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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A decrease in renal tubular reabsorption of inorganic phosphate (Pi) can be observed in hypercalcemia of malignancy. In the present study we investigated the effect of serum-free conditioned medium (CM) from cells, derived from a lung carcinoma (BEN) of a hypercalcemic patient, and of PTH on cyclic AMP (cAMP) production and sodium-dependent Pi transport (NaPiT) in epithelia of two renal cell lines. In opossum kidney cells (OK), PTH is known to enhance cAMP production and inhibit NaPiT; in contrast, in LLC-PK1 cells, PTH has no effect on NaPiT since this kidney cell line is devoid of PTH receptors. In OK cells, BEN CM induced a three- to fourfold increase of cAMP production, which was blunted by the PTH inhibitors bPTH(3-34) and bPTH(7-34). NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a dose-dependent manner by BEN CM, with an effect maximal between 1h30 and 6 hr of incubation (40 +/- 4% and 47 +/- 4%, respectively), corresponding to the effect produced by 1-3 nM bPTH(1-34). The Na-dependent transport of a glucose analog was affected neither by BEN CM nor by PTH. In LLC-PK1 cells, neither BEN CM nor PTH altered cAMP production nor NaPiT after 1h30 of incubation. At 6 hr, BEN CM caused a slight decrease in NaPiT. In conclusion, these results constitute the first evidence of a direct and selective inhibition by tumor-derived factor(s) of NaPiT in cultured renal epithelia. Most of the renal NaPiT inhibitory activity produced by the lung tumor required the presence of a PTH receptor-adenylate cyclase system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factor derived from human lung carcinoma associated with hypercalcemia mimics the effects of parathyroid hormone on phosphate transport in cultured renal epithelia. 321 17

Neoplastic tissue in general shows a high rate of glucose consumption under both anaerobic and aerobic conditions. Using positron emission tomography (PET) we measured the rate of uptake of the glucose analogue 18fluoro-2-deoxy-D-glucose (18FDG) in 12 patients with carcinoma of the lung. The tumor types were six squamous cell, two large cell, two oat cell, one adenocarcinoma, and one undifferentiated carcinoma. In each patient a transaxial plane was selected that contained the bulk of the tumor tissue. Regional density and blood volume were measured. Following the intravenous injection of 18FDG, the rates of uptake in the tumor and normal lung tissue were assessed from sequential scans over 1 hour. In each patient the rate of uptake of 18FDG in the tumor tissue was significantly increased relative to normal lung tissue. For the group the rate of uptake by the tumor was 211.4 +/- 69.4 ml/100 g/hr (mean +/- SD) compared to 31.9 +/- 13.2 in the contralateral lung (P less than 0.05). The tumor-to-normal tissue ratio of 6.6 (range, 2.7 to 14.6) was higher than previously reported ratios for brain and liver tumors. In contrast to brain tumors there was little correlation between tumor type and rate of 18FDG uptake. Measurements of glucose metabolism taken in vivo in human pulmonary tumors may lead to advances in screening, staging, and therapy.
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PMID:Glucose utilization in vivo by human pulmonary neoplasms. 349 69

The radiation sensitivity and potentially lethal damage recovery (PLDR) capacity of A549 human lung carcinoma cells have been studied. For unfed monolayer cultures, radiation sensitivity was greater in plateau phase than in log phase of growth. PLDR was observed when plateau-phase cells were held in their own spent medium postirradiation, such that the dose-response curve with 24 h holding was similar to that for log-phase cells plated immediately after irradiation. The high PLDR capacity of A549 plateau-phase cells (recovery factor between 40 and 70 for 24 h holding after 10 Gy) was reduced 10-fold or more by alkalinizing the pH of the spent medium immediately after irradiation from a value of 6.5 +/- 0.1 to a value of 7.6. Medium alkalinization resulted in an increase in the rate of glycolysis, with subsequent reacidification to a pH of 7.3 within 2 h of the pH adjustment. No change in cell cycle distribution was observed in the plateau-phase cultures up to 32 h after change of medium pH, and no increase in cell density was found after 48 h. A slight increase in the rate of incorporation of radiolabeled thymidine into acid-precipitable material was observed at 4 and 24 h after alkalinization of the medium. While it is not possible at present to define a mechanism for this pH effect, our results demonstrate that, at least for this cell line, variables such as medium pH and glucose concentration can profoundly influence the observation of PLDR.
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PMID:The effect of pH on potentially lethal damage recovery in A549 cells. 377 69

Lewis lung carcinoma cells are able to bind sugar residues, mainly alpha-D-glucosyl and alpha-D-mannosyl derivatives as assessed by fluorescent neoglycoproteins binding assay. We have investigated the binding efficiency and shown that: 3LL tumor cells are heterogeneous with regards to their capability to recognize neoglycoproteins, as shown by fluorescence microscopy and flow cytofluorometry analyses; basically two distinct subpopulations could be evidenced which were called glucose-receptor-rich (or glucose-specific lectin-rich, GLR 3LL) and glucose-receptor-poor (or glucose-specific lectin-poor, GLP 3LL) cells; those two subpopulations could be separated on the basis of their binding properties to neoglycoprotein-substituted microcarriers onto which GLR 3LL cells were able to rapidly adhere (2 h) while GLP 3LL cells were not. Some aspects of the biological behavior of these two selected populations were investigated in order to determine the possible involvement of 3LL cell membrane sugar receptors in cell-cell recognition and adhesion to other cells: namely C57 B1/6 mouse pulmonary cells maintained in primary culture. The two 3LL sublines bind to pulmonary cells but their adhesion kinetics were markedly different. Adhesion inhibition studies showed the adhesion process to be dependent upon the specificity of membrane lectins present on both the tumor cell surface (alpha-D-glucose-specific) and on the pulmonary cells (alpha-L-fucose-specific). Surface sugar-specific receptors on mouse pulmonary cells were shown to bind beta-D-galactose-, alpha-L-fucose and alpha-L-rhamnose substituted serum albumin. A neoglycoprotein bearing alpha-L-rhamnose residues was an efficient binder under the conditions of cell adhesion experiments and a potent cell adhesion inhibitor. A fucose-containing neoglycoprotein was shown to have a high inhibitory activity when used concomitantly to alpha-D-glucose-containing neoglycoproteins. Adhesion inhibition experiments, performed with cells the sugar specific receptors of which have been selectively inactivated, showed that the alpha-L-fucose specific receptors on pulmonary cell surface are partly responsible for the specificity of this cell-cell recognition process.
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PMID:Involvement of membrane sugar receptors and membrane glycoconjugates in the adhesion of 3LL cell subpopulations to cultured pulmonary cells. 380 41

Although weight loss has an adverse impact on cancer patient survival, the ability of caloric provision via total parenteral nutrition (TPN) to favorably influence outcome in chemotherapy-treated populations is not established. In randomized trials, no significant improvement in either response or survival was associated with TPN addition to chemotherapeutic treatment of adult patients with lymphoma, sarcoma, colon cancer, adenocarcinoma and small cell carcinoma of the lung, or testicular carcinoma. In two instances, TPN addition was associated with decreased survival, again raising the concern that caloric support in the absence of effective antitumor therapy might stimulate cancer growth. In any event, the hypothesis that nutritional repletion of a malnourished cancer patient receiving chemotherapy will improve clinical outcome remains to be critically tested, as studies demonstrating sequential improvement in lean body mass have not been reported. Most recently, consideration of potential mechanisms underlying the development of cancer cachexia has led to new strategies for nutritional intervention. For example, hypogonadism or low testosterone levels have been described in male patient populations with advanced cancer and correlated with weight loss and adverse outcome, leading to trial of replacement therapy with nandrolone decanoate. Similarly, the frequent identification of abnormal glucose metabolism in the patients with cancer cachexia has stimulated clinical trials with agents such as hydrazine sulfate and insulin designed to reverse the metabolic abnormality. Whether such efforts designed to alter metabolic abnormalities associated with cancer cachexia will improve clinical outcome will be determined in ongoing clinical trials.
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PMID:Critical evaluation of the role of nutritional support with chemotherapy. 391 60

A randomized trial was initiated to compare the effects of peripheral i.v. nutrition (PIVN)-associated chemotherapy (adriamycin, vincristine, VP-16-213, and cyclophosphamide) versus a chemotherapy control group in patients with oat cell lung carcinoma. Thirty-nine evaluable patients were randomized. The test group included 19 patients, whereas 20 were followed in the control group. PIVN was scheduled each day the patient underwent chemotherapy. Each patient received 1,550 kcal day which included 10% glucose, 20% lipids, and amino acids which may or may not have been mixed in the same infusion bottle. The results show ten PIVN patients presently in complete remission at the end of three courses of treatment, compared to nine over the same time period in the chemotherapy control group. Thirty-three percent of patients are still alive after 15 months after the beginning of treatment. There was no significant difference in either general health or side effects, frequency or duration of complete remission, or survival time. After 1 year of treatment, 8 of 19 PIVN patients are still in complete remission, compared to 7 of 20 patients in the control groups.
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PMID:Follow-up of a randomized trial for oat cell carcinoma evaluating the efficacy of peripheral intravenous nutrition (PIVN) as adjunct treatment. 627 49

The endocrine status of 106 patients with undifferentiated small cell carcinoma of the lung was evaluated before treatment was begun. Almost one half of the patients had evidence of abnormal control of the secretion of adrenal cortical steroids, manifested by loss of diurnal rhythmicity or dexamethasone suppressibility. Only two had the clinical syndrome of ectopic ACTH secretion. Evidence of inappropriate secretion of vasopressin was found in 38% of the patients, most of whom also had abnormalities of corticosteroid secretory pattern. About one half of the patients had evidence of abnormal glucose tolerance, and many also had a paradoxical rise of plasma growth hormone concentration after glucose administration. The levels of the other hormones studies were normal. The pattern of hormone abnormality observed in these patients appears to be relatively specific for small cell undifferentiated carcinoma, and is different from that observed in other pulmonary tumors. Patients with abnormal control of plasma cortisol had a worse prognosis than those with normal adrenal function, largely because of decreased response rates to chemotherapy. Other endocrine abnormalities were of no prognostic significance.
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PMID:Endocrine function in small cell undifferentiated carcinoma of the lung. 629 25

Misonidazole, SR-2508, nitrofurazone and other nitroheterocycles stimulated release of 14CO2 from [1-14C]glucose but not from [6-14C]glucose when incubated with mouse Ehrlich ascites cells or human A549 lung carcinoma cells in vitro. This demonstrated that the nitro compounds activated the hexose monophosphate shunt and is evidence that an important pathway of nitro reduction in these cell lines is electron transfer from NADPH-dependent cytochrome c reductase to the nitro group. Shunt activity was stimulated under both aerobic and anaerobic conditions. For catalase-free Ehrlich cells, aerobic effects were greater than anaerobic, indicating that NADPH was used for reduction of H2O2, via GSH peroxidase and reductase, as well as for one-electron nitro reduction, under aerobic conditions. Several of the compounds tested stimulated 14CO2 release from [2-14C]glucose as well as from [1-14C]-glucose. This shows that the cellular requirement for NADPH, in the presence of nitro drug, was great enough to cause recycling of pentose phosphates. Recycling could decrease the availability of ribose-5-P needed for nucleic acid synthesis, which could partly explain the inhibition of DNA synthesis observed upon prolonged aerobic incubation of cells with nitro compounds. Comparison of the rate of disappearance of nitrofurazone from anaerobic A549 cell suspensions with the rate of 14CO2 release suggests that the drug reduction in this cell line was catalyzed almost entirely by NADPH-requiring enzymes.
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PMID:Nitroheterocycle metabolism in mammalian cells. Stimulation of the hexose monophosphate shunt. 642 13

During 1965 to 1968, 80 workers who had been engaged in the production of 2, 4, 5-sodium trichlorphenoxyacetate and butylester of trichlorphenoxyacetate acid became ill. The cause of the illness was 2, 4, 7, 8-tetrachlordibenzo-p-dioxin. A 10-yr study has been conducted for 55 exposed individuals. The majority of the patients developed chloracne, and 11 manifested porphyria cutanea tarda. Approximately one-half of the patients suffered from metabolic disturbances, i.e., pathologically elevated lipids with abnormalities in the lipoprotein spectrum, and two-fifths of the patients had pathological changes in the glucose tolerance test. One-third of the patients had biochemical deviations indicative of a mild liver lesion. Histological examination revealed light steatosis, or periportal fibrosis, or activation of Kupffer cells. Fluorescence of the liver tissues was present in ultraviolet light. In 17 persons symptoms of nervous system focal damage existed, with predominance of peripheral neuron lesion of the lower extremities (verified by EMG examination). The majority of patients suffered from various psychological disorders. As of this date, two patients have died of bronchogenic lung carcinoma; one of liver cirrhosis; one of a rapidly developed, extremely unusual type of atherosclerosis precipue cerebri; and two patients have died in traffic accidents. The conditions of most other patients have improved.
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PMID:The development and prognosis of chronic intoxication by tetrachlordibenzo-p-dioxin in men. 746 93

Radiographic imaging techniques have proved to be of limited value in characterizing chest masses. Likewise, scintigraphic techniques with tumor-seeking single photon emitting agents have shown marginal practical benefit. In contrast, high resolution PET with [F-18]-2-fluoro-2-D-deoxyglucose (FDG) offers a unique opportunity to distinguish benign from malignant processes by determining metabolic characteristics. PET scan results, including graphical analysis of tumor transfer constants (Patlak plot) in 21 patients with primary lung cancer, were compared to clinical outcome (histologic proof or clinical follow-up of longer than 1 year) in 54 patients who had chest masses identified by CT and/or plain film. The patients were categorized into three groups. The first group (N = 23) had primary, unknown, lung masses. Differentiation of benign from malignant tumors by PET had a sensitivity of 100% and a specificity of 67%. The second group (N = 13) had proven lung carcinoma or lymphoma and post-therapy PET scanning for recurrent tumor. In this setting, PET had a sensitivity of 83% and a specificity of 80%. The third group (N = 18) had extrathoracic malignancies and suspected pulmonary metastases. Metastatic lesions were identified with a sensitivity of 87% and specificity of 83%. Glucose uptake by normal tissue is variable and inflammatory/infectious processes can have high FDG uptake and overlap with the glucose uptake of malignant tissue. FDG PET is useful in characterizing chest tumors based on the level of their metabolic activity. Malignant tissue has a high glucose uptake. Elevated FDG uptake by an active inflammatory process may produce overlapping results.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of chest masses by FDG positron emission tomography. 778 82


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