Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By combining two-frequency excitation with 1H NMR STEAM spectroscopy, it is possible to measure two volumes of interest simultaneously without an increase in measuring time compared to single-volume STEAM. Spatial selectivity and spectral resolution of this approach are demonstrated for test solutions and for human 1H NMR brain spectroscopy. First results with a tumor patient are also presented.
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PMID:Two-volume acquisition in image-guided proton spectroscopy. 216 8

We have obtained localized, water-suppressed proton magnetic resonance spectra from eleven astrocytomas in vivo. Localized phosphorus spectra were also obtained from three of these tumors. All tumors were examined prior to surgery, radiotherapy or chemotherapy. Examinations were performed with a commercially available 1.5 Tesla combined imaging and spectroscopy system using a stimulated echo pulse sequence for protons and an ISIS pulse sequence for phosphorus. A relatively high lactate resonance intensity correlated with a more malignant histological tumor grade and more aggressive behaviour. The resonance intensity of N-acetylaspartate/creatine was decreased and choline/creatine was increased, but these did not reliably discriminate between tumor grades. Other unidentified resonances not present in spectra of normal brain were sometimes seen. Proton magnetic resonance spectroscopy provides a new method for determining the metabolic behaviour of astrocytomas that may be useful in the clinical assessment of patients with these tumors.
NMR Biomed 1990 Aug
PMID:Proton and phosphorus magnetic resonance spectroscopy of human astrocytomas in vivo. Preliminary observations on tumor grading. 216 42

We have used 31P NMR spectroscopy to study 22 patients with suspected sarcomas prior to any treatment. The spectra are characterized by the same peaks noted in murine tumors. The mean pH was 7.14 +/- 0.08 and PCr/Pi was 1.18 +/- 0.83. Comparison of pH and PCr/Pi ratios in human and a murine tumor with a low hypoxic cell fraction revealed no significant differences. Six patients subsequently received chemotherapy and three responded to therapy (based on pathologic examination and/or tumor reduction greater than 50%). The three responding patients were noted to have significantly lower PDE/PME in their pretreatment spectra than the three nonresponding patients. The three responding patients with sarcomas also showed a rise of greater than 100% in PDE/PME during the first cycle of therapy. Two of the responding patients had an increase of 0.37 pH units during this interval, which was not detected in the nonresponding patients. These data suggest that 31P NMR spectroscopy may be a useful prognostic indicator in conjunction with other clinical parameters.
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PMID:31P NMR spectra of extremity sarcomas: diversity of metabolic profiles and changes in response to chemotherapy. 217 8

Imaging methods are essential in the diagnosis of erectile dysfunction. With sonography the penile cavernous tissue and the deep arteries can be shown. This visualization is optimized by high-resolution ultrasonography with pulsed Doppler spectrum analysis or angiodynography. Pharmacocavernosonography combined with pharmacocavernosometry is the method of choice to verify pathologic venous leakage from the penis. Phalloarteriography is absolutely necessary before surgery for revascularization of the penis. In investigations of fertility sonography of the scrotum only plays a subordinate role, as an occlusion of the epididymis cannot be diagnosed in this way. In contrast, good visualization of any small intraparenchymous tumor of the testicle is possible. Transrectal sonography allows the best assessment of the vesicular glands. A persisting varicocele is visualized by retrograde phlebography of the internal spermatic vein. Antegrade phlebography of the spermatic vein with Valsalva maneuver is used by some workers in preference to the above-mentioned method, but has not yet been fully evaluated. Scrotal thermography can visualize a varicocele in a satisfactory manner. Obstacles to ejaculation can sometimes be visualized with retrograde urethrography and/or voiding urethrography. Focused x-rays of the sella turcica are necessary if there is any suspicion of a prolactinoma. Mammography will help to differentiate between gynecomasty and alimentary pseudo-gynecomasty. CT and NMR are used to diagnose tumors of the adrenal and pituitary glands; these methods are rarely used to diagnose abdominal cryptorchidism. Radiologic representation of the ductus deferens with contrast medium (vasography) now has to be rejected as harmful and obsolete.
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PMID:[Diagnostic imaging in male reproductive medicine]. 220 Jan 92

The reoperation of patients with recurrence of cerebral glioma is a technique offering survival with a good quality of life. The accepted criteria are a Karnofski index until reoperation greater than or equal to 70, young age, and a favourable histologic grade of tumor. NMR offers better sensitivity than other neuroimaging techniques for the detection of tumoral extension, local and at a distance, and allows a good tumoral resection. We report a patient with recurrence of a cerebral astrocytoma grade II with the criteria for reoperation, but when we performed NMR a dissemination of the tumor to the posterior fossa was seen, and reoperation was consequently counter-indicated. We discuss the mechanism of the extension of cerebral gliomas, the value of neuroimaging techniques and the role of reoperation in this context. We consider it necessary to perform NMR prior to reoperation in this special group of patients with a cerebral glioma recurrence.
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PMID:[Reintervention in gliomas: the necessity of nuclear magnetic resonance]. 224 70

Several halogenated alkenes are nephrotoxic; some others induce renal tubular adenocarcinomas in rodents after lifelong administration. A bioactivation mechanism accounting for the organ-selective tumor induction has been elucidated: conjugation of the parent compounds with glutathione (GSH), catalyzed by hepatic GSH S-transferases, results in the formation of haloalkyl and halovinyl glutathione S-conjugates. Formation of S-conjugates (identified by NMR and mass spectrometry) could be demonstrated with trichloroethene, tetrachloroethene, hexachlorobutadiene, perfluoropropene, trichlorotrifluoropropene, and dichloroacetylene in incubations with rat liver microsomes and in the isolated perfused rat liver. The GSH conjugates formed are eliminated from the rat liver with the bile and may be translocated to the kidney, intact or after metabolism to the corresponding cysteine S-conjugates that are metabolized in the kidney by renal tubular cysteine conjugate beta-lyase (beta-lyase) to reactive intermediates, most likely thioacylchlorides and thioketenes. Interaction of these potent electrophiles with DNA [demonstrated for intermediates formed from S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine] causes mutagenicity in bacteria, genotoxicity in cultured renal cells, and cytotoxicity in kidney cells. As an alternative to beta-lyase-catalyzed cleavage, the cysteine S-conjugates may be acetylated to the corresponding mercapturic acids, which have been identified in urine. The ability of the kidney to concentrate GSH and cysteine S-conjugates and the intensive metabolism of GSH S-conjugates to cysteine S-conjugates in this organ are evidently responsible for the organotropic carcinogenicity.
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PMID:A mechanism of haloalkene-induced renal carcinogenesis. 227 3

We have developed a system for the perfusion of a stirred suspension of multicellular spheroids during nuclear magnetic resonance spectroscopy. Measurement of the medium temperature, pH, oxygen tension, and glucose and lactate concentrations demonstrated that the macroenvironmental conditions around the spheroids during perfusion matched those in standard spinner culture flasks. Spheroids cultured in the NMR perfusion chamber for up to 48 h were virtually identical to spheroids cultured under standard conditions in terms of volume and cell number growth, the extent of central necrosis, cellular clonogenicity, and proliferative status. To avoid problems in interpreting the NMR spectra, we have used a medium containing 10% of the normal inorganic phosphate concentration; comparative growth and NMR studies showed that this medium had no effect on the results reported. 31P NMR spectroscopic analysis demonstrated that the mean pH, nucleotide triphosphate (NTP) to inorganic phosphate (Pi) ratio, the total amount of NTP, and the total energy charge were essentially constant over 8 h of analysis. Stopping the stirring of the spheroid culture during analysis resulted in depletion of the nucleotide phosphate pool in 30 min, with an accumulation of Pi and a shift to a more acid intracellular pH. This effect could be reversed if stirring was resumed within 30 min. Stopping the perfusion while maintaining stirring resulted in a deterioration of the 31P spectra until no high energy phosphates remained at 120 min and the pH fell to approximately 6. This effect was also partially reversible after 30 min of reperfusion, with recovery to a normal 31P spectrum requiring 10 h. The combination of the spheroid model system with 31P NMR spectroscopic analysis will provide a powerful tool for investigating basic questions about the regulation of tumor cell energy metabolism and viability.
NMR Biomed 1990 Oct
PMID:A system for viably maintaining a stirred suspension of multicellular spheroids during NMR spectroscopy. 228 58

A series of platinum complexes of the form cis-M[PtA2(PC)] (I) has been prepared and tested for antitumor activity in mice. Compounds in this series contain either two monodentate amine ligands (A), such as NH3 or isopropylamine, or one bidentate diamine (A2), such as ethylenediamine, 1,2-diaminopropane, or 1,2-diaminocyclohexane. The PC ligand is a bidentate, O-bound, phosphono carboxylate chelate of the form -O2C(CR1R2)nPO3-, where n = 0 or 1 and R1 and R2 are chosen from H, methyl, ethyl, propyl, butyl, phenyl, or pentanoic acid substituents. The resulting complexes (I) were prepared as the free acids (M = H) or as sodium salts (M = Na). Members of this series have demonstrated good activity in a number of tumor screens. A total of 18 platinum-phosphono carboxylate (Pt-PC) complexes were tested against Sarcoma 180 ascites (S180a) in CFW mice, with 13 analogues showing activity above the 50% ILS level. Antitumor activity was also observed vs L1210 leukemia in CDF1 mice, where six of the 12 compounds tested gave ILS values in the 60-160% range, and vs M5076 reticulum cell sarcoma (sc tumor, iv drug), where four of the four compounds tested gave ILS and T-C values comparable to that of cisplatin. Each of the Pt-PC complexes was characterized by NMR (195Pt, 13C, and 31P), HPLC, and elemental analysis. These compounds, which are anionic at neutral pH, display excellent solubility and stability in aqueous media, such as phosphate-buffered saline and fetal calf serum. On the basis of a comparative study of BUN and serum creatinine levels in treated mice, representative complexes from this series are also less kidney toxic than cisplatin. The results of these studies demonstrate that the platinum-phosphono carboxylate complexes are a promising new class of antitumor agents.
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PMID:cis-diamineplatinum (II) complexes containing phosphono carboxylate ligands as antitumor agents. 229 7

The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19F NMR spectroscopy. The human studies were conducted in a 1.5-T Magnetom magnetic resonance imager (Siemens), and the rabbit studies were conducted in a 4.7-T GE/Nicolet 33-cm bore magnet. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism we had previously documented using 19F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. In this initial experience, patient response to chemotherapy may correlate with extent of trapping free 5FU in the human tumors. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients).
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PMID:Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits. 229 5

A structural comparison between the synthetic, tumor-associated 19-9 tetrasaccharide, NeuAc alpha 2----3Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 and its Lea blood group antigen component, Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 was carried out by two-dimensional 1H NMR spectroscopy and hard-sphere energy calculations. Significant chemical shift differences between the two molecules were detected only for protons at or near the linkage site of NeuAc to the Lea trisaccharide core. Coupling constants for the ring protons of both molecules did not suggest major deviation from the 4C1 chair conformation for Gal and GlcNAc, the 1C4 conformation for Fuc, or the 2C5 conformation for NeuAc. Two-dimensional nuclear Overhauser enhancement experiments revealed through-space, inter-proton interactions that corresponded to some extent with those predicted by diffraction data and hard-sphere energy minimization programs for both saccharides. However, a significant number of interactions did not obey the distance dependence predicted from a rigid structure model. These data suggest that, while the average conformation of the 19-9 antigen's Lea core may be invariant to NeuAc alpha 2----3Gal linkage, the dynamics of the Lea trisaccharide are altered upon sialylation. Data also indicate that the terminal NeuAc linkage is more flexible than the inter-residue bonds of the core trisacharide. This analysis, in combination with the fact that the monoclonal anti-19-9 antibody CO 19-9 does not cross-react with the Lea antigen, provides evidence in favor of NeuAc as an epitope-creating unit involved directly at the antibody binding site. However, given the possible role of variable dynamics in epitope formation, these results do not preclude crucial roles in antibody recognition for regions on the 19-9 antigen that are distanced from NeuAc.
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PMID:Conformational analysis of the tumor-associated carbohydrate antigen 19-9 and its Lea blood group antigen component as related to the specificity of monoclonal antibody CO19-9. 229 37


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