RESUMO
PURPOSE: To evaluate the imaging features of anorectal gastrointestinal stromal tumors (GISTs) with clinical and histopathologic correlation. MATERIALS AND METHODS: In this Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 16 patients (12 men; mean age 66 years (30-89 years)) with pathologically proven anorectal GISTs seen at our institution from January 2001 to July 2011 were identified. Electronic medical records were reviewed to obtain clinical data. Pretreatment imaging studies (computed tomography (CT) in 16 patients, magnetic resonance imaging (MRI) in 9 patients and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT in 8 patients) were evaluated by 2 radiologists until consensus. The location, size and imaging features of the primary tumor and metastases at presentation, if any, were recorded, and correlated with clinical data and pathologic features (histologic type, presence of necrosis, mitotic activity, risk category, immunohistochemical profile). RESULTS: The mean tumor size was 6.9 × 6.0 cm. Of the 16 tumors, 11 (68.7%) were infralevator, 4 (25%) supra and infralevator and 1 (6.3%) supralevator; 9 (56.2%) were exophytic, 6 (37.5%) both exophytic and intraluminal, and 1 (6.3%) was intraluminal. The tumors were iso- to minimally hypoattenuating to muscle on CT, iso- to minimally hypointense on T1-weighted images, hyperintense on T2-weighted images and showed variable enhancement. Necrosis was seen in 4 (25%), and hemorrhage and calcification in 2 (12.5%) patients each. The tumors were FDG avid with a mean maximum standardized uptake value of 11 (8.4-16.8). All tumors were positive for KIT and CD34. Distant metastasis to liver was seen in 1 patient (6.3%) at presentation. CONCLUSION: Anorectal GISTs are well-circumscribed, non-circumferential, predominantly infralevator, intramural or exophytic, FDG-avid, hypoattenuating masses, and present without lymphadenopathy or intestinal obstruction.
Assuntos
Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
In previous studies, we observed decreased uptake of 14C-labeled L-aspartate and L-glutamate in s.c. transplants of several rapidly growing hepatomas relative to that in normal liver. The present report extends these observations to isolated cells and indicates that circulation differences cannot be the major factor. Mean net uptakes for the two dicarboxylic amino acids in cells from the rapidly growing Morris Hepatomas 7288ctc and 7777 were 5 to 26% of corresponding values for normal hepatocytes. Rates for net uptake in Hepatoma 7787 cells were intermediate between those of the rapidly growing hepatomas and hepatocytes, while the rates for Hepatoma 5123C cells and hepatocytes were similar. The contribution of sodium-dependent uptake to the mean total net uptake of [14C]aspartate and [14C]glutamate tended to be higher in hepatoma cells than in hepatocytes. Studies with isolated hepatocytes and Hepatoma 5123C cells showed no significant effect on uptake by 10 mM alpha-(methylamino)isobutyric acid and 10 mM 2-amino-2-carboxybicyclo[2.2.1]heptane. On the other hand, L-cysteic acid, L-alanosine, and N-phosphonacetyl-L-aspartic acid were shown to be effective inhibitors of sodium-dependent uptake in Hepatoma 5123C cells. The data suggest that the A and L systems are not major contributors to the uptake of dicarboxylic amino acids in hepatic cells. It was concluded that decreased uptake of dicarboxylic amino acids in rapidly growing hepatomas may accompany decreased metabolism of these dietary nonessential amino acids.
Assuntos
Aminoácidos Cíclicos , Aminoácidos Dicarboxílicos/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Fígado/metabolismo , Alanina/análogos & derivados , Alanina/farmacologia , Aminoácidos/farmacologia , Ácidos Aminoisobutíricos/análogos & derivados , Ácidos Aminoisobutíricos/farmacologia , Animais , Antibióticos Antineoplásicos/farmacologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacologia , Masculino , Nitrosaminas/farmacologia , Ácido Fosfonoacéticos/análogos & derivados , Ácido Fosfonoacéticos/farmacologia , Ratos , Sódio/fisiologiaRESUMO
In contrast to the increased uptake of amino acids which has been found in many neoplastic cells, we have observed a decrease in the net uptake of [14C]aspartate and [14C]glutamate in rapidly growing hepatomas relative to rat host liver. When measured 10 min after s.c. injection, the radioactivity from 14C-labeled dicarboxylic amino acids was greater in liver than in all other tissues examined (blood, skeletal, muscle, heart, spleen, lung, and brain) except kidney, where there was an approximately 2-fold greater uptake of aspartate and 10-fold greater uptake of glutamate. Mean uptakes in the rapidly growing Morris hepatomas 7288CTC and 7777 were 19 to 26% of corresponding values for the host livers. Comparison with uptake of 3H2O indicated that these low values were not solely due to differences in circulation. Decreased uptake was not accompanied by equivalent decreases in the concentration of aspartate and glutamate in the tumors. There were small changes in the net uptake of these amino acids in the slowly growing hepatoma 7787 and no significant differences in regenerating liver and hepatoma 5123C, a tumor of intermediate growth rate. The net uptake of [14C]arginine and [14C]lysine in the hepatomas was similar to that in host livers, except for a 250% increase in uptake of [14C]lysine in hepatoma 5123C. A decreased uptake of the magnitude seen with dicarboxylic amino acids in rapidly growing hepatomas has not been observed with other amino acids.
Assuntos
Aminoácidos Dicarboxílicos/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Animais , Transporte Biológico , DNA de Neoplasias/metabolismo , Feminino , Neoplasias Hepáticas Experimentais/irrigação sanguínea , Regeneração Hepática , Ratos , Fatores de TempoRESUMO
Thiocyanate was found to resemble cyanate in its inhibitory effects on [3H]thymidine incorporation and the uptake of [32P]phosphate and [3H]amino acids in transplanted tumors of the BUF rat. The capacity to inhibit metabolite uptake in hepatomas and a colon tumor under conditions in which uptake was unchanged or increased in host liver was concluded to be a common feature of the action of cyanate and thiocyanate. Inhibition of [32P]phosphate uptake and [3H]thymidine incorporation into DNA of tumors was also observed after treatment of rats with amygdalin. With this drug, however, the action on tumors and livers of host rats was similar.
Assuntos
Amigdalina/farmacologia , Neoplasias do Colo/tratamento farmacológico , Cianatos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Tiocianatos/farmacologia , Aminoácidos/metabolismo , Animais , Neoplasias do Colo/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Neoplasias Experimentais/tratamento farmacológico , Fosfatos/metabolismo , Ratos , Ratos Endogâmicos BUF , Timidina/metabolismoRESUMO
The nature of soluble factors from liver and hepatomas which inhibit [3H]thymidine incorporation into DNA was studied in Novikoff hepatoma cells. The decreased activity in hepatoma preparations was due to loss of a high-molecular-weight heat-labile factor. Although this factor cochromatographed with arginase activity on Sephadex G-150, it does not appear to result from this activity as judged by the failure of arginine to prevent the inhibitory effect on [3H]thymidine incorporation. Both liver and hepatomas contained a heat-stable factor with inhibitory activity. Studies with ethanol-soluble material suggested that the action was not solely attributable to the presence of unlabeled thymidine, since the apparent molecular weight was too high and since the factor(s) inhibited [3H]leucine incorporation into protein in addition to inhibiting [3H]thymidine incorporation in DNA.
Assuntos
DNA de Neoplasias/biossíntese , Neoplasias Hepáticas Experimentais/metabolismo , Fígado/metabolismo , Animais , Arginase/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Citosol/metabolismo , Feminino , Temperatura Alta , Masculino , Peso Molecular , Ratos , Timidina/metabolismoRESUMO
Injection of L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) at a level of 10 mg/100 g body weight inhibited the incorporation of 3H-labeled amino acids into protein in Morris hepatomas 7777and 9618A2. The degree of inhibition was similar in cytoplasmic proteins and in histone and nonhistone nuclear protein fractions. There was no inhibitory effect on 3H-labeled amino acid incorporation in the livers of the tumor-bearing rats. The inhibitory effect of N-tosyl-L-lysine chloromethyl ketone (TLCK) on incorporation of 3H-labeled amino acids was observed in both the slowly growing hepatoma 7787 and the rapidly growing hepatoma 7777. In hepatoma 7777, TLCK (2.5 mg/100 g body wt) exerted a greater inhibitory effect on incorporation when administered 60 minutes before [3H]leucine injection than when injected simultaneously. Studies on tissue uptake of amino acids, thymidine, and phosphate indicated that inhibitory effects of TPCK and TLCK on active transport may be a major factor in the action of these drugs on macromolecular synthesis. The inhibitory effects of TPCK and TLCK seen in transplanted hepatomas and a colon tumor were not generally seen in normal tissues of the tumor-bearing rats.
Assuntos
Clorometilcetonas de Aminoácidos/farmacologia , Aminoácidos/metabolismo , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Fígado/efeitos dos fármacos , Fosfatos/metabolismo , Tosilina Clorometil Cetona/farmacologia , Tosilfenilalanil Clorometil Cetona/farmacologia , Animais , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Ratos , Ratos Endogâmicos BUF , Timidina/metabolismoAssuntos
Carcinoma Hepatocelular/metabolismo , DNA de Neoplasias/biossíntese , Dimetil Sulfóxido/farmacologia , Neoplasias Hepáticas/metabolismo , Timidina/metabolismo , Aminoácidos/metabolismo , Animais , Relação Dose-Resposta a Droga , Feminino , Proteínas de Neoplasias/biossíntese , Neoplasias Experimentais/metabolismo , RNA Neoplásico/biossíntese , Ratos , Uridina/metabolismoAssuntos
Clorometilcetonas de Aminoácidos/farmacologia , Carcinoma Hepatocelular/metabolismo , Neoplasias do Colo/metabolismo , Replicação do DNA/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Tosilfenilalanil Clorometil Cetona/farmacologia , Animais , Neoplasias do Colo/induzido quimicamente , Dimetilidrazinas/análogos & derivados , Feminino , Cinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Regeneração Hepática/efeitos dos fármacos , Neoplasias Experimentais/metabolismo , RatosRESUMO
The uptake of alpha-aminoiso[3H]butyric acid and 32Pi was observed to be inhibited by sodium cyanate in transplanted hepatomas but was increased in the livers of the tumor bearing rats. Incorporation of 32Pi into macromolecules in hepatomas was also inhibited by cyanate. Treatment with this drug did not influence circulating concentrations of isotope-labeled materials. There were relatively small effects on uptake of 36Cl- in cyanate-treated rats and the action was not tissue specific. The data were compatible with an inhibitory effect of cyanate on active transport in hepatomas which was not seen under the same conditions in host liver.
Assuntos
Ácidos Aminoisobutíricos/metabolismo , Carcinoma Hepatocelular/metabolismo , Cianatos/farmacologia , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Fosfatos/metabolismo , Animais , Transporte Biológico Ativo , Proteínas Cromossômicas não Histona/metabolismo , Histonas/metabolismo , Cinética , Fígado/efeitos dos fármacos , Masculino , Neoplasias Experimentais/metabolismo , Fosfoproteínas/biossíntese , RatosRESUMO
The effects of exogenous proteins on the incorporation of [3H]-thymidine into DNA was studied in Novikoff hepatoma ascites cells incubated in Eagle's minimal essential medium. A liver cytosol fraction (8 mg protein/ml) caused approximately 80% inhibition of isotope incorporation. The inhibitory activity of cytosol fractions from Morris hepatomas 9618A2, 5123C, and 20 were inversely related to their growth rate. Under conditions in which there appeared to be a density dependent inhibition of growth, a mean 10-20% stimulation of isotope incorporation was observed after addition of total calf thymus histones and individual fractions in the concentration range of 100-400 microgram/ml. In experiments with lower cell concentrations, a 60% or greater increase in [3H]-thymidine incorporation could be obtained with total calf thymus histone and with F1 and arginine-rich histones from rat liver. At concentrations of 1-2 mg/ml, histones inhibited DNA synthesis. Bovine serum albumin had little effect on DNA synthesis. Polylysine caused an 80-90% inhibition at a concentration of 1 mg/ml, but stimulatory effects were detected under certain conditions at 10 microgram/ml. The results suggest critical dependence on the ratio of cell and exogenous protein concentration in the action of proteins on DNA synthesis.
Assuntos
Carcinoma Hepatocelular/metabolismo , Replicação do DNA/efeitos dos fármacos , DNA de Neoplasias/biossíntese , Histonas/farmacologia , Proteínas/farmacologia , Animais , Citosol/fisiologia , Relação Dose-Resposta a Droga , Cinética , Fígado/fisiologia , Neoplasias Hepáticas , Lisina , Proteínas de Neoplasias/farmacologia , Neoplasias Experimentais/metabolismo , Peptídeos/farmacologia , Protaminas/farmacologia , Biossíntese de Proteínas , Ratos , Soroalbumina Bovina/farmacologiaRESUMO
The uptake of isotope by three transplanted kidney tumors after i.p. injection of 3H-labeled orotate was less than 5% of that in the host kidney cortex. A decrease of similar magnitude in the uptake into the acid-soluble tissue fractions from the kidney tumors was observed with very low incorporation into RNA relative to the host kidney cortex. Total uptake of orotate-3H and incorporation into RNA were several fold higher in the normal kidney cortex than in the kidney medulla and for the kidney cortex both parameters were less in young than in old rats. The uptake of uracil-3H by two kidney tumors was approximately 40% of that in the kidney cortex of host rats. Although the uptake of orotate-3H in kidney cortex was greater than that for uracil-3H the reverse situation was observed with kidney tumors, indicating that renal neoplasia in the rat is accompanied by an altered pattern of uptake of these metabolites.