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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the U.S., there has been a steeper rise of the incidence of lung adenocarcinoma than of squamous cell carcinoma of the lung among cigarette smokers. Since 1950, the percentage of all cigarettes sold that had filter tips increased from 0.56 to 92% in 1980 and to 97% in 1990. The tobacco of the filter cigarettes is richer in nitrate than that of the nonfilter cigarettes manufactured in past decades. Because the smoker of cigarettes with lower nicotine yield tends to smoke more intensely and to inhale the smoke more deeply than the smoker of plain cigarettes, the peripheral lung is exposed to higher amounts of nitrogen oxides, nitrosated compounds, and lung-specific smoke carcinogens. It is our working hypothesis that more intense smoking, deeper inhalation of the smoke, and higher smoke delivery of the organ-specific lung carcinogen NNK to the peripheral lung are major contributors to the increased risk of cigarette smokers for lung adenocarcinoma. Bioassay data and biochemical studies in support of this concept are discussed.
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PMID:The biological significance of tobacco-specific N-nitrosamines: smoking and adenocarcinoma of the lung. 868 61

In 1950, the first large-scale epidemiological studies demonstrated that lung cancer is causatively associated with cigarette smoking, a finding subsequently confirmed by the Royal College of Physicians in London, the U.S. Surgeon General, and the World Health Organization. Although cigarette consumption has gradually decreased in the United States from a high of about 3800 cigarettes per adult per year in 1965 to about 2800 cigarettes in 1993, death from lung cancer has reached a high among males at the rate of 74.9/100,000/year and among females at the rate of 28.5. However, in the younger cohorts, the lung cancer death rate is decreasing in both men and women. In this overview we discuss the steeper increase during recent decades of lung adenocarcinoma incidence compared with squamous cell carcinoma of the lung. In 1950, the ratio of these two major types of lung cancer in males was about 1:18; today it is about 1:1.2-1.4. This overview discusses two concepts that are regarded as contributors to this change in the histological types of lung cancer. One factor is the decrease in average nicotine and tar delivery of cigarettes from about 2.7 and 38 mg in 1955 to 1.0 and 13.5 mg in 1993, respectively. Other major factors for the reduced emission of smoke relate to changes in the composition of the cigarette tobacco blend and general acceptance of cigarettes with filter tips; the latter constitute 97% of all cigarettes currently sold. However, smokers of low-yield cigarettes compensate for the low delivery of nicotine by inhaling the smoke more deeply and by smoking more intensely; such smokers may be taking up to 5 puffs/min with puff volumes up to 55 ml. Under these conditions, the peripheral lung is exposed to increased amounts of smoke carcinogens that are suspected to lead to lung adenocarcinoma. Among the important changes in the composition of the tobacco blend of the U.S. cigarette is a significant increase in nitrate content (0.5% to 1.2-1.5%), which raises the yields of nitrogen oxides and N-nitrosamines in the smoke. Furthermore, the more intense smoking by the consumers of low-yield cigarettes increases N-nitrosamines in the smoke 2- to 3-fold. Among the N-nitrosamines is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in animals that is exclusively formed from nicotine. This organ-specific tobacco-specific nitrosamine (TSNA) induces adenocarcinoma of the lung. All of these factors, the more intense smoking, the deeper inhalation of the smoke, and the increased yields of N-nitrosamines in the smoke of low-yield cigarettes, are considered major contributors to the drastic increase in lung adenocarcinoma among cigarette smokers in recent years. This overview also discusses the differences in the major lung cancer types in female compared with male smokers as well as the likely underlying factors for increased lung cancer risk among African Americans compared with that among white Americans. Although the only sure way to prevent smoking-related diseases is giving up the tobacco habit, there must be a measure of protection for those who cannot accomplish this. Therefore, setting upper permissible limits of tar levels for the smoke of U.S. cigarettes, similar to strategies already taken in Western Europe, should be considered.
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PMID:The changing epidemiology of smoking and lung cancer histology. 874 74

Twelve patients (aged 70 +/- 9 years) who were scheduled for resection of rectosigmoid colon adenocarcinoma but were otherwise healthy were randomly allocated after surgery to receive either peripheral parenteral nutrition alone ([PPN] n = 6) or in combination with recombinant human growth hormone (rGH) at a daily dose of 0.15 U x kg(-1) x d(-1)(PPN + rGH, n = 6). The daily nutritional regimen was 0.1 g nitrogen x kg(-1) x d(-1) and 20 kcal x kg(-1) x d(-1) (nonprotein energy was supplied as 60% lipid and 40% carbohydrate), and it was maintained for 6 days before and 6 days after surgery. Protein kinetics were studied in all 12 patients during the fasted and fed states before and 6 days after surgery using an 8-hour 13C-leucine tracer infusion. Daily urinary nitrogen, gaseous exchange, and plasma insulin, growth hormone, and insulin-like growth factor-I (IGF-I) were determined before and after surgery. Surgery was responsible for significant increases in postabsorptive whole-body protein flux and synthesis and leucine oxidation (P < .01). Supplementation of PPN with rGH contributed to a significant attenuation of the postoperative increase in leucine oxidation (P = .02), with a significant increase in whole-body protein synthesis (P = .02) and no effect on protein breakdown (P = .40). During the fed state, leucine oxidation increased significantly (P = .005), with the greatest change occurring in the PPN group. Feeding was associated with a significant decrease in whole-body protein breakdown before and after surgery in both groups (P = .001). Postoperative urinary nitrogen excretion was lower but was not statistically significant in the PPN + rGH group compared with the PPN group. There was a significant increase in oxygen consumption (VO2) and carbon dioxide production (VCO2) as a result of feeding and surgery (P < .01). Supplementation with rGH caused a decrease in the respiratory quotient (RQ) (P = .04), particularly after surgery, indicating a direct effect of rGH on fatty acid oxidation. Circulating plasma insulin increased significantly in both groups with feeding and rGH supplementation (P < .05). This was enhanced after surgery, particularly in the rGH group (P < .05). Plasma growth hormone decreased after surgery in the PPN group (P < .05), but did not change as a result of feeding. The circulating levels increased in the PPN + rGH group following subcutaneous administration before or after surgery. Plasma IGF-I decreased after surgery in the PPN group (P < .05), and no changes occurred in the PPN + rGH group with feeding. The present findings suggest a distinct positive effect of rGH on protein synthesis in catabolic patients receiving a moderate intake of nitrogen and calories. This is achieved by modulation of amino acid oxidation. The acute effect of intravenous (IV) nutrients on protein metabolism during the catabolic phase of surgical stress caused a direct decrease in protein breakdown with no effect on protein synthesis.
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PMID:Growth hormone modulates amino acid oxidation in the surgical patient: leucine kinetics during the fasted and fed state using moderate nitrogenous and caloric diet and recombinant human growth hormone. 900 64

Future effective therapies for hepatic metastases may depend on a better understanding of perfusion to these tumors. The purpose of this project was to define blood flow to colorectal cancer liver metastases using quantitative autoradiography (QAR). Liver tumors were established in F1 hybrids of WF x BN rats by intrasplenic injection of a DMH-induced rat colon adenocarcinoma. Rats underwent laparotomy 4-5 weeks later and [14C]iodoantipyrine (a radiotracer) was infused via the hepatic artery (HA) or portal vein (PV). Livers were harvested, frozen in liquid nitrogen, and sectioned at 20 microns through all tumors. QAR compared optical density of cross sections of tumors to surrounding normal liver tissue. Tumor:liver perfusion ratios (T/L PR) and tumor center:tumor periphery perfusion ratios (C/P PR) were calculated. All groups were analyzed with regard to tumor location and size. Seventy-seven tumors in 6 rats in the HA infusion group were analyzed; 74 tumors in 8 rats in the PV group were analyzed. Statistical analysis was by repeated measures analysis of variance. Mean HA T/L PR = 0.97 +/- 0.13, mean PV T/L PR = 0.25 +/- 0.11. Mean HA T/L PR for deep tumors was 1.38 +/- 0.17 and for superficial tumors was 0.57 +/- 0.15 (P < 0.01). Mean HA T/L PR for small tumors was 1.09 +/- 0.12 and for large tumors was 0.86 +/- 0.21 (P = 0.27). Mean PV T/L PR for deep tumors was 0.27 +/- 0.14 and for superficial tumors was 0.24 +/- 0.15 (P = 0.71). Mean PV T/L PR for small tumors was 0.31 +/- 0.15 and for large tumors was 0.20 +/- 0.14 (P = 0.54). Mean HA C/P PR = 1.15 +/- 0.15, mean PV C/P PR = 0.81 +/- 0.14 (P = 0.06). Mean HA C/P PR for small tumors was 1.37 +/- 0.16 and for large tumors was 0.92 +/- 0.17 (P = 0.01). Mean PV C/P PR for small tumors was 0.78 +/- 0.18 and for large tumors was 0.72 +/- 0.13 (P = 0.71). HA perfusion of tumors is significantly higher than PV perfusion compared to surrounding normal liver tissue. HA perfusion varies significantly depending on tumor location. There was a trend toward HA perfusion to the tumor center being slightly greater than to the periphery whereas the reverse was seen for PV perfusion. Tumor size did not affect overall perfusion but it did affect regional HA tumor perfusion.
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PMID:Perfusion to colorectal cancer liver metastases is not uniform and depends on tumor location and feeding vessel. 907 65

Twelve otherwise healthy patients undergoing elective surgery for resection of rectosigmoid adenocarcinoma were randomly allocated to two groups: one group receiving intravenous dextrose 5% 600 to 800 kcal.d-1 (DX, n = 6) and the other group receiving the same amount of dextrose intravenously plus recombinant human growth hormone (DX + rGH, n = 6). Supplementation with rGH started on the day of surgery and continued postoperatively for 5 days. No nitrogen was provided in the diet. This regimen was started 3 days before surgery and continued for 5 days after surgery. Protein kinetics were studied over a period of 8 hours in all patients. Following an overnight fast, a primed constant infusion of L-[1-13C]leucine was maintained for 4 hours (fasted state) and continued for a further 4 hours (fed state) during which 5% beet dextrose (low 13C content) with or without rGH was administered. The isotope studies were performed on the day before surgery and 6 days after surgery. Other measurements included urinary nitrogen excretion, gaseous exchange, and plasma concentrations of insulin, GH, and insulin-like growth factor-I (IGF-I). Addition of rGH to the dextrose diet had a significant positive effect on protein synthesis (P = .02). Surgery was responsible for a significant increase in postoperative whole-body protein breakdown and synthesis and leucine oxidation (P < .01), although lesser changes were observed in the DX group. An interaction between rGH and surgery was associated with a significant increase in protein synthesis (P = .009), but not with changes in either protein breakdown or leucine oxidation. Carbohydrate provision in the form of beet dextrose during the fed state of the isotopic study did not attenuate the significant decrease in protein synthesis (P = .01) or breakdown (P = .003) either before or after surgery, probably reflecting the absence of nitrogen in the diet. No significant interaction was found between rGH and feeding. These results of leucine kinetics indicate that addition of rGH to a low-dextrose intake in the absence of dietary nitrogen can actually promote protein synthesis. The low levels of leucine oxidation could be explained by the fact that amino acids resulting from protein degradation were directed preferentially toward resynthesis of new proteins rather than to oxidative pathways. There was a significant increase in plasma insulin and GH in the group receiving rGH (P < .05). The postoperative plasma concentration of IGF-I did not change in the latter group compared with the DX group, in which IGF-I concentration decreased significantly (P < .05) as part of the response to combined surgery and dietary restriction. Although both IGF-I and insulin are independently capable of stimulating protein synthesis, elevated levels of either hormone or GH itself may primarily modulate protein synthesis, even with a low intake of carbohydrates.
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PMID:A nitrogen-free hypocaloric diet and recombinant human growth hormone stimulate postoperative protein synthesis: fasted and fed leucine kinetics in the surgical patient. 922 34

A series of combretastatin A-4 (CA-4) analogues were synthesized, and their cytotoxic effects against murine Colon 26 adenocarcinoma and inhibitory activity on tubulin polymerization were evaluated. Since CA-4 has limited aqueous solubility, the target compounds were designed to improve solubility by introduction of a nitrogen-containing group. Among the compounds synthesized, those with an amino moiety in place of the phenolic OH of CA-4 showed potent antitubulin activity and cytotoxicity against murine Colon 26 adenocarcinoma in vitro. Some of the compounds which were potent in vitro were evaluated in the murine tumor model Colon 26 in vivo. Among these, 13bHCl, 21aHCl, and 21bHCl showed significant antitumor activity in the animal model, while CA-4 was ineffective. 13bHCl and 21aHCl were further evaluated in two murine tumor models (Colon 38 and 3LL) and human xenografts HCT-15. These compounds showed potent antitumor activity comparable or superior to that of CDDP. The structure-activity relationships of this series of compounds are also discussed.
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PMID:Novel combretastatin analogues effective against murine solid tumors: design and structure-activity relationships. 968 42

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.
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PMID:Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. 974 41

Nitric oxide (NO), an endogenous free radical, has been implicated in a wide range of biological functions. NO is generated enzymatically from the terminal guanidinonitrogen of L-arginine by nitric oxide synthase (NOS). Despite intensive investigations, the role of NO--either as the primary product of the L-arginine/NOS pathway or provided from the NO donor sodium nitroprusside (SNP)--in carcinogenesis and tumour cell growth remains unclear and controversial. The objective of this study was to examine the growth effects of NO on a ductal pancreatic adenocarcinoma in the rat and on a human pancreatic tumour cell line (HA-hpc2). In vivo, both SNP and endogenous induction of NO by endotoxins [lipopolysaccharide (LPS)] plus L-arginine significantly reduced the tumour growth. To investigate the mechanisms of NO anti-tumour growth action, the effects of either the SNP or L-arginine/NOS pathway were analysed on the HA-hpc2 cell line. Nitrite/nitrate production, NOS activity and iNOS expression [assessed by reverse transcription-polymerase chain reaction (RT-PCR)] were tested and related to growth (assessed by [3H]thymidine incorporation assay) and apoptosis (assessed by internucleosomal DNA cleavage). SNP exerted a dual effect on tumour cells: stimulation of the proliferation up to 1 mM and inhibition at higher concentrations. These effects were related to NO production. Both proliferative and cytostatic responses were inhibited by NO scavenger 2-phenyl-4,4,5,5-tetramethyl-hemidazoline-1-oxyl3-oxide (carboxy-PTIO). The marked apoptotic DNA fragmentation induced by SNP was also abolished by PTIO association. Unlike macrophages, the human pancreatic tumour cells did not seem to express intrinsically the L-arginine/NOS pathway. Macrophages were activated by HA-hpc2 cells as well as by LPS plus cytokines [interleukin (IL)-1beta plus tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma]. In HA-hpc2/macrophage co-cultures, NOS activity and inducible NOS (iNOS) transcription were stimulated, whereas an antiproliferative response was observed. These effects were related to both macrophage amount and NO production. Addition of LPS plus cytokines to co-cultures doubled iNOS activity, nitrite/nitrate production and tumoricidal effect. These data suggest the involvement of NO in pancreatic tumour growth and support the fact that generation of high levels of NO with potential production of endogenous reactive nitrogen intermediates may contribute to induction of apoptosis and tumour growth inhibition.
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PMID:Role of nitric oxide in pancreatic tumour growth: in vivo and in vitro studies. 976 73

When cyclophosphamide (CY) (100-120 mg kg(-1)) was administered intravenously (i.v.) to normal F-344 rats, oliguria occurred over the 5-day observation period. Conversely, in rats bearing matrix metalloproteinase-9 (MMP-9) producing 13762NF mammary adenocarcinoma (MTLn3 clone), polyuria occurred chiefly during the first 24 h after CY treatment. In parallel with urine volume, a decrease in the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was observed during the first 5 days after CY treatment in normal rats, but it increased in MTLn3-bearing rats. No elevation in blood urea nitrogen (BUN) or serum creatinine (Cr) values was observed for either group. Both urine volume and urinary excretion of NAG after CY treatment were lower in rats bearing the MTC clone (lower production of MMP-9) than for those bearing the MTLn3 clone. In the case of treatment with cisplatin (CDDP, 4-6 mg kg(-1)), urine volume, urinary NAG excretion and BUN and serum Cr values all increased in normal rats and were all found to be higher in MTLn3-bearing rats than in normal rats. The diuretic response to these drugs in tumour-bearing (TB) rats may be associated with MMP-9 produced by the tumour cells. This report suggests that the nephrotoxicity due to anti-cancer drugs may change when the drugs are used for the treatment of patients bearing a MMP-9-producing tumour.
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PMID:Diuretic response to cyclophosphamide in rats bearing a matrix metalloproteinase-9-producing tumour. 979 46

The cytotoxicities of 6,7-modified-5,8-quinoxalinedione derivatives and heterocyclic quinoxaline derivatives containing nitrogen, sulfur, and oxygen on human lung adenocarcinoma cell (PC 14), human gastric adenocarcinoma cell (MKN 45), and human colon adenocarcinoma cell (colon 205) were examined in vitro using MTT assay. Pyrido[1,2-a]imidazo[4,5-g]quinoxaline-6,11-dione (10) was markedly cytotoxic against MKN 45 compared with adriamycin and cis-platin used as anticancer drugs. The IC50 value of compound 10 was 0.073 microM while those of adriamycin and cis-platin were 0.12 microM and 2.67 microM, respectively.
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PMID:Cytotoxic effects of quinoxaline derivatives on human cancer cell lines. 984 81


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