Showing papers on "Cancer cell published in 1974"

The influence of host immunity on the arrest of circulating cancer cells, and its modification by neuraminidase

Abstract: The patterns of initial tumour cell arrest of a methylcholanthrene-induced fibrosarcoma and the Gardner lymphosarcoma were determined after injection of 125IudR-labelled tumour cells into the systemic circulation of mice. Experiments were performed with normal mice, mice sensitized by bearing ascites or subcutaneous variants of these tumours and animals hyperimmunized with X-irradiated tumour cells. Tumour-bearing and hyperimmunized mice were shown to produce humoral and cell-mediated tumour-immune responses by membrane immunofluorescence tests and migration inhibition assays of peritoneal exudate cells. In normal mice more than 90% of injected fibrosarcoma cells became localized in the lungs whereas the lymphosarcoma cells were localized primarily in both liver and lungs. The fibrosarcoma cells showed a decreased localization in the lungs and a corresponding increase in the livers, lymphoid tissues and kidneys of sensitized mice. However, the lymphosarcoma cells showed greater localization in the lungs of tumour-bearing and immunized mice compared with that in control animals. Prior treatment of both tumour types with Vibrio cholerae neuraminidase modified the pattern of cell arrest to some extent in both normal and tumour-sensitized mice. The relevance of these expriements as a model of the haematogenous metastasis of cancer cells is discussed.

Relation of human blood-groups MN to cancer cell surface antigens and to receptors for oncogenic viruses.

Abstract: It has been shown by us that the human blood-group MN antigenic determinants are not the products of allelomorphic genes as believed so far, but that N is the precursor substance of M and that the allelomorph to the M gene is amorph. The determinant structure of the N antigen is branched and possesses as non-reducing termini beta-d-galactopyranosyl (Gal) and alpha-N-acetylneuraminic acid (NANA) linked to beta-Gal. The M substance differs from N only in that alpha-NANA covers the terminal beta-Gal of the N determinant. Vicia graminea anti-N reacts with terminal beta-Gal of the N antigen as well as its precursor. A human blood-group N-like antigen in the cell surface of the TA3 mammary adenocarcinoma (ascites form) has been found by us. The TA3 cancer occurs as the non-strain specific Ha subline and as the strain-specific St subline. This is the first description of an N-like antigen in a non-primate as well as a tumor. This antigen reacts with Vicia anti-N. In serological specificity the Vicia agglutinin is closely related to the Thomsen-Friedenreich anti-T agglutinin present in most human and animal sera. These sera plus complement kill ordinary TA3-St cells and sialidase-treated Ha cells to less than 95 percent. Untreated TA3-Ha cells are fully resistant even though they absorb cytotoxin. Beta-galactosidase treatment of either Ha or St cells abolishes the killing activity of the sera. The cancer cells absorb anti-T but they lose this capability after exposure to beta-galactosidase. An immunological cross-relationship between the human blood-group MN antigens and the receptor for an oncogenic virus, the avian subgroup B leukosis sarcoma virus has been observed.

Cellular Sites of Immunoglobulins

Abstract: The distribution of immunoglobulin (Ig)- containing cells in the gastric antral mucosa of patients with various abnormalities of the stomach was studied by fluorescent antibody techniques. IgA-containing cells comprised about 80% of all Ig-containing cells and were diffusely distributed in the interstitial spaces of gastric glands. IgA was observed in the apical portion of the cytoplasm of cells in some pyloric glands, and IgM was seen extracellularly between the epithelial cells and in the lumen. At the base of gastric cancers, adjacent to the invading cancer mass, IgG-containing immunocytes were found in intermuscular spaces, and some cells that appeared to be cancer cells reacted with anti-IgG or anti-IgM.

Cancer Immunity after Treatment of Ehrlich Tumor with Diphtheria Toxin

Abstract: Summary In vivo and in vitro treatment of Ehrlich cancer cells with diphtheria toxin resulted in loss of oncogenicity and in immunization against these tumor cells in mice. The animals that survived a 1st i.p. transplantation of virulent cancer cells treated with diphtheria toxin failed to develop an ascites tumor after a 2nd transplantation up to 200 days later. Ehrlich cancer cells lost oncogenicity also by prolonged incubation in phosphate-buffered saline in the presence of diphtheria toxin. This loss of oncogenicity was time dependent and influenced by the pH. Cells incubated for 8 hr with diphtheria toxin failed to induce an ascites tumor in both normal and immunosuppressed mice. Incubations performed at 5 pH9s ranging from 6.5 to 7.5 demonstrated that the lower values were more effective in inhibiting oncogenicity than were the higher ones. Eighty % of the normal mice that survived an i.p. transplantation of 1 × 10 6 cancer cells incubated with diphtheria toxin became resistant to a challenge with 1 × 10 6 virulent cancer cells. Only 50% of the immunized mice survived a challenge with 2 × 10 6 cancer cells, while the survival rate fell to nearly 0% after a challenge with 5 × 10 6 cells. In Swiss albino mice immunized with Ehrlich cancer cells, a cross-resistance against ascites Sarcoma 180 was observed, while all Ehrlich tumor-immunized DBA/2 mice died within 10 days after a challenge with L1210 tumor.

Inhibition of cancer cell stickiness by the blocking of platelet aggregation.

Abstract: The mechanisms of the early stage of metastasis formation by blood-borne cancer cells is descriptionbed.

The selective effect of heat in cancer.

Abstract: Heat (42°C) exerted an inhibitory effect on the oxygen uptake of the rabbit VX2 carcinoma in vitro and led to a decrease in viability and growth potential of the cells as measured by vital dye uptake and their ability to produce tumours on injection into a host. Normal host tissue cells were unaffected by elevated temperatures. After heating in vivo, tumours showed an 80-95% reduction in volume, with marked necrosis of the tumour cells. Later, macrophage invasion and replacement fibrosis were evident. There was a 50% survival rate in animals treated by local heating and a 30% survival rate in those treated by total body heating, while all the control rabbits died at 10 weeks. The selective inhibitory effect of heat on cancer cells and its application to human neoplasms are discussed.

Rational Design of Purine Nucleoside Analogs

Abstract: The rational design of cancer chemotherapeutic agents must ultimately be based on an exploitable biochemical difference between normal host cells and the invading cancer cells. Although much is known about the biologic activity of certain agents, such as 6-mercaptopurine and 6-thioguanine, the basis of their selective action on cancer cells is still not fully understood. This selectivity could result from greater catabolism of the drug by normal cells, since it is known that the xanthine oxidase level of cancer cells is generally lower than that of normal cells (Bergel et al., 1957). The metabolic state of treated cells must also be important, since established solid tumors with a low growth fraction do not normally respond well to antimetabolites, purines or otherwise (Laster et al., 1969). Because of our limited knowledge about the basis of selective toxicity of purine antagonists, we must base the design of new agents on what is known about the metabolism and the mechanisms of action of purine analogs and the effects of structural changes on both of these. Although some of these topics will be discussed in more detail later in this volume, our knowledge of the biologically active purine analogs will be summarized briefly here.

Molecular pathology of the cancer cell.

Abstract: The recognition that a common feature of all cancer cells is a disorganization of the stringent controls involved in normal cell differentiation has been so obvious for such a long time that the statement assumes the character of a well worn cliche. Perhaps for this reason the impression is widespread that progress in understanding these cellular control mechanisms is being made only very slowly, but nothing could be further from the truth. Within the past decade dramatic advances have been made in understanding cellular function. These have provided a substantial framework on which it is now possible to erect models which can be tested by incisive experimentation. Most of these advances have emerged directly from the fundamental advances which were made in our understanding of biological processes as a result of the impact of molecular biology. Molecular biology implies the interpretation of biological phenomena in molecular terms. A large component of molecular biology is, therefore, biochemistry but molecular biology also exploits a wide range of associated disciplines such as biophysics and genetics. Much of the classical work of molecular biology had to do with the elucidation of the details of protein synthesis and its control; the 'central dogma' of the discipline lays down the principle that genetic information for proteins is encoded in DNA, transcribed from it into messenger RNA, and then translated from the messenger RNA, by a machinery employing ribosomes, transfers RNA and other factors to give proteins. Most of our basic understanding of these processes has been gained from studies with microorganisms but, within the past decade, there has been an increasing accumulation of information about the molecular biology of eukaryotic cells, particularly about protein synthesis. This has made it possible to recognize abnormalities of these mechanisms and it is the study of these which is defined as molecular pathology. Molecular pathology is particularly relevant to the study of cancer because there is now ample 4 evidence that the lesions which result in the formation of a cancer cell are very often, and possibly invariably, associated with abnormalities of nucleic acid and/or protein synthesis. In this communication some of these will be briefly discussed.

Induction of C-Type Particles in Mammalian Cancer Cells

Abstract: Temin postulated (1,2) that the viral DNA synthesized by the oncorna virion-associated reverse transcriptase (3,4) integrates into the host cell DNA as an essential step in the cellular transformation process. The studies of Hill and Hillova, who demonstrated that permissive cells were transformed by purified DNA molecules from transformed cells (5), confirmed Temin’s hypothesis. Thus, the oncorna virus-transformed cell contains viral DNA sequences in the cellular genome. The mechanism which leads to the integration of the viral DNA molecules into the cellular DNA is not yet known. Also, the cellular mechanisms which control the expression of the viral DNA are not yet understood. In permissive cells, transformation is accompanied by virus production, while in nonpermissive cells transformation occurs but without virus production. These findings suggest that in nonpermissive cells, the transcription of the viral DNA is controlled by the host cell process. Although the viral DNA is repressed in the nonpermissive cells, it was demonstrated (6) that virus synthesis could be induced by fusion of transformed cells with permissive cells. Treatment with 5-bromodeoxyuridine (BUdR) also induced virus replication (7), similar to the effect of arginine deprivation on nonpermissive cells (8). Although the mechanism of virus induction is not understood, the induction of virus replication was used to study the presence of oncorna viruses in cancer cells.