Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphological changes produced by the treatment with the D-tryptophan-6 analog of luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) and mitoxantrone (novantrone) were studied in the Dunning R3327H rat prostate cancer model. Microcapsules of D-Trp-6-LH-RH, calculated to release a controlled dose of 25 micrograms/day, were injected intramuscularly once a month. Novantrone (0.25 mg/kg body weight) was injected intravenously once every 3 weeks. The pathology of tumors was studied in two experiments. In the first experiment, the treatment was started 135 days after tumor transplantation, and the therapy was continued for 105 days. In the second experiment, the treatment was initiated 45 days after tumor transplantation, and was carried on for 70 days. The rats were divided into four groups: 1) untreated control, 2) microcapsule-injected, 3) novantrone-injected, and 4) combination of microcapsules and novantrone-injected. In both experiments, similar results were obtained, which included significant reduction in the tumor volume and weight, a very striking decrease in the number of epithelial tumoral cells with atrophy of the glandular epithelium, and an increase in the stromal connective tissue. All these changes were more prominent in the group treated with the combination of microcapsules and novantrone than in the groups treated with microcapsules or novantrone alone. Pathological results support the view that combined therapy may be more efficacious than the treatment with single agents.
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PMID:Histological findings in the rat prostate cancer model during treatment with a luteinizing hormone-releasing hormone agonist and novantrone. 295 93

A case of hyperandrogenism and virilization is described in an elderly female. She had elevated testosterone levels, but normal DHEAS and 24-h urinary 17-oxosteroid excretion, suggesting an ovarian tumor. Stimulation and suppression tests, and radioisotopic and radiological scans proved unhelpful in the diagnosis although hyperthecosis of the ovary was later suggested by ultrasound. Testosterone and gonadotropin levels fell during therapy with cyproterone acetate and subsequently ethinyl estradiol. Because of side effects encountered on these drugs, she was treated with a synthetic, slow-release preparation of an LHRH agonist, D-TRP-6-LHRH (Decapeptyl), with symptomatic and biochemical improvement. Long term LHRH agonists might be a valuable treatment for hyperandrogenic states in elderly patients.
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PMID:The treatment of a hyperandrogenic and virilizing state in an elderly female with a synthetic LHRH agonist. 297 52

Retrovirus without oncogenes often exert their neoplastic potential as insertional mutagens of cellular proto-oncogenes. This may be associated with the production of chimaeric viral-host transcripts; in these cases; activated cellular genes can be identified by obtaining cDNA clones of bipartite RNAs. This approach was used in the analysis of chicken nephroblastomas induced by myeloblastosis-associated virus (MAV). One tumor contained a novel mRNA species initiated within a MAV LTR. cDNA cloning revealed that this mRNA encodes a protein of 189 amino acids, identical to that of normal human Ha-ras-1 at 185 positions, including positions implicated in oncogenic activation of ras proto-oncogenes; there are no differences between the coding sequences of presumably normal Ha-ras cDNA clones from chicken lymphoma RNA and the tumor-derived cDNAs. The chimaeric mRNA in the nephroblastoma is at least 25-fold more abundant than c-Ha-ras mRNA in normal kidney tissue, and a 21-kd ras-related protein is present in relatively large amounts in the tumor. We conclude that a quantitative change in c-Ha-ras gene expression results from an upstream insertion mutation and presumably contributes to tumorigenesis in this single case. Little or no increase in c-Ha-ras RNA or protein was observed in other nephroblastomas.
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PMID:Identification of a provirally activated c-Ha-ras oncogene in an avian nephroblastoma via a novel procedure: cDNA cloning of a chimaeric viral-host transcript. 301 1

We have analyzed transmission of (LTR, v-src, LTR) cryptic structure integrated in the H-19 mammalian tumor cell line. From this cell line different isolates of transforming virus were rescued in heterokaryons produced by fusion with chicken fibroblasts infected by replication-competent avian leukosis virus RAV-1. One of them (F6) was used for the transformation of avian cells in the absence of the helper virus. In four transformed cell lines studied, the (LTR, v-src, LTR) structure was again integrated at a unique position in the cell DNA of each line. This indicated that the (LTR, v-src, LTR) structure is transmitted by the helper virus without recombination. This point has been further supported by the finding that a src-containing species corresponding in size to the nonpolyadenylated src mRNA is present in the RNA isolated from the rescued F6 transforming virus which might serve as template for the synthesis of (LTR, v-src, LTR) structure by the reverse transcriptase provided by RAV-1.
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PMID:Transmission of (LTR, v-src, LTR) without recombination with a helper virus. 301 94

Human sequences that are related to the mouse mammary tumor virus (MuMTV) genome were cloned from breast tumor cell DNA. Of 100 recombinants, only 1 hybridized with two different probes from separate regions of the MuMTV genome (gag-pol and long terminal repeat [LTR]). This sequence, NMWV 4, was shown to have a proviruslike structure. Hybridization to digests of normal and tumor cell DNA indicated that NMWV 4 and a few closely related sequences are endogenous to the human genome. The regions that contain homology to the MuMTV LTR were sequenced. Long repeated sequences with the hallmarks of retroviral LTRs were identified. The NMWV 4 LTR contains transcription initiation and termination signals and is flanked by a polypurine tract (5' LTR) and a primer-binding site (3' LTR). The primer-binding site is complementary to tRNA lysine, the primer used by MuMTV and HTLV-III. The polypurine tract is also similar to those of these two retroviruses.
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PMID:Structure of a human retroviral sequence related to mouse mammary tumor virus. 302 6

In addition to its antiviral and antibacterial activities, recombinant human gamma-interferon (rHuIFN-gamma) can exert an antiproliferative effect on human cell lines. The mechanisms involved in this antiproliferative activity are poorly understood, but it is known that IFN-gamma can induce indoleamine 2,3-dioxygenase, which enhances tryptophan metabolism and thus depletes the cellular pool of this amino acid. In the present study we have examined the effect of different tryptophan concentrations on the antiproliferative activity of rHuIFN-gamma on four human tumor cell lines, HeLa 229, HEp-2, A549, and T24. Cells were grown in the presence of rHuIFN-gamma (0.01 to 100 ng/ml) and/or tryptophan (10 to 400 micrograms/ml) for 7 days at which time they were counted. rHuIFN-gamma (4 ng/ml) inhibited the growth of A549 and T24 cells by 50%. Hep-2 and HeLa 229 cells were more sensitive to the rHuIFN-gamma induced antiproliferative effects, requiring only 0.4 ng/ml for a 50% inhibition. Addition of tryptophan to the media at concentrations from 10 to 100 micrograms/ml resulted in a significant blockage of the antiproliferative activity of rHuIFN-gamma. For example, when 50 micrograms/ml of tryptophan were added to the media, 10 times more rHuIFN-gamma (4 ng/ml) was needed to inhibit HeLa 229 cells by 50% of the control. The A549 was the most sensitive cell line to the modulatory activity of the tryptophan. Addition of 10 micrograms/ml of tryptophan changed the amount of rHuIFN-gamma needed to produce a 50% inhibition from 4 ng/ml to 100 ng/ml. In summary, in the four human tumor cell lines tested, the antiproliferative activity of rHuIFN-gamma could be modulated by the concentration of tryptophan in the media.
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PMID:Dependence of the in vitro antiproliferative activity of recombinant human gamma-interferon on the concentration of tryptophan in culture media. 312 Nov 72

Carcinoma of the urinary bladder is the most common malignancy in Egyptians. At the National Cancer Institute in Cairo, it accounts for 27.6% of all cancers--38.5% of cancers in the male and 11.3% in the female. This very high frequency is attributed to underlying schistosomiasis. The infection can lead to malignancy through local tissue damage, mechanical irritation, bilharzial toxins or through secondary bacterial infection. Bacterial products include nitrate reductase capable of synthesizing nitrosoamines and beta glucuronidase enzymes, active at pH 7. Through liver involvement and dysfunction, tryptophan metabolism is disturbed, with the excretion of carcinogenic metabolites. Vitamin A deficiency is responsible for the squamous metaplasia and the high frequency of squamous cell carcinoma observed in the bladder. The characteristic clinico-pathological features of cancer of the urinary bladder are outlined, mainly the occurrence at a young age, the male predominance, especially farmers, and the high association with schistosomiasis. The tumors are often first seen in an advanced stage, arising from the posterior bladder wall and vault. The trigone is only affected in 8.5% of the cases. Histologically, squamous cell carcinomas of low grade are the most frequent cell type. Lymph node involvement is low in spite of the advanced stage of the tumor. Therefore, the results of radical surgery are encouraging. The results of a special study correlating the above parameters with the intensity of ova deposition are presented. Patients with heavy infection at a slightly earlier age but other tumor parameters the same are similar to those of egg-negative cases. This study indicates that other factors also play a role in the induction of tumors that are enhanced by the schistosomal infection. In Fayoum Province, schistosomiasis is decreasing while bladder cancer is increasing. Urine cytology as a screening tool is effective in detecting early bladder cancer. Studies are now in progress to detect tumor associated antigens in sera and urine of patients.
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PMID:Carcinoma of the urinary bladder associated with schistosomiasis in Egypt: the possible causal relationship. 314 81

The potential mechanisms of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha action on tumor cells have been investigated in a model of mouse fibroblasts transformed by distinct retroviral vectors carrying the v-mos, c-myc, and v-Ha-ras oncogene, respectively. Treatment with both cytokines not only caused growth inhibition of v-mos- and c-myc-transformants, but also a reversion of transformation-induced suppression of major histocompatibility complex (MHC) class I antigen expression in all transformed cell lines. The phenotypical reversion of transformants was preceded by a selective modulation of LTR-controlled oncogene expression. TNF-alpha primarily affected stability of oncogene-specific RNAs without influencing the activity of retroviral promoters. In contrast, IFN-gamma was effective at the transcriptional level, apparently due to inhibition of LTR activity as revealed from reduced CAT activity in IFN-gamma-treated LTR-CAT transformants. This IFN-gamma-mediated down-regulation of retroviral promoter activity seemed to be selective for Moloney-virus-derived promoters, since the activity of other viral and cellular promoters was not suppressed by IFN-gamma.
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PMID:Distinct mechanisms of interferon-gamma and tumor necrosis factor-alpha action in oncogene-transformed mouse fibroblasts. 314 85

The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the diagnosis of prostate cancer is made, might inhibit the proliferation of androgen-dependent and -independent cells, improve further the therapeutic response, and increase the survival rate.
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PMID:Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model. 315 90

The depletion of an essential amino acid, tryptophan, caused by indoleamine 2,3-dioxygenase induction in vitro, has been shown to be due to a mechanism that is used in self-defense against inhaled microorganisms and tumor growth. In this communication, we report the results of measuring dioxygenase activity in the peritoneal exudate cells and tumor cytotoxicity at the transplantation loci after in vivo transplantation of tumor cells into the peritoneal cavity of syngeneic or allogeneic strains of mice. The enzyme was induced only when the tumor cells were being rejected from allogeneic animals and no change was observed when the cells continued to grow in syngeneic animals. Furthermore, when the syngeneic tumor cells in a diffusion chamber were i.p. transplanted simultaneously with i.p. injection of allogeneic tumor cells, the enzyme was induced not only in allografted tumor cells but also in the syngeneic tumor cells. Under these conditions, the tumor cells in the diffusion chamber ceased to grow and 50% of the cells were rejected. To determine the type of cells containing the induced enzyme, the peritoneal exudate cells (tumor cells and host cells--mostly small lymphocytes) were separated into six fractions by sedimentation under gravity and by differential centrifugation. Approximately 80% of total enzyme activity was localized in a tumor-rich fraction (98.9% purity), whereas only 0.2% of the activity was found in a lymphocyte-rich fraction (99.5% purity). The localization of indoleamine 2,3-dioxygenase in the tumor cells was confirmed by complement-dependent lysis with specific antibodies against tumor and host cells.
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PMID:Tryptophan degradation in transplanted tumor cells undergoing rejection. 326 68


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