Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the mechanism of metastatic spread in Lewis lung carcinoma-bearing C57BL/6 mice exposed to 42 degrees C total-body hyperthermia (TBH) by water immersion. When the mice were treated with 42 degrees C TBH 24 h after resection of the primary tumor, the spread of lung metastasis was inhibited (P less than 0.01). When tumor-bearing mice were exposed to 42 degrees C TBH followed by resection of the primary tumors 24 h later, the spread of lung metastasis was greater than in the control group from which tumors were removed 6 days after inoculation (P less than 0.05). When normal mice were subjected to 42 degrees C TBH and Lewis lung carcinoma cells were subsequently injected i.v., lung metastasis increased significantly in those mice that had received tumor cell injection between immediately after and 48 h after TBH treatment (P less than 0.02-0.001). Tumor-bearing mice were subjected to 42 degrees C TBH, and changes in the lung tissues were examined. Between 12 and 48 h after TBH, alveolar collapse, edema, and cellular infiltration into the alveolar walls were seen. Tumor-bearing mice were exposed to 42 degrees C TBH and blood was taken from the inferior vena cava. The number of tumor cells in the blood increased significantly 12 h after TBH exposure (P less than 0.05). We suggest that TBH promotes the intravascular invasion of tumor cells and that histological changes in the host lung facilitate the implantation of tumor cells.
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PMID:Mechanism of metastatic spread by 42 degrees C total-body hyperthermia in Lewis lung carcinoma. 394 87

The Cavitron Ultrasonic Surgical Aspirator (CUSA) (Cooper Medical, Stamford, CT) is a relatively new surgical modality. The risk of tumor seeding during tumor surgery has not been studied until now. Hanks balanced salt solution, normal saline, distilled water, and Dakin's solution were used as irrigation fluids during CUSA fragmentation of Lewis lung carcinoma in C57B1/10 female mice, using the machine at 40% of its maximal output. All four irrigation fluids contained viable tumor cells--growing in vitro as well as in vivo--after tumor aspiration. Normal saline was also used when the machine was operating at its maximal output. Under these conditions, the irrigation fluid contained viable tumor cells as well.
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PMID:Viability of tumor cells in the irrigation fluid of the Cavitron Ultrasonic Surgical Aspirator (CUSA) after tumor fragmentation. 400 1

Cimetidine (CM), a drug widely prescribed for ulcers, readily undergoes nitrosation to form nitrosocimetidine (NCM), a genotoxic agent. In a test of the chronic effects of NCM in mice, (C57BL/6 X BALB/c)F1 mice were exposed chronically to NCM (113 or 1130 ppm) in the drinking water from preconception through prenatal and neonatal development and adult life. Each group consisted of 40 to 80 mice of each sex, and median survival time was 27 months. Other groups were given CM alone or in combination with NaNO2 (184 or 1840 ppm), or NaNO2 alone. None of the chemical treatments had large effects on reproductive parameters, survival, or incidence of nonneoplastic lesions. CM treatment was associated with a small but significant increase in incidence of lymphomas in females, 41 of 59 (69%), compared with 31 of 66 controls (47%, P = 0.01). No females receiving either dose of NCM developed mammary carcinomas (0 of 91), compared with an incidence of four of 66 controls (6%, P = 0.03). Males given the high-dose combination of CM and NaNO2 showed a higher incidence of lung tumor bearers than controls (71 of 79 versus 30 of 52, P less than 0.01) and also experienced a significant, dose-dependent increase in numbers of large lung tumors (greater than 1 cm in diameter), lung carcinoma, and metastatic lung tumors. Females given the higher dose of NCM had significantly greater incidence of mice with large lung tumors than controls (nine of 41 versus three of 66, P = 0.009). The possibility of carcinogenicity of cimetidine, nitrosocimetidine, and cimetidine plus nitrite is discussed.
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PMID:Effects of cimetidine, nitrite, cimetidine plus nitrite, and nitrosocimetidine on tumors in mice following transplacental plus chronic lifetime exposure. 401 36

A natural product, named Viva-Natural, extracted from a dietary seaweed Undaria pinnantifida has been found to be therapeutically active against Lewis lung carcinoma (LLC). Viva-Natural also demonstrated moderate prophylactic activity against LLC in allogeneic mice. The active principle(s) which was concentrated in the water-insoluble fraction of Viva-Natural was essentially noncytotoxic in KB cell cultures, and probably a polysaccharide. Viva-Natural was found to be significantly effective in enhancing the natural cytolytic activity of peritoneal macrophages against KB cells as targets in in vitro assay, suggesting that the antitumor action of Viva-Natural might be indirect through the activation of nonspecific immune systems. A combination therapy of Viva-Natural and standard anticancer drugs was additively or synergistically effective.
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PMID:Anticancer activity of a natural product, viva-natural, extracted from Undaria pinnantifida on intraperitoneally implanted Lewis lung carcinoma. 406 51

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.
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PMID:[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas]. 622 95

Experimental studies with orally administered MCNU, a water-soluble nitrosourea, yielded the following results. MCNU produced a significant increase in life span, and 60-day survivors were observed by various schedules in L1210 leukemia. The therapeutic ratios of MCNU were almost similar to those of CCNU. With Lewis lung carcinoma and Ehrlich ascites carcinoma implanted into the stomach wall, its antitumor activity by oral administration was slightly more effective than by intravenous route. In Beagle dogs, hematologic toxicity and gastrointestinal toxicity (vomiting, diarrhea) were noted by oral administration, similar to intravenous administration, but its toxicity was mild. The maximum blood level of MCNU was noted at 30 minutes after oral administration in Beagle dogs. The half life (23.7 min) by oral administration was similar to that by intravenous route. From these results, the oral administration of MCNU deserves the consideration as a form of treatment now given other MCNU routes.
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PMID:[Experimental studies on oral administration of nitrosourea anti-tumor agent, MCNU]. 623 61

Previous studies have suggested that ectopic production of adrenocorticotropic hormone (ACTH) or antidiuretic hormone (ADH) may occur commonly in patients with small cell carcinoma of the lung (SCCL) and that evidence of such production may be elicited only by provocative tests of water excretion and adrenal function. We studied 28 patients with SCCL and 29 patients with other cancers. Adrenal function, assessed by measuring the 8 am plasma cortisol, the 8 am to 4 pm diurnal variation in plasma cortisol, and the suppressibility of the 8 am plasma cortisol following administration of 1 mg of dexamethasone, was found to be abnormal in 28.5, 71, and 25 percent, respectively, of the patients with SCCL, compared with 18, 65, and 29.5 percent in patients with other types of cancer (P greater than 0.3). The possibility of ectopic ADH secretion was assessed by a standard water loading test, which showed excretion impairment in 60 percent of patients with SCCL and 68 percent of patients with other cancers (P greater than 0.9). Neither the stage of neoplastic disease, sites of metastatic deposits, nor performance status of the patients correlated with abnormalities of water and cortisol metabolism, indicating that such abnormalities are common in patients with all types of cancer. These data do not suggest that subclinical disturbances of adrenal function or water excretion are characteristic of any histologic type of cancer. The precise mechanism(s) underlying these abnormalities are unknown.
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PMID:Frequency of abnormalities of cortisol secretion and water metabolism in patients with small cell carcinoma of the lung and other malignancies. 628 Sep 29

From 1976 to 1980, 18 of the 250 patients (7%) seen with small cell carcinoma of the lung had clinically evident inappropriate secretion of antidiuretic hormone (ADH). Hyponatremia was usually severe (116 +/- 7 meq/l), and eight patients showed symptoms of water intoxication at the time of diagnosis. Of the eight patients who had plasma ADH measured at diagnosis, seven had elevated values (mean 52.0, range 16.1 - greater than 250 pg/ml). Intensive combination chemotherapy produced objective tumor responses in all patients, and syndrome of inappropriate ADH secretion (SIADH) resolved in 16 of 17 evaluable patients within three weeks of initiation of treatment. ADH values after therapy were normal, and all patients maintained a normal serum sodium during the period of tumor remission in spite of unrestricted fluid intake. All 17 evaluable patients have developed progressive cancer, but only 10 have manifested recurrent SIADH. Patient survival was similar to the overall population of small cell carcinoma patients without SIADH. The indirect methods of treatment for SIADH (fluid restriction, demeclocycline, lithium, urea) are frequently of transient value while awaiting a response to chemotherapy or in patients with resistant tumors. However, the initial treatment of choice for SIADH associated with small cell carcinoma of the lung is combination chemotherapy.
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PMID:Management of the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. 629 92

A new macromolecular peptide antibiotic, named AN-3, was isolated from the culture broth of Streptomyces albulus. From 19 liters of culture broth containing AN-3 with 90 units/ml activity, a 400 mg sample with a specific activity of 109 units/mg was obtained. Purified AN-3 gave a single band on polyacrylamide gel electrophoresis. AN-3 was a basic polypeptide with a molecular weight of 12,000 approximately 12,500 and an isoelectric point of pH 7.6. It showed a peak of absorption at 280 nm and seemed to have no nonprotein chromophoric component. It was soluble in water but insoluble in ethanol, butanol and acetone, and was stable at pH 4 approximately 9 but unstable at pH2. AN-3 had no antibacterial activity against Gram-positive and Gram-negative bacteria so far as tested. But, it showed a strong inhibitory effect on a macromolecule permeable mutant of Escherichia coli. It was not mutagenic. It appeared to inhibit synthesis of DNA and RNA without affecting DNA itself. It also inhibited the in vitro cell growth of L1210 and its ED50 was 5 micrograms/ml. AN-3 had antitumor activity against Lewis lung carcinoma in mouse in vivo.
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PMID:The fermentation, isolation and characterization of a macromolecular peptide antibiotic: AN-3. 635 39

A new macromolecular peptide antibiotic, named AN-1, was isolated from the culture broth of Streptomyces albus AJ9003. From 18 liters of culture broth (110 units/ml activity) a 300 mg sample of AN-1 was obtained with a specific activity of 1,160 units/mg was obtained. AN-1 is a basic polypeptide with a molecular weight of 12,000, isoelectric point of pH 8.3, and gives a single band on SDS polyacrylamide gel electrophoresis. It is soluble in water but insoluble in ethanol, butanol and acetone. It was stable at pH 6 approximately 9 but very unstable at pH 2. The UV absorption spectrum shows a maximum at 280 nm. AN-1 had no antibacterial activity against the Gram-positive and Gram-negative bacteria tested, but shows strong inhibitory activity toward Escherichia coli MP2, a macromolecule permeable mutant. In addition to being highly mutagenic, AN-1 inhibits the in vitro cell growth of L1210 (ED50 0.41 micrograms/ml). However, AN-1 had no antitumor activity against mouse leukemia L1210 or Lewis lung carcinoma in mouse.
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PMID:The fermentation, isolation and characterization of a macromolecular peptide antibiotic: AN-1. 636 71


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