Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past five years we observed many advances in the study of the polymer drug, "SMANCS". This first polymeric drug was approved by the Japanese Ministry of Health and Welfare in 1994 as a drug for primary liver cancer, in which the arterial injection of oily formulation in Lipiodol (a lipid contrast medium) is the standard procedure. The advantage of this tactic is the most extraordinary cancer targeting efficiency with the least systemic side effect and very prolonged slow release of SMANCS. The mechanism of tumor selective accumulation of SMANCS and polymeric drugs in general is discussed in view of the so called-EPR (enhanced permeability and retention) effect of solid tumor. The mode of action of SMANCS at the cellular level seems to accompany the generation of superoxide radical which damages DNA; strand break and modification of guaninine by 8-hydroxylguanine. Immunological potentiation involves either the cellular (M phi, T-cell, NK-cell) or molecular level (induction of cytokines, including interferon gamma). The in vivo effect of SMANCS is most pronounced in the tumor vessels where more concentrated SMANCS is accessible due to the EPR effect, and perhaps the generation of O2.-. Nitric oxide generated by both inducible form of NO synthase (iNOS) by the infiltrated macrophages and NOS of endothelial cells, and superoxide from SMANCS will readily react to form peroxynitrite (O2- + NO-->ONOO-), which is a very potent cytotoxic molecule and will damage (nitrate and oxidize) DNA and proteins. Thus, tissue damage and vascular injury or collapse will be the principle tumor toxic mechanism of SMANCS at tissue level. The dose of SMANCS (or grade I-IV tumor filling) and tumor regression parallel each other, and a profile of AFP-value and technical issues of SMANCS/Lipiodol administration intraarterially are also discussed.
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PMID:[Recent advances in research on SMANCS]. 951 80

To investigate the prognostic factors of primary liver cancer (PLC) and improve the long-term results, 1,248 cases of PLC were analysed. Univariate analysis demonstrated that discovery approach, staging of PLC, original gamma-GPT, resection, radical resection, original AFP, tumor size, tumor number, and tumor capsule have very significant effects on prognosis of PLC (all P < 0.001); cirrhosis, HBsAg, local resection, and tumor embolus in portal vein were also significant difference (all P < 0.05); age, sex, original AFP, hepatitis, and differentiation of PLC cells were no significant difference (all P > 0.05). Multivariate analysis demonstrated that original gamma-GPT, radical resection, tumor size, and tumor number were the most significant prognostic factors (all P < 0.001). Some aspects improving long-term survival were discussed.
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PMID:[Prognostic factors of primary liver cancer]. 959 43

Combined hepatocellular (HCC) and cholangiocellular carcinoma (CCC) (mixed carcinoma) is a rare subtype of primary hepatic carcinoma. We report a case of mixed carcinoma that developed in a non-cirrhotic liver, in a patient who was serologically negative for both hepatitis B and C viruses. A 65-year-old Japanese woman with a 25-year history of chronic rheumatoid arthritis had been treated with steroids and anti-inflammatory drugs, and was diagnosed by ultrasonography with an asymptomatic solitary tumor in the right lobe of the liver. On computed tomography scan and hepatic arteriography, the tumor was well enhanced by contrast medium in the early phase. Based on the findings of elevated serum alpha-feto protein (AFP, 245 ng/ml) and normal carcino-embryonic antigen (CEA, 2.6 ng/ml) levels, a preoperative diagnosis of hepatocellular carcinoma was made. Right lobectomy of the liver was performed on January 7, 1997. Histological examination showed that the resected tumor consisted of combined CCC cells and HCC cells in an intermingled form, with CCC being far more dominant than HCC. The tumor was therefore determined to be a combined carcinoma, subclassified as intermingled type. This case appears to indicate that mixed type carcinoma developed in a non-cirrhotic liver, with CCC being dominant; such a finding is extremely unusual, based on previously published reports.
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PMID:Combined hepatocellular and cholangiocellular carcinoma in a non-cirrhotic liver. 971 50

Surgical resection remains the best option for potential cure and long-term survival in patients with HCC. The question of to what extent transplantation for HCC should be performed remains controversial. There appears to be a definite role for OLT in the treatment of HCC, with many series showing improved survival over resection, especially with "favorable" tumors. What remains to be determined are the best patients and the best protocol. There is little question that patients with small unifocal tumors do well after OLT. It is the patient who falls outside of these narrow guidelines that poses a problem in clinical decision making and organ allocation. The ability to determine relative risk of recurrence of HCC would perhaps allow a more equitable allocation of a scarce resource. Currently, we evaluate each patient with HCC on an individual basis, making the best decision possible based on the patient's clinical status, our most advanced current imaging studies, and known clinical prognostic factors (Table 6). Adequate staging is essential to determine suitable candidates. Advances in multimodal adjuvant therapy are needed for patients with poor prognostic factors to achieve results similar to what is seen in those who receive transplants for nonmalignant diseases. Attempts at resection should be performed for those patients presenting with Child's class A cirrhosis, because these are the patients who would tolerate a resection with acceptable morbidity and mortality. Limited resections based on segmental anatomy may be consider in "good risk" Child's class B cirrhotics, considering the current organ shortage. Child's class C and decompensated Child's class B patients without significant risk factors should be evaluated for transplantation, and preoperative chemoembolization should be considered to prevent spread while the patient is on the waiting list. These patients should be monitored with imaging studies and by AFP levels on a regular basis while they await their transplant. After transplantation, chemotherapy should be considered for those patients with moderate to high risk of recurrence, within the guidelines of an institutional or multicenter protocol. In patients with multiple poor prognostic factors, or those who are too ill to undergo resection or transplantation, palliative measures may be used. As the need for organs increases, and the wait continues to grow, it becomes increasingly difficult to justify the use of a scarce resource for patients with a known less desirable outcome. On the other hand, we must be careful not to exclude an entire group of patients from a potentially curative procedure. We now have evidence that survival after transplantation for HCC in carefully chosen patients can equal that of benign disease. We need to be selective and cautious in our choice of recipients, but not exclusive, using prior experience and the knowledge we now possess regarding a set of fairly well-delineated risk factors.
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PMID:Surgical options for hepatocellular carcinoma: resection and transplantation. 974 1

To investigate a new kind of anti-tumor immunological cells and improve surgical results of hepatocellular carcinoma by anti-recurrence application, we activated T cells isolated from tumor infiltrating lymphocytes by double stimulating signals: the one was autologus HCC cells which were treated with IFN-gamma and TNF-alpha for enhancing expression of MHC class I and presented tumor antigen, and the other was costimulation signals which was from ICAM-1 and B7 molecules expressed on treated HCC cells as well as CD28 mAbs. Activated T cells which bound to HCC cells were expanded selectively as tumor specific cytotoxic T lymphocytes (TS-CTLs), their cytotoxic activity in vitro and anti-tumor effects in vivo were observed. Our results suggested that TS-CTLs expressed high cytotoxicity against autologous HCC cells with MHC class I restriction manner. Adoptive TS-CTLs treatment could decrease serum AFP level, inhibit ascites formation and prolong survival in SCID mice bearing human HCC. In clinical trail of 12 cases of HCC, TS-CTLs treatment was able to delay tumor recurrence after HCC resection. Our data demonstrated that TS-CTLs as new immunological treatment modality, are of great value in further application of tumor comprehensive management.
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PMID:[Experimental and clinical research of cytolytic T lymphocytes specific for hepatocellular carcinoma]. 1037 86

Using Northern blot method, we examined the expression of c-met in human hepatocellular cancer. Of 30 patients tested, the expression of c-met mRNA was not significantly different in HCC tissues from corresponding noncancerous parenchyma (P > 0.05). There was no significant relationship between c-met expression and grade of differentiation, stage of clinic, AFP, HBsAg (P > 0.05). Our results suggest that c-met may play different roles in the pathogenesis and metastasis of human hepatocellular carcinoma.
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PMID:[c-met expression in human hepatocellular cancer]. 1037 71

Serum transforming growth factor beta 1 (TGF beta 1) concentration was determined in 47 patients with primary hepatic carcinoma (PHC) and 77 patients with various liver diseases and gastrointestinal tumors by means of enzyme-linked immunosorbent assay system. The result revealed that serum TGF beta 1 level of PHC patients were significantly higher (257.6 +/- 126.0 micrograms/L) than those in normal subjects (81.5 +/- 43.5 micrograms/L), in patients with hepatitis (152.4 +/- 98.4 micrograms/L), cirrhosis (191.8 +/- 96.3 micrograms/L), hepatic benign tumor (91.9 +/- 37.9 micrograms/L), metastatic liver cancer (146.4 +/- 73.7 micrograms/L) and gastrointestinal tumor (128.7 +/- 56.4 micrograms/L) (P < 0.01 or 0.05). Serum TGF beta 1 level was elevated in 34 of 47 (72.3%) PHC patients, including 5 of 7 (91.4%) small (< 5 cm) PHC patients. The sensitivity and specificity of diagnosis of TGF beta 1 in PHC were 72.3% and 77.9%, respectively. The diagnostic positivity was 78.5% in AFP-negative PHC patients. The combined assay of serum TGF beta 1 and AFP could further raise the detection rate of PHC up to 93.6%. Above results suggest that serum TGF beta 1 might be a candidate for a novel tumor marker for diagnosis and monitoring of PHC.
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PMID:[Clinical evaluation of serum transforming growth factor beta 1 assay in the diagnosis of primary hepatic carcinoma]. 1043 81

The AFP regulatory sequences are among the best known tumor-specific transcriptional regulators. A number of groups have demonstrated that a variety of genes can be expressed in an HCC-specific manner under the control of the AFP regulatory sequences in vitro and in vivo. It would appear that, with the development of a suitable delivery system, HCC-directed gene therapy using the AFP regulatory sequences holds a promising future.
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PMID:Human alpha-fetoprotein transcriptional regulatory sequences. Application to gene therapy. 1081 Jun 14

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

Five hundred fifty patients hospitalized to our hospital during 1990 to 1999 were studied. Subjects consisted of 413 males and 102 females and mean age was 62.1 years. Association with HBV infection, HCV infection and both infection was 11.1%, 78.4% and 2.5% respectively. According to the criteria based in Liver Cancer Study of Japan, 5 year survival rate in clinical stage I, II, III was 42.3%, 38.8% and 17.5%. Tumor morphology was nodular type in 78.9%, massive type in 9.1% and diffuse type in 10.5% of cases. Portal tumor thrombus and distal metastasis were observed in 19.9% and 6.3% of all cases. The 1-, 3- and 5-year survival rate in patients received any therapy was 80.8%, 44.6% and 28.7%, respectively. Analysis by the proportional hazard model showed that HBV infection, advanced clinical stage, multiple tumors, a tumor diameter in excess of 5 cm and AFP positivity were shown as significant factors on poor prognosis.
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PMID:[Prognostic factors of hepatocellular carcinoma: analysis by the proportional hazard model]. 1121 86


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