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)

The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
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PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

Ecteinascidins (Ets), isolated from the Caribbean tunicate Ecteinascidia turbinata, protect mice in vivo against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts. Crystal structures of two tris(tetrahydroisoquinoline) Ets were investigated with single crystals of the 21-O-methyl-N12-formyl derivative of Et 729 and the natural N12-oxide of Et 743. Representatives of an additional class of Ets, Et 722 and Et 736, isolated from the same organism, were assigned tetrahydro-beta-carboline-substituted bis(tetrahydroisoquinoline) structures by NMR and fast atom bombardment MS spectra.
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PMID:Additional antitumor ecteinascidins from a Caribbean tunicate: crystal structures and activities in vivo. 145 34

Four bi-antennary glycan fractions of the N-acetyllactosamine-type, derived from a Lewis lung carcinoma (LL2) cell subline resistant to the Aleuria aurantia agglutinin were studied by 400 MHz 1H-NMR spectroscopy. By this method, their antennae were found to be terminated either by alpha(2-3 or 6)-linked N-acetylneuraminic acid or alpha(1-3)-linked galactose residues. The primary structure of glycans of these four glycopeptide or derived oligosaccharide-alditols has been determined in full detail.
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PMID:Structures of the alpha(1-3)-galactose-containing asparagine-linked glycans of a Lewis lung carcinoma cell subline resistant to Aleuria aurantia agglutinin: elucidation by 1H-NMR spectroscopy. 166 29

In 158 plasma samples, obtained from patients with lung carcinoma, lung metastases, and infectious or inflammatory lung diseases and from healthy controls, the NMR relaxation times T1 and T2 of water protons were measured at a resonance frequency of 20 MHz by pulsed NMR techniques and adjusted to a standardized total plasma protein concentration. For one-third of these samples water-suppressed 500-MHz 1H NMR spectroscopy at 37 degrees C was used (a) to determine the widths of the composite lipid methyl and methylene signals, and (b) to quantitate individual lipid methylene signal components that could be detected in resolution-enhanced spectra. In addition, hematological parameters and the plasma levels of several acute phase proteins and apolipoprotein-A were monitored. No diagnostically significant differences between lung carcinoma patients and patients with nonmalignant lung disease could be found for any of the plasma NMR parameters, nor could T1 or lipid linewidth data distinguish between any patient group and healthy controls. However, the mean T2 was significantly shortened by about 15% for any kind of lung disease compared to healthy controls. Similar but less significant results were found for apolipoprotein-A levels. A linear discriminant function, calculated from the apolipoprotein-A and T2 data, did not improve the differentiation between malignant and nonmalignant lung disease but did improve the discrimination between tumor patients and healthy controls up to a sensitivity and specificity of 80 and 96.5%, respectively. T2 correlates inversely with plasma fibrinogen levels and the blood sedimentation rate and, therefore, appears to monitor a general inflammatory status of a tumor patient rather than the presence or absence of cancer. For all groups except healthy pregnant women, the lipid methylene composite signal linewidth correlates inversely with the fraction of mobile triglyceride present (mainly as VLDL), as estimated from resolution-enhanced spectra.
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PMID:Investigations concerning the potential for using 1H NMR relaxometry or high-resolution spectroscopy of plasma as a screening test for malignant lung disease. 231 28

As an alternative to naturally occurring pyrrolo[2,1-c][1,4]benzodiazepines (e.g., antramycin) which possess properties of DNA alkylation, we have designed several antileukemic chromeno[4,3-b][1,5]benzodiazepine derivatives with potential activity toward leukemia cell membranes and the cyclic nucleotide system. The cis and trans diastereoisomers were characterized by NMR. The absolute configurations of the enantiomers were established by X-ray diffraction and circular dichroism (CD) measurements. By means of absorption spectroscopy and determinations of fluorescence and fluorescence decay, it was found that the cancerostatically active compound (+)(6aR, 13aS)-3,4-dimethoxy-10,11-dimethyl-6,6a,7,8,13, 13a-hexahydrochromeno[4,3-b][1,5]benzodiazepine (ZIMET 54/79) and its biologically inactive (-) enantiomer (ZIMET 55/79) interact with liposomal membranes. At pH values of 6.0 and 7.3 the long-wave absorption bands of these agents showed weak bathochromic and hypochromic effects upon addition of neutral, and positively and negatively charged phosphatidylcholine and phosphatidylcholine/cholesterol liposomes. Such spectral changes are interpreted as resulting from the binding of both agents to phospholipid bilayers. Steady-state determinations using the membrane probe 1-anilino-8-naphthalenesulfonic acid (1,8-ANS) led to the observation of a small decrease in fluorescence intensity in the presence of either agent. Time-resolved measurements demonstrate that the mechanism of action of the agents occurs mainly through the partial displacement of probe molecules from regions of hydrophobic binding to areas of greater solvent accessibility. No significant differences in binding between the cancerostatically active and inactive enantiomers with liposomes (archiral systems) were detectable on the basis of spectrophotometric and fluorescence determinations. Cell membrane bound adenylate cyclase is stimulated by ZIMET 54/79, resulting in an increase of 103% in the level of cAMP in mouse L1210 leukemia cells. On examination of structure-activity relationships, it was found that the biological activity (leukemia L1210, P388, Lewis lung carcinoma, melanoma B16, increase in cAMP) is correlated with the particular configuration (6aR,13aS) and type of substituent at positions 3 and 4 of the benzo ring in the case of alkoxy groups and positions 10 and 11 for methyl groups. No activity was detected toward DNA/RNA using microbial test systems.
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PMID:Physiochemical characterization of substituted chromeno[4,3-b][1,5]benzodiazepine stereoisomers designed as cell membrane active antitumor agents. 239 75

High-quality, high-resolution, proton-decoupled natural-abundance 13C NMR spectra have been obtained in vitro at 100.6 MHz from unprocessed human pathology specimens of tumors and adjacent nonneoplastic control tissues from lung, colon, and prostate. In these preliminary studies, specific molecular parameters were identified from the spectra that distinguished neoplastic from nonneoplastic tissue of a given organ in all sites studied. The NMR results were congruent with data derived from histochemical and biochemical examinations of the tissues and with previous studies using non-NMR methods. In particular, a comparison of the spectra of prostatic adenocarcinoma with that of adjacent hyperplastic tissue revealed the following differences: The tumors contained (1) larger amounts of triacylglycerols, (2) smaller amounts of citrate, and (3) acidic mucins. These transformation-associated deviations from the normally high amounts of citrate and low amounts of lipids in the prostate are consistent with an alteration in either the concentration or the activity of ATP-citrate lyase in the tumors. The 13C NMR spectra of colonic adenocarcinoma tissue showed that this tumor type contained (1) smaller signals from triacylglycerols, (2) larger signals from phospholipids and lactate, and (3) decreased lipid fatty acyl chain saturation, when compared to spectra from adjacent normal colon. Colloid carcinoma, another variant of colonic carcinoma, showed prominent 13C resonances from glycoproteins, which were absent from the spectra of normal colon, and from spectra from the more common pattern of colonic adenocarcinoma. Smaller 13C NMR signals from mucins and other proteins, and the presence of triacylglycerol signals distinguished poorly differentiated lung carcinoma and from nonmalignant lung tissue. These results indicate that natural-abundance 13C NMR spectroscopy may constitute a unique, nondestructive method, for the simultaneous measurement of a large number of tissue metabolites and structural components of significance to the study and diagnosis of a wide range of human tumors.
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PMID:Differentiation of human tumors from nonmalignant tissue by natural-abundance 13C NMR spectroscopy. 245 80

Clinical, echographic, radiological (CT, NMR), and histopathological findings in a 57-year-old male patient who presented with proptosis of the left eye and diplopia caused by a histologically proven metastasis of a clinically silent small-cell carcinoma of the lung. Echographic problems of the differential diagnosis of orbital metastases are discussed.
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PMID:[Echographic findings in metastization in an extraocular muscle]. 282 18

NMR proton spin-lattice (T1) and spin-spin (T2) relaxation times were measured ex vivo on Lewis lung carcinoma after in vivo single irradiation with an absorbed dose of 4 Gy. The results were compared to tumoural volume evolution, pathological examinations, and cell kinetic measurements. Tumour growth decreased between the third and the sixth day after irradiation while relaxation times, especially T1, is increased 2 days before the clinical recurrence of the tumour is observed. Pathological morphometric measurements tempted to show that necrosis is less extended after irradiation. Cell cycle analysis demonstrated the G2/M phase blockade by radiation after one day, and its release 4 days later. These phenomena could be important for in vivo radiotherapy follow-up using determination of relaxation times by magnetic resonance imaging (MRI).
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PMID:Proton NMR relaxation times of experimental Lewis lung carcinoma after irradiation. 318 71

1. 2-Fluoroputrescine has a high affinity for spermidine synthase (Km 12 microM) and obeys normal Michaelis-Menten kinetics. 2. The only product of the spermidine synthase-catalysed aminopropylation of 2-fluoroputrescine is 6-fluorospermidine. Formation of the isomeric 7-fluorospermidine could not be detected. 3. 2,2-Difluoroputrescine has even a higher affinity for spermidine synthase than putrescine and 2-fluoroputrescine; however, at concentrations greater than 25 microM one observes inhibition of the aminopropylation reaction. 4. Competition experiments between putrescine and 2,2-difluoroputrescine revealed mixed type inhibition. 5. HTC cells in suspension culture incorporated only small amounts of 2-fluoroputrescine, and even less in the case of 2,2-difluoroputrescine, if they were exposed to 10 microM concentrations of these diamines for up to 24 hr. However, in the presence of 0.5 mM DFMO, a concentration not sufficient to decrease cell growth significantly, but sufficient to decrease cellular putrescine and spermidine concentrations, the uptake of the chain-fluorinated diamines and their transformation into the fluorinated polyamine analogues was dramatically enhanced. In comparison with the difluoro analogues the accumulation rate of monofluoropolyamines was greater by a factor of about two. 6. 6-Fluorospermidine and 6-fluorospermine could be detected in significant quantities in nearly all tissues of mice 48 hr after a single dose (500 mg/kg) of 2-fluoroputrescine. In an analogous experiment with 2,2-difluoroputrescine, the formation of chain-fluorinated polyamines was considerably smaller. 7. Pretreatment of Lewis lung carcinoma bearing C57BL mice with alpha-difluoromethylornithine enhanced the incorporation of 2-fluoroputrescine into all organs, except the brain. Tumor and small intestines showed by far the highest accumulation of 6-fluoropolyamines. 8. Under identical experimental conditions the accumulation of chain-fluorinated polyamines in tumor tissue was more than twice as high with 2-fluoroputrescine as precursor than with the same dose of 2,2-difluoroputrescine. In normal tissues the difference between the uptake of 2-fluoroputrescine and 2,2-difluoroputrescine was usually even greater. 9. From the fact that the accumulation of 6-fluoropolyamines is less selective in tumors than that of 6,6-difluoropolyamines, and from the lower detection sensitivity due to its lower fluorine content, we conclude that 2,2-difluoroputrescine is more advantageous as a tumor marker than 2-fluoroputrescine for detection with 19F-NMR spectroscopy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chain-fluorinated polyamines as tumor markers--IV. Comparison of 2-fluoroputrescine and 2,2-difluoroputrescine as substrates of spermidine synthase in vitro and in vivo. 324 83

The T1 and T2 NMR relaxation times of water protons in plasma, obtained from patients with lung carcinoma, healthy volunteers, and patients with nontumor diseases were measured at a resonance frequency of 20 MHz. Additionally hematologic parameters were determined. In tumor patients the mean plasma T2 was shortened by about 20%, and an increase in the blood sedimentation rate (BSR) was noted. Similar but less pronounced results were found for the nontumor group of patients, indicating that the shortening of T2 in plasma is a secondary host response. However, a plot of plasma 1/T2 versus BSR from tumor patients showed a significant correlation between these two parameters. No such correlation could be detected in the nontumor group of patients. The correlation of 1/T2 with BSR, found solely in the tumor patient group, increased the diagnostic sensitivity of T2 measurements and may help to differentiate between malignant and nonmalignant disease. No significant variation in the T1 spin-lattice relaxation time was observed.
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PMID:NMR relaxation times T1 and T2 of water in plasma from patients with lung carcinoma: correlation of T2 with blood sedimentation rate. 343 14


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