Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 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

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

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

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

According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.
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PMID:Alpha-fetoprotein, prealbumin, albumin, alpha-1-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors. 7 70

Mice bearing the BW7756 hepatoma were passively immunized using rabbit antiserum to murine alpha-fetoprotein (AFP) administered in constant or increasing doses. Control tumor-bearing mice were inoculated with saline or nonimmune rabbit serum (NRS) (constant or increasing doses), or were left untreated. The tumor growth curves from mice receiving constant or increasing doses of anti-AFP or constant doses of NRS showed suppression of hepatoma growth; but in both groups of anti-AFP-treated mice this was accompanied by gross anatomical changes, including necrosis, more extensive than in the NRS-treated or other control mice. AFP blood levels roughly paralleled the tumor growth responses. Since an immunological response against the rabbit serum was elicited in the host, it is possible that circulating immune complexes play some role in tumor suppression. Changes observed in liver- and spleen-to-body weight ratios may also reflect a response to circulating immune complexes.
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PMID:Immunobiologic studies in hepatoma-bearing mice passively immunized to alpha-fetoprotein. 9 91

Three human alpha-fetoprotein (AFP)-producing gastric cancers (AFPGC) were xenotransplanted into the lateral abdominal wall of nude mice. Two tumors were established and passed over ten generations. These tumors retained their ability to secrete AFP and their characteristic hepatoid features microscopically. Serum levels of AFP in the mice were elevated as the tumors grew. Through serial transplantation, the degree of differentiation was not altered. Neither local invasion nor distant metastasis were encountered during the observation periods. Both strains had an aneuploid pattern of DNA by flow cytometric examinations. The responses of these tumors to five chemotherapeutic agents were investigated using various doses. The high AFP-titer strain (AFPGC-2) showed a marked regression or suppression of tumor growth after administration of both mitomycin C (MMC) and cisplatin (CDDP). The low-titer strain (AFPGC-1) had substantial sensitivity only to MMC. The growth of both tumors was not suppressed by 5-fluorouracil, doxorubicin, or epirubicin. These findings suggest that the characteristics of AFPGC are preserved in the xenograft model of nude mice. In addition, MMC and CDDP may be active to some extent against this rare, but highly malignant cancer.
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PMID:Xenotransplantation of alpha-fetoprotein-producing gastric cancers into nude mice. Characteristics and responses to chemotherapy. 137 Sep 17

Reaction of picomolar quantities of human or rodent alpha-fetoprotein (AFP) with nanomolar quantities of 17 beta-estradiol (E2) generates a product of unknown structure, designated AFP/E2, that inhibits estrogen-stimulated growth of mouse uterus. We describe herein the effect of rodent AFP/E2 on the in vivo growth of two estrogen-dependent breast cancers, the MCF-7 human breast cancer and the MTW9A rat mammary cancer. Both cancers were grown as xenografts under the kidney capsule of cyclosporine-immunosuppressed male BDF1 mice. In addition, the MTW9A tumor was grown as a homograft in syngeneic ovariectomized Wistar-Furth female rats. Estrogen support was provided by s.c. Silastic E2 implants. Injecting AFP/E2 that was generated by incubating 1.0 microgram of AFP with 0.5 microgram of E2 for 1 h at room temperature resulted in cessation of growth and, in most cases, regression of MCF-7 tumor xenografts. It also produced regression of MTW9A tumor homografts and significantly inhibited growth of MTW9A xenografts. Treatment with AFP alone or E2 alone did not inhibit growth of these tumors. The data suggest that AFP/E2 has a unique property which causes attenuation or shut-down of the biochemical reactions through which estrogen-dependent tumor growth is mediated.
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PMID:Inhibition of estrogen-dependent breast cancer growth by a reaction product of alpha-fetoprotein and estradiol. 168 12

Conjugates between chemotherapeutic agents and antibodies, linked by a dextran bridge, were previously shown to be effective in suppression of hepatoma growth in vitro and in vivo. However, scaling up of production of such conjugates may lead to a high degree of variation in molar ratios of drug to antibody in different batches. In this study, an alternative link between drug and antibody was evaluated. A conjugate between adriamycin and murine IgGI monoclonal antibodies to human alpha-fetoprotein was prepared using a polyglutamic-acid bridge. The simple and reproducible method of linking adriamycin to a specific site on the antibody enabled the binding of the drug to alpha-fetoprotein with a high yield (63% to 68%); the molar ratio of drug/antibody was in the range of 110:1 to 120:1. The conjugate retained its capacity to bind to purified alpha-fetoprotein. Incorporation of [3H]-thymidine or [3H]-leucine into hepatoma cells, which express alpha-fetoprotein, was inhibited by the conjugate, compared with unconjugated antibody. Furthermore, 90% of this pharmacological activity was preserved, compared with free adriamycin. In vitro, the inhibitory activity of the polyglutamic acid conjugate was higher than that of a conjugate in which dextran was used as the linker between drug and antibody. In vivo, both conjugates were equally effective in suppression of hepatoma growth transplanted subcutaneously in athymic mice. However, this effect lasted only during the treatment period of 2 to 3 wk. Six days after discontinuation of therapy, reacceleration of tumor growth was observed regardless of the conjugate used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of anti-alpha-fetoprotein-adriamycin conjugate on a human hepatoma. 169 30

A case of immature presacral teratoma in an adult female presenting in pregnancy is described. She remains free of disease 12 months following treatment with a combination of chemotherapy, radiotherapy, and surgery. Serum alpha-fetoprotein levels appeared to correlate more with tumor "aggression" than with tumor growth.
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PMID:Immature presacral teratoma in an adult female. 169 4


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