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

There have been no studies on photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) in patients with metastatic skull tumors. Here, we present a case of skull metastasis of hepatocellular carcinoma (HCC) successfully treated by intraoperative PDD using 5-ALA. A 63-year-old man with HCC presented with a subcutaneous mass in the left occipital region. CT showed a hyperdensity mass and severe osteolytic change in the left side of the occipital bone. MRI revealed an extra-axial enhanced mass that compressed the left occipital lobe and enhancement was spreading to the adjacent subcutaneous soft tissue. In order to intraoperatively evaluate the extent of tumor invasion, PDD using 5-ALA was performed. Intraoperative PDD comfirmed that the tumor itself was highly fluorescent. Surgery was completed after comfirming the absence of residual fluorescence in the surgical field. The tumor was diagnosed HCC. Histopathological analysis confirmed that PDD accurately assessed the extent of tumor invasion. The patient was discharged home at 10 days after surgery. PDD using 5-ALA is convenient and inexpensive, and because adverse reactions are minimal, it may be useful in not only malignant glioma, but also other brain tumors.
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PMID:[Skull metastasis of hepatocellular carcinoma successfully treated by intraoperative photodynamic diagnosis using 5-aminolevulinic acid: case report]. 1786 12

A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene imine) (PEI) and low transfection efficiency of PEGylated PEI (PEG-PEI), we linked a cell specific target molecule folate (FA) on poly(ethylene glycol) (PEG) and then grafted the FA-PEG onto hyperbranched PEI 25kDa. The FA-PEG- grafted-hyperbranched-PEI (FA-PEG-PEI) effectively condensed plasmid DNA (pDNA) into nanoparticles with positive surface charge under a suitable N/P ratio. Tested in deferent cell lines (i.e., HEK 293T, glioma C6 and hepatoma HepG2 cells), no significant cytotoxicity of FA-PEG-PEI was added to PEG-PEI. More importantly, significant transfection efficiency was exhibited in FA-targeted cells. Reporter assay showed that FA-PEG-PEI/pDNA complexes had significantly higher transgene activity than that of PEI/pDNA in folate-receptor (FR) positive (HEK 293T and C6) cells but not FR-negative (HepG2) cells. These results indicated that FA-PEG-PEI might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.
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PMID:Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery. 1820 60

Loss of T-cadherin expression has been reported in a number of human cancers. We previously reported that T-cadherin re-expression suppressed cell growth and motility in glioma. Here, we report that the T-cadherin expression was significantly decreased in human hepatocellular carcinoma (HCC) compared to adjacent normal liver. In addition, T-cadherin expression in HCC with metastasis was significantly lower than in HCC without metastasis. To determine the mechanism underlying the reduced T-cadherin expression in HCC, we examined T-cadherin promoter methylation. We found that methylation of the T-cadherin promoter was present in 40% of HCC, but absent in all adjacent liver tissues. In the HCC with T-cadherin promoter methylation, the T-cadherin expression was significantly decreased compared to HCC without methylation. To provide a functional link between T-cadherin promoter methylation and T-cadherin growth regulation, we used the HepG2 hepatoma cell line that exhibits T-cadherin promoter methylation. Treatment of HepG2 cells with the demethylating agent 5-aza-2-deoxycytidine resulted in increased T-cadherin expression and reduced cell proliferation. These results demonstrate that the T-cadherin down-regulation by promoter methylation is associated with the development and progression of HCC, and suggest that T-cadherin is an important tumor suppressor in liver cancer.
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PMID:Reduced T-cadherin expression and promoter methylation are associated with the development and progression of hepatocellular carcinoma. 1842 32

Contusugene ladenovec (Advexin; INGN-201; Introgen Therapeutics Inc) is a replication-impaired, non-integrating, serotype 5 adenoviral vector that carries the p53 gene under the control of the CMV promoter. Deletion or mutation of the p53 gene has been observed in approximately half of malignancies in patients with cancer and p53 pathway dysfunction was observed in the majority of others, thereby providing the rationale for p53 restoration in the treatment of cancer. Advexin has demonstrated a consistent safety profile and clinical efficacy as a monotherapy, as well as in combined modality regimens with chemotherapy and radiation. Additive or synergistic effects have been observed in a variety of tumor types, including NSCLC, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, glioma, and breast, prostate and colorectal cancers. The identification of biomarkers may help direct research in tumor-specific therapeutics.
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PMID:A review of contusugene ladenovec (Advexin) p53 therapy. 1916 60

Sodium borocaptate (BSH) is widely used for boron neutron capture therapy (BNCT) of brain tumors. One drawback is the large uptake by the liver causing a decrease of its availability at the tumor region as well as bringing about toxicity problems. A novel carborane-based compound containing a boron payload very similar to that of BSH has been synthesized and tested on rat glioma (C6) cells, hepatoma tissue culture (HTC) cells, and hepatocytes. The newly synthesized system consists of an o-carborane unit (C(2)B(10)H(11), o-CB) conjugated to a glutamine residue through a proper spacer, namely, o-CB-Gln. As compared with BSH, it showed the same uptake by C6 cells, but a 50% decrease in uptake by HTC cells and an 80% decrease in uptake by healthy hepatocytes. On this basis o-CB-Gln appears an interesting candidate for BNCT of brain tumors as it is expected to have a therapeutic index analogous to that of BSH accompanied by a much lower liver toxicity.
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PMID:Towards improved boron neutron capture therapy agents: evaluation of in vitro cellular uptake of a glutamine-functionalized carborane. 1936 Apr 42

The stem cell marker CD133/prominin-1, is a pentaspan membrane glycoprotein, which has also been identified as a cancer stem cell (CSC) marker in several solid tumor types, including those of the prostate, liver, colon and brain. The function of CD133 in these tumors is still unknown. We hypothesize that the function of CD133 is correlated with the characteristics of the CD133+ CSCs and may affect the growth of the tumor cell population as a whole. In this study we used antisense oligodeoxynucleotides (ASODNs) of CD133 to knock-down (KD) CD133 expression. We showed that the CD133-KD inhibited proliferation of U251 human glioma cells, decreased the colony forming ability and altered the cell cycle distribution in Huh-7 human hepatocellular carcinoma cells. Our data suggest that CD133 may play an important functional role in the growth of these tumor cells. Moreover, this study also showed that prominin-2, another protein in the same family as CD133/prominin-1, may not have a similar function.
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PMID:Effect of CD133/prominin-1 antisense oligodeoxynucleotide on in vitro growth characteristics of Huh-7 human hepatocarcinoma cells and U251 human glioma cells. 1972 56

In this paper, antineoplastic activities of protein-conjugated silver sulfide nano-crystals with different shapes were described in detail. Transmission electron microscope analysis demonstrated that stable and well-disperse protein-conjugated silver sulfide nano-particles, nano-rods, and nano-wires could be prepared by aqueous chemistry method. The Fourier transform infrared spectrograph analysis indicated the strong coordination between silver sulfide surfaces and -OH and -NH groups in bovine serum albumin. The antineoplastic activities of protein-conjugated silver sulfide nano-crystals were examined by cell viability analysis, optical and electron microscopy methods. The results showed that nano-particles, nano-rods and nano-wires could inhibit the proliferations of human hepatocellular carcinoma Bel-7402 cells and C6 glioma cells, and the activities were size-dependent.
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PMID:Antineoplastic activities of protein-conjugated silver sulfide nano-crystals with different shapes. 1990 30

The energy charge potential (ECP) is the ratio among adenosine 5'-triphosphate (ATP), -diphosphate (ADP), and -monophosphate (AMP); it reflects the high-energy-bond content in biological systems. Under normal physiological conditions, the value of ECP is between 0.7 and 1.0. In this study, two different methods were used to extract adenosine nucleotides (ATP, ADP, and AMP) for determination of the ECP in the C6 glioma and the HepG-2 human hepatoma cell lines. In the first method, cells were removed from culture plates by trypsinization before the nucleotides were extracted using perchloric acid. Some of the trypsinized cells were used for a cell count, thereby allowing the calculation of an average nucleotide level per cell. In the second method, perchloric acid was added directly to the culture plate immediately after the medium was removed. This method resulted in an instant termination of any enzymatic process that might degrade the nucleotides and alter their levels in cells. Adenosine nucleotides were determined by high-performance liquid chromatography. The direct extraction method yielded a total adenosine nucleotide (TAN) level more than twofold higher than that obtained following trypsinization. For the C6 glioma cells, the ratio of ATP to ADP to AMP in the TAN pool was 0.70:0.15:0.15, as compared to 0.36:0.27:0.37 when cells were extracted following trypsinization. Similarly, for the HepG-2 cells, the ratio was 0.62:0.15:0.23 following direct extraction, as compared to 0.15:0.28:0.57 following trypsinization. Using the results from the direct extraction method, the value of the cellular ECP was 0.78 +/- 0.06 for the C6 glioma cells and 0.70 +/- 0.06 for the HepG-2 cells. Compared to the ECP values obtained using the trypsinization method (0.50 +/- 0.05 and 0.29 +/- 0.12, respectively), the ECP values derived using the direct extraction method were significantly greater in both cell lines and were suggestive of the energy status of normal, healthy cells.
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PMID:Determination of Energy Charge Potential in the C6 Glioma and the HepG-2 Cell Culture. 2002 Nov 87

EGF promoter polymorphisms are observed to modulate EGF levels and thought to have effect on susceptibility to various carcinomas but the results are inconsistent. In this meta-analysis, we assessed published studies of the association between three EGF polymorphisms and cancer risk from 21 studies with 14,609 subjects for EGF G61A, from two studies with 2,535 subjects for G-1380A and A-1744G, respectively. For EGF G61A, the contrast of homozygote (OR=0.80, 95% CI=0.65-0.98), allele (OR=0.90, 95% CI=0.81-0.99) and dominant model (OR=0.86, 95% CI=0.74-0.99) produced significant association among 21 studies with relatively large heterogeneity (Pheterogeneity<0.001). Through the stratified analysis, heterogeneity decreased significantly. In the stratified analysis by racial descent, the significant risks were found among Asians for homozygote contrast (OR=0.83, 95% CI=0.69-0.99, Pheterogeneity=0.506) and Americans for the contrast of homozygote (OR=0.50, 95% CI=0.30-0.84, Pheterogeneity=0.051), allele (OR=0.70, 95% CI=0.51-0.96, Pheterogeneity=0.008) and dominant model (OR=0.57, 95% CI=0.42-0.77, Pheterogeneity=0.28). No significant associations were found in all Caucasians genetic models. In the subgroup analyses by cancer types, for gastric cancer and esophageal cancer significant associations were found in all genetic models without heterogeneity. Significant risk was also found in the contrast of homozygote (OR=0.41, 95% CI=0.20-0.81, Pheterogeneity=0.184) and recessive model (OR=0.53, 95% CI=0.33-0.85, Pheterogeneity=0.384) for hepatoma and recessive model (OR=0.72, 95% CI=0.53-0.99, Pheterogeneity=0.474) for glioma. For EGF G-1380A and A-1744G, no significant associations were found in all genetic models. This meta-analysis suggests that the EGF G61A polymorphism most likely contributes to decreased susceptibility to cancers among Asians and Americans, and A allele may be a protective factor for gastric cancer, esophageal cancer, hepatoma and glioma. Both EGF G-1380A and A-1744G is marginally associated with cancer susceptibility.
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PMID:Association between EGF promoter polymorphisms and cancer risk: a meta-analysis. 2003 94

The delivery of genes or viruses via liposomes is a common approach used to enhance delivery efficiency. In the current study, to enhance delivery efficiency, proteoliposomes (PLs) containing adenovirus (Ad) were synthesized with dimyristoylphosphatidylcholine (DMPC), cholesterol, and apolipoprotein A-I (apoA-I). Wildtype apoA-I (WT) or V156K-apoA-I (V156K) was then used as an apolipoprotein to compare the structural and functional differences of the PLs. The particle diameter of V156K-PL-Ad was slightly larger than that of WT-PL-Ad, based on native gel electrophoresis. V156K showed more rapid phospholipid bilayer formation than did the WT, based on DMPC clearance. In addition, V156K exhibited maximal fluorescence that was more blue than that of WT in the PL state. Moreover, isothermal denaturation in response to the addition of guanidine hydrochloride (Gnd-HCl) revealed that V156K was more resistant, with no denaturation until 3 M Gnd-HCl was added. In addition, electron microscopy revealed that the viral particles were well associated with PL particles, which had a discoidal structure and were shaped like rouleaux. In addition, treatment of Ad in the PL state showed enhanced green fluorescent protein (GFP) expression when compared with treatment with Ad alone or with DMPC-Ad in hepatoma and brain glioma cells. Cells treated with WT-PL-Ad and V156K-PL-Ad showed approximately 50% more GFP expression than cells treated with Ad alone or with DMPC-Ad after 24 hr of incubation at 37 degrees C, indicating that viral stability was highly increased in the PL state. Furthermore, V156K-PL-Ad showed the highest expression of GFP in adult zebrafish (9 weeks old) at 5 days postinjection (10.5- and 3.8-fold more GFP expressed than by Ad only and DMPC-Ad, respectively). In conclusion, the efficiency of viral delivery and the stability of the virus were significantly enhanced when PLs containing apoA-I were used in cellular and zebrafish models.
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PMID:Enhanced delivery of adenovirus, using proteoliposomes containing wildtype or V156K apolipoprotein A-I and dimyristoylphosphatidylcholine. 2003 14


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