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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of an "oncodevelopmental" protein, alpha-fetoprotein (AFP), has been systematically studied in rats during normal development and during regeneration of the liver by fetal rat hepatocytes in vitro, in rats bearing transplantable hepatomas, in rats fed chemical carcinogens, and in mice that spontaneously develop hematomas. AFP is a serum protein made normally during fetal and neonatal stages by liver and yolk sac cells. In newborn rats at approximately 4 weeks of age, the production of AFP is abruptly terminated, a process which is closely associated with cessation of liver cell proliferation. In adult rats, AFP production recurs following the reinitiation of hepatic DNA synthesis induced by partial hepatectomy or by the administration of heaptotoxic chemicals. Detailed metabolic and direct labeling studies of fetal rat hepatocytes in vitro also demonstrate a kinetically similar pattern of hepatocyte DNA synthesis and AFP production. In vitro studies utilizing combined autoradiography for DNA-synthesizing cells and immunofluorescence for AFP-containing cells demonstrates that replicating hepatocytes produce AFP, however, available data do not yet permit a distinction between G1 (pre- or postmitotic) and/or G2 production. During growth of an AFP- producing tumor, the serum concentration of AFP may be used as a accurate index of tumor growth, and, if a transplanted tumor is removed, as a marker for metastatic growth of the tumor. Using this model, we have shown that radiation to the lung at the time of surgical removal of a growing tumor in the leg will prevent establishment and growth of pulmonary metastases and that anti-AFP serum treatment may inhibit growth of a transplantable hepatoma that produces AFP. The exposure of rats to chemical hepatocarcinogens results in the appearance of evaluated serum AFP concentration as early as within 1 week of feeding; noncarcinogenic chemical analogs do not cause an elevation. AFP elevation also occurs with low doses of the hepatocarcinogen in the absence of detectable cell injury (by morphological examination of serum enzyme levels) or any other known morphological or biochemical change. This may represent a highly selective derepression of protein synthesis that occurs following the formation of a complex between the metabolites of the carcinogen and specific chromatin loci. Although every rat so far treated with even subcarcinogenic doses of hepatocarcinogens has elevated serum AFP concentrations, many primary carcinogen-induced hepatomas do not produce detectable AFP. Either there is a subsequent change in the preneoplastic AFP-producing cell that occurs prior to irreversible neoplastic alteration, or the hepatocytes originally influenced by the carcinogens to produce AFP are not necessarily the same cells that are the progenitors of the hepatoma produced by more prolonged exposure...
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PMID:Expression of an oncodevelopmental gene product (alpha-fetoprotein) during fetal development and adult oncogenesis. 6 4

The demonstrations that "fetal" isozymes and other fetal or "oncodevelopmental" antigens are present in tumor cells has led to the general concept that genes normally silent in adult tissues are activated during the neoplastic process. Recent evidence that some chromatin proteins of tumor cells are fetal antigens has suggested that some of the "switches" involved in gene activation for tumor growth may also be fetal or oncodevelopmental. These results have led to current theoretical concept that fetal gene derepressors interact with the genome to produce messenger RNA for the protein products involved for growth, invasiveness, and metastasis. These processes may not be controllable in adult cells because of the lack of inhibitors, which were present during embryonic development but are not produced in adult tissues.
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PMID:A general concept for molecular biology of cancer. 6 6

With the in vivo tumor neutralization test (Winn test), growth of a transplanted (KMT-17) from Wistar-King-Aptekman rats was inhibited by allogeneic tumor (AH-66 from Donryu rats)-sensitized syngeneic lymphoid cells admixed with mitomycin C (MMC)-treated AH-66 cells. The observed tumor inhibition may be immunologically nonspecific, since no cross-antigens were detected by membrane immunofluorescence on the surfaces of KMT-17 and AH-66 cells. Close contact among KMT-17, AH-66-sensitized lymphoid cells and MMC-treated AH-66 cells was required for the inhibition of KMT-17 growth. AH-66 cells pretreated with formalin or ultrasonication lost tumor inhibitory activity when they were admixed with AH-66-sensitized lymphoid cells, and only MMC-treatment effectively preserved the tumor inhibitory activity of AH-66 cells. The sensitized spleen cells, draining lymph node, or peripheral blood cells inhibited tumor growth when they were admixed with MMC-treated AH-66 cells, whereas nucleated cells from bone marrow, thymus, or distal lymph node did not. Growths of KMT-17 were inhibited by admixed sensitized spleen cells and MMC-treated AH-66 even when pre-irradiated rats were used as recipients.
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PMID:Nonspecific inhibition of tumor growth in vivo by admixed allogeneic tumor-sensitized lymphoid cells and identical inactivated allogeneic tumor cells. 6 98

The effects of coupled tumor specific antigens (CTSA) on the suppression of tumor growth in inbred mice were investigated. Seventy six week old C3H/HEJ female mice were used in the experiment. They were divided into seven groups; each group consisted of ten mice, and each group received a different treatment. The treatments for the different groups were: Human gamma globulin coupled with tumor specific antigens and emulsified in Freund's complete adjuvant (group I); Tumor specific antigens emulsified in Freund's complete adjuvant (group II); Freund's complete adjuvant (group III); Tumor specific antigens (group IV); Human gamma globulin (group V); Groups VI and VII were untreated. Animals in groups (I to V) were given two injections per week for two weeks prior to the transplantation of tumor tissue. They were subsequently given sixteen more injections during an eight week period. The sixth group was transplanted with tumor tissue and the seventh group was neither treated nor transplanted with tumor. The proliferation of the tumor tissue in the different animals was monitored by computing tumor volume at weekly intervals. The results showed that animals in group I developed a state of immune resistance against the transplanted tumor. At the conclusion of the experiment, the average tumor volume in this group was six times smaller than the average volume in the untreated group and twelve times smaller than the average volume in the group treated with Freund's complete adjuvant. Varying degrees of suppression were also noted in the other treated groups.
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PMID:Effects of coupled tumor specific antigens (CTSA) on the growth of transplanted tumors in C3 H/HEJ mice. 6 31

PARA-7 membrane-associated antigen was prepared by treatment of the tumor cells with pH 9.4 glycine buffer, or by concentration of spent cell culture medium. When admixed with sensitized effector cells, both preparations could specifically block cellular cytotoxicity for PARA-7 target cells. Pretreatment of target cells with antigen did not result in blocking. Incubation of antigen extract with simian virus 40 (SV40) anti-serum caused neutralization of antibody-dependent cellular cytotoxicity (ADCC) with concomitant formation of a factor which blocked at the target cell level but not at the effector cell level. Serum from tumor-bearing hamsters exhibited blocking characteristics comparable to those of the antigen-SV40 teristics comparable to those of the antigen-SV40 antiserum preparation. Washing experiments indicated that PARA-7 antigen was more efficient than PARA-7 antigen-antibody complexes in blocking cell-mediated immunity in vitro. Material extracted from untransformed hamster embryo fibroblasts either by itself or when admixed with SV40 antiserum exhibited no significant blocking activity. These observations support the concept that loss of serum ADCC during progressive tumor growth is due to immune complex formation.
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PMID:Membrane-associated antigen from the SV40-induced hamster fibrosarcoma, para-7. I. Role in immune complex formation and effector cell blockade. 6 26

Three of 42 (7%) monkeys given aflatoxin B1 (AFB1) for longer than 2 years have developed primary malignant neoplasms of the liver. Liver biopsies performed at intervals during aflatoxin administration revealed that neoplasia was preceded by pathologic lesions of the liver, including toxic hepatitis, proliferation of pseudotubules, and hyperplastic nodules. Serum alpha-fetoprotein levels, monitored in one of the monkeys by radioimmunoassay, paralleled tumor growth and recurrence of the hepatocellular carcinoma. Normal serum alpha-fetoprotein levels were noted for a monkey with hemangioendothelial sarcoma. Our results implicate AFB1 as a liver carcinogen in monkeys and add additional support to the hypothesis that humans exposed to this substance may be at risk of developing liver cancer.
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PMID:Carcinogenicity of aflatoxin B1 in rhesus monkeys: two additional cases of primary liver cancer. 6 57

Spleen, lymph node and thymus cells from normal C57BL/6 mice or mice given injections 6 to 20 days previously with syngeneic methylocholanthrene-induced fibrosarcoma (B6MCA) cells were tested for their ability to mediate growth stimulation and/or inhibition of B6MCA cells in vitro. At an effector cell to tumor cell ratio of 10:1,, nucleated spleen cells from mice bearing the tumor for 6 days enhanced tumor cell growth. Neither lymph node nor thymus cells from tumor-bearing mice were stimulatory. Tumor cell growth was inhibited by either spleen or lymph node cells only when a ratio of 1000:1 was exceeded. Thymocytes, however, were inhibitory at a ratio of 100:1,. Lymphoid cells from normal mice were not stimulatory at low ratios or inhibitory at any ratio tested. Both stimulatory and inhibitory activities disappeared by Day 20. Filtration of sensitized spleen cells through a glass wool column did not remove stimulatory or inhibitory activities. Subsequent passage through a nylon wool column resulted in a loss of stimulation, but not inhibition, of tumor cell growth. Stimulatory activity was completely abrogated by treatment with either anti-theta or rabbit anti-mouse gamma-globulin serum. A 1:1 mixture of spleen cells treated with either antisera did not restore stimulation. Spleen cells from T-cell- or B-cell-deficient mice bearing the tumor for 6 days were also not stimulatory. The results suggest that immunostimulation of tumor growth in vitro is mediated by a lymphoid cell that is distinct from the cytotoxic effector cell.
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PMID:In vitro stimulation and inhibition of tumor cell growth mediated by different lymphoid cell populations. 6 82

Sixteen necropsies and 4 cases of hepatic resection in which the liver had a solitary hepatocellular carcinoma smaller than 4.5 cm, or a few tumor nodules smaller than 3.5 cm, have been analyzed. Clinically, these patients presented with signs and symptoms compatible with cirrhosis and, of the 16 autopsy cases only 2 had been diagnosed correctly. In all but 4 cases, the noncancerous parenchyma showed advanced cirrhosis of the mixed type, with irregularly sized multilobular nodules and thin strands of stroma, different from typical alcoholic cirrhosis. The primary lesion was grossly encapsulated in the majority, suggesting a slow, expanding growth. Histologically, most primaries were relatively well differentiated. Serum alpha-fetoprotein was generally low, and it served as the major diagnostic clue in only 5 cases. In patients with mildly abnormal alpha-fetoprotein levels, continuous monitoring seems important in order to detect a steady rise, the first warning for tumor growth.
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PMID:Clinicopathological studies of minute hepatocellular carcinoma. Analysis of 20 cases, including 4 with hepatic resection. 6 81

The main findings of the present study are: (a) highly reactive cytotoxic lymphocytes (CTL) against syngeneic and allogeneic murine leukemia cells were generated in vitro in macro 'one-way' mixed leukocyte-tumor cultures (MLTC). Cultures set up in large tissue culture flasks contained up to 400 X 10(6) normal spleen cells (responder cells) and 20--40 X (10(6) mitomycin C-treated leukemia cells (stimulator cells). Successful sensitization in macrocultures was greatly dependent upon the responder cell density and the responder/stimulator cell ratio. Cytotoxic activity, as measured by the 51Cr-release assay, peaked on day 5--7. (b) Sensitized 'memory' lymphocytes produced in primary MLTC could be restimulated with the original tumor cells to give a more rapid and stronger secondary cytotoxic response. (c) lymphocytes sensitized to allogeneic leukemia cells reacted equally well with sensitizing leukemia cells and with the corresponding normal lymphoid target cells, whereas lymphocytes sensitized to syngeneic leukemia cells did not react with the homologous normal lymphocytes. (d) Cryopreserved normal splenocytes and leukemia cells were as efficient as fresh cells in generating allogeneic and syngeneic CTL. (e) Using a Winn-type tumor neutralization assay, it was shown that both allogeneic and syngeneic splenocytes sensitized in vitro to EL4 leukemia (of C57BL/6 mice) and to YAC leukemia (of A mice) were capable of preventing tumor growth in the syngeneic host, whereas cultured normal splenocytes frequently showed a tumor-enhancing effect. Long-term survivors, remaining after inoculation of leukemia cells and sensitized lymphocytes, also became resistant to a tumor challenge that was up to 10,000 greater than the minimum lethal dose.
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PMID:In vitro induction of cell-mediated immunity to murine leukemia cells. II. cytotoxic activity in vitro and tumor-neutralizing capacity in vivo of anti-leukemia cytotoxic lymphocytes generated in macrocultures. 6 86

Antibodies to autologous alpha-fetoprotein (AFP) were produced in mice by immunization with rat AFP. C57L/J mice with or without such antibodies were inoculated sc or ip with controlled numbers of cells of the syngeneic, AFP-producing, BW 7756 hepatoma. There was a linear relationship between circulating AFP and tumor mass, with elevated AFP being detectable earlier than the tumor. The AFP levels of the immunized mice were generally lower than those of control mice, and tumors could be detected before elevated concentrations of AFP appeared in the circulation. An extensive series of transplantations with varying protocols for immunization did not protect against tumor and did not affect the rate of tumor growth.
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PMID:Effect of specific immunotherapy with preimmunization against alpha-fetoprotein on a mouse transplantable hepatoma. 6 32


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