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D Tarin

Publications and source records attributed to D Tarin.

At least 91 records · Page 5Linked to original sources
PubMed1984

Artificially induced metastasis by cells from spontaneous Lucké renal adenocarcinoma.

This communication reports the development of tumour colonies in various organs after vascular dissemination of disaggregated cells from spontaneously arising Lucké renal adenocarcinomata in Cyclosporin-A-treated allogeneic frogs, Rana pipiens. The sites of tumour cell colonies were mesonephros, lung, bladder, mesentery, fat body and muscle. It was also found that digestion of these tumours with collagenase is an effective means of obtaining sufficient dissociated viable cells for large experiments and that cryo-preservation does not abrogate the ability of these cells to form metastatic deposits. This report, therefore, introduces a new tumour system for the study of factors affecting metastasis using naturally occurring tumours.

Adenocarcinoma↗
PubMed1984

Temperature-dependent elaboration of collagenase by the renal adenocarcinoma of the leopard frog, Rana pipiens.

Naturally occurring renal adenocarcinoma in North American leopard frogs, Rana pipiens, metastasize frequently (77%) when these ectothermic animals are kept in a warm environment but not when they are kept cold. We have found that explants of these tumors secrete collagenase, an enzyme capable of dissolving connective tissue fibers and found previously to be closely correlated with metastatic colony-forming capability of murine mammary tumors, and that the amount released sequentially rises and falls as the ambient temperature is shifted between metastasis-permissive and -inhibitory levels. In contrast, normal frog renal tissue has low collagenase output, unaffected by temperature changes.

Adenocarcinoma↗
PubMed1984

Absence of metastatic sequelae during long-term treatment of malignant ascites by peritoneo-venous shunting. A clinico-pathological report.

This communication records a remarkable case illustrating both the clinical value of peritoneo-venous shunting in the management of malignant ascites, and the unique opportunity afforded by this procedure for investigation of factors which influence metastatic colony formation by disseminating human tumour cells. The study of patients treated with peritoneo-venous shunts for the purpose of obtaining information on metastasis is ethically sound because such treatment is used solely for relief of the patient's clinical condition, and investigative procedures involving the patient are limited to those necessary for good clinical management. The patient we present survived for 27 months following insertion of a peritoneo-venous shunt, and for most of this time had a functioning shunt judged by clinical criteria. At autopsy she was found to have no established metastases in any organ, although viable, clonogenic cancer cells clearly capable of forming large secondary growths in the abdominal cavity were delivered directly into the bloodstream.

Ascites↗
PubMed1984

Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts.

The technique of peritoneovenous shunting for the alleviation of abdominal pain and distension in malignant ascites due to inoperable cancer, returns the fluid to the circulation via a one-way, valved, anastomosis between the peritoneum and the jugular vein. Surprisingly, although the patients treated with this technique receive direct infusions of malignant tumor cells into the blood, this study of 29 patients, 15 of whom came to autopsy, shows that they did not all develop metastases, some being completely free of such lesions despite long survival. Even when metastases do form, they are small and clinically asymptomatic, and the technique is therefore not hazardous. In some patients, inert tumor cells identifiable by natural markers were recognized in the tissues, but no growing metastases were observed. In others, the distribution of secondary deposits was unexpected in that metastases did not form in the organ containing the first capillary bed encountered, although hematogenous metastases had formed in other organs. Despite the fact that various factors such as (a) the small numbers of patients treated with the technique; (b) the sensitive nature of studies on terminally ill patients; and (c) the absence of consistency in the sample population with regard to factors such as length of survival and site of neoplasm, combine to reduce the number of suitable cases for study, the approach has unrivaled power and interest for those seeking to understand mechanisms underlying tumor metastasis in humans.

Adenocarcinoma↗
PubMed1983

Peritoneovenous shunts in the management of malignant ascites.

Peritoneovenous shunts have been inserted into 26 patients to control malignant ascites. All benefitted and most required no further paracentesis until death from progressive malignancy. Shunt blockage, which is the major problem at present, occurred in 8 patients. Five patients suffering from far advanced malignancy died within a month of operation. There was no clinical evidence of enhanced tumour spread or disseminated intravascular coagulation. We do not consider that the procedure is the first line of management, neither has it much to offer the patient with viscous, bloodstained or loculated ascites. We suggest criteria which help to identify the patient most likely to benefit from a peritoneovenous shunt.

Adult↗
PubMed1983

Effect of enzymic removal of cell surface constituents on metastatic colonisation potential of mouse mammary tumour cells.

Trypsin treatment of viable cells from 24 spontaneous murine mammary carcinomas resulted in a mild but reproducible diminution in their capability to colonise the lung after i.v. reinoculation but did not alter the distribution of deposits formed. The effects were similar on tumours of high and of low colonisation potentials. Neuraminidase and hyaluronidase did not exert any effect on metastatic colonisation potential, although all 3 enzymes were shown to be active and specific in cleaving their purified substrates, under the conditions in which they were used on the cells. Trypsin and neuraminidase were also shown to release characteristic components from the surfaces of living tumour cells, although hyaluronidase did not release detectable quantities of N-acetyl glucosamine indicating that there is little hyaluronic acid-related mucopolysaccharide on the surface of these mammary tumour cells. The results provide direct evidence suggesting that surface protein composition exerts an effect on the metastatic colonisation capability of mammary tumour cells.

Animals↗
PubMed1983

Observations on organ distribution of fluorescein-labelled tumour cells released intravascularly.

By labelling cells with fluorescein isothiocyanate (FITC) and other fluorescent dyes and examining frozen sections of several organs of the recipients with an ultraviolet microscope, it has been demonstrated that viable tumour cells arrive in all organs examined within 15 min of inoculation either intravenously or arterially and are still detectable in various organs 30 days later. Although the method is not quantitatively accurate, its advantages are that the cells can be directly visualised and it can be confirmed that the label is attached to whole viable cells and not to cellular fragments. The findings effectively dispose of the possibility that the consistent absence of deposits in certain sites in animals inoculated with cells from spontaneous murine mammary tumours is due to failure of the cells to reach them. It has also been confirmed that FITC-labelled cells are still capable of forming deposits and occasional fluorescent cells are detected in these secondary neoplasms.

Animals↗
PubMed1983

Organ preferences in metastatic colony formation by spontaneous mammary carcinomas after intra-arterial inoculation.

We have demonstrated earlier that cells from some spontaneous murine mammary tumours heavily colonise the lungs of every inoculated animal when injected intravenously, whereas those from others do so weakly or not at all. Extrapulmonary deposits are rare when cells are inoculated by this route. In the current experiments, we have found that if the cells are inoculated retrograde along the subclavian artery into the arch of the aorta, or directly into the abdominal aorta, they are capable of colonising organs other than the lungs and that individual tumours have reproducible preferences for establishing colonies in certain sites. The combination of organs favoured vary from tumour to tumour but most still showed a predilection for forming pulmonary deposits. Several organs are not colonised by any tumour in any recipient. It is concluded that the distribution of metastatic colonies formed by these spontaneous mammary tumours is influenced by interplay between intrinsic properties of tumour cells, microenvironmental influences in the organs in which the cells arrest, and rheological considerations.

Animals↗
PubMed1982

Investigations of the mechanisms of metastatic spread of naturally occurring neoplasms.

Much of the effort of this laboratory in recent years has been directed towards developing a reliable protocol for the experimental analysis of factors affecting metastatic spread from naturally occurring (i.e. not transplanted) neoplasms. The objective of this has been to develop a data base on the variations in metastatic behaviour between spontaneously arising neoplasms and to examine the tumour-specific and host-specific mechanisms accounting for this. This paper details the experimental technique and underlying conceptual basis which have been developed for reproducible investigations of this subject. It also reviews our conclusions from such work on the role in metastatic spread of tumour cell surface properties, collagenase secretion, microenvironmental effects on tumour cell growth in various organs, tumour macrophage content, and degree of cell shedding into the bloodstream.

Animals↗
PubMed1982

Correlation of collagenase secretion with metastatic-colonization potential in naturally occurring murine mammary tumours.

We report evidence for the secretion of a true mammalian collagenase active against Type 1 collagen, by naturally-occurring mammary tumours of the mouse and show that tumours capable of heavily colonizing the lungs secrete significantly more of this enzyme than those with low pulmonary-colonization potential, or non-neoplastic proliferating (e.g. lactating) mammary tissue. Plasminogen activator is secreted in greater quantity by tumours than by normal tissues, but there is no significant difference in the amount produced by tumours with high or low pulmonary-colonization potential. These findings correlate well with our earlier morphological observations of marked connective tissue destruction in the vicinity of invading tumours and metastatic deposits, and indicate that protease release is implicated in the mechanism of tumour spread.

Animals↗
PubMed1982

Experimental analysis of factors affecting metastatic spread using naturally occurring tumours.

This paper describes the applications and latest results of recently developed techniques in metastasis research using naturally occurring animal and human tumours. Intravenous inoculation of cells from murine mammary tumours into syngeneic recipients has shown that some are consistently capable of heavy pulmonary colonisation (HCP) while others have low colonisation potential (LCP). These distinct characteristics are stable over wide cell-dose ranges. Autopsies on a sample of 100 consecutive tumour-bearing C3H/Avy mice revealed that the incidence of spontaneous metastasis is 26%. When inoculated intravenously, cells from some of the spontaneously metastatic primary tumours had HCP and others LCP. We now report that, knowing the degree of pulmonary colonisation of a particular tumour after intravenous inoculation, the degree of its spontaneous metastasis in the original host, and the dose-response relationships mentioned above, it is possible to back-titrate the degree of cell shedding from the tumour into the blood stream. Other experiments reported here demonstrate that separate mammary tumours on the same animal have independent colonisation potentials and growth rates, that tumours appearing later on an animal are not necessarily more capable of metastatic spread than the earlier ones, and that tumour weight and length of presence on the host do not show any strong correlation with spontaneous metastatic spread. A moderately significant association between pulmonary colonisation potential and tumour growth rate is reported and evidence corroborating our earlier observations that ability to colonise the lungs is possessed only by neoplastic mammary cells is also presented. Similar investigation are, of course, much more difficult to organise on tumour spread in man because of ethical and logistic considerations but it is possible to circumvent some of these difficulties and we refer to some of our ongoing studies.

Adipose Tissue↗
PubMed1981

Macrophage content and colony-forming potential in mouse mammary carcinomas.

The macrophage content of cell suspensions from naturally occurring mouse tumours has been assessed by the Fc-mediated phagocytosis assay, and the results compared with the individual tumour's capacity for spontaneous metastasis and with its pulmonary colonization potential after i.v. inoculation. It was found that these tumours differ in their properties from the transplantable fibrosarcomas studied previously by other investigators, in that the macrophage content of all the tumours was uniformly low, ranging from 2 to 9% (mean 4.2 +/- 1.8%) and there was no inverse correlation with frequency of spontaneous metastasis, which was low. When the tumours were inoculated i.v. there was also no correlation with colony-forming capability, which varied greatly between tumours. Lung secondary deposits contained 1.7-6% macrophages (mean 4.4 +/- 0.6%) with a lower phagocytic activity for antibody-coated red cells than in the primary tumour.

Animals↗
PubMed1981

Lectin agglutinability of mammary tumours with differing metastatic colonisation potentials.

A new fully quantitative method for assessment of lectin agglutinability has been used in this investigation to compare the surface composition of cells from tumours with high and low pulmonary colonisation potential. As in our previous work, we have used only primary (i.e., naturally-occurring) mammary tumours in mice. It was found that agglutinability with the lectins Concanavalin-A and Wheatgerm agglutinin bore no relationship to the pulmonary colonisation potential of the primary mammary tumour. However, cells from disaggregated secondary deposits of tumours which manifested high colonisation potential were consistently less agglutinable than the cells of the primary tumours from which they were derived.

Agglutination↗
PubMed1981

Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors.

This communication reports experiments demonstrating that some sites in which tumor cells lodge reproducibly fail to support secondary colony formation by a particular tumor, even though cells from the same tumor are already proven to have high colonization potential in other organs. The effect is not an expression of nonspecific hostility to tumor growth, since cells from certain other tumors readily colonize the same site. Cell suspensions obtained by disaggregation of a series of naturally occurring murine mammary tumors were each inoculated by four different routes into separate batches of syngeneic animals, and the resulting degree and distribution of colonization were studied 90 days later at autopsy. Standard doses of 1 million viable tumor cells were injected either i.p. or s.c. into the tail vein or the hepatic portal vein. It was found that some tumors could reproducibly colonize by all routes, whereas others could colonize only by a few, and the combination of sites colonized varied from tumor to tumor; still others were unable to grow in any site. Cells from nonneoplastic lactating mammary glands did not establish any colonies. We have demonstrated previously that individual naturally occurring mammary tumors differ in their pulmonary colonization potentials after i.v. inoculation and that the potential of a given tumor is an intrinsic property of its constituent cells. The current findings are evidence that the microenvironment of an organ can inhibit or permit expression of this intrinsic potential and that the degree and sites of colonization are thus the results of interaction between tumor and organ-specific factors. It was also found that circulatory anatomy partially influenced the distribution of colonies and that colonization of distant organs after blood-borne dissemination is distinct from general tumor transplantability.

Animals↗
PubMed1980

Combined temporal arteriography and selective biopsy in suspected giant cell arteritis.

Superficial temporal arteriography was studied by selective biopsy of abnormal arterial segments and random biopsy of the main stem in 33 patients with clinically supected giant cell arteritis. Of the total of 33 temporal arteriograms 9 showed definite abnormalities (7 in the periphery and 2 in the main stem). Selective biopsy of the 7 peripheral abnormal segments showed arteritis in only 2, narrowing of the vessels in the remainder being due to atheroma (3) and fibrointimal thickening (2)--that is, 5 'false positives' for temporal arteritis on arteriography. Histological evidence of arteritis was found in 9 patients, only 5 of whom had clearly abnormal arteriograms--that is, 4 'false negatives'. Thus temporal arteriography appears to have low sensitivity for identifying arteritic lesions and also frequently gives 'false positive' results. It is concluded that temporal arteriography is not a satisfactory alternative to biopsy, and that its value as an adjunct to selective biopsy is limited because of its frequent failure to detect lesions found histologically.

Aged↗
PubMed1979

Metastatic colonization potential of primary tumour cells in mice.

A model has been developed for studying the capability of cells from primary murine mammary tumours to establish colonies in distant organs. The model involves the i.v. inoculation of disaggregated tumour cells into autologous and syngeneic recipients. The results show that the metastatic colonization potential of cells from a given tumour is consistent within the animals of an inoculated batch. Also, the findings are uniform in the autologous host and the syngeneic recipients. Tumours vary in their colonization potential and can be classified in 2 main groups designated high and low. These findings indicate that: (i) cells from 37% of mammary tumours can heavily colonize the lungs when inoculated i.v., even though the incidence of metastatic spread of these tumours in the undisturbed animal is almost zero. Thus, the relative infrequency of spontaneous metastasis from murine mammary tumours is not due to inability of the tumour cells to survive and colonize once free in the blood stream; and (ii) the colonization potential of the tumours is an intrinsic property of the tumour cells rather than of the host, whose prior acquaintance with the cells does not seem to confer resistance to colonization. The model presents opportunities for identification of possible differences between tumours of high and low colonization potential, and is being used to study cellular properties which favour colonization of distant organs by comparison of observations in vitro with the behaviour of cells from the same tumour in vivo.

Animals↗