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D Tarin

Publications and source records attributed to D Tarin.

At least 73 records · Page 4Linked to original sources
PubMed1987

Vascular dissemination of tumor cells in relation to temperature-dependent metastasis in frogs.

Metastasis is a temperature-related phenomenon in the North American leopard frog (Rana pipiens) affected with the Lucké renal adenocarcinoma. The frog is a poikilothermic vertebrate whose internal body temperature closely follows that of the environment, and tumor-bearing frogs living in a warm (28 degrees C) environment have a much higher incidence of metastasis (greater than 75%) than those in cold (4 degrees C) conditions (less than 6%). In this investigation it was found that Lucké tumor cells labeled with fluorescein isothiocyanate could be detected in frozen sections of all organs examined within 15 minutes, regardless of whether the hosts were adapted to a warm or a cold environment. Separate experiments involving inoculation of isotope-labeled tumor cells demonstrated that large numbers of cells arrived in the liver and other organs of animals kept at either end of the temperature range. These findings show that the infrequency of metastasis by Lucké adenocarcinomas in chilled frogs is not due to failure of dissemination of tumor cells consequent upon temperature-mediated changes in blood viscosity or flow patterns. Thus they establish the important baseline that the effects of temperature on metastasis in this vertebrate are exerted directly on the tumor cells and/or the internal environment of the host and that the system therefore provides new opportunities for probing the biology and biochemistry of tumor metastasis.

Adenocarcinoma↗
PubMed1986

Biological and clinical studies relevant to metastasis of breast cancer.

The progression of neoplastic epithelial proliferation in the breast does not inevitably lead to an infiltrating carcinoma. The carcinoma-in-situ which do metastasize apparently produce cells whose first moves through tissue are facilitated by lysing inert intercellular material (types I and IV collagen). Metastasis, defined as the capability of tumor cells to disseminate to distant sites in the body and set up secondary neoplasms, is a property separate and additional to tumorigenicity or local invasiveness. The driving engine of the metastatic process is identified as regulatory genomic disturbances in the population of cells within the tumor. Success or failure of secondary tumor growth in distant sites depends upon the outcome of interaction with local microenvironmental factors and systemic endocrine and immunological conditions.

Adult↗
PubMed1986

Analysis of organ-specific effects on metastatic tumor formation by studies in vitro.

After entry into the blood, cells from disseminating malignant tumors are rapidly distributed to many organs, but they only grow to form metastases in certain sites. Clinical and pathologic observations on tumor metastasis in humans and in animals have confirmed that the distribution of these secondary neoplasms is related to the site and type of the primary neoplasm. Numerous studies now indicate that success or failure in producing metastatic deposits is influenced by interaction between the tumor cells and the microenvironment of the organ in which they lodge. In the present investigation, the mechanisms by which the microenvironmental conditions of specific organs may influence tumor cell survival and behavior and hence metastasis distribution were investigated in vitro with the use of spontaneous mouse mammary carcinomas from C3H/Avy mice. Some organs (lung, ovary) promoted the survival and the attachment of the tumor cells to the substratum, while others (liver, thyroid gland) consistently diminished survival of the tumor cells in the flask. These effects were shown to be due to soluble substances diffusing out of the organs, the dose dependency of which was demonstrated. It is known that in vivo murine mammary tumors develop metastases mainly in the lungs and occasionally in the kidneys or ovaries (if inoculated via the aorta). The effects of these same organs on tumor cells in vitro were thus in good agreement with the in vivo observations. The findings are compatible with the hypothesis that normal organs can usually suppress the formation of tumor metastases and that tumors that succeed in establishing metastases have evolved means of escaping the inhibitory effects of organs in which the deposits are found.

Animals↗
PubMed1985

Surgical and pathologic complications associated with peritoneovenous shunts in management of malignant ascites.

Forty-three peritoneovenous shunts have been inserted to palliate malignant ascites in 33 patients. Ascites was controlled for a time in every patient, but 18 shunts eventually blocked. Further shunt revision successfully controlled ascites until death in five of these patients and for prolonged periods in another five. The authors observed a marked difference between the performances of the two available shunts, but emphasize that the two groups of patients were not selected at random and therefore may not be comparable. Twelve postmortem examinations have been performed in the 33 patients to ascertain causes of shunt malfunction and to identify possible evidence of abnormal or accelerated tumor spread. The postmortem findings highlight great variability in the capacity of iatrogenically introduced showers of tumor cells to seed. There was a spectrum of tumor growth in the lung from a complete absence of tumor cells through dormant tumor clumps to developing metastases. The authors found no evidence either clinically or at autopsy, that the procedure had adversely affected the prognosis, except in one patient who died from pulmonary edema immediately after the operation.

Abdominal Neoplasms↗
PubMed1985

Collagenase secretion by human breast neoplasms: a clinicopathologic investigation.

Evidence is presented that biopsy specimens from fibroadenomas, benign cystic lesions, and carcinomas of the human breast can produce in organ culture a neutral protease capable of digesting type I collagen. This enzyme activity, measured with the use of a radioactive release assay, was characterized as true vertebrate collagenase and occurred in both active and latent (requiring trypsin activation) forms. For the two types of benign breast lesion studied, collagenase secretion was significantly higher from fibroadenomas than from benign cystic tissue. Breast carcinomas, however, exhibited a wide quantitative spectrum of collagenase secretion, encompassing the extremes observed for the benign lesions and showing no correlation with histologic type. These results, while providing a plausible mechanism for the marked collagen degradation seen in disseminating neoplasms, demonstrate that high collagenase secretory activity is not pathognomonic of invasive behavior. The findings, however, indicate disordered regulation of collagenase activity in malignant tumors.

Adenofibroma↗
PubMed1984

Clinicopathological observations on metastasis in man studied in patients treated with peritoneovenous shunts.

Fourteen patients with inoperable cancer treated with peritoneovenous shunts for malignant ascites were studied post mortem. Clinical observations and findings at necropsy indicated that peritoneovenous shunting does not result in the establishment of clinically important haematogenous metastases and that metastases do not necessarily develop even when large numbers of viable tumour cells regularly enter the blood. Peritoneovenous shunting provides a unique opportunity for collecting data on the spread of tumours in man.

Aged↗
PubMed1984

Degradation of basement membrane collagens by metalloproteases released by human, murine and amphibian tumours.

In this investigation it has been found that naturally-occurring (i.e. indigenous, not transplanted) tumours of diverse organs in a spectrum of vertebrates from frogs to man can secrete enzymes which degrade basement membrane collagens (type IV and V). The enzymes are inhibited by chelating agents (EDTA) but not by other protease antagonists and are, therefore, specific metalloproteases. Individual tumours do not necessarily secrete collagenases active against all collagen types (I, IV and V) and release of these different enzymes does not, therefore, appear to be coordinated. These biochemical findings support those reported for serially transplanted tumour cell lines and provide a plausible mechanism for the destruction of basement membranes and stromal collagen fibres observed morphologically in tumour spread.

Adenocarcinoma↗
PubMed1984

Temperature-dependent metastasis of the Lucke renal carcinoma and its significance for studies on mechanisms of metastasis.

Metastasis is temperature dependent in the renal adenocarcinoma of the North American leopard frog, Rana pipiens. Widespread, multiple, metastatic colonies occur in tumor-bearing frogs kept at 28 degrees C for 50 days while tumor-bearing frogs kept at 7 degrees C for 98 days or more have either no secondary deposits or they have only an occasional small metastatic nodule. An attractive aspect of the frog tumor is that invasion and metastasis can be permitted or inhibited by the manipulation of temperature alone-no exogenous chemicals or drugs are required for the effect. Because of this, biological variables which reproducibly and specifically associate with metastasis permissive conditions when ambient temperature is cycled between permissive and inhibitory values are strong candidates for being causal elements in the multistep process leading to metastasis. Intravascularly injected labelled renal tumor cells reached all organs studied in as little as 15 minutes at both metastasis restrictive and permissive temperature. The results with tumor cell inoculation dispose of the possibility that failure of metastasis in chilled animals is due to cold-induced changes in blood flow. Histologically typical metastatic colonies developed in frogs, kept at the permissive temperature, after injection with disaggregated tumor cells which were previously cryopreserved. Frog tumors elaborate type I collagenase in a temperature dependent manner. Type IV collagenase has been demonstrated as well. Tumor cell detachment in vitro, assembly and disassembly of tumor cell cytoplasmic microtubules, and invasion in vitro, are all temperature dependent.

Animals↗
PubMed1984

The relationship of myocarditis to dilated cardiomyopathy.

Three patients with congestive cardiomyopathy are reported in whom high neutralizing antibody titres to Coxsackie B viruses were detected. At post-mortem examination, all three had histologically demonstrable chronic inflammation of the myocardium. The hearts of ten patients dying in cardiac failure due to other causes showed no comparable inflammatory infiltration. This provides further evidence that Coxsackie B viral myocarditis is involved in the pathogenesis of some cases of dilated cardiomyopathy. One patient also had pulmonary veno-occlusive disease. This has been reported in association with myocarditis once previously in an infant. A viral aetiology has been postulated. It seems likely in this patient to have also been due to a Coxsackie B virus.

Adolescent↗
PubMed1984

Temperature-dependent dissociation of Lucké renal adenocarcinoma cells.

Fragments of Lucké renal adenocarcinoma were subjected to dissociation by rapid shaking after exposure to a divalent cation-free electrolyte solution, with or without 5 X 10(-4) M ethylenediaminetetraacetate (EDTA), at 7 degrees C and 28 degrees C. More cells detached at 28 degrees C than at 7 degrees C. Dissociation of cells from normal mesonephros fragments was minimal at both temperatures. It has been shown else-where that this frog tumor elaborates collagenase in a temperature-dependent manner. More collagenase is detected at 30 degrees C than at 7 degrees C. Normal kidney elaborates low levels of collagenase at both temperatures. Because our results suggested the possibility that some dissociation of the tumor cells may have been attributable to tumor-elaborated collagenase, we studied the effect of two collagenase inhibitors on dissociation. Both EDTA at high concentration and cysteine inhibit collagenase and both diminished tumor-cell dissociation.

Adenocarcinoma↗
PubMed1984

Cytoplasmic microtubules of normal and tumor cells of the leopard frog. Temperature effects.

The cytoplasmic microtubule complex (CMTC) was examined in monolayer cultures of normal tadpole mesonephros, primary renal adenocarcinoma, and an established cell line derived from a pronephric renal adenocarcinoma (PNKT-4B) of the leopard frog, Rana pipiens. Immunocytochemistry revealed typical arrays of microtubules extending from the cytocentrum to the cell periphery in all three cell types when cultured at 28 degrees C; similar results were obtained at 20 degrees C. However, the CMTC was disorganized in both tumor types, in contrast to the retention of a typical CMTC in normal tissue cultured at 7 degrees C. The response of PNKT-4B cells differed from that of normal tadpole mesonephros when treated with the microtubule inhibitor drug nocodazole. At 28 degrees C, PNKT-4B and tadpole mesonephros cells lost their CMTC with nocodazole treatment, and both were able to reconstitute CMTC when nocodazole was removed. Similarly, both lost CMTC organization with nocodazole and culture at 70 degrees C. However, while normal cells could effect a recovery at 7 degrees C after the removal of nocodazole, PONKT-4B cells were unable to restructure CMTC under the same conditions. Metastasis in the frog renal adenocarcinoma is temperature-dependent, with an elevated prevalence of metastasis in tumor-bearing frogs maintained at 28 degrees C. Few metastatic colonies are detected in tumor-bearing frogs maintained at a low temperature (7 degrees C). Other studies have indicated that microtubules, which are essential for cell motility, play an important role in the invasion by tumor cells of normal tissue fragments in vitro. The effects of temperature on metastasis of the Lucke renal adenocarcinoma are consistent with temperature-mediated changes in tumor-cell CMTC.

Adenocarcinoma↗
PubMed1984

Spontaneous and induced metastasis of naturally occurring tumors in mice: analysis of cell shedding into the blood.

The lung colonization capability (after iv inoculation) of each of 77 autochthonous virus-induced mammary tumors in C3H/Avy female mice was compared with its own spontaneous metastatic behavior. Twenty-four of these neoplasms had spontaneously metastasized to the lungs of the tumor bearer. The results were interpreted in the framework of dose-response studies on experimentally induced metastasis. These results indicate that tumors of high lung colonization potential (HCP) overgrow the lungs with iv doses as low as 10(4) cells, whereas tumors of low lung colonization potential (LCP) require at least 250 times this dose to achieve the same result. No general similarity was found between spontaneous and induced metastatic capability. Although some tumors showed good correspondence, others showed discrepancies and provided new information on mechanisms of cell shedding from primary tumors and on rate-limiting steps in metastasis. For example, from the dose-response studies, nonmetastatic tumors of HCP (iv) are deduced to be shedding very few cells. These findings suggest that escape from the primary tumor is an active process or else passive leakage of cells into vessels by hemorrhage, necrosis, or palpation should have resulted in spontaneous metastasis. Spontaneously metastatic tumors of LCP corroborate the view that metastasis is effected by a highly active subpopulation with special properties; otherwise, the required scale of passive cell release into the blood would be unrealistically large. Blood bioassay and time-course studies on pulmonary deposit formation indicate that shedding of metastatic cells occurs early in mammary tumor development.

Animals↗
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↗