The sequence of events in haematogenous metastasis from colonic carcinoma was analysed, using 1541 necropsy reports from 16 centres. The findings are consistent with the cascade hypothesis that metastases develop in discrete steps, first in the liver, next in the lungs and finally, in other sites. Deviations of necropsy findings from the cascade model are largely explained on the basis of false negative reports. In only 216 of 1194 cases was there suggestive evidence that metastatic patterns (excluding lymph nodes) were causally related to lymphatic or non-haematogenous pathways. The incidence of metastatic involvement in 'other' (quaternary) sites correlated with target organ blood-flow (ml min-) per g, only when bone marrow and thyroid were excluded. In the thyroid the incidence was lower than expected on the basis of blood flow per g tissue; this may indicate that the thyroid is an unfavourable site for metastatic growth of colonic carcinoma. In the bone marrow it is higher; the latter may be due to delivery of cancer cells via both arterial blood and the vertebral venous plexus. Recognition of this pattern of metastases in the bone marrow could be important with respect of diagnosis and therapy, in patients with colonic carcinoma.
Cancer can be viewed as a disorder generating from an uncoupling of gene expression that controls cellular proliferation and differentiation. Therefore, much attention has been paid to cancer cell lines that can be induced to differentiate after in vitro exposure to chemical or chemotherapeutic agents (for reviews, see refs. 1-3). The K-562 human leukemia cell line provides a useful system for studying human erythroid differentiation because it expresses markers of erythroid lineages, such as hemoglobin.Of the variety of chemotherapeutic agents used in cancer treatment, some can induce cell differentiation (4). In our previous studies we used drugs directed against key enzymes of purine and pyrimidine metabolism (5-7). Activities of target enzymes of these drugs were those that were tightly linked with in vivo and in vitro proliferative activity (5,8,9). The activity of IMP dehydrogenase (IMP:NAD' oxidoreductase; EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, markedly increased in various types of cancer cells; therefore, this enzyme was suggested as a sensitive target for anticancer chemotherapy (5, 10).
Tiazofurin (2-i-D-ribofuranosyl-4-thiazolecarboxamide;NSC-286193) potently inhibits the proliferation ofa variety of experimental and human neoplasms and is now in phase I and II clinical trial (11, 12
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.