Stimulation of mouse peritoneal cells by neutral glycerides. A study by light and electron microscope autoradiography using tritiated glycerides.
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Biomedical subjects
Publications and source records attributed to I Carr.
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In order to determine whether neoplastic invasion, as it occurs in colonic carcinoma, represents a recapitulation of embryonic events, the development of the crypts and basal lamina of the rat colon was examined in foetuses between 16 and 21 days gestation by light and transmission electron microscopy, autoradiography and morphometric techniques. The thickness of the basal lamina increased from days 16 to 18 of gestation. On days 19 and 20 the basal lamina was found to be significantly thicker in the intercryptal areas than at the base of the crypt. This difference disappeared at 21 days gestation. It was also demonstrated that cell migration and renewal occur in the same manner in the foetal colon as in the adult colon. These features do not resemble closely those seen in neoplastic invasion.
When 5 million cells of the ascitic form of the RMT 13762 are injected into syngeneic F344 rat footpads there is consistent metastasis to the popliteal node more rapidly than when the solid form is used. A greater number of tumor cells escapes from the footpad to the draining node via the afferent lymph than with the solid tumor. Local intralymphatic injection of 5FU produces cure or retardation of nodal metastasis in a significant number of animals (p less than 0.002).
Primary human colorectal carcinomas which had already metastasized to the draining lymph nodes have been studied by transmission electron microscopy and tissue culture. The invasive edges were identified by examining mirror-image blocks for light and electron microscopy. In the invasive edge there are single cells and small clusters of cells which have ultrastructural features suggestive of active cell movement; clusters of cells are found in the lymphatic trunks and in the subcapsular sinus of draining lymph nodes. Small clusters of cells survive in short-term culture; some of these cells are actively motile. These findings support the view that there is a sub-population of motile and invasive cells at the edge of human colorectal cancers.
The cell nuclei within primary and nodal secondaries of colorectal carcinomas were analysed morphometrically in order to identify a primary subpopulation with similar characteristics to cells involved in lymphatic metastasis. No significant difference in nuclear area was seen between cell populations of the primary and secondary. However, a regional variation in mean nuclear area was present, suggesting a relationship between cells at the invasion front and in early nodal metastasis. This subpopulation differed from the cell populations of the primary and more advanced secondaries. These results are consistent with the existence of a morphometrically identifiable metastatic subpopulation within the invasion front of colorectal carcinoma.
The invasive areas in 24 unselected human colorectal cancers were examined by light and electron microscopy and it was shown that the invasive process involves tubes of cells rather than single cells, that degenerative changes take place in specialized cells ahead of the invasive cancer cells and that the endothelium of the lymphatic vessels disintegrates, leaving gaps in the endothelial lining.
This review examines ways in which histopathologists can attempt to predict the degree of malignancy from the microscopic examination of surgically removed samples of human neoplasms. These include mitotic counts, measurement of DNA content, analysis of DNA turnover, measurement of proliferation antigens, measurement of nucleolar organizing areas, counting nucleoli, morphometry of nuclei, identification of genetic change, measurement of lysis of basement membrane, and measurement of invasion in vitro. The latter two are not currently of practical value. Of the rest none is uniformly capable of predicting the degree of malignancy of a human neoplasm. After further refinement and control measurement of several such parameters may however contribute more to the prediction of malignancy than present subjective assessments.
The aim of this study was to determine whether tumor cells move actively through the linings of lymph node sinuses. Using 13762 carcinoma in F344 rats, and Walker carcinoma in Wistar rats, 20 X 10(6) tumor cells were injected into the footpad, and the ipsilateral popliteal lymph node examined by transmission electron microscopy. The same tumors were examined by making standard cell spots on plastic or glass surfaces, and examining these by phase and reflection contrast microscopy, fluorescent microscopy after anti-actin and phallacidin staining and transmission electron microscopy. The 13762 cells do not migrate through the lining of the lymph node sinusoid, nor move actively in vitro. Ultrastructural appearances of the Walker rat carcinoma cells suggest that they move actively through the sinus lining. After 24 h in vitro the Walker rat carcinoma cells in the centre of the spot are adherent to the surface. There is some movement of the edge of the sheet, and individual tumor cells at the edge of the sheet move actively and independently. We conclude that the Walker rat carcinoma invades the lining of the lymph node sinusoid by active cell movement, and the 13762 carcinoma does not.