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)

Human uterine leiomyosarcoma is a rare gynecological malignancy with a generally poor prognosis. We have established a human uterine leiomyosarcoma tumor line in nude mice, designated UTS-1, and describe the characteristics of this tumor. The UTS-1 tumor doubled in 12.1 days and retained the histological characteristics of leiomyosarcoma, even after 14 serial generations. Ultrastructurally, the tumor is characterized by nuclear pleomorphism typical of smooth muscle, intracytoplasmic filaments with dense bodies, a relative paucity of micropinocytotic vesicles, and an incomplete external lamina. Immunohistochemically, the UTS-1 cells reacted with antibodies against vimentin, desmin, smooth-muscle actin and myosin, but not with antibodies against keratin, CEA and S-100 protein. Serum levels of AFP, CA125, CEA and SCC ranged within normal limits in tumor-bearing mice. The serum level of immunosuppressive acidic protein correlated well with an activity of the tumor. Estrogen and progesterone receptors were not detected in the tumor. Chromosomal analysis showed a human karyotype with some marker chromosomes and a modal number of 85 chromosomes. The UTS-1 tumor should prove a useful model to explore the biological characteristics and treatment of human uterine leiomyosarcoma.
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PMID:Establishment and characterization of human uterine leiomyosarcoma heterotransplanted into nude mice. 150 Feb 17

We studied the toxicity, pharmacokinesis and radiosensitizing effect of a newly developed 2-nitroimidazole-1-methylacetohydroxamate (KIN-804) in C3H/He mice bearing SCC-VII tumor. They were compared with misonidazole. LD50/7 of KIN-804 and misonidazole were 3200 and 2000 mg/kg. The concentration of KIN-804 in the brain and sciatic nerve was at a very low level and its clearance from the sciatic nerve was rapid. Enhancement ratios calculated using the growth delay method were 1.50 for KIN-804 and 1.36 for misonidazole respectively when they were administered by intraperitoneal injection with a dose of 100 mg/kg. KIN-804 was considered to be a promising radiosensitizer because it obtained less toxicity and a higher radiosensitizing activity than misonidazole.
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PMID:[Radiosensitizing effect of a 2-nitroimidazole hydroxamate (KIN-804) to murine tumors]. 150 43

The correlation between mean arterial blood pressure (MABP) and vascular perfusion in SCC-VII/St tumors in mice was compared following administration of three vasoactive drugs: flavone acetic acid (200 mg/kg), hydralazine (5 mg/kg), or nicotinamide (500, 750, and 1000 mg/kg). MABP was measured by the direct method in unanesthetized, unrestrained mice bearing a carotid catheter. Vascular perfusion of the tumor was measured using the 86RbCl extraction method. Body temperature was maintained at 36 degrees to 37 degrees C after drug administration when necessary. All three drugs reduced MABP from a control value of 125 +/- 2 (s.e.) mm Hg in mice without tumors. Flavone acetic acid at this dose had the least effect on blood pressure, with a minimum of 86% of control values at 10 to 20 min, and a return to control values by 1 hr. However, it produced a profound reduction in tumor perfusion that lasted more than 48 hr. Hydralazine and nicotinamide reduced blood pressure to minima between 55% and 69% of control values within 30 min, followed by a gradual return toward control values by about 8 hr. The reduction in tumor perfusion by hydralazine paralleled its effect on blood pressure. However, nicotinamide produced a transitory, although not statistically significant, increase in tumor perfusion at the highest dose given. These data demonstrate that tumor blood flow modification by drugs is not necessarily the result of changes in MABP, and blood pressure changes alone do not inevitably lead to changes in tumor perfusion.
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PMID:Pharmacological modification of tumor blood flow: lack of correlation between alteration of mean arterial blood pressure and changes in tumor perfusion. 153 Jul 55

The radiosensitizing activity, pharmacokinetics and toxicity of RP-170, 2-nitroimidazole nucleoside analog, were investigated and compared with those of etanidazole (SR-2508). An intravenous administration (i.v.) of 100 mg/kg of RP-170 or the same dose of etanidazole showed an equal sensitizer enhancement ratio (SER) of about 1.4 to solid EMT6 tumor under in vivo-in vitro assay and a virtually equal SER of 1.4-1.5 to solid SCC VII tumor under tumor growth delay assay. As predicted from the low partition coefficient, lower drug levels in neural tissue and more rapid serum elimination of RP-170 and etanidazole produced lower acute toxicity than lipophilic sensitizers (e.g., misonidazole). The major advantage of RP-170 over etanidazole is that it has a second route of administration. In contrast to etanidazole, in which the administration route is limited to intravenous injection, with RP-170 oral administration also exhibited effective distribution to tumors, sensitizing radiation activity to solid EMT6 and SCC VII tumors. Moreover, LD50 in mice of RP-170 (4.3 g/kg on i.v.) was increased to 5.2 g/kg by oral administration. This availability of two routes of administration indicates RP-170 as a promising hypoxic cell radiosensitizer for clinical use.
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PMID:Radiosensitization by 2-nitroimidazole nucleoside analog RP-170: radiosensitizing effects under both intravenous and oral administration. 153 Dec 14

The very rapid growth rate (1 population doubling/day) of normal human epidermal keratinocytes (HK) cultured in serum-free medium can be utilized for wound closure in burn treatment. However, rapid growth in vitro may present the possibility of neoplastic transformation. To investigate this possibility, HK were cultured from primary isolation to large populations in MCDB 153 medium supplemented with epidermal growth factor (EGF, 10 ng/ml), insulin (5 micrograms/ml), hydrocortisone (0.5 micrograms/ml), and Bovine Pituitary Extract (BPE, 70 micrograms/ml). HK were studied for their ability to form tumors in athymic mice after subcutaneous inoculation. Sixteen separate HK strains were inoculated from primary cultures, or from secondary cultures either before or after storage in liquid nitrogen. Transformed cell lines, SCC 13 and FL, derived from human epithelial carcinomata were used as controls for tumor formation. HK formed no tumors (0/79) after 26 weeks incubation, SCC 13 formed nodular tumors (3/5) after 20 weeks incubation, and FL formed tumors (5/5) after 4 weeks incubation. HK cells were not found by histological examination of inoculation sites of keratinocyte cultures derived from primary culture from skin. In contrast, palpable tumors from both SCC 13 and FL were returned to tissue culture and continued to proliferate. These results support the conclusion that the rapid growth rate of human epidermal keratinocytes in vitro can be attributed to permissive culture conditions, and not to neoplastic transformation.
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PMID:Absence of tumorigenicity in athymic mice by normal human epidermal keratinocytes after culture in serum-free medium. 154 Sep 41

Beta-core fragment (beta-CF), a fragment of the hCG beta-subunit missing its carboxyterminal peptide, can be detected in the urine of women throughout pregnancy or in trophoblastic disease. It is also found in the urine of patients with nontrophoblastic cancers. We examined the beta-CF level in urine samples from patients with cervical cancer and assessed its value as a tumor marker. beta-CF was measured by an enzyme immunoassay with hCG beta-core directed monoclonal antibody No. 229. Based on the cut-off value (0.2ng/ml) from control subjects, the overall positivity rate for urinary beta-CF in the cervical cancer group was 45% (57 of 128 patients), increasing from 32% (23 of 73) in stage I to 100% (2 of 2) in stage IV. These positivity rates exceeded or equaled those of the other markers, SCC, CEA, CA19-9 and CA125, simultaneously measured in the patients' serum. There was no significant difference between the positivity rates for the two histological types of cancer, squamous cell carcinoma and adenocarcinoma. Serial determination in 28 patients with increased urinary beta-CF prior to therapy showed that 24 patients had a decreased concentration after successful treatment, but 2 of 4 patients with still increased urinary beta-CF during or after treatment subsequently relapsed. The determination of urinary beta-CF may provide a useful tool in monitoring the response to treatment in patients with cervical cancer.
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PMID:[Assessment of urinary beta-core fragment of hCG as a tumor marker of cervical cancer]. 154 71

An examination of the effects of radiation combined with either 5-fluorouracil, Mitomycin C, or both drugs in vitro has been made using a mouse squamous tumor cell line SCC VIITo and cell viability as an endpoint. Depending on how the survival endpoint was calculated, the interaction of 5-fluorouracil, Mitomycin C, or 5-fluorouracil plus Mitomycin C with radiation was greater than additive (plating efficiency) or only additive (viable cells per flask). These results suggest that the cytostatic effect of these drugs may be an important aspect of their action clinically.
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PMID:Mode of interaction of 5-fluorouracil, radiation, and mitomycin C: in vitro studies. 155 79

We investigated potentially lethal damage repair by quiescent tumor cells in vivo. SCC VII tumor-bearing C3H/He mice were irradiated after being given 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all the proliferating cells in their tumors, and the tumors were then excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (Cyt-B, a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labelling was determined using immunofluorescence staining to BUdR. The micronucleus frequency was then used to determine the surviving fraction of unlabelled cells on the basis of the regression line obtained for the micronucleus frequency and the surviving fraction of all tumor cells not labeled by BUdR, which can be regarded as the quiescent cells in a tumor for all practical purposes. Assessment performed 0, 3, 6, 9, and 24 hr after irradiation showed that quiescent cells had more potentially lethal damage repair capacity than the tumor cell population as a whole. Assays were also performed immediately after irradiation alone, 24 hr after the injection of cis-diamminedichloroplatinum(II) (CDDP), mitomycin C (MMC), or misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] (MISO) following irradiation, and 24 hr after irradiation alone. It was found that CDDP and MISO (especially the latter) inhibited potentially lethal damage repair more strongly in quiescent cells than in the tumor cell population as a whole. This assay method thus appears to be quite useful for detecting the responses of quiescent tumor cells to various chemical agents.
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PMID:Potentially lethal damage repair by quiescent cells in murine solid tumors. 155 89

The CaSki cell line derived from an epidermoid carcinoma of the uterine cervix produces and releases a tumor associated-antigen, TA-4. The authors have already reported that EGF stimulated the production and secretion of TA-4 by the CaSki cells. EGF receptor is known to be one of the proteins phosphorylated by C-kinase. In order to elucidate a possible role of signal transduction systems (cAMP-A-kinase, diacyglycerol-C-kinase and Ca(2+)-calmodulin) in the regulation of TA-4 production and secretion by human cervical epidermoid carcinoma cells, the effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on TA-4 production and secretion by CaSki cells were evaluated. TA-4 in the cultured cells and media were measured with a SCC RIA-Kit. The addition of PMA or Ca2+ ionophore to the medium caused increases in the cellular levels of TA-4 and TA-4 levels in the medium in a dose-dependent manner shortly after the addition. Combined treatment with PMA and Ca2+ ionophore did not cause additive increases in TA-4 levels in the cells and medium compared to the treatment with PMA alone or Ca2+ ionophore alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of signal transduction systems in the regulation of production and secretion of TA-4 by cultured cervical epidermoid carcinoma cells (CaSki)]. 160 73

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.
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PMID:CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung. 166 Jan 44


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