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)

Two mechanisms are discussed regarding etiology and pathogenesis: the direct mechanism by radioeffect on teeth, lying in irradiation field, and the indirect mechanism by alteration of the secretion from salivary glands (hypo- and dyssalivation, xerostomia), alteration of the physiological mouth-flora (dominance of Streptococcus mutans) and deficient mouth and tooth hygiene by the patients. Clinically four types of radiogenic tooth defects are discerned: the superficial carious destruction of the necks of the teeth, the change of the tooth-colour to brown-black, an early gradual fuse of the edges and occlusal plane of teeth and generalised superficial defects. With the tumor diagnosis and before the beginning of radiotherapy a total dental examination of the whole mouth-cavity is to do. The therapeutic measures conform to the dimension of dental caries and the bone reduction in consequence of parodontopathies. On principle as many teeth as possible are restored and preserved, only all teeth, that can not be restored in fact and have an uncertain prognosis, are extracted selectively considering a most careful atraumatic surgical technique. The programme for mouth hygienics and tooth prophylaxis carrying out during and for many years after radiotherapy includes a careful and routine cleaning of teeth of films and tartar, frequent rinsing of the mouth with Bepanthene-, Subcutin- or sodium chloride-sodium bicarbonate solution, daily fluoride-dose by mean of fluorine gel or gel carrier, a thorough instruction and motivation of the patients and an after-care in short intervals, to recognize a reduction of cooperation, to diagnose complications as soon as possible and to begin a suitable therapy. Extraction of teeth after radiotherapy was contraindicated absolutely in the past because of the risk of following osteoradionecroses. Recent reports however show, that the risk of a postradiotherapeutic tooth extraction is not so high as suspected primarily, if the indication is paid attention to and the extraction is done according respected technical regulations. Special care has to be given to manufacture and fitting in artificial teeth. It has not to be done until all essential therapeutic effects are eased off, that usually occurs 1 to 1 1/2 years after the end of therapy.
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PMID:[Radiation caries]. 267 77

New reactions of methyl 2,2-difluoro glycosides are described that were utilized for synthesis of some novel nucleoside derivatives. Thus, treatment of methyl 2-deoxy-2,2-difluoro-3,4-O-isopropylidene-alpha (beta)-D-erythro-pyranoside (2) with anhydrous HCl resulted in selective displacement of one fluorine atom with chlorine to give a 2-deoxy-2-chloro-2-fluoro glycoside 3. Reaction of 3 with silylated uracil in the presence of SnCl4 provided a 2-deoxy-2-fluoro-2-uracil-substituted glycoside 4. 2-Fluoro-2-deoxy glycosides substituted with other pyrimidines at C-2 were prepared similarly by the reaction of acylated 2,2-difluoro or 2-fluoro-2-bromo derivatives (5 and 6, respectively) with silylated pyrimidines. The resulting 2'-fluorinated isonucleosides were evaluated for their antitumor and antiviral activities. Compounds 7a,b, 8a,b, and 10a,b demonstrated 50% tumor cell growth inhibition in vitro (IC50) at 10(-4)-10(-5) M. At similar concentrations no antiviral activity was observed in vitro. Therapeutic activity was obtained with 7a,b and 8a,b in DBA/2 mice with L1210 leukemia. Administration of 7a,b at 500 mg/kg, ip daily, for 5 consecutive days, resulted in a 55% increase in life span (% ILS) while administration of 8a,b in the same manner at 200 mg/kg caused a 29% ILS. Treatment with 7a,b to mice with drug-resistant L1210 sublines (5-FU and araC) resulted in 22 and 57% increases in life span, respectively. Lewis lung carcinoma and M5076 sarcoma in mice also responded to the administration of 7a,b with reductions in tumor growth for both tumors and significant increases in life span in mice with Lewis lung carcinoma. Although the mechanism of action of 7a,b is not known, it has been found to be a relatively fast-acting, cell-cycle nonspecific cytotoxic agent that decreases [3H]deoxyuridine incorporation, blocks L1210 cells at the G2 phase of the cell cycle, and is not reversed by exogenous thymidine. These 2'-fluorinated isonucleosides have demonstrated biological activity and may have potential as antitumor drugs.
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PMID:2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides. 270 26

Feasibility of fluorine-18 labeled L-dopa for melanoma imaging was investigated. In B16 melanoma-bearing mice given 2-[18F]fluoro-L-dopa, the radioactivity in the B16 decreased for the first 60 min and then remained constant, while all other tissues investigated decreased with time. High tumor uptake ratios for all other tissues except for the pancreas were obtained at 120 min. 6-[18F]Fluoro-L-dopa showed a similar tissue distribution. However, the B16 uptake was about half that value for the 2-fluoro analogue. A higher incorporation rate of 2-[18F]fluoro-L-dopa into the acid-precipitable fraction of the melanoma also showed that the 2-[18F]fluoro-L-dopa was a preferable melanin precursor. Among the four kinds of non-melanoma tumors in mice or rats three tumors showed an uptake of 2-[18F]fluoro-L-dopa similar to the B16 at 60 min. However, larger melanoma-to-tissue uptake ratios were observed when compared to non-melanoma tumors.
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PMID:Feasibility study of fluorine-18 labeled dopa for melanoma imaging. 277 77

Positron emission tomography (PET) was used in the follow-up of patients with colorectal malignancies to differentiate between recurrent colorectal tumor and scar. Patients were examined with oxygen-15-labeled water and with fluorine-18-labeled deoxyglucose (FDG). FDG was injected intravenously to assess tumor metabolism. The tracer concentration was quantitatively evaluated by means of a region-of-interest technique and standardized for both injected dose and body volume. Of 29 patients, 21 had recurrent colorectal malignancy, and eight had a nonmalignant mass. All malignancies were seen on the PET cross sections. Nonmalignant lesions had a low FDG accumulation on images obtained 60 minutes after injection. While the tumor-soft tissue ratio was highest shortly after the intravenous injection of FDG, the tumor-scar ratio was highest 60 minutes after injection. It was possible to differentiate tumor from non-malignant tissue with FDG with the use of standardized concentration values and tumor-soft tissue ratios. Imaging with O-15-labeled water gave no additional information.
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PMID:Recurrence of colorectal tumors: PET evaluation. 278 94

A new fluorine-containing anthracycline derivative, ME2303, showed excellent antitumor activity against various experimental tumor models. The i.p. or i.v. administrations of ME2303 on Day 1 or on Days 1, 5, and 9 against i.p.-implanted L1210 leukemia cells rendered more than 50% of mice tumor free at wide ranges of nontoxic doses, whereas the incidence of cure obtained with Adriamycin (ADM) was less than that obtained with ME2303. ME2303 given i.p. or i.v. on Day 1 or Days 1, 5, and 9 was also effective against i.p.-implanted P388 leukemia cells, and higher incidences of cure were obtained than with ADM. ME2303 administered i.v. on Days 1, 8, 15, and 22 showed prominent antitumor activity against s.c.-implanted colon adenocarcinomas 26 and 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma. Against colon adenocarcinoma 26, ME2303 induced cure in 16 of 20 mice at doses of 35 to 71 mumol/kg, whereas no cure was observed with ADM. Significant growth inhibition of colon adenocarcinoma 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma cell lines was also observed at a dose of 18 to 106 mumol/kg. ME2303 was effective against human and murine multidrug-resistant cells in vitro. For example, human myelogenous leukemia K562 resistant to ADM (K562/ADM) was only 2.8-fold more resistant to ME2303, while the cells were 200-fold more resistant to ADM when the values for the concentration of drug required for 50% inhibition of cell growth were compared. ME2303 was also more effective than ADM against human leukemia CCRF-CEM resistant to vinblastine, human ovarian carcinoma A2780 resistant to ADM, human epidermoid carcinoma KB cells resistant to colchicine, and mouse leukemia P388 resistant to ADM and vincristine. Therapeutic effects were obtained in vivo against ADM- and, especially, vincristine-resistant P388 leukemia. ME2303 is one of the most interesting potential antitumor agents to be studied further.
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PMID:A fluorine-containing anthracycline (ME2303) as a new antitumor agent against murine and human tumors and their multidrug-resistant sublines. 279 Jul 78

Computerized tomography (CT) and positron emission tomography (PET) using fluorine-18-deoxyglucose were performed in a patient with malignant glioma over a one-year period. Postoperatively and during radiation therapy, there was slight improvement in metabolic activity in the hemisphere ipsilateral to the tumor. After radiation therapy and during chemotherapy, there was a rapid and then gradual decline in whole brain metabolic rate by 39%. This might have been explained by radiation effect on brain. The tumor area was metabolically similar to the adjacent brain until one year after diagnosis, when an area of abnormal increased activity was noted. Even though CT scans showed minimal evidence of tumour growth, a large glioblastoma multiforme was found at autopsy at the site of the increased activity. Radiation leukoencephalopathy was also observed at autopsy. It is concluded that PET studies may offer new information regarding the metabolic effects of anti-tumor therapy, and may demonstrate regrowth of tumor prior to CT.
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PMID:Sequential computerized tomography and positron emission tomography studies in a patient with malignant glioma. 282 89

Positron emission tomography (PET) with rubidium-82 (82Rb) and fluorine-18-fluorodeoxyglucose (18F-FDG) was used to diagnose active tumor recurrence and to differentiate this from radiation injury after interstitial irradiation of malignant gliomas. Patients were studied when they presented with radiological or clinical deterioration after an initial period of posttreatment stabilization. Forty studies were performed in 34 patients. The 82Rb was used as a blood-brain barrier tracer to localize the lesion. Uptake of 18F-FDG by the lesion was then compared to uptake by adjacent brain in order to make a diagnosis of active tumor recurrence (higher or equal lesion uptake) or no active tumor (lower uptake). Radiation injury was diagnosed by the exclusion of active tumor. A retrospective clinical diagnosis was established in 38 cases by following the patients' progress for 8 to 142 weeks after the PET study. In two cases, no follow-up diagnosis could be determined. The PET results agreed with the follow-up diagnosis in 15 of 17 cases of active tumor and 17 of 21 cases of radiation injury. Histological examination of surgically resected tissue obtained after the PET study was performed in 18 patients (nine with tumor regrowth and nine with radiation injury). This showed apparently viable tumor as well as necrosis in all cases, regardless of eventual clinical outcome. Some cells from the irradiated volume may appear morphologically intact, but have little or no metabolic or clinical activity. The functional nature of the PET-FDG technique allows diagnosis of tumor activity, which cannot be demonstrated by anatomic imaging studies or by histological examination. The addition of a blood-brain barrier tracer to the 18F-FDG study aids in differentiating normal brain uptake from tumor activity and improves the accuracy of the technique.
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PMID:PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome. 284 11

Fluorine-19 NMR spectrometry was used to monitor the metabolism of two antineoplastic fluoropyrimidines, 5-fluorouracil (5FU) and 5'-deoxy-5-fluorouridine (5'dFUrd), in cell cultures of human pancreatic (Capan-1) and colon (HT-29) adenocarcinoma. The preliminary results showed, for the two tumor cell lines treated with 5FU, the presence in nonperfused cells of three signals corresponding to intracellular metabolites: 5FU, F-nucleotides and F-nucleosides. When the cells were perfused only the signals of F-nucleotides and 5FU were present. The F-nucleosides observed during the analysis of the nonperfused cells came from the conversion of F-nucleotides. During the NMR recording of Capan-1 cells at 37 degrees C the first metabolite of the catabolic pathway of 5FU, 5,6-dihydro-5-fluorouracil, occurred. At the beginning of the NMR recording of Capan-1 cells treated with 5'dFUrd, two signals corresponding to F-nucleotides and F-nucleosides (consistent with 5'dFUrd) were observed; during the analysis, a supplementary signal corresponding to 5FU appeared. Even after pretreatment with methotrexate the signal of 5FU incorporated into RNA was not detected. Our experiments, performed in attempts to observe the signal of the ternary complex between thymidylate synthetase (TS), 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and 5,10-methylene-tetrahydrofolate (5,10-CH2FH4), allowed detection in some cases of a broad signal, whose chemical shift was similar to that reported in the literature following incubation of TS with FdUMP and 5,10-CH2FH4, but our results were not always reproducible.
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PMID:Noninvasive fluorine-19 NMR study of fluoropyrimidine metabolism in cell cultures of human pancreatic and colon adenocarcinoma. 294 69

Treatment of laboratory mice and rats with the adrenal steroid, dehydroepiandrosterone (DHEA), produces antiobesity and broad spectrum tumor chemopreventive activity. Certain side effects are associated with DHEA administration which could limit its usefulness as a drug. DHEA can be metabolized into both testosterone and estrone and also increases liver weight and liver catalase activity. We have developed two synthetic steroids, 16 alpha-fluoro-5-androstan-17-one and 16 alpha-fluoro-5 alpha-androstan-17-one, which, unlike DHEA, do not stimulate uterine weight in sexually immature female rats or seminal vesicle weight in castrated male rats, nor stimulate liver weight and liver catalase activity in mice. 16 alpha-Fluoro-5-androsten-17-one is also about three times as potent as DHEA as an antiobesity agent and is more active when administered p.o. in inhibiting [3H]-7,12-dimethylbenz(a)-anthracene binding to skin DNA and tetradecanoylphorbol-13-acetate stimulation of epidermal [3H]thymidine incorporation in the mouse, two effects believed to be important in the tumor preventive action of DHEA. 16 alpha-Fluoro-5 alpha-androstan-17-one is as active as 16 alpha-fluoro-5-androsten-17-one in inhibiting [3H]-7,12-dimethylbenz(a)anthracene binding to skin DNA and tetradecanoylphorbol-13-acetate stimulation in epidermal [3H]thymidine incorporation but, on the contrary, is not more active than DHEA as an antiobesity drug. Compounds such as 16 alpha-fluoro-5-androsten-17-one and 16 alpha-fluoro-5 alpha-androstan-17-one, which lack specific side-effects of DHEA treatment and demonstrate greater potency, may have therapeutic application as drugs for humans.
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PMID:Novel dehydroepiandrosterone analogues with enhanced biological activity and reduced side effects in mice and rats. 297 Feb 93

Treatment of HT29 cells with the tumor promoting phorbol ester PMA resulted in an attenuation of VIP-stimulated cAMP production in intact cells and VIP-stimulated adenylate cyclase activity in cell membranes. PMA did not decrease the ability of cholera toxin and forskolin to elevate cAMP levels in intact cells. Fluoride-stimulated adenylate cyclase activity in HT29 cells homogenates was not affected by PMA. The maximal VIP binding capacity of homogenates prepared from HT29 cells treated with PMA was decreased by 50%. It is concluded that protein kinase C regulates VIP receptor function possibly through phosphorylation of the VIP receptor.
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PMID:Phorbol ester induces loss of VIP stimulation of adenylate cyclase and VIP-binding sites in HT29 cells. 302 47


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