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)

(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice. DWA2114R was effective against murine tumor lines, Colon 26 and Colon 38 carcinomas, M5076 ovarian sarcoma and P388 L1210 leukemias, implanted subcutaneously (s.c.). Triple injection every other day of DWA2114R was more effective than a single injection at each sublethal dose. The antitumor effects of DWA2114R against these tumors were more effective than or were similar to those of CBDCA and CDDP. The antitumor effect against CDDP-resistant L1210 leukemia implanted s.c. was only observed in the treatment of DWA2114R, but not in CBDCA and CDDP. No excellent antitumor effects of three platinum complexes were observed against Lewis lung carcinoma and B16 melanoma implanted s.c. even at triple injection every other day, and no effect was obtained against Meth-A fibrosarcoma under similar conditions. While the treatment of CDDP showed marked increases in levels of blood urea nitrogen and of urinary protein and sugar at effective doses in the antitumor evaluations, the treatment of DWA2114R as well as CBDCA showed no increase in these parameters. These results indicate that DWA2114R represents a desirable second generation antitumor platinum complex.
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PMID:Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP), in mice. 156 81

Treatment of mouse skin with tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA), 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) or 8-methoxypsoralen and ultraviolet light (PUVA) caused a marked decrease in the expression of p48, an acidic epidermal protein. This protein was specifically identified in mouse epidermis and confluent PAM 212 mouse keratinocytes in culture. Extraction of p48 required strong denaturing conditions (greater than 8 M urea) as well as a reducing agent, indicating that this protein was associated with the cytoskeleton. Positive immunoblot staining of p48 with antikeratin monoclonal antibodies following two-dimensional polyacrylamide gel electrophoresis suggested that this protein may be related to the acidic keratins. The sensitivity of this protein to topically applied mitogens and tumor promoters implies that p48 expression is important in normal epidermal cell growth and differentiation.
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PMID:Altered expression of a mouse epidermal cytoskeletal protein is a sensitive marker for proliferation induced by tumor promoters. 160 Jun 17

This study examined the effect of a trimodality therapy of the combination of recombinant human tumor necrosis factor alpha (TNF), whole-body hypertheria (WBH), and cis-diamminedichloroplatinum(II) (CDDP) or cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (CBDCA) on a fibrosarcoma and normal tissue in F344 rats. TNF (1 x 10(5) units/kg) increased the antitumor effect of both CDDP (1.5 mg/kg) + WBH (2 h at 41.5 degrees C) and CBDCA (30 mg/kg) + WBH. Tumor growth delay, which was 1.9 days for CDDP + WBH and 2.7 days for CBDCA + WBH (P less than 0.01 compared to control), was significantly increased to 2.9 days with TNF + CDDP + WBH and 5.4 days with TNF + CBDCA + WBH (P less than 0.05). WBH, TNF, CDDP or CBDCA alone, TNF + CDDP, TNF + CBDCA, or TNF + WBH had no significant effect on tumor growth. In contrast, administration of TNF did not enhance the CDDP- or CBDCA-mediated dose limiting normal tissue toxicity. CDDP + WBH-mediated acute renal injury and CBDCA + WBH-mediated acute myelosuppression, as determined by blood urea nitrogen and peripheral blood cell counts, respectively, were not increased with the addition of TNF to either dual modality therapy. Histopathologically, addition of TNF produced no significant alterations in the kidney and the bone marrow as compared to CDDP + WBH or CBDCA + WBH. These data show that TNF enhanced the platinum + WBH-mediated antitumor effect without increasing normal tissue toxicity, suggesting that TNF may increase the therapeutic efficacy of CDDP or CBDCA combined with WBH.
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PMID:Increased therapeutic efficacy induced by tumor necrosis factor alpha combined with platinum complexes and whole-body hyperthermia in rats. 163 21

To evaluate the role of Ca2+ influx on hormone secretion induced by cell swelling, we have utilized a prolactin (PRL)-secreting rat tumor cell line, MMQ, which has plasmalemma dopamine receptors. Medium hyposmolarity or osmotically equivalent isotonic urea caused prompt cell swelling and a rise in both [Ca2+]i and PRL secretion in a dose-dependent manner. Dopamine inhibited the induced increase in both [Ca2+]i and PRL secretion in a dose-dependent manner but the maximum inhibition was only 50%. This effect of dopamine was prevented by haloperidol. Depletion of medium Ca2+ or blocking Ca2+ influx with nifedipine completely abolished the osmotically induced rise in both [Ca2+]i and PRL secretion. These data indicate that Ca2+ influx through nifedipine-sensitive Ca2+ channels is an essential component of PRL secretion induced by osmotic cell swelling in MMQ cells and that a dopaminergic receptor-linked mechanism influences the opening of these channels.
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PMID:Dopamine inhibits cell swelling-induced prolactin secretion in MMQ cells by blocking Ca2+ influx. 166 67

The elimination and metabolism of sulofenur [N-(5-indanesulfonyl)-N'-(4-chlorophenyl)urea, LY186641] was examined in mice, rats, monkeys, and humans. The compound, which is efficacious in a wide number of solid-tumor in vivo models, is currently being developed as an anticancer agent. Its diarylsulfonylurea structure is unique among such agents, and the basis of its activity is unknown but apparently novel. A major goal of these studies was to determine whether p-chloroaniline is formed in significant quantities during the course of sulofenur metabolism. p-Chloroaniline, capable of being formed by hydrolysis of this diarylsulfonylurea, is known to induce methemoglobinemia and/or hemolytic anemia. In animal studies using rats and monkeys, as well as in clinical trials of sulofenur, elevated levels of methemoglobin have been noted. The metabolism was thus compared to the known metabolism of p-chloroaniline. Sulofenur (I) is well absorbed in both monkey and human; practically all of the excreted radiolabel from an oral dose is in the urine. Metabolism is extensive; the major excretion products are the 1-hydroxyindanyl (II) and 1-ketoindanyl (III) derivatives in all species, along with significant amounts of the 3-hydroxyindanyl (IV) and 3-ketoindanyl (V) metabolites in the mouse and rat. Dihydroxyindanyl secondary metabolites also are present, but no sulofenur is observed in the urine samples. Known metabolites account for over 95% of the radiocarbon present in urine samples from a patient given [14C-p-chlorophenyl]sulofenur.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism and disposition of the anticancer agent sulofenur in mouse, rat, monkey, and human. 167 39

The breast cancer-associated epitope (mammary serum antigen or MSA) defined by monoclonal antibody (Mab) 3E1.2 is a neuraminidase-sensitive carbohydrate expressed on MUC-1-encoded molecules. However, the reactivity of Mab 3E1.2 is also reduced by protease treatment of the mucin, which suggests that 3E1.2 binds to multimers of the sialylated carbohydrate in a protein conformation-dependent manner. The common N-acetyl derivative of neuraminic acid (5-acetylneuraminic acid) is not involved in the epitope, since lectins specific for 5-acetylneuraminic acid (linked to GalNAc or Gal) are nonreactive with MSA-positive molecules. However, the N-glycolyl derivative, 5-glycolylneuraminic acid (Neu5Gc), forms a major part of the epitope since both free Neu5Gc and porcine stomach mucin (greater than 90% neuraminic acid as Neu5Gc) inhibit the binding of Mab 3E1.2, while bovine or ovine submaxillary mucins, fetuin, bovine gangliosides, and other carbohydrates do not. Indeed, the presence of Neu5Gc on human tumor mucin was confirmed by electrospray mass spectrometry. Neu5Gc is attached to an O-linked carbohydrate, since the expression of MSA by MCF-7 breast cancer cells is inhibited by the O-glycosylation inhibitor phenyl-N-acetyl-alpha-D-galactosaminide, but not by the N-glycosylation inhibitor tunicamycin, and the epitope is removed by treatment with O-glycanase but not N-glycanase F, endoglycosidase F, or endoglycosidase H, which are specific for N-linked glycans. This is likely to be a core glycan since 3E1.2 reacts after treatment of the mucin with trifluoromethanesulfonic acid, which removes most backbone and peripheral carbohydrates. Treatment with galactosidase or N-acetyl glucosaminidase enhances the binding of Mab 3E1.2, indicating that the Neu5Gc is not attached to galactose or N-acetyl galactosamine. Furthermore, the susceptibility of MSA to treatment with Arthrobacter urea-faciens neuraminidase [which is specific for alpha (2-6)-linked NeuNAc] and the loss in reactivity of GalNAc-specific lectins after periodate oxidation [alpha (2-3)-linked but not alpha (2-6)-linked NeuNAc protects GalNAc from periodate oxidation] indicate that the Neu5Gc may be attached alpha (2-6) to peptide-linked GalNAc. These results show that MSA is a Neu5Gc-containing O-linked core glycan, which represents a unique tumor-associated epitope not previously identified on human mucins.
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PMID:The breast tumor-associated epitope defined by monoclonal antibody 3E1.2 is an O-linked mucin carbohydrate containing N-glycolylneuraminic acid. 171 85

1-(2-[4-Pridyl)-2-imidazoline-1-yl]-ethyl)-3-(4-carboxyphenyl)urea (CGP15'720A) is an experimental antineoplastic agent with marked activity against carcinogen-induced lung tumors in Syrian hamsters and human lung tumor xenografts in nude mice. A preclinical toxicity study of this agent was carried out in mice and dogs which demonstrated the relatively nontoxic nature of the agent. In mice, single intraperitoneal dosage of 12 g/m2 did not produce lethality; however, lethality (30% of treated mice) was seen during treatment with 6 g/m2 daily for 5 days. No hematological, serum-chemistry or histopathological changes were detected in mice after single or five consecutive treatments with 12 g/m2. Dogs were treated with doses ranging from 5 g/m2 to 80 g/m2, with deaths occurring in a non-dose-related fashion after 10, 20, and 40 g/m2. Acute neurological toxicity after infusion was the dose-limiting toxicity in dogs. There were no consistent hematological or serum-chemistry aberrations in the treated dogs. The most consistent histopathological finding was prostatic atrophy, which was detected in 5/12 dogs in this series.
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PMID:Prostatic atrophy in dogs after intravenous administration of a ureido-ethylimidazoline derivative (CGP15'720A). 174 61

Low-frequency electromagnetic fields enhance the induction of mammary gland tumors in rats using nitrosomethyl urea. The incidence of tumors depended on the duration of exposure to static (dc) and variable (ac) magnetic fields. Variable magnetic fields induced mammary gland cancer much more frequently than static ones. Apart from increasing the incidence of mammary gland tumors, household low-frequency electromagnetic fields reduced the mean latent period of tumor development and led to predominance of malignant tumors in the exposed animals as compared to controls. Mammary gland tumors developed rarely under the effect of static or variable magnetic fields per se, without preliminary administration of a carcinogen. Household low-frequency electromagnetic fields may potentially present an oncogenic hazard for animals and humans.
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PMID:Low-frequency electromagnetic radiation enhances the induction of rat mammary tumors by nitrosomethyl urea. 176

It was previously found that rabbit serum contains a growth-inhibitory substance for a tumorigenic rat liver cell line RSV-BRL. In the present study, the growth inhibitor was purified from normal rabbit serum to show a homogeneous protein band with a molecular weight (Mr) of 56 k on SDS-polyacrylamide gel electrophoresis under non-reducing conditions. The purified growth inhibitor, tentatively named rabbit serum-derived growth inhibitor (RSGI), potently inhibited the growth of RSV-BRL and nine kinds of other cell lines including three human tumor cell lines at a concentration of 20 ng/ml or higher. The growth-inhibitory effect of RSGI was reversible and appeared to be cytostatic rather than cytotoxic. RSGI was stable to heating at 56 degrees C for 30 min or treatment with 0.1 M 2-mercaptoethanol, but labile to heating at 100 degrees C for 3 min or treatment with 1 M acetic acid (pH 2.3), 6 M urea, 50% (v/v) 1-propanol, or 0.1% (w/v) trypsin. These properties of RSGI suggested that it was different from type beta transforming growth factors, tumor necrosis factor-alpha, and other known growth-regulatory factors.
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PMID:Purification and properties of growth inhibitor from normal rabbit serum. 176 70

The study reported here was undertaken to determine the nephrotoxicosis associated with the administration of cisplatin, an antineoplastic agent, to dogs when administered during 6-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface, IV, every 21 days) was given to 61 dogs with malignant neoplasia with a total of 185 doses in 1 (n = 9 dogs), 2 (n = 26 dogs), 3 (n = 4 dogs), 4 (n = 9 dogs), 5 (n = 2 dogs), and 6 (n = 11 dogs) treatments. The cisplatin was given over a 20-minute period after 0.9% NaCl solution (saline solution) was administered IV for 4 hours at a rate of 18.3 ml/kg of body weight/h. After the cisplatin infusion, saline solution diuresis was continued at the same rate for 2 hours. Before each treatment with cisplatin, dogs were evaluated with at least a physical examination, CBC, determination of serum urea nitrogen concentration, and in most cases, determination of serum creatinine concentration and urine specific gravity. Four of the 61 dogs (6.6%) developed clinically evident renal disease after 2 (1 dog), 3 (2 dogs), and 4 (1 dog) doses of cisplatin were administered. Three of the 4 dogs had preexisting disease of the urinary tract prior to the start of treatment. The survival time in dogs that developed renal disease (median, 145 days; range, 15 to 150 days) was similar to that of all dogs in this study (median, 154 days; range, 30 to 500 days), with 13 dogs still alive at the conclusion of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of nephrotoxicosis associated with a short-term saline solution diuresis protocol for the administration of cisplatin to dogs with malignant tumors: 61 cases (1987-1989). 178 22


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