Showing papers on "Cancer cell published in 1976"
TL;DR: It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.
Abstract: THE development of cancer following exposure to chemical carcinogens or to various forms of irradiation is almost invariably slow and prolonged. Although the process can be initiated by a brief exposure to a carcinogenic stimulus, there is no evidence that target cells so altered are cancer cells. Rather, there is abundant indirect evidence from many systems that what is induced is an altered cell or cell population from which malignant neoplasia can gradually develop or evolve1,2. Neoplastic development therefore resembles a chain reaction, triggered by exposure to a carcinogen, in which the links are new populations with altered organisational, structural and biochemical properties. These slowly proliferative new lesions are characteristically focal in distribution, implying that only a small proportion of the original target cell population in any organ or tissue participates. It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.
825 citations
TL;DR: Evidence is presented in normal lymphocytes that aerobic glycolysis not only is associated with cellular proliferation, but more specifically is temporally related to DNA synthesis.
Abstract: GLYCOLYSIS, for most mammalian cells, is only a prelude to the complete respiratory oxidation of glucose. Lactate production is usually barely, if at all, detectable in aerobic conditions1. Consequently, when Warburg2,3 observed that various tumours showed active aerobic glycolysis, he postulated that defective tumour cell respiration was the reason and was, moreover, the basic difference between normal and cancer cells. Although aerobic glycolysis by tumour tissue has been confirmed many times, defective respiration in cancer cells has not been established4. The failure to uncover a respiratory defect in cancer cells has led to other explanations. It has been suggested, for example, that aerobic glycolysis is linked to cell growth rather than to malignancy5, and for several hepatomas a correlation could be made between the amount of lactate produced and the cell doubling time6,7. It follows that if aerobic glycolysis is related to cell growth, it might be possible as much in normal as malignant cells. There is some evidence for this. Aerobic glycolysis has been noted in proliferating fibroblasts during the period of maximum increase in cell numbers8,9. Human lymphocytes have shown an increase in respiration and also produced lactate when stimulated by the mitogen phytohaemagglutinin10,11. In chick embryo and skeletal muscle fibroblasts12,13, glycolysis increased during log phase growth, but several factors seemed to influence lactate production. Medium composition, aggregation state of cells, culture pH and cell density were all considered more important in determining glycolytic activity than growth rate. It should be noted, however, that these factors are also important to the proliferative rate of these cells. We believe that the important question is not whether culture conditions can influence lactate production, but rather whether glycolysis is linked to cell division. So far no systematic study of the relationship of the appearance of aerobic glycolysis to cell proliferation or the phases of the cell cycle has been reported. This report presents evidence in normal lymphocytes that aerobic glycolysis not only is associated with cellular proliferation, but more specifically is temporally related to DNA synthesis.
312 citations
TL;DR: In this article, the central importance of the cell surface in determining many features of tumor-cell behavior has served to stimulate a massive research effort to identify differences in the surface properties of normal cells and their neoplastic counterparts.
Abstract: (Second of Two Parts) Cell-Surface Modifications on Cancer Cells The central importance of the cell surface in determining many features of tumor-cell behavior has served to stimulate a massive research effort to identify differences in the surface properties of normal cells and their neoplastic counterparts. This effort has been successful to the extent that an enormous catalogue of differences between normal and tumor-cell populations has been accumulated (Fig. 5).22 , 23 We now have little insight, however, into the mechanisms by which these manifold changes in surface properties arise in tumor cells and how these changes are maintained. Of more immediate importance . . .
156 citations
TL;DR: It is shown that normal breast fibroblast and epithelial cells do not directly interact with each other even when they are not physically separated, and it is speculated that loss of this specificity of communication may be a factor in the development of neoplasia.
Abstract: INTERACTIONS between animal cells in multicellular organisms are probably important in the coordinated control of growth and function during the normal and abnormal development of specific tissues and organs. Although much of the coordination is lost when cells are separated from each other and grown in tissue culture, direct communication can be detected between cultured cells which may be electrically coupled1,2, and which can show metabolic co-operation3,4. Indirect evidence suggests that this direct exchange of ions or small molecules between touching cells, occurs through gap junctions5–7. We have been interested in the question of whether fibroblasts and epithelial cells from the same tissue can interact directly and whether such an interaction is important in the growth of epithelial tumours such as carcinomas of the breast. Although the two cell types are separated by a basement membrane in the normal adult breast, the invasion of the basement membrane, characteristic of malignant cancer cells, allows contact to occur between epthelial cells and fibroblasts. In this situation, the direct communication between the cell compartments of the two types of cell could have a profound effect on the growth and development of the tumour. We show here that normal breast fibroblast and epithelial cells do not directly interact with each other even when they are not physically separated, and speculate that loss of this specificity of communication may be a factor in the development of neoplasia.
86 citations
Journal Article•
TL;DR: A cell line (HGC-27) was established by culture of the metastatic lymph node from a gastric cancer patient diagnosed histologically as undifferentiated carcinoma, probably derived from Gastric cancer cells, as their origin from mesenchymal tissues can be excluded morphologically and enzyme-histochemically.
Abstract: A cell line (HGC-27) was established by culture of the metastatic lymph node from a gastric cancer patient diagnosed histologically as undifferentiated carcinoma. HGC-27 cells were polygonal or short spindle-shaped and adhered to glass surfaces as a monolayer. The cells were probably derived from gastric cancer cells, as their origin from mesenchymal tissues can be excluded morphologically and enzyme-histochemically. Enzyme activities were generally negative or low, except for adenosine triphosphatase, lactic dehydrogenase and leucine aminopeptidase. These scanty findings might reflect the undifferentiated character of the original tumor cells. The cloning efficiency was 5.3% in liquid medium and 1.0% in soft agar. The doubling time was about 17 hr. Chromosomal analysis revealed a mode of 109 and 110 chromosomes.
51 citations
TL;DR: Physiologic concentrations of estrogen stimulate precursor incorporation and growth in several lines of human breast cancer cells in long term tissue culture andThymidine kinase specific activity is increased by estradiol and may, in part, explain enhanced thymidine incorporation.
49 citations
TL;DR: These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action ofcyclic nucleotides in this respect are discussed.
Abstract: The survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10(-3) mmol g-1 body weight of adrenaline and other beta-adrenergic agonists, inflammatory agents (including local x-irradiation), convulsive seizures, "tumbling" or physical restraint. Lowering of innate resistance of the host to growth of seeded tumour cells induced by states of topical and systemic stress, and by the addition of an excess of lethally irradiated (LI) tumour cells to i.v. injected intact tumour cells, were all potentiated by treatment of rats with aminophylline, an inhibitor of cyclic AMP phosphodiesterase. Enhancement of tumour growth by systemic stress was inhibited by bilateral total or medullary adrenalectomy and is attributed to the release and actions of endogenous adreno-medullary hormones. Alpha-adrenergic and most non-adrenergic agents administered in maximum tolerated doses did not significantly affect host resistance to tumour growth in the lungs. These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed.
39 citations
TL;DR: This work has tested the ability of cyclic AMP derivatives to inhibit the entry into S phase of 3T3 cells, but not their malignant counterparts, transformed by SV40.
Abstract: THE therapeutic usefulness of many anti-cancer agents depends on their selective toxicity for cells in the S (DNA synthesising) phase of the cell cycle1. Thus, rapidly proliferating cancer cells are more effectively killed by these agents than are normal cell populations, which have a lower proportion of cells in S. In theory, it should be possible to reduce the toxicity of such agents significantly by further slowing the entry of normal cells into S. We have tested this possibility in vitro by exploiting the ability of cyclic AMP derivatives to inhibit the entry into S phase of 3T3 cells, but not their malignant counterparts, transformed by SV40.
32 citations
TL;DR: Changes in the in vivo cell kinetics of the Yoshida sarcoma after curative heating at 42 °C are described, with emphasis on stimulation of non-proliferating tumour cells into cycle.
Abstract: HYPERTHERMIA (temperatures in excess of 40 °C) is at present receiving widespread interest as a potential method of treating cancer. High temperature can selectively destroy several types of cancer cell in vitro and in vivo1–3, and extensive lysis has been achieved clinically in limb tumours maintained at 41.5–43.5 °C for 6–8 h (ref. 1). In spite of these encouraging findings, fundamental information is needed on the factors governing tumour response to heat before the place of this approach in cancer therapy can be defined. Inadequate heating of the Yoshida rat sarcoma (in terms of temperature and/or time relative to tumour volume) increased tumour metastasis and suggested an influence of population kinetics on the outcome of heating4,5. Work in vitro has shown hyperthermic cell killing to be preferentially cycle6,7 and phase8–11 oriented. Implication of cell kinetics in the response to heat is further suggested by work on the rabbit VX2 carcinoma. A single heat application (intratumour temperature 42 °C for 1 h) does not destroy this tumour, whereas three such treatments if applied within the tumour cell generation time are curative12. This report describes changes in the in vivo cell kinetics of the Yoshida sarcoma after curative heating at 42 °C, with emphasis on stimulation of non-proliferating tumour cells into cycle.
26 citations
Journal Article•
TL;DR: A chronology of early development appears that the counterparts of a number of tumor proteins appear as early as gametogenesis and as late as 10 weeks of gestation.
Abstract: The two oncotrophoblast proteins, Regan isoenzyme (placental-type alkaline phosphatase) and human chorionic gonadotrophin, are readily studied oncodevelopmantal gene products in human cancer patients and in three experimental model systems. The latter consists of (a) HeLa sublines TCRC-1 and TCRC-2, which produce Regan and non-Regan isoenzymes, (b) HEp-2 and FL amnion cell lines as models for the reciprocal expression of developmental genes, and (c) modulation in vivo of developmental gene expression in HeLa cells. In the case of the third model, for example, HeLa TCRC-1 cells grow in immunosuppressed rats to form a tumor nodule, which expresses a new oncoamnion (FL) isoenzyme, while the Regan isoenzyme disappears. Return of the tumor cells to cell culture medium results in a disappearance of the oncoamnion (FL) species and the reappearance of Regan isoenzyme. This interesting model is expected to bridge the interpretation of experiments done in cell culture with observations made on tumors of cancer patients. Most helpful in interpretation of all these studies has been a chronology of early development. It appears that the counterparts of a number of tumor proteins appear as early as gametogenesis and as late as 10 weeks of gestation.
20 citations
TL;DR: The cytochemical demonstration of ATPase and acid phosphatase activities of peritoneal macrophages activated by various agents, such as Corynebacterium parvum , fluid thioglycolate medium, or starch, are compared in cell suspensions and in cell cultures.
Patent•
08 Oct 1976
TL;DR: In this article, it has been determined that cancer cells have a specific surface protein existing as a glycoprotein which functions to stimulate specific cell-mediated immune response in the host directed toward the specific cancer.
Abstract: It has now been determined that cancer cells have a specific surface protein existing as a glycoprotein which functions to stimulate specific cell-mediated immune response in the host directed toward the specific cancer. The following disclosure includes the method of identification of the specific cell surface protein and procedures utilizing the protein, or preferably the active peptide in testing for specific cancers and immunization. Having identified the specific cell surface protein for a cancer, the n-terminal tridecapeptide or the active portion of the peptide may be synthesized and utilized in testing and immunization. Further, the specific cell surface protein and active peptide for ductal carcinoma (brest cancer) is identified herein.
Journal Article•
TL;DR: The results suggest that the proximal convoluted tubule cells previously damaged by dimethylnitrosamine treatment were marked for mutation and were transformed to cancer cells by additional treatment with NDPS in such a way as to disturb the permeability of the membrane system of the cell and to condense chromatin fibers.
Abstract: Summary Renal cell carcinoma was induced in rats by p.o. administration of dimethylnitrosamine, 500 ppm daily, followed by N -(3,5-dichlorophenyl)succinimide (NDPS), 5000 ppm daily. Fine structural changes of the proximal convoluted tubule cells were observed by sequential examinations of the kidney cortices at 3, 5, 12, and 24 weeks after drug administration. Early prominent structural changes of the cells induced by dimethylnitrosamine alone were the appearance of microspherules in nucleoli and of numerous lamellar bodies on the membrane structure of the cells. With the addition of NDPS, the cells exhibited edematous cytoplasm that, in contrast to the relatively intact nuclear structure, contained numerous small vesicles and dark mitochondria, with markedly disarranged microvilli. After prolonged treatment with these drugs, some of the cells showed regenerating features, while others became necrotic. In the former case, large clear nuclei appeared with enlarged nucleoli containing a large amount of granular components. Ribosomes in the cytoplasm also increased in number in accordance with nucleolar changes, and edema in cytoplasm and microvilli markedly decreased. However, a considerable number of vesicles still remained in some cells. Mitochondria decreased in number and showed pleomorphism and relatively high electron density. At 24 weeks, when clear cell carcinoma was induced, the cells in the cancer tissue exhibited a variety of features in their nuclei and cytoplasm. Some cells showed intact nuclear structure and dark cytoplasm containing a large number of vesicles; others had large round clear nuclei with enlarged nucleoli and clear cytoplasm containing no vesicles. Among these cells were mixed populations of large clear cells, showing a structure similar to the cells at 12 weeks, i.e. , to nodular hyperplastic cells. The starting point of malignant transformation seemed to be 1 week after treatment with NDPS ( i.e. , cells at 5 weeks) and, of the precancerous stage, at 12 weeks. These results suggest that the proximal convoluted tubule cells previously damaged by dimethylnitrosamine treatment were marked for mutation and were transformed to cancer cells by additional treatment with NDPS in such a way as to disturb the permeability of the membrane system of the cell and to condense chromatin fibers.
01 Apr 1976
TL;DR: The immunohistological study of alpha1-acid glycoprotein suggests that the intracellular concentration of the protein may decrease in the cytoplasm of hepatocytes in hyperplastic nocules, but may increase in the CytopLasm of bile duct cells, oval cells, transitional cells, and cancer cells.
Abstract: The relationship between morphological changes in the liver during azo dye hepatocarcinogenesis in rats and cell proteins, especially alpha1-fetoprotein and alpha1-acid glycoprotein, was investigated by the immunofluorescence method. The isoelectric focusing fractionation was made to isolate alpha1-acid glycoprotein from normal rat plasma and to obtain a crude antigen containing alpha1-fetoprotein from rat amnionic fluid. The specific fluorescence of alpha1-fetoprotein was detected in the cytoplasm of the transitional cell and the cancer cell with rather a small ratio of cytoplasm/nucleus. The immunohistological study of alpha1-acid glycoprotein suggests that the intracellular concentration of the protein may decrease in the cytoplasm of hepatocytes in hyperplastic nocules, but may increase in the cytoplasm of bile duct cells, oval cells, transitional cells, and cancer cells. Based on these findings, a rational doubt is cast on the general assumption that the cancer cell originates from the hepatocyte in the hyperplastic nodule.
TL;DR: Cell suspension of a human breast cancer cell line was injected intraperitoneally into an athymic nude mouse to produce ascites form breast cancer and histology of the infiltrating tumor in the peritoneum and omentum was that of poorly differentiated adenocarcinoma.
Abstract: Cell suspension of a human breast cancer cell line (Hattori line) was injected intraperitoneally into an athymic nude mouse to produce ascites form breast cancer (peritoneal carcinomatosis). Subsequent serail transfers of cancer cells in ascites were also successful in mice. All male and female nude mice injected 1 X 10(7) tumor cells died of accumulation of ascites after a latency period averaging 4 weeks, with one exception which died of a wasting disease. Multiple lung metastases were observed in some mice. The tumor cells retained cytological characteristics of the original cell line, and histology of the infiltrating tumor in the peritoneum and omentum was that of poorly differentiated adenocarcinoma. Differentiation not only toward acinar or duct lining cells but also toward myoepithelial cells was observed by histochemistry, immunohistochemistry, and electron microscopy.
TL;DR: The potency of excision repair of a cell in S phase which has not been demonstrated by the detection of unscheduled DNA synthesis could be quantitated using the immunofluorescent-Feulgen double staining.
Abstract: The ability of excision repair of a single Ehrlich ascitic cancer cell was quantitated by cytofluorometry of unrepaired pyrimidine dimer-FITC complex per single nuclear Feulgen DNA. UV-irradiated Ehrlich ascitic cancer cells were made react with antibodies to denatured UV-DNA using the antisera which were absorbed with MBSA and heat denatured DNA. Then the immunofluorescent staining specific for pyrimidine dimers was combined with subsequent Feulgen nuclear reaction using the method reported in the previous paper (Fukuda et al., 1976).Then simultaneous cytofluorometric measurement of the amounts of pyrimidine dimer-FITC complex and nuclear Feulgen DNA was performed on a single tumor cell at various times of incubation after UV-irradiation. Before the occurrence of excision repair of UV-DNA lesions, the amount of pyrimidine dimers per unit amount of nuclear DNA was found equal in all tumor cells at various stages of cell cycle.After incubation for 3 hours, unrepaired pyrimidine dimers were largest in amount in polyploid cells and least in diploid cells; some diploid cells had no nuclear fluorescence of FITC with a faint fluorescence in the cytoplasm. It might indicate their completion of excision repair of UV-induced pyrimidine dimers followed by transport of them to the cytoplasm within the period. Thus the potency of excision repair of a cell in S phase which has not been demonstrated by the detection of unscheduled DNA synthesis could be quantitated using the immunofluorescent-Feulgen double staining. The order of the increase in the magnitude of excision repair in Ehrlich ascitic cancer cells at different stages of cell cycle was polyploid cells
TL;DR: Hyperthermia was disruptive to a synchrony procedure involving a blockade of DNA synthesis by excess thymidine, and hyperthermic treatment of synchronized SDB monolayer cell populations with maximum replication rate sensitized the cells to subsequent destruction by cell specific antibody.
TL;DR: The results obtained indicate great tumor-angiogenic ability that can be indirectly explained by action of an angiogenesis factor diffusing from cancer cells, which may open new possibilities for the treatment of carcinoma of the larynx based on anti-ANGiogenesis.
Abstract: • Injection methods were used for the study of the blood vascular system in 50 specimens from total or subtotal laryngectomy in patients with extensive cancer of the larynx, and in 24 normal postmortem larynges. All specimens were injected via the superior laryngeal arteries. A silicone rubber technique was found to be the most suitable for the aims of this study. A chaotic distribution of abnormal vessels that differ in shape, a rich neovascular network within the tumor, and capillary hypertrophy in its vicinity are the main features of the blood vascular system in laryngeal cancer. The results obtained indicate great tumor-angiogenic ability that can be indirectly explained by action of an angiogenesis factor diffusing from cancer cells. This may open new possibilities for the treatment of carcinoma of the larynx based on anti-angiogenesis. ( Arch Otolaryngol 102:65-70, 1976)
TL;DR: The development of a new form of cancer chemotherapy by selectively harnessing and stimulating the lipotropic response of the host to a tumour is discussed in terms of the administration of fatty acids which possess specific properties while as the same time raising plasma NEFA concentrations and maintaining them at an elevated level.
Journal Article•
TL;DR: The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation, and strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes.
Abstract: Cells from methylcholanthrene-induced tumor (MC-tumor), Ehrlich ascites cancer or mouse ascites hepatoma (MH-134) were subcutaneously implanted in dorsal area of mice to examine the specific cell mediated immunity following implantation. The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation. The MI-activity increased under all three implantations, reached maximum at a certain period, decreased gradually and disappeared. The maximum MI-activity coincided with the proliferation period of the implanted tumor cells. This peak occurred on the tenth postimplantation day with MC-tumors, on the fifth day with Ehrlich ascites cancer and on the sixth day with MH-134 cancer. In lymphoid tissues of animals with MC-tumor and Ehrlich ascites cancer, strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes. The MI-activity of the splenic lymphoid cells resembled the axillary lymph nodes cell activity. The MI-activity of venous blood lymphoid cells was parallel to the average value of lymphoid cells of the spleen and axillary and mesenterial lymph nodes.
TL;DR: The idea that elevated temperature increases the efficiency of the immune system and that the cell loses its random properties is concluded.
TL;DR: It is suggested that the use of these PAGE separate antigens would eliminate the need for removal of the virion antibody from the cancer sera prior to testing them for the NV-specific antibody.
Abstract: Data are reported on the HSV nonstructural antigens detected in GPK and RK cells after infection with the same strain of virus. Both the HSV types 1 and 2 NV antigens consist of more than one component for which the immunized guinea pigs produce distinct antibodies. It was possible to separate by PAGE, HSV-induced markers not only from cells undergoing lytic infection by the virus but also from viable cells from squamous cell carcinoma of the head and neck and the urogenital tract. These fractions were tested with sera from cancer patients, and the percentages of their CF reactivity are reported. The specificity of the antibody to the antigen from the cancer cells was less high than that of the antibody to the antigen from HSV-infected cells. It is suggested that the use of these PAGE separate antigens would eliminate the need for removal of the virion antibody from the cancer sera prior to testing them for the NV-specific antibody.
01 Jan 1976
Journal Article•
TL;DR: Electron histochemical studies show that changes in the nucleoside triphosphatase activity in plasma membranes of cancer cells can proceed in different directions, while others have a low enzymic activity which is present only in certain regions of the membranes, the remaining cells possessing no enzyme activity at all.
Abstract: Electron histochemical studies show that changes in the nucleoside triphosphatase activity in plasma membranes of cancer cells can proceed in different directions. Some cells show a high activity of magnesium-dependent NTPase over the whole membrane surface (perimeter), while others have a low enzymic activity which is present only in certain regions of the membranes, the remaining cells possessing no enzyme activity at all. These changes are not strictly characteristic of cancer cells alone.
01 Jan 1976
TL;DR: It has been postulated that the modified DNA acted as a vaccine in active immunotherapy of the host from which tumour DNA was extracted, and a new approach has been obtained by getting DNA antiserum from rabbits with the DNA isolated from tumours as antigens and chemically modified.
Abstract: Approaches to immunotherapy of neoplastic diseases can be improved by two kinds of methods: one non-specific, the other has specific aims. Our studies concerned mostly the latter. It is known that the biological substrates of neoplastic processes are contained in DNA and RNA molecules of cancer cells. DNA and RNA are involved whatever the etiology of neoplasms: on the one hand, the possible modification of the genome by direct mutation of DNA or by incorporation of oncogenic viruses; on the other hand, the oncorna viruses and messenger RNA as possible causes of neoplastic transfromation of cells. Based on this hypothesis, previous work on animal tumours has shown the cytostatic effect of DNA isolated from the same tumours and chemically modified. It has been postulated that the modified DNA acted as a vaccine in active immunotherapy of the host from which tumour DNA was extracted. With passive immunotherapy, a new approach has also been obtained by getting DNA antiserum from rabbits with the DNA isolated from tumours as antigens and chemically combined with rabbit gammaglobulins; the DNA being considered as a hapten. In another study, RNA extract from tumours was used in the same way and chemically modified for active immunotherapy assays and to produce interferon-like substances.