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Biomedical subjects

P M Ward

Publications and source records attributed to P M Ward.

32 records · Page 2Linked to original sources
PubMed1984

Target organ patterns of tumors in mice following the arterial dissemination of B16 melanoma cells.

The arrest of B16 melanoma cells and the subsequent development of tumors have been studied following left intraventricular injections (LVI) into mice of radiolabelled and unlabelled cells respectively; the proportions of cardiac output going to different target organs were also determined by LVI of radiolabelled microspheres. B16 cell arrest in the various target organs was as predicted by relative arterial blood supply, except in the lungs and liver where more radioactive counts were detected than could be accounted for in terms of initial arterial dissemination alone; and the numbers of counts remaining in all organs after 24 h were related to the numbers of counts initially obtained. When the incidence of tumor-bearing organs was related to the cell arrest patterns, the organs could be divided into two major distinct groups. Within both of these groups, the patterns of tumor incidence were correlated with cancer cell delivery. These results on a model system suggest that the two major hypotheses used to account for metastatic patterns are not mutually exclusive: the "soil" effect divides the target organs into the two major groups; however, within these groups the incidence of tumors is explicable in terms of the "mechanical" hypothesis.

Animals↗
PubMed1983

Liver-to-lung traffic of cancer cells.

Following the injection of B16 melanoma cells into the portal veins of mice, all animals developed liver tumors, but only 16% developed lung tumors. Portal vein injections of radiolabelled B16 and Walker 256 cancer cells into mice and rats, respectively, revealed that all of the cells were temporarily arrested in the liver and most were then slowly released. Bioassays indicated that of 8 X 10(4) B16 cells released from the liver over 24 h after portal vein injections of 10(5) cells, only approximately 1% were delivered to the lungs in a viable state. Experiments made with radiolabelled B16 cells showed that transit through either the liver or lungs following portal vein or tail vein injections, respectively, resulted in massive death of cancer cells. It is suggested that the death of most circulating cancer cells passing through the first organ encountered after leaving their primary tumor, serves to severely limit their further direct spread to other organs. It is therefore expected that metastases to these other organs would, to a large extent, be generated by cancer cells from metastases in the "first organs" as distinct from direct seeding from cancer cells released from the primary tumor. If the results of the present experiments have general application, they serve to emphasize the importance of metastasis of metastases in the natural history of the spread of cancer. In a previous publication (Weiss, 1980), studies of lung-to-liver traffic of cancer cells in rats revealed that, after tail vein injections, most Walker 256 cells were temporarily arrested in the pulmonary vasculature and then slowly released. A large proportion of the released cancer cells were dead or lethally injured on release from the lungs, and this "first organ processing" apparently accounted for the comparative rarity of extrapulmonary tumors following tail vein injections. In this communication, the concept of "first organ processing" of circulating cancer cells is further examined with respect to the liver-to-lung traffic of B16 melanoma and Walker 256 cells injected into the portal veins of mice or rats respectively. Both of these cell types grow well in the lungs following tail-vein injection.

Animals↗
PubMed1983

Cell detachment and metastasis.

Cancer cell detachment in three distinct and critical parts of the metastatic cascade is discussed. The detachment of cancer cells from their parent tumors is an initial early event in metastasis. The site of detachment with respect to proximity to blood vessels may determine the initial dissemination route. Many factors affect cell detachment; we specifically consider the effects of growth-rate, necrosis, enzyme activity, and stress on cell release in terms of metastasis-promoting mechanisms. Detachment is also discussed in relation to active cancer cell locomotion, where localized detachment from the substratum is a prerequisite for translatory movement. The importance of active cell movement in tissue invasion has only recently been assessed, and, in the case of at least some human malignant melanomas, a zone of actively moving cancer cells is believed to precede the growing body of the tumor. The secondary release of cancer cells from temporary arrest sites at the vascular endothelium consequent upon intravascular dissemination is also a major area of investigation. Circulating cancer cells arrest at vascular endothelium or are impacted in small vessels, however, most are released into the circulation and subsequently perish. The blood stream is a hostile environment, and it is probable that cancer cells are sufficiently damaged in translocation by hemodynamic trauma and humoral factors such that they easily detach or are 'sheared-off' the vascular endothelium by blood flow. Another possibility is that in some cases they are processed by 'first organ encounters' and perish before or shortly after arriving in a second organ. Animal studies have shown that, following intravenous injection, 60-100% of the injected dose of viable cancer cells are initially arrested in the lungs, but very few remain after 24 hr. As it is only those retained cells which produce tumors, the mechanisms involved in this secondary release, which occurs in all organs so far examined, are critical to any understanding of the metastatic cascade and metastatic inefficiency. The arrest of cancer cells at the vascular endothelium and their subsequent release have been associated with the presence of platelets, and the deposition of fibrin and manipulation of platelet-aggregating mechanisms and fibrinolysis are discussed in terms of their antimetastatic effects. The role of the reticuloendothelial system, natural killer cells, and polymorphs is discussed in relation to cancer cell clearance from blood vessels and also to inherent cancer cell properties which may act to inhibit their metastasis. Although detachment of cancer cells from a primary tumor may be regarded as metastasis promoting, secondary release of cancer cells may be associated with inhibition of metastasis.

Blood Vessels↗
PubMed1983

Do metastases arise from pre-existing subpopulations of cancer cells?

The hypothesis that metastases arise from pre-existing metastatic sub-populations of cancer cells with heritable metastasis-related characteristics, was tested by comparing the metastatic behaviour of cancer cells derived from pulmonary metastases with those from corresponding primary tumours, after implanting them subcutaneously in mice. In the case of KHT osteosarcomas and B16 melanomas, injected minces of metastases gave rise to more pulmonary metastases than cells derived from minces of the primary cancers generating them. However, in the case of 3LL and T241 cancers, the primary tumour minces gave rise to more pulmonary metastases than those derived from minced metastases. It is therefore concluded that the subpopulation hypothesis cannot be accepted as a general rule. When fragments of solid tumours were implanted into animals, no differences were detected between the metastatic behaviour of implants taken randomly from pulmonary metastases and the volume/age matched primary tumours generating them. These experiments thus provide no support for the hypothesis that metastases arise exclusively or predominantly from pre-existing metastatic subpopulations of cancer cells. Finally, implants of matched fragments from 3LL tumours of different volume and age, essentially produced no statistically significant differences in numbers of metastases. These observations do not therefore support the concept of a progressive evolution of subpopulations of cancer cells with heritable metastatic phenotypes during tumour growth.

Animals↗
PubMed1983

Histochemical changes in mucus in duodenal ulceration.

In duodenal ulceration the Alcian blue staining acid mucosubstances in goblet cells are reduced and the goblet cells themselves disappear. At the same time periodic acid-Schiff (PAS) staining neutral mucosubstances appear in the cells of the surface epithelium. These changes have been measured quantitatively with the help of a Vickers M86/0010 Scanning and Integrated Microdensitometer. During healing the changes are reversed. It is suggested that these changes suggest a metaplasia towards a gastric type mucosa as a protective response to the presence of ulceration.

Cell Count↗
PubMed1982

Residential movement among the poor: the constraints on housing choice in Latin American cities.

"The paper examines the validity of current theories of intra-city migration, subjecting those theories to the test of explaining new data collected in a total of 13 low-income settlements in three Latin American cities: Bogota, Mexico City, and Valencia, Venezuela. The study focuses attention upon the principal reception points for migrants; the location of previous place of residence for contemporary barrio dwellers; [and] the tenure and dwelling characteristics of previous places of residence. The authors conclude that residential patterns in Latin American cities are less the outcome of migrant choice, as some theories argue, and more the product of constraints imposed upon the land and housing markets."

Agriculture↗
PubMed1982

Arrest and retention of circulating cancer cells in the lungs of animals with defined metastatic status.

The arrest and retention patterns in lung tissues of [125I]-5-iododeoxyuridine-labeled Lewis lung carcinoma cells injected into the systemic circulation of tumor-bearing (TB) mice with defined metastatic status and non-tumor-bearing mice were determined. The presence of overt lung metastases did not significantly alter the arrest or subsequent rates of release of cancer cells compared with non-tumor-bearing controls. However, the percentage of cancer cells retained in the 3-week TB animals was significantly greater than that in the 1-week TB mice. In 3-week TB animals, 4 times as many cancer cells were arrested in the "noninvolved" lung tissues than in the metastases. The relative vascularities of the metastases and lung tissues were assessed following injection of 51Cr-labeled erythrocytes, and from these and published data it is suggested that major factors determining the differential distribution of cancer cells are the relative areas of microvascular endothelium and blood flow per g in the lungs and metastases.

Animals↗
PubMed1981

Trends in adolescent pregnancies.

Pregnancies in adolescents aged under 17 years constitute about 1.3% of all births in Queensland. A study of 189 adolescent pregnancies at the Royal Women's Hospital, Brisbane in 1977-1979 showed adequate antenatal care, and antenatal complications similar to those of a control group. There were greater incidences of unplanned Caesarean section, postpartum haemorrhage and puerperal infection. The major difference in the adolescent group was a perinatal mortality more than double that for the overall hospital population. The role of inadequate education in reproduction in the genesis of many adolescent pregnancies is stressed.

Adolescent↗
PubMed1977

Confirming heptachlor and heptachlor epoxide in food samples by gas-liquid chromatography of their photoderivates.

The food sample extract is cleaned up on a Florisil column and the 6% ethyl ether in petroleum ether cluate is subjected to repeated concentrations, using a micro-Snyder column, to expel volatile materials that absorb ultraviolet (UV) light. The sample and standard solutions of heptachlor and heptachlor epoxide are placed in quartz cells and exposed to UV radiation in the dark. Characteristic photoderivatives of the respective pesticides which form in the sample extract are identified and measured by comparison with those formed in the irradiated standard solutions, using electron capture gas-liquid chromatography. Recoveries of the 2 pesticides from 13 products, fortified at levels from 0.01 to 0.3 ppm and determined after derivatization, ranged from 67 to 110%.

Chromatography, Gas↗
PubMedDate not supplied

The relationship between lymphogenous and hematogenous metastasis in rats bearing the MT-100-TC mammary carcinoma.

Temporal and quantitative aspects of lymphogenous and hematogenous metastasis were examined using the rat MT-100-TC mammary carcinoma injected into the hind feet of syngeneic rats. Metastases first appeared in the draining popliteal nodes and then progressed in an invariable pattern to regional and then distal nodes: 'skipped' negative nodes within a chain of positive nodes were not observed. Metastatic progression in the lymphatic system occurred metachronously, with nodal metastases acting as 'generalizing' sites for 'downstream' nodes. Perturbation of lymph flow was apparent when nodes were involved with tumor, and resulted in retrograde seeding of contralateral nodes. Lung involvement was first observed by ectopic bioassay in 50 per cent of animals after 1 and 2 weeks of primary tumor growth; in contrast, all animals had popliteal involvement after 1 week. These results indicate that lymph nodes and lungs are not seeded synchronously, and the lungs are seeded after nodal metastases. Thus, a phase of metastasis has been identified, during which resection of the primary tumor and local nodes may well be curative in the 50 per cent of cases in which the disease is confined to these sites.

Animals↗