Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C57BL/6 mice are relatively more resistant to hepatocarcinogens than C3H and C57BL/6 x C3H F1 (hereafter called B6C3F1) mice; however, the basis for this strain-dependent difference is not clear. In order to address this issue, male C57BL/6 mice were treated i.p. with 5 mg/kg diethylnitrosamine when 15 days old and the histological features of induced hepatocellular neoplasms were assessed at intervals over the ensuing 80 weeks. In many respects the natural history of the tumors was similar to that previously reported for hepatic neoplasms in B6C3F1 mice; they invaded hepatic vein branches while still microscopic (18 weeks after diethylnitrosamine) and developed into metastasizing trabecular carcinomas by 80 weeks. However, the tumors in the C57BL/6 mice were unique in their early focal development of cells containing inclusions of secretory protein within the endoplasmic reticulum. At 12 weeks after diethylnitrosamine, more than 90% of the neoplasms contained inclusions. Over the ensuing months, the inclusions increased in size and number and the regions containing them became more sharply defined. In mice killed 48 weeks after carcinogen, the extent of inclusion formation was correlated with [3H]thymidine labeling indices. Mean labeling indices were higher in the inclusion-poor than in the inclusion-rich areas: 5.4% versus 1.5% for the 36 neoplasms smaller than 1 mm in diameter and 14% versus 6% for the 18 neoplasms larger than 1 mm. Thus, we suggest that the focal slowing of hepatocellular tumor growth in C57BL/6 mice contributes to the strain's apparent resistance to hepatocarcinogenicity. However, the impairment does not appear to block tumor progression and the ultimate development of trabecular carcinomas. In addition, the data indicate that, independent of the presence or absence of inclusions, larger tumors have higher labeling indices, and presumably higher growth rates, than smaller ones. While the reason for the association between cytoplasmic inclusions and the low labeling indices is not known at present, at the very least the inclusions serve as unique markers for the growth retardation.
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PMID:Focal impairment of growth in hepatocellular neoplasms of C57BL/6 mice: a possible explanation for the strain's resistance to hepatocarcinogenesis. 273 37

Clinically applicable markers for tumor progression may be uncovered by selective analysis of biochemical parameters, supposedly participating in this complex process. Owing to the importance of specific protein-carbohydrate interactions in diverse biological processes, the pattern of the receptor part in this glycobiochemical recognition system, the sugar receptors (lectins), conceivably reflects biological properties of tumor cells in glycobiochemical terms. Therefore, we established and characterized xenografts from surgically removed specimens of a human primary colon adenocarcinoma and its metastatic lesions to liver of the same patient and of a histomorphologically similar primary colon adenocarcinoma of another patient in nude mice. Xenotransplantation and subsequent glycobiochemical analysis of material from early passages with a standardized procedure had been preferred to cell culture in monolayer on account of maintenance of a higher degree of organized histotypic assembly. Despite histomorphological similarities, the sugar receptor profile revealed significant differences in tumor-tumor and tumor-metastasis comparison, especially for alpha- and beta-galactoside-binding proteins. Tumor-metastasis differences were substantiated by a second successfully xenotransplanted pair of specimens. Comprehensive expansion of these initial data may eventually lead to desirable functional correlations with the different biological properties of histomorphologically similar primary colon adenocarcinomas and of the metastatic phenotype and to a rational development of therapeutic modalities to restrict tumor growth and spread.
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PMID:Detection of metastasis-associated differences for receptors of glycoconjugates (lectins) in histomorphologically unchanged xenotransplants from primary and metastatic lesions of human colon adenocarcinomas. 275 8

Female Swiss albino mice were placed on seven dietary regimens for five weeks. These regimens differed only in magnesium and/or manganese contents. At the end of the feeding period, the animals were inoculated with Ehrlich ascites tumor. Ten days after transplantation, Ehrlich ascites carcinoma (EAC) cells were harvested, and all animals were killed. EAC cells and plasma samples were subjected to several biochemical tests. The results suggest several conclusions. 1. Dietary supplements of magnesium and/or manganese have no effect on retarding tumor growth in vivo. 2. Dietary restriction of manganese and combined magnesium and manganese gave promising effects on retarding tumor growth in vivo. 3. Dietary magnesium deficiency, per se, had no significant effect on tumor regression in vivo. 4. In contrast to in vitro studies, manganese supplementation appeared to exert no effect on tumor progression in vivo. 5. Magnesium supplementation seemed to have no effect on tumor progression in vivo, which is in agreement with in vitro studies.
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PMID:Role of dietary magnesium and/or manganese variables on Ehrlich ascites tumor-bearing mice. 277 4

Cytogenetic analysis of early in vitro cultures derived from human melanomas, two primary tumors (Me 10538, Me 1402) and two metastatic lesions in the same patient (Me 665/1, Me 665/2) showed non-random involvement of C-heterochromatin in clonal chromosome rearrangements. Marker chromosomes with C- and DA-Dapi-positive bands were identified in one of the metastases, Me 665/1 (m1) and in the two primary tumors, Me 10538 (m2) and Me 1402 (m3). C-positive fragments predominated in the other metastasis, Me 665/2, which lacked C-regions intercalated in rearranged chromosomes, and were also detected with appreciable frequency in the Me 665/1 and Me 1402 cells. The frequencies of marker chromosomes and their mean number per cell allowed m2 and m1 to be considered as early markers of tumor formation and m3 as a marker of tumor progression. Dissection of chromosome structure, including the origin of the intercalated C-band, has so far been achieved only with the m2 chromosome of the primary tumor Me10538. This was the only cell line which displayed few C-fragments and a narrow chromosomal distribution with a well defined mode. A gradient of malignancy could be detected in the four cell lines, by local and disseminated tumor growth in xenotransplanted mice, with the two primary melanomas 10538 and the 1402 cells at the lowest and upper extremes. This gradient closely parallels the increase in cytogenetic heterogeneity and C-heterochromatin lesions from the 10538 to the 1402 cells.
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PMID:High incidence of chromosomal lesions involving C-heterochromatin in four human melanoma lines. 277 68

The efficacy of a leukemia cell transplant model to measure potential chemotherapeutic activity was tested with five different chemicals that had previously been evaluated in 2-year studies. Leukemic spleen cells from Fischer rats were injected subcutaneously into syngeneic recipients and the effects of chemical treatment on tumor progression were evaluated at 70 days post-transplant. The data from the short-term assay were in all cases correlated with the trends reported for mononuclear cell leukemia in 2-year studies, where two chemicals were reported to decrease the incidence and three chemicals were reported to increase the incidence of leukemia. Short-term treatment with the two chemicals which caused negative trends for leukemia (2-ethoxyethanol or ethylene glycol monoethyl ether; 4-hexylresorcinol) delayed and/or reduced tumor growth in the transplant model in a dose-related fashion, as exhibited by reduction or elimination of splenomegaly and leukoblastosis, and a reversal in the depression of red blood cell indices or platelet counts. By contrast, the rate of tumor progression was increased in the short-term assay of the three chemicals which previously caused increased trends for leukemia in 2-year studies (pyridine; 2,4,6-trichlorophenol, dichlorvos). The severity of the mononuclear cell leukemia in the transplant recipients, as measured by histopathological examination of spleen and liver, was correlated with the changes in tumor growth rates. The in vivo leukemia transplant model is a short-term assay that could be used to screen a variety of potential chemotherapeutic agents, or to study structure-activity relationships within one class of chemicals.
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PMID:Development and validation of a cellular transplant model for leukemia in Fischer rats: a short-term assay for potential anti-leukemic chemicals. 279 89

The role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.
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PMID:Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation. 283 Mar 39

The role of chemotherapy in the treatment of retinoblastoma (RB) is unsatisfactory and clinical research is severely limited. A xenograft model for testing chemotherapeutic and other agents has been developed by the heterotransplantation of human RB cells into the anterior chamber of the nude mouse eye. A grading system for visually monitored tumor growth was designed to allow serial observations and documentation of the response to therapy in the model. This method of monitoring compared favorably with histopathologic, photographic, or other criteria in the reproducible, sequential evaluation of tumor status. Six chemotherapeutic agents [vincristine (VCR), doxorubicin (DOX), actinomycin D (ACT-D), dimethyltriazeno-imidazole carboxamide (DTIC), cyclophosphamide (CPM), and diaziquone (AZQ)] were then tested in the model against a patient-derived xenograft line. Results were expressed as the delay in tumor progression judged by serial grading. CPM produced a consistent response in all treated tumors, as did DTIC to a lesser, more variable extent. In 3 of 10 tumors treated with CPM and in 1 of 18 treated with DTIC, complete responses were maintained for at least 20 weeks. VCR, DOX, and ACT-D were ineffective, producing patterns of tumor progression no different from those in the control group. AZQ was most effective, producing responses far exceeding those of conventional agents. The model allows quantitative documentation of the response to therapy in heterotransplanted human RB. Further testing of new agents and combinations is warranted. AZQ may be active against RB.
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PMID:Evaluation of response to chemotherapy in retinoblastoma heterotransplanted to the eyes of nude mice. 291 May 12

Using murine transplantable transitional cell carcinoma (MBT2), the effect of ethylchlorformate (ECF) polymerized tumor protein was compared with that of bacillus Calmette-Guerin (BCG). Seventy-five C3H/He mice were challenged with an intradermal inoculation of 5 X 10(5) viable MBT2 tumor cells and divided into five groups. Each group was intradermally administered with 0.01 mg of ECF (low ECF), 0.25 mg of ECF (high ECF), 0.1 mg of ECF and 10(6) CFU BCG (ECF/BCG), 10(6) CFU of BCG alone or normal saline (control) weekly for 10 weeks. The mean survival rate for the treatment groups was 64 to 73 days and significantly longer than that for the control group (P less than 0.001, Savage). The incidence of biologically active tumor progression was significantly less for the treatment groups (low ECF, 53%; high ECF, 33%; ECF/BCG, 7%; BCG, 27%) compared with the control group (87%; P less than 0.5, chi-square. The mean rate of tumor growth was significantly lower for all treatment groups than for the control group (P less than 0.001, ANOVA and SNK), and the ECF/BCG group had the lowest growth rate despite a higher incidence of local granulomatous reaction. In this study, immunotherapy significantly prolonged the survival rate, decreased the incidence of biologically active tumor progression, and slowed the rate of tumor growth. The combination of ECF polymerized tumor protein and BCG had the greatest effect, suggesting that the effect of the vaccine was increased with BCG.
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PMID:Ethylchlorformate polymerized tumor protein immunotherapy of the murine bladder tumor. 291 72

This report describes the results of a long term prospective study of 30 women with hyperprolactinemia who were not treated and who underwent yearly clinical, hormonal, and radiographic evaluation for an average of 5.2 yr (range 3-7 yr). At entry into the study 18 women had amenorrhea, 8 had oligomenorrhea, and 4 had regular menstrual periods. The initial mean serum PRL levels did not differ in women grouped according to menstrual function. Nine women (35%) had improvement in clinical symptoms. Serum PRL decreased, and menstrual periods normalized more often in those who initially had oligomenorrhea or regular menstrual periods. In most amenorrheic women serum PRL levels did not decline, and menstrual symptoms did not improve. Six of 30 women had an increase in serum PRL, 14 had no change, and 10 had a decrease, in 6 of whom serum PRL was normal at the last observation. Twenty-seven women had serial radiographic studies. Four (15%) of the 13 women with initially abnormal radiographic findings had normal studies later, 2 had tumor progression, and 7 no change. Four of 14 women who had normal radiographic studies initially developed radiographic evidence of a pituitary tumor, although the radiographic changes were minimal, and no patient developed a macroadenoma or pituitary hypofunction. Increases or decreases in serum PRL did not accurately predict changes in tumor size. Prior estrogen use and previous pregnancies did not increase the likelihood of tumor appearance or enhance tumor growth. The clinical presentation of the patient was an important factor in predicting which patients had a decline in serum PRL and resolution of symptoms. We conclude that patients with hyperprolactinemia are unlikely to have progression of their disease and may, in fact, have clinical and radiographic improvement.
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PMID:The natural history of untreated hyperprolactinemia: a prospective analysis. 291 52

The biological activities and antitumor mechanism of an immunopotentiator, Ge-132, is reviewed herein. Ge-132 exhibited antitumor activity against certain syngeneic and allogeneic experimental tumors. It was shown that T-cells and macrophages were involved when tumor-bearing mice were protected by the compound. This protective effect could be transferred to tumor-bearing mice, not treated with the compound, by a macrophage fraction and serum specimens obtained from Ge-132-treated mice. Interferon gamma (IFN gamma) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFN gamma antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFN gamma antiserum, Ge-132 did not induce serum IFN and failed to protect against death due to ascites tumor progression. The in vivo administration of monoclonal anti-Thy 1.2 antibody prevented the expression of the antitumor activity of Ge-132. However, serum specimens obtained from Ge-132-treated mice effectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFN gamma, this suggested that Ge-132 may first stimulate T-cells to produce IFN gamma in the expression of the observed antitumor efficacy. In addition, sera obtained from Ge-132-treated mice did not show any antitumor activity in mice depleted of macrophage functions. Additionally, passive transfer of macrophages from mice treated with these serum specimens to tumor-bearing mice also resulted in the inhibition of tumor growth. Pretreatment of these serum specimens with anti-IFN gamma antiserum effectively prevented the generation of cytotoxic macrophages. Also, tumor-bearing mice treated exogenously with this antiserum did not differ significantly in survival as compared to controls, despite the administration of Ge-132. Furthermore, the antitumor activity of Ge-132 was detected in NK cell-depleted mice. Therefore, the antitumor mechanism of Ge-132 in the murine ascites tumor system may be expressed as follows: (a) Ge-132 stimulates T-cells to induce IFN gamma when mice are treated orally with the compound, (b) IFN gamma activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.
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PMID:Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review). 297 86


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