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J E Price

Publications and source records attributed to J E Price.

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

Effects of altering surface glycoprotein composition on metastatic colonisation potential of murine mammary tumour cells.

This study has examined cells from naturally-occurring murine mammary tumours to ascertain whether cell surface glycoproteins play a significant role in colonisation of the lungs after intravenous inoculation. It was found that gel electrophoretic analysis of membrane extracts and lectin adsorption studies did not reveal any consistent differences in glycoprotein composition of cells from tumours which can heavily colonise the lungs relative to ones from tumours which cannot do so or to cells from pulmonary metastases. Also, alteration of structural and functional properties of surface glycoproteins by treatment with succinylated lectins or with drugs such as tunicamycin and swainsonine, which inhibit glycosylation of membrane proteins, had no specific effects on metastatic colonisation of the lungs. Tunicamycin apparently decreased capability to form experimental metastases but also diminished tumourigenicity on subcutaneous inoculation, although it did not affect tumour cell viability in vitro. This information supports earlier studies from this laboratory involving enzymic digestion of the surface of living tumour cells before inoculation and demonstrates that the pulmonary colonisation capability of these mammary tumour cells can withstand global disorganisation of membrane glycoprotein structure and composition. This implies that either the surface glycoproteins are not important in the colonisation process, or that these tumour cells have great capability for rapid repair of their surfaces. It is concluded that a clear answer to whether surface glycoprotein composition has a decisive role in pulmonary colonisation by these mammary tumour cells requires introduction of stable heritable traits into tumour cell populations by genetic manipulation.

Alkaloids↗
PubMed1986

Clonogenicity and experimental metastatic potential of spontaneous mouse mammary neoplasms.

Spontaneous primary mammary tumors of C3H-Avy mice differ in metastatic colonization potential, some producing many lung deposits (high-colonization potential) and others producing few or none (low-colonization potential) after iv inoculation of cells. The degree of metastasis from undisturbed neoplasms also varies from tumor to tumor. This study examined whether these differences between tumors could be accounted for by differences in clonogenic or stem cell content. Tests for clonogenic cells were: growth in 0.3% agarose and limiting dilution assays. Mammary tumor cells of known colonization potential were inoculated iv at serially reduced doses, and the relationship between number of cells injected and number of lung deposits formed was determined. Parallel in vitro dose-response assays in 0.3% agarose were performed with the use of cells from the same primary tumors. Colony-forming efficiency in 0.3% agarose cultures varied between individual primary mammary tumors and was positively associated with experimental metastatic potential, suggesting that the stem or clonogenic cell content of primary tumors is one of the important determinants of the metastatic phenotype.

Agar↗
PubMed1986

Different deficiencies in the prevention of tumorigenic-low-metastatic murine K-1735b melanoma cells from producing metastases.

To produce metastasis, malignant tumor cells must be able to complete a sequence of many steps that depend not only on tumor cell properties but also on ability of the tumor cells to interact effectively with host homeostatic mechanisms to avoid destruction. Therefore, it should be possible to isolate clonal populations non- or low metastatic. In a study of K-1735 clones introduced into normal syngeneic hosts, the reasons for the lack of or low ability of metastasis production did indeed differ among different clones. Some clones were identified that were low metastatic in syngeneic C3H/HeN mice because of antigenic characteristics. Others failed to give rise to metastases because they could not survive and grow once arrested in the lung parenchyma. These data suggested that the success of future studies dealing with genetic analysis of the metastatic phenotype could depend on the use of appropriate tumor cell populations.

Animals↗
PubMed1986

Evidence that the process of murine melanoma metastasis is sequential and selective and contains stochastic elements.

Malignant neoplasms are heterogeneous for many different biological characteristics, including invasion and metastasis. The pathogenesis of metastasis involves a series of sequential steps which must be completed by metastatic cells. In the present study we examined the metastatic behavior of three highly metastatic and three nonmetastatic subpopulations isolated from the K-1735 melanoma syngeneic to the C3H/HeN mouse. Cells were labeled with [125I]iodo-2'-deoxyuridine, and their initial organ distribution, fate, and production of experimental metastases were determined. Highly metastatic cells survived in lung parenchyma to produce metastases, whereas nonmetastatic cells did not. However, even with the highly metastatic cells only 2% of the original inoculum was responsible for the final production of metastases. The results support the concept that the fate of tumor cells released into the bloodstream is determined by sequential and selective events and introduces a third regulatory factor. Cells endowed with metastatic properties have a higher probability of forming metastases than cells not so endowed, but this probability is not 100%. Hence, metastasis should be considered as a sequential, selective, and stochastic process.

Animals↗
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

Injection of cells and monoclonal antibodies into mice: comparison of tail vein and retroorbital routes.

Organ distribution and blood concentration profiles were compared following injection of mice with radiolabeled test agents via the lateral tail vein or retroorbital venous sinus. Monoclonal antibodies directed against B16 melanoma of C57BL/6 origin were labeled with iodine-125. Thymocytes from BALB/c mice and B16 melanoma cells were labeled with technetium-99m sodium pertechnetate (Na 99mTcO4). Animals were injected with 5 microCI of iodinated antibody, 5 X 10(5) syngeneic thymocytes, 2.5 X 10(5) melanoma cells, or 10 microCi Na 99mTcO4 in 0.2 ml saline via either route. In non-tumor-bearing C57BL/6 mice radiolabeled monoclonal antibody was found primarily in the gastrointestinal tract, liver, and blood. Na 99mTcO4 localized in the gastrointestinal tract, 99mTc-labeled thymocytes in the spleen and liver, and 99mTc-labeled B16 melanoma cells in the liver and lungs. Pharmacokinetic analysis of blood samples taken 4, 8, and 12 min following injection of the labeled agents suggested that the iodinated antibody had less vascular permeability than Na 99mTcO4 and that thymocytes and B16 melanoma cells were trapped in the pulmonary vasculature as they passed through the lungs. It is noteworthy that no biologically significant differences in organ distribution patterns or blood decay profiles were found between lateral tail vein and retroorbital routes. The data clearly indicate that these routes can be used interchangeably with one another for intravenous injections.

Animals↗
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

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

Initial clinical experience with "low bleed" breast implants.

Considerable data indicate that "low bleed" breast implants could lead to a reduction in the incidence of clinically evident capsular contraction. This paper represents an initial clinical evaluation of "low bleed" breast implants. Initial data indicate that there is a reduction of the incidence of capsular contraction in patients in which "low bleed" implants have been used.

Breast↗
PubMed1983

Capsular contraction and deflation associated with inflatable implants.

In 9 patients who had inflatable implants placed and underwent open capsulectomy and replacement of these implants, severe degrees of capsular contraction were found in all patients. In addition, 7 of the 9 patients had some degree of deflation of the implant causing noticeable breast distortion or loss of breast volume. Many of the capsules removed showed actual crystalline material present in the capsules with a more severe degree of encapsulation than found with other types of implants. Inflatable implants offer no advantages over gel implants and are certainly not to be used in preference to other forms of breast implants.

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↗