachment and penetration through blood vessels of distant organs and angiogenesis [5]
Neoplasm Metastases Determination: Since anti-metastatic therapeutic would be rather preventive than indiscrimination cytotoxic against normal and neoplasm tissues, we used a low dosage of Bisdioxopiperazine compounds (Biz) compounds (1/10 to 1/5 LD50) to basically offset a possible lethal or mutational toxicity of conventional therapies involved in such experimental study
Summary
There have been two most difficult problems in cancer biology and therapeutics, neoplasm metastasis and multi-drug-resistances (MDR). Bisdioxopiperazine compounds (Biz), including ICRF-154, Razoxane (ICRF-159, Raz), ICRF-186 and ICRF-187 (two stereo-isomers of Raz) and ICRF-193, developed in the UK, have been a series of serendipitous agents found to be effective against a model of spontaneous metastasis (Lewis lung carcinoma, 3LL) [9, 10]. Ever since their development in 1969, many studies have addressed their potential use and mechanisms of action.
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