Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiolabeled monoclonal antibodies reactive with tumor-associated antigens can selectively deliver cytotoxic or diagnostic isotopes to malignant cells in vivo. To achieve maximum retention of radiolabel in tumor and a more rapid clearance of radioisotope from normal tissues, six linker immunoconjugates were evaluated in studies using nude mice and beagle dogs. All radioimmunoconjugates contained a mouse monoclonal IgG (QCI) reactive with human ferritin. Different chemical linkages were inserted between immunoglobulins and the radiolabeled chelate (DTPA). Three linkers (ITCB, DSS and BSOCOES) were stable in in vitro and in vivo studies. Three linkers (EGS, DST and DSP) were labile in in vitro and in vivo studies. Indium-111 labeled antiferritin-containing ITCB or DSS linker showed high uptake in human hepatoma xenografts in nude mice. In addition, long blood half-lives and higher normal liver uptakes were noted. Studies of whole body retention of radioimmunoconjugates showed approximately three-fold faster elimination of radioimmunoconjugates containing a labile linker (EGS). EGS linker is the labile linker with the highest therapeutic ratio: higher tumor uptake, but low normal liver uptake and a shortened blood half-life of the radioimmunoconjugate. The differences in normal tissue uptake (liver) between EGS and ITCB were confirmed in beagle dogs. Urine elimination studies and incubation or radioimmunoconjugates in serum or tissue homogenates of tumor, liver or muscle, showed that enzymes in serum and liver homogenates were able to cleave the labile linkers, which led to a more rapid elimination of low molecular weight radioactive metabolites in urine. The metabolism of linker radioimmunoconjugates in tumor was less effective. The labile linker DSP appears less useful because sulphydryl groups that are generated by cleavage of cause higher uptake radioactivity in normal kidney. Biodistribution studies in nude mice were confirmed by serial immunoscintigraphy studies on individual mice. The immunoscintigraphy studies are semi-quantitative only, but enable the use of lower numbers of experimental animals. This is of particular significance in large experimental animals such as beagle dogs. The labile linker approach can reduce normal tissue radiation exposure. The study also provides an example of preclinical optimization of radioimmunoconjugates. Continued use of the appropriate preclinical animal models will accelerate more successful applications of radioimmunoconjugates in cancer patients.
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PMID:Effects of linker chemistry on the pharmacokinetics of radioimmunoconjugates. 997 40

The aim of this study was to determine the usefulness of quantitative analysis of multiphasic dynamic contrast-enhanced magnetic resonance (MR) imaging in differentiating early homogeneously enhancing hemangiomas from hepatocellular carcinomas (HCCs). Four-phased dynamic MR imaging at 10 sec (first phase of dynamic contrast-enhanced imaging, P1), 35 sec (second phase, P2), 60 sec (third phase, P3) and 300 sec (delay phase, P4) immediately after intravenous administration of 0.1 mmol/kg Gadolinium-DTPA was obtained with 1.5-T unit with breath-hold multisection FLASH (fast low angle-shot) sequence (TR/TE, 113-130 msec/4.1 msec; flip angle, 80 degrees). Thirty-three HCCs and 18 hemangiomas, homogeneously enhanced on P1, were included in the study. The images were evaluated quantitatively (SNR, signal-to-noise ratio; and CNR, contrast- to- noise ratio of lesions). Quantitatively, mean CNR was higher for hemangiomas than for HCCs on all phases, and the difference in CNRs between hemangioma and HCCs was statistically significant on P3 and P4 (p < 0.0001). When the cutoff for CNR was set at a value of 7.00 on P3 and 1.00 on P4, sensitivity, specificity and accuracy were 94.4%, 93.9%, and 94.1% on P3, and 94.4%, 81.8%, and 86.3% on P4, respectively. There was no statistically significant difference in SNRs between HCC and hemangioma. The differential diagnosis between early, homogeneously enhancing hemangiomas and HCCs was more confidently made with CNRs of lesions on P3 and P4 in dynamic contrast-enhanced MR imaging.
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PMID:Early homogeneously enhancing hemangioma versus hepatocellular carcinoma: differentiation using quantitative analysis of multiphasic dynamic magnetic resonance imaging. 1041 37

To investigate the correlation between nuclear medicine parameters determined by technetium-99m-DTPA-galactosyl-human serum albumin (Tc-99m-GSA) and liver function tests, canonical correlation analysis was performed. Tc-99m-GSA studies were performed on 47 patients with hepatocellular carcinoma (HCC) who had undergone transcatheter arterial embolization (TAE). The nuclear medicine parameters LU15, HH15 and LHL15, which are results of nuclear imaging tests, were chosen in combination with the following liver function tests: the serum bilirubin level (T.Bil), the serum albumin level (Alb), serum cholinesterase activity (Ch-E), the clearance rate of indocyanine green (KICG), the hepaplastin test (HPT) and the prothrombin time (PT). The canonical correlation coefficient was 0.7345 and the upper tail probability was 0.00167. A significant correlation was observed between the two sets of variables. The high structural coefficients of Ch-E, KICG and HPT indicated a close relationship with the nuclear medicine parameters, supporting the notion that these nuclear medicine parameters are useful for the estimation of liver damage. The structural coefficients of the nuclear medicine parameters were also high, with LU15 being a parameter as useful as both HH15 and LHL15. T.Bil may evaluate a liver function that is not measured by nuclear imaging techniques, so we should take T.Bil results into account before considering TAE.
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PMID:Evaluation of liver function parameters by Tc-99m-GSA using multivariate analysis: a study of 47 clinical cases. 1056 31

Based on the fact that somatostatin (SST) analogs have given promising results for treatment of hepatocellular cancer, we performed both in vitro and in vivo investigations to define the role of a depot formulation of the long acting SST-analog lanreotide (LAN). A decrease of cells in the S-phase as compared to controls (p<0.03) followed by a significant, dose-dependent induction of apoptosis could be demonstrated in Hep G2 cells along with a dose-dependent influence of the peptide on cellular proliferation. Northern blotting demonstrated the presence of mRNA for SSTR subtypes 2, 3 and 4 in Hep G2 cells, but only slight SSTR expression in normal liver tissue. In addition, 21 untreated patients with advanced HCC not amenable to surgery were administered 30 mg of LAN by deep intramuscular injection every 14 days until documented disease progression. Fifteen of these patients also underwent scanning with commercially available 111In-DTPA-D-Phe1-Octreotide (111In-OCT) to define the in vivo expression of SSTR. No positive 111In-OCT scans were obtained, indicating the absence of relevant amounts of functional SSTR2 in HCC. One patient (5%) showed a partial response to treatment, 8 patients had stable disease (38%), while the remaining patients progressed during treatment. The median survival was 4.2 months (range 1.2-13+), and the median time to progression was 2.5 months (range, 1.5-7+). However, 4 patients (19%) had an increase in WHO performance status lasting between 2.5 and 6 months, 5 patients (24%) had an increase in body weight, while pain markedly improved in 1 additional patient (5%). In total, 5 patients (24%) had a decrease in serum-AFP levels by at least 30%. Our results clearly indicate the ability of LAN to decrease the S-phase fraction along with induction of apoptosis in Hep G2 cells in a dose-dependent manner. Our data suggest clinical potential of SST-analogs in HCC and indicate that suboptimal doses of the peptide might have been administered in our series.
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PMID:Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo. 1081 95

Recent advances in the treatment of hepatocellular carcinoma (HCC) have prolonged patient survival. However, the number of patients with bone metastases identified during follow-up examinations has increased. Tc-99m Sn-N-pyridoxy-5-methyltryptophan (Tc-99m PMT) has been reported to accumulate at a high rate in HCC lesions and bone metastases. In the patient described here, whole-body scintigraphy showed accumulation of DTPA galactosyl human serum albumin (Tc-99m GSA) and Tc-99m PMT in bone metastases from HCC. The authors suggest that asialoglycoprotein receptors may be present in bone metastases from well-differentiated HCC. Tc-99m GSA whole-body imaging can be used to detect bone metastases from HCC and to evaluate hepatic reserve.
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PMID:Utility of Tc-99m GSA whole-body scintigraphy in detecting bone metastases from hepatocellular carcinoma. 1124 14

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.
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PMID:Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging. 1129 45

5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in acute intermittent porphyria (AIP) due to enzymatic deficiencies in the heme biosynthetic pathway Its accumulation has been associated with several symptoms, such as abdominal pain attacks, neuromuscular weaknesses, neuropsychiatric alterations and increased hepatocellular carcinoma (HCC) incidence. The use of exogenous ALA to elevate porphyrin levels in tumor photodynamic therapy, adds further significance to ALA toxicology. Under ferritin mediated and metal catalyzed oxidation, ALA produces reactive oxygen species that can damage plasmid and isolated DNA in vitro, and increases the steady-state level of 8-oxo-7,8-dihydro-2'-deoxyguanosine in liver, spleen and kidney DNA and 5-hydroxy-2'-deoxycytidine in liver DNA of ALA-treated rats. The in vitro DNA damage could be partially inhibited by SOD, catalase, DTPA, mannitol and melatonin. ALA also promotes the formation of radical-induced base degradation products in isolated DNA. 4,5-Dioxovaleric acid, the final oxidation product of ALA, alkylates guanine moieties within both nucleoside and isolated DNA, producing two diastereoisomeric adducts. Dihydropyrazine derivatives of ALA generated by its dimerization, promote DNA strand-breaks and 8-oxodGuo formation in the presence of Cu2+. Together these results reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in individuals suffering from AIP.
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PMID:Is 5-aminolevulinic acid involved in the hepatocellular carcinogenesis of acute intermittent porphyria? 1193 Sep 45

The new complex of Gd(III) with the 1,7-bis[(N-dimethyl(carbomoyl)methyl)-1,4,7-triazaheptane-1,4,7- triacetate[Gd(DTPA-BDMA)] is a non-ionic paramagnetic complex designed for use as an extracellular magnetic resonance imaging (MRI) contrast agent. The R1 relaxivity value of [Gd(DTPA-BDMA)] is 4.13 +/- 0.2 mM-1S-1, which is similar to that of [Gd(DTPA)]2- (4.08 mM-1S-1). The purpose of this study is to examine the acute toxicity and MRI characteristics of [Gd(DTPA-BDMA)]. Our results show that the lethal dose (LD50) of the [Gd (DTPA-BDMA)] is 10.58 mmol/kg in ICR mice, which is higher than that of [Gd (DTPA)]-2-(6.40 mmol/kg). The MR images demonstrate that the enhancing effect and renal clearance of [Gd(DTPA-BDMA)] are similar to that of [Gd(DTPA)]2- either in control group or CHA (Cheng hepatoma ascites) tumor model in Wistar rats (p > 0.05). These findings indicate that [(DTPA-BDMA)] has similar characteristics of [Gd(DTPA)]2- and has the potential of becoming a safe and reliable magnetopharmaceutical for the extracellular MRI contrast agent.
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PMID:[Gd(DTPA-BDMA)] as a magnetic resonance contrast agent: acute toxicity test and preliminary images. 1205 72

Dynamic studies employing contrast agents have been used in the detection of hepatocellular carcinoma (HCC). Some studies have indicated that the detectability of small nodules in liver is significantly better with MRI dynamic study than with CT dynamic study. However, the reasons for this are unclear. In an attempt to clarify this difference, we compared contrast resolution using two contrast phantoms made for MRI and CT. Both phantoms were constructed using the same ratios of dilution of the contrast materials Gd-DTPA and iodine. The signal intensity of different dilution ratios of contrast medium were measured in order to compare the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast. The results showed that the contrast of phantoms in MRI and CT dynamic studies was almost the same except for certain MRI scan techniques. In terms of SNR and CNR, MRI dynamic study was superior to CT dynamic study. In addition, T(1) relaxation of the contrast agent should be considered for suitable scanning, because the contrast of MRI was affected by scan parameters.
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PMID:[Comparison of contrast resolution between dynamic MRI and dynamic CT in liver scanning]. 1252 67

Labeled biotin has been used mainly for pretargeted therapy, an approach for increasing the amount of radioactivity delivered to a cancer cell. The aim of this investigation was to prepare (153)Sm-DTPA-bis-biotin and (99m)Tc-DTPA-bis-biotin in order to study their in vitro and in vivo uptake in rat AS-30D hepatoma cells found in ascites and in implanted tumor. DTPA-bis-biotin (pH 8) was (153)Sm labeled with (153)SmCl(3) and (99m)Tc-DTPA-bis-biotin was prepared via SnCl(2) reduction. Radiochemical purity was >98% in both cases. AS-30D hepatoma cells were obtained from ascites of a rat with hepatoma and were propagated in the peritoneum cavity of normal rats. In vitro ascites cell (153)Sm-DTPA-bis-biotin uptake was compared with (153)SmCl(3) cell uptake. The ratio cell (153)Sm-DTPA-bis-biotin/(153) SmCl(3) was 39.6 and when avidin was added it increased to 50. The ratio (99m)Tc-DTPA-bis-biotin/TcO(4)Na was 8.7. Concentration of (153)Sm-DTPA-bis-biotin in tumor 2, 3 and 24 h after administration, was 5, 15 and 3 times higher than in normal muscle (T/nT). Biodistribution in a 0.083-24 h time period showed that (153)Sm-DTPA-bis-biotin was taken up only by ascites tumor cells and hepatoma cells. Two and 3 h ratio ascites/liver (As/Lv) was 6.4 and 6.0. For (99m)Tc-DTPA-bis-biotin 2 and 3 h T/nT was 15.7 and 4.7 and 2 h As/Lv was 1.4. In conclusion, both radiopharmaceuticals show high uptake in rat AS-30D hepatoma cells in ascites and in implanted tumor. Since lung, thyroid, kidney, liver or pancreas carcinomas are ascites producing cancers (153)Sm-DTPA-bis-biotin would be an adequate therapeutic radiopharmaceutical for these patients whose life quality would be enhanced with control of ascites, and a reduction of the primary tumor and its metastases.
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PMID:Uptake of 153Sm-DTPA-bis-biotin and 99mTc-DTPA-bis-biotin in rat as-30D-hepatoma cells. 1262 12


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