Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of adenosine dialdehyde (AD) on in situ tumor growth and host survival was evaluated in the C1300 murine neuroblastoma tumor model prepared by implantation of murine neuroblastoma cells into A/J mice. AD was administered s.c. by one of the following treatment regimens: regimen A, single daily dose for 5 days; regimen B, minipump infusion for 7 days; regimen C, minipump infusion for 14 days; regimen D, minipump infusion for two 7-day periods interspersed by a 7-day drug free interval. AD doses of 1.5 to 2.5 mg/kg/day infused over a 7-day period (regimen B) significantly increased the mean life span of tumor bearing mice from 20.9 +/- 1.2 days (mean +/- 2 SEM) in diluent treated controls to 35.3 +/- 2.1 days in AD treated animals (mean increase +/- 2 SEM: 69 +/- 10%; P less than 0.0001). This treatment regimen also produced a 56 +/- 13% decrease in tumor diameter (P less than 0.0001). Administration of AD for two 7-day infusion periods, interspersed by a 7-day drug free interval (regimen D), increased mean life span 80% (controls, 21.3 +/- 4.4 days; AD treated 38.4 +/- 5.6 days; P less than 0.0005). Hematopoietic toxicity was not observed when doses between 2 and 3 mg/kg/day of AD were infused for 7 days (regimen B). These data suggest that steady state infusions of AD can significantly suppress murine neuroblastoma tumor growth with little systemic toxicity. In contrast, single daily injections of AD were ineffective and toxic to the tumor bearing host.
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PMID:Inhibitory effect of adenosine dialdehyde on in situ murine neuroblastoma growth. 316 45

Physiochemical properties of an estrogen binding protein were characterized in three human melanoma cell lines, UISO-MEL-1, UISO-MEL-2, and UISO-MEL-4. Estrogen binding to melanoma cytosol was saturable, specific for estrogens, and represented by a single class of high-affinity, limited-capacity binding sites (Kd 5.5 x 10(-10) M, 2.7 +/- 0.5 fmol/mg of cytosol protein, UISO-MEL-2; 2.2 x 10(-10) M, 7.8 +/- 3.3, UISO-MEL-4) (SEM). UISO-MEL-1 cytosols did not bind estradiol. The binding protein in UISO-MEL-2 and -4 sedimented at 8.5S and 9.2S, respectively, in the presence of 10 mM sodium molybdate. Solid-phase radioimmunoassay with a monoclonal antibody specific for human estrogen receptor (H222 sp lambda) showed good correlation (r = 0.84) with a hydroxyapatite biochemical assay of identical melanoma cytosols. Exposure of UISO-MEL-2 to estradiol produced a time- and temperature-dependent increase in total nuclear receptor for estrogen in vitro. Estradiol treatment of athymic mice also significantly increased cytosol progesterone receptor content in UISO-MEL-2 and UISO-MEL-4 xenografts. Estradiol had no effect on the plating efficiency or growth of any melanoma cell line or normal melanocytes in vitro. Tamoxifen also had no effect on melanoma growth in vitro. In contrast, chronic exposure of athymic mice carrying estrogen receptor-positive UISO-MEL-2 to estradiol resulted in a sex-dependent increase in tumor latency and overall inhibition of tumor growth. Taken together, these observations suggest that a subset of human melanomas contains limited amounts of an estrogen binding protein similar to that observed in other estrogen-responsive tissues. The lack of effect of estradiol on melanocyte and melanoma growth in vitro, coupled with a decrease in tumor growth in athymic mice, suggests that, while inhibition may be receptor mediated, possible indirect actions of estradiol must also be considered.
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PMID:Effect of 17 beta-estradiol on the growth of estrogen receptor-positive human melanoma in vitro and in athymic mice. 319 86

The rate of protein synthesis in vivo was assessed in tumor tissue, skeletal muscle, liver, and the whole body of rats bearing either the Yoshida sarcoma or Novikoff hepatoma after 18 days of tumor growth and compared to tumor-free controls. Changes in size of the whole animal and tumor (i.e., growth) were measured, and fractional rates of growth, synthesis, and degradation were estimated. Muscle protein synthesis and whole-body growth were significantly reduced in both groups of tumor-bearing rats after 18 days of tumor growth. In addition to reductions in muscle protein synthesis, whole-body protein synthesis was significantly reduced in the Yoshida tumor-bearing group (587 +/- 36 versus 401 +/- 40 mg/h; mean +/- SEM; control versus Yoshida group, respectively, P less than 0.01). Tumor protein synthesis was not statistically different between the Yoshida tumor (76 +/- 21 mg/h) and the Novikoff tumor (50 +/- 8) after 18 days of growth despite the fact that the Yoshida tumors were significantly larger (33.9 +/- 4.2 g versus 11.9 +/- 1.2 g; P less than 0.01). The fractional synthesis rate (Ks) was, in fact, significantly slower in the Yoshida versus the Novikoff tumor (36.8 +/- 7.6 versus 55.1 +/- 4.8%/day). Tumor growth (Kg) followed first order growth rates for both tumor types (r = 0.945, 0.869; Kg = 17.2 +/- 1.6, 15.5 +/- 1.9%/day; Yoshida and Novikoff, respectively). The fractional degradation rate of tumor protein (Kd) was determined as the difference between the two first order rate constants Ks and Kg. The tumor protein degradation rate was significantly reduced in the Yoshida tumors compared to the Novikoff tumors (19.6 +/- 8.2% versus 39.6 +/- 4.2%/day, respectively). The greater size in the Yoshida sarcoma can be attributed to reduction in fractional protein degradation rather than change in synthesis rates, which supports the theory that some tumors can regulate their growth by alteration in tumor protein degradation rates (J. A. Tayek et al., Cancer Res., 46:5649-5654, 1986).
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PMID:Alterations in whole body, muscle, liver, and tumor tissue protein synthesis and degradation in Novikoff hepatoma and Yoshida sarcoma tumor growth studied in vivo. 334 28

Sclerosing or morphea-like variant of basal cell carcinoma (BCC) is characterized by an extensive connective tissue stroma, and histopathology has suggested that the extracellular matrix is largely composed of collagen. In addition, fibronectin deposition has been proposed to modulate tumor growth in BCC. In this study, we examined the expression of genes coding for type I, III, and IV procollagens, as well as for fibronectin, in tissue from 10 patients with sclerosing BCC. For comparison, tissues from 5 patients with nodular BCC and 4 controls were examined. Total RNA was isolated by CsCl density gradient centrifugation, and messenger RNA (mRNA) steady-state levels were determined by slot-blot hybridizations with human sequence specific complementary DNAs (cDNAs). The abundance of type I procollagen mRNA in sclerosing BCC tissue was increased to 233.6 +/- 36.7% of the controls (mean +/- SEM). The corresponding value for type III procollagen mRNA in sclerosing BCC was 281.8 +/- 54.8% of the controls. Consequently, the steady-state ratio of type I/III procollagen mRNAs in sclerosing BCCs (5.0 +/- 1.2; mean +/- SD) was within the control range. Thus, there is a coordinate increase in type I and type III procollagen mRNA levels in sclerosing BCC. In contrast, the values for type I and type III procollagen mRNAs in nodular BCC were not different from the controls. In addition, type IV procollagen and fibronectin mRNA levels were not different from the controls either in sclerosing or nodular BCCs, attesting to the selectivity of the increase in type I and III procollagen mRNA levels in sclerosing BCC. These observations may relate to the excessive deposition of the extracellular matrix stroma surrounding the tumor cells in sclerosing BCC.
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PMID:Selectively enhanced procollagen gene expression in sclerosing (morphea-like) basal cell carcinoma as reflected by elevated pro alpha 1(I) and pro alpha 1(III) procollagen messenger RNA steady-state levels. 336 Nov 39

The human fibrosarcoma cell line HT-1080 exhibits rapid growth following s.c. inoculation in 4-6-week-old male athymic mice. Cytosols from tumors carried in athymic mice bind glucocorticoid (Kd, 1.8 +/- 0.48 X 10(-8) M; Bmax, 240.5 +/- 35.3 fmol/mg cytosol protein, mean +/- SEM). Receptor sediments primarily in the 8-9S region on 5-20% sucrose gradients and is specific for the glucocorticoids. HT-1080 growth in vitro (as measured by cell count) was inhibited over a range of 10(-6)-10(-8) M after 7 days of incubation with dexamethasone and triamcinolone acetonide. Progesterone, estradiol, and dihydrotestosterone had no effect on HT-1080 growth in vitro. Preincubation with a 100-fold excess of progesterone reversed the growth inhibition observed with triamcinolone acetonide but not dexamethasone acetate. HT-1080 tumor cell growth responded biphasically to dexamethasone in vivo. Athymic mice given s.c. injections every other day with 5 or 25 micrograms dexamethasone showed an increase in tumor size inversely proportional to dose. In contrast, 200 micrograms of dexamethasone significantly inhibited tumor growth. Adrenalectomy did not significantly alter HT-1080 growth or glucocorticoid binding to tumor cytosols (Kd, 3.4 X 10(-8) +/- 1.1, Bmax, 236.9 +/- 9.9 fmol/mg cytosol protein, mean +/- SEM) although tumor incidence was decreased in sham adrenalectomized mice. Glucocorticoid binding in tumors grown in vivo was decreased by increasing amounts of dexamethasone. High pharmacological doses of glucocorticoids inhibit the growth of human fibrosarcomas in vivo and in vitro.
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PMID:Effects of glucocorticoids on the growth of human fibrosarcoma cell line HT-1080. 375 54

To elucidate the environmental influence on the growth of a tumor, bromodeoxyuridine (BrdU) uptake in multiple tumor foci within the intracranial cavity was studied immunohistochemically with a monoclonal antibody. Walker 256 tumor implanted intracerebrally produced multifocal tumors presented as intraparenchymal solid tumor, tumor in the choroid plexus, and leptomeningeal dissemination. The BrdU-labeling indices, or the S-phase fractions (% of nuclei labeled by BrdU divided by the number of tumor cell nuclei scored; LI), of those tumors were 48.4 +/- 1.1, 59.1 +/- 1.3, and 27.9 +/- 5.9, respectively (mean +/- SEM). These differences in LI, or the tumor growth activity, are discussed in relation to the different environmental conditions in different host structures. These host structure-related modification of tumor growth would be important in evaluating the proliferative activity of tumors growing at various intracranial structures.
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PMID:Growth activity of tumors at different intracranial structures: immunohistochemical study with bromodeoxyuridine. 377 68

Using autoradiography after 1 h of pulsed labeling with tritiated thymidine in endoscopic biopsy specimens from normal-appearing mucosa, cell proliferation was determined at six predetermined sites of the whole colon in patients with neoplastic disease of the large bowel and was compared with that of subjects without macroscopic colonic pathology. The labeling index (the percentage of cells incorporating [3H]thymidine) was 8.6 +/- 0.5 (mean +/- SEM) in 13 patients with colon carcinoma (p less than 0.001 vs. 16 control patients whose labeling index was 4.9 +/- 0.2) and 9.1 +/- 0.4 in 11 patients with a large adenoma in the colon (p less than 0.001 vs. controls). Twenty-one patients with one or more small adenomas (diameter less than 1 cm) had a moderately increased cell proliferation compared with controls (labeling index 6.2 +/- 0.3, p less than 0.02 vs. controls). In patients with neoplastic disease an enlargement of the proliferative compartment was found, whereas 6 patients with Crohn's colitis had values for labeling index and a distribution of labeled cells along the crypt comparable to that of control subjects. An increased cell proliferation was found along the entire colon under each of the neoplastic conditions studied. These findings indicate that although neoplastic lesions develop in a limited area of the colon, the entire large bowel may be at risk for tumor growth.
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PMID:Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. 381 91

A transplantable transitional cell murine bladder tumor induced by N-[4-(5-nitro-2-furyl)-thiazolyl] formamide (FANFT) was characterized by tumor growth, survival time and response to chemotherapy drugs, cis-dichloro-trans-dihydroxy-bis-iso-propylamine platinum IV (CHIP), cis- diaminedichloro platinum II (DDP), cyclophosphamide (CTX) and methotrexate (MTX). Nontreated tumor-bearing mice were observed to survive 43 +/- 7 days (mean +/- SEM) with an average tumor burden of 8.45 +/- 0.65 g (mean +/- SEM) of solid tumor tissue. Lung metastasis was observed in 3 animals after 42-49 days post implantation. Microscopically, the primary tumor and the lung metastasis were structurally similar. In response to chemotherapy, tumor growth was significantly retarded (p less than 0.005) in the DDP-treated group, and survival was significantly increased in the CTX-treated group (p less than 0.001). Lung metastasis was observed in all treatment and control groups. This model has specific reproducible characteristics which make it a useful murine tumor model to study locally invasive bladder cancer.
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PMID:Evaluation of chemotherapy in a murine model for bladder cancer. 653 60

Growth characteristics, survival time, and various other parameters such as chromosome studies and DNA synthesis were evaluated in a transplantable transitional cell mouse bladder tumor induced by N-[4-5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT). When the tumor was implanted subcutaneously, the mice were observed to survive mean 43 + 7 days (mean +/- SEM) with an average tumor burden of mean 8.45 +/- 0.60 gm (mean +/- SEM) of solid tumor tissue. In the tumor control animals, lung metastasis was noted in 3 animals at 42-49 days post implantation. The histological appearance of the primary tumor and the lung metastasis presented an undifferentiated anaplastic tumor with many spindle cells. The modal number of chromosome is 65 with several markers identifiable as abnormal in morphology. A significant decrease (p less than 0.001) in DNA synthesis was noted between 13 days and 20 days post implantation. In the evaluation of chemotherapy drugs, Cis-dichloro-trans-dihydroxy-bis-iso propylamine platinum IV (CHIP), Cis-diaminedichloroplatinum II (DDP), Cyclophosphamide (CTX) and Methotrexate (MTX) tumor growth was significantly retarded (p less than 0.005) in the DDP treated groups, however survival was not improved. Survival was significantly improved in the CTX treated group (p less than 0.001), although no significant decrease was noted in tumor growth. Lung metastasis was noted in all groups. This model has certain characteristics which make it a good model to study locally invasive bladder cancer.
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PMID:A murine model for bladder cancer. 654 40

Noninbred Sprague-Dawley rats bearing N-methyl-N-nitrosourea (MNU)-induced mammary tumors were ovariectomized at 2.5, 3.5, and 4.5 months after the first MNU injection to determine the response to castration as a function of the time of tumor appearance. Tumor number and tumor size recorded at weekly intervals revealed that the tumors in the control rats continued to grow during each of the three observation periods, but that tumor growth was significantly less during the third period. Ovariectomy performed at 2.5 months after the first MNU injection produced a stabilization of tumor number; when performed at 3.5 or 4.5 months, it resulted in a slight decline in tumor number. Although tumor size decreased slightly in rats that were ovariectomized at 2.5 months, many of the tumors regrew during the last 2 weeks of observation. This was not true, however, for rats that were ovariectomized at either 3.5 or 4.5 months after the first MNU injection. The level of receptors for 17 beta-estradiol (E2), progesterone, and prolactin were significantly reduced by ovariectomy. E2 receptors, which ranged from 2.04 +/- 18 to 2.24 +/- 0.24 (mean +/- SEM) pmol/g tissue for the first and second groups of control rats, declined to 0.93 +/- 0.14 pmol/g tissue for the ovariectomized rats at the end of the last interval studied (5.5 mo after the first MNU injection). This study suggests that hormone responsiveness (response to ovariectomy) of MNU-induced mammary tumors increases slightly with the age or time of appearance of the tumors.
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PMID:Response to ovariectomy of N-methyl-N-nitrosourea-induced mammary tumors in the rat. 677 43


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