Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Samples of graded, human lung cancer and of normal lung were assayed for total iron, ferritin, and ferritin iron saturation. Both kinds of tissues contained highly variable amounts of total and ferritin iron and had a range of ferritin iron:protein ratios. No quantitative correlations were found between cancer histopathology and these parameters, in contrast to previous findings for transplantable rat hepatomas. Examination of pooled ferritins isolated from normal lung and lung tumors by quantitative polyacrylamide gel electrophoresis, isoelectric focusing before and after acid-urea dissociation, and SDS electrophoresis, revealed no structural differences. It is concluded that at least for the human lung, malignancy of the kind examined causes no change in ferritin gene expression, and that ferritin assays would not be useful in the grading or detection of human lung cancer.
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PMID:Concentration, structure and iron saturation of ferritins from normal human lung and lung tumors with graded histopathology. 707 83

A new technique has been used for culturing human keratinocytes. The cells grow on the basement membrane-like capsules of bovine lenses. Lens cells were removed from the capsules by rigid trypsinization. In order to exclude any contamination with remaining living cells the isolated capsules were irradiated with X-rays at a dose of 10,000 rad. In this way human epithelial cells can be brought in culture from individual hair follicles. Since feeder cells are not used in this culture technique, the biosynthesis of keratinocyte proteins can be studied in these cultures. The newly synthesized proteins can be separated into a water-soluble, a urea-soluble, and a urea-insoluble fraction. Product analysis has been performed on the first two fractions revealing protein patterns identical to those of intact hair follicles. Product analysis of the urea-soluble fractions of microdissected hair follicles shows that the protein pattern of the cultured keratinocytes resembles the protein pattern of the hair follicle sheath. Studies on the metabolism of benzo(a)pyrene revealed that the enzyme aryl hydrocarbon hydroxylase (AHH) is present in cultured hair follicle cells. A possible use of our culture system for eventual detection of inherited predisposition for smoking-dependent lung cancer is discussed.
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PMID:Protein biosynthesis in cultured human hair follicle cells. 744 61

The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl urea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. The compounds tested showed an in vitro anticancer activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU, chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the ureas seems to play a role in the general selectivity of our compounds. The N1-methyl and N1-2-chloroethyl urea derivatives are more selective for central nervous system cell lines and the N1-allyl urea derivatives are more selective for lung cancer cell lines. The N1-propargyl ureas did not show any particular selectivity in the 60 human cell lines tested.
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PMID:In vitro cytotoxicity and differential cellular sensitivity of derivatives of diamino acids. I. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl ureas. 764 69

Understanding the extent to which changes in whole-body protein kinetics contribute to the commonly observed weight loss and decrease in lean body mass (LBM) in patients with cancer is currently obscured by conflicting reports in the literature. While several studies have reported significant increases in whole-body protein turnover (WBPT), synthesis (WBPS), and catabolism (WBPC) in patients with cancer, others have failed to confirm these observations. We have measured whole-body protein kinetics using a primed constant infusion of 15N-glycine in a homogenous group of 32 newly diagnosed advanced lung cancer patients with comparable staging and before any antineoplastic treatment, and in 19 normal healthy volunteer controls. Urinary urea and ammonia 15N enrichment was determined in individually collected urine samples obtained during the 24-hour study period and averaged for the determination of protein kinetics. During the last 6 hours of urine collection, samples were obtained hourly for determination of 15N plateau enrichment. Twenty-four-hour urinary nitrogen and creatinine excretion was determined from 24-hour pooled urine samples. Resting metabolic expenditure (RME) was determined by indirect calorimetry and LBM was estimated from deuterium oxide dilution. Age body weight, LBM, RME, and 24-hour urinary nitrogen excretion did not differ between cancer and control subjects. WBPT, WBPC, and WBPS (g/kg/d) were significantly increased in lung cancer patients. However, when the same results were expressed either per kilogram LBM or per gram 24-hour urinary creatinine excretion, WBPT, WBPC, and WBPS rates were not statistically different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein turnover in advanced lung cancer patients. 848 46

The effect of radiation therapy on substrate metabolism was evaluated in five patients with head and neck or lung cancer. Stable isotope tracer methodology was used to determine urea, amino acid, glucose, and lipid kinetics during postabsorptive conditions before initiation, near the midpoint (after receiving 2,672 +/- 36 rads), and at completion (after receiving 6,072 +/- 307 rad) of a 6- to 8-week course of radiation therapy. Nutritional status was maintained throughout the treatment period by providing supplemental enteral feedings as needed. Postabsorptive plasma insulin, catecholamine, and amino acid concentrations did not change during the course of treatment. Before radiation therapy was initiated, values for the plasma rate of appearance (Ra) of urea (3.35 +/- 0.33 micromol x kg(-1) x min(-1)), alpha-ketoisocaproate ([alpha-KIC] 2.16 +/- 0.19 micromol x kg(-1) x min(-1)), phenylalanine (0.59 +/- 0.052 micromol x kg(-1) x min(-1)), and glucose (10.56 +/- 1.31 micromol x kg(-1) x min(-1)) were in the normal range. However, glycerol and palmitate Ra values (3.11 +/- 0.30 and 2.01 +/- 0.33 micromol x kg(-1) x min(-1), respectively) were 25% higher than values observed previously in normal subjects. Substrate flux did not change during radiation therapy, and measurements obtained during the midpoint and at completion of treatment were similar to initial values. These results demonstrate that large doses of radiation therapy, administered over 6 to 8 weeks to the upper body, do not cause significant metabolic stress.
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PMID:Metabolic response to radiation therapy in patients with cancer. 863 53

Extravascular, intratumoral fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumour growth. This is the first report on the presence and distribution of fibrinogen/fibrin in primary (14 glioblastomas) and metastatic (nine samples of lung cancer origin) human brain tumours detected by immunofluorescent techniques. All tissue samples showed specific staining for fibrinogen/fibrin. In glioblastomas fibrin deposits could be detected within and around tumour foci, while in metastatic brain tumours the tumour cell nodules were surrounded by fibrin deposits localized almost exclusively in the connective tissue compartment of tumours. Double-labelling reactions for von Willebrand factor and fibrinogen/fibrin has revealed that fibrin deposition occurred throughout the tumour stroma independently of tumour vasculature. The overlapping reactions for fibrinogen/fibrin and factor XIII subunit A, as well as the urea-insolubility of the deposits indicate the crosslinked, highly stabilized nature of fibrin both within and around tumours. Staining with Ki M7 monoclonal antibody specific for phagocytosing macrophages showed these cells to be scattered in the nonnecrotic areas in glioblastomas and to be accumulated at the interface of tumorous parenchyma and connective tissue in both primary and metastatic tumours. The close association between fibrin deposition and macrophage accumulation strongly suggests the active participation of tumour associated macrophages in the formation of stabilized intratumoral fibrin network in human brain neoplasms.
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PMID:Fibrin deposition in primary and metastatic human brain tumours. 887 64

We have previously reported on the secretion of a family of high Mr plasminogen activators (PAs) by a human lung cancer cell line [Harvey et al. (1991) Biochim. Biophys. Acta 1078, 360-368]. We have now extended these studies to several human cancer cell lines and a human embryonic lung cell line. In the present study with HPL-SK-1 lung cancer, A431 epidermoid cancer, ovarian carcinoma, and embryonic lung cell lines, we show that the 900- and the 660-kDa PAs are disulfide-bonded multiprotein oligomeric complexes. They are functionally and immunologically related to human urinary PA (uPA). Their size and PA activity are not destroyed by strong denaturants such as 8 M urea or 2% sodium dodecyl sulfate (SDS), suggesting that the uPA moiety is covalently associated with the rest of the molecule. It is only under strong denaturing conditions with 1.4 M beta-mercaptoethanol and 2% SDS that the uPA moiety could be released as a 21- to 23-kDa fragment along with two major polypeptide chains of 70 and 40 kDa, respectively. The presence of the uPA active center in the reduced PA660 was demonstrated by [3H]diisopropylphosphorofluoridate labeling and by Western blot using a monoclonal antibody to uPA B chain. N-terminal amino acid sequencing of the 70- and 40-kDa polypeptides, respectively, showed homology to the neural cell adhesion molecule and the beta chain of haptoglobin. A minor fragment of 18 kDa obtained under strong reduction conditions was also sequenced and shown to share homology with the alpha chain of haptoglobin. Western blot analysis of the reduced PAs with monoclonal antibody to the neural cell adhesion molecule and rabbit anti-haptoglobin confirmed the homologies obtained by the sequence data. Further, immobilized monoclonal antibodies to the neural cell adhesion molecule, uPA B chain, and rabbit anti-haptoglobin bound the multiprotein complexes with uPA activity, from A431, ovarian cancer, and embryonic lung cell lines. The bound material, after dissociation, exhibited PA activity that was inhibited by monoclonal antibody to the uPA B chain. These data suggest that in tumor and embryonal cell lines, in addition to proper folding and assembly of proteins by intramolecular disulfide bond formation in the endomembrane compartment, intermolecular disulfide bonds could also occur, producing multiprotein oligomers as in the present case. Formation of such oligomers may have a selective advantage for such cells in the focalization of proteolytic activity through the interaction of the neural cell adhesion molecule domain with the extracellular matrix and in immunosuppression of lymphocytes by the haptoglobin portion of the complex.
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PMID:Cancer cells release a covalent complex containing disulfide-linked domains from urinary plasminogen activator, neural cell adhesion molecule, and haptoglobin alpha and beta chains. 930 1

The antitumor effects of "half-mustard type" phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propylureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of "half mustard type" phenothiazines.
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PMID:The primary in vitro antitumor screening of "half-mustard type" phenothiazines. 941 80

The bicarbonate-urea method for measuring CO2 production was applied to eight free-living patients (mean age, 68 +/- 10 years; mean weight, 69 +/- 10 kg; mean height, 1.65 +/- 0.10 m) with unresectable small-cell lung cancer for a period of 1 day (n = 5) or 2 days (n = 3). The basal metabolic rate (BMR) was measured in all subjects. The technique was first validated against whole-body indirect calorimetry over an additional 24-hour period in five of these subjects. The bicarbonate-urea method predicted net CO2 production to be 102.1% +/- 3.4% of that measured by whole-body indirect calorimetry, and energy expenditure, 101.5% +/- 3.8% of the measured calorimeter value (8.1 +/- 1.6 MJ/d). The 24-hour recovery of label in CO2 excreted by the body was 95.6% +/- 0.5%. In free-living conditions, the bicarbonate-urea method predicted energy expenditure to be 9.0 +/- 2.6 MJ/d. BMR was elevated by a mean of 6% (P < .05) compared with the Schofield standards. The physical activity level ([PAL] the ratio of total energy expenditure [TEE] to BMR) was variable (1.15 to 1.87), but the mean value was only 1.36 +/- 0.22, considerably less than that of moderately active healthy subjects with estimated PAL values of 1.55 (P < .05) to 1.65 (P < .01) and the mean results obtained by doubly labeled water (previous studies) in healthy age- and sex-matched subjects. This is the first time a tracer method for measuring CO2 production and energy expenditure has been validated against whole-body 24-hour indirect calorimetry in patients with lung cancer or a systemic inflammatory reaction. The agreement between the two methods is similar to that observed in normal subjects. This is also the first time a tracer method has been used to measure energy expenditure in free-living patients with lung cancer. The results suggest that TEE and the energy requirements necessary to maintain energy balance were not increased despite basal hypermetabolism, because of the associated decrease in physical activity.
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PMID:Total energy expenditure in patients with small-cell lung cancer: results of a validated study using the bicarbonate-urea method. 943 35

In order to prevent the nephrotoxicity induced by cisplatin (CDDP), prostaglandin E1 (PGE1) was administered intravenously after anticancer chemotherapy to six patients with lung cancer. All patients underwent two courses of multi-drug chemotherapy with the same regimen including a single administration of 80 mg/m2 CDDP. From the 7th day of the 2nd course of chemotherapy, 120 micrograms PGE1 had been administered for five days. During the two courses of chemotherapy, serum creatinine, blood urea nitrogen, creatinine clearance (Ccr), 24-h excretions of beta 2-microglobulin (beta 2-MG) and N-acetylglucosaminidase (NAG) in urine were measured every week in all patients. The mean value of Ccr was higher in the 2nd course than in the control course (65 ml/min vs. 74 ml/min). The 24-h excretions of beta 2-MG and NAG were also reduced in the 2nd course. Out of six patients, only one was complicated by mild phlebitis at the PGE1 infusion site. From these results it was suggested that PGE1 was effective for prevention of CDDP nephrotoxicity.
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PMID:[Preventive effect of prostaglandin E1 on cisplatin-induced nephrotoxicity]. 1009 47


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