Alpha-fetoprotein reactive to pisum sativum agglutinin (AFP-R-P) in liver tumor tissues, surrounding noncancerous tissues and peripheral blood from 25 cases of primary liver cancer were measured. Their medium and standard deviation were 41 ?26%, 30?27% and 36?25%, respectively. AFP-R-P levels were lower in the tumors with a diameter of less than 3cm, intact capsule, no invasion of surrounding liver tissues and no tumor thrombus. The patients with lower AFP-R-P levels had a longer survival. The results indicate that AFP-R-P is secreted mainly by tumor cells possessing more malignant behaviour, diffused directly in surrounding liver tissues and entered into peripheral blood, resulting in elevated serum AFP-R-P.

The increased binding of serum a-fetoprotein (AFP) from patients with hepatocellular carcinoma (HCC) to fucose-recognizing lectins has been reported. In order to study the enzymatic basis of this alteration, the serum activities of a-L-fucosidase (AFU) and fucosylated AFP (F-AFP) were determined in serum samples from 90 patients with HCC. Serum F-AFP levels were not related with serum AFU activities in HCC patients. When HCC patients grouped according to AFU activities were analyzed, the mean F-AFP level in 47 patients with a AFU activity below 550 nmol. ml-1. h-1 was 40%?23%, while the corresponding value for 43 patients with a AFU activity above 550 nmol . ml-1. h-1 was 45%?22%. No statistical significance was found between these values. The results indicate that changes in sugar chain structure of AFP in HCC patients do not result from increased or decreased activities of serum AFU.

Objective To study the protection against hepatic ischemia-reperfusion injury by human IL-10 gene transduction in rats. Methods Ad-hIL10-EGFP (1. 0 ? 109 plaque forming units/ml) was administered into SD rats by intravenous injection 72 hours before hepatic ischemia-reperfusion injury was induced. Liver function were tested and HE pathology was observed. The expression of hIL-10 was studied with ELISA or immunohistochemical method, the expression of EGFP was observed in frozen sections under the fluoroscopy. The apoptosis of hepatocytes was observed with Tunel's assay. Results Compared with control rats, the expression of EGFP and hIL-10 was observed, serum hIL-10 level was (815.74 ? 284. 76) ng/ml, liver function of treatment rats were improved, the paraffin sections showed that the hepatocytes were not significantly swelling and liver pathology ameliorated, the number of apoptosis cells decreased (P

Gallbladder carcinoma is a common malignant tumor of the biliary system characterized by poor specificity of early symptoms， a high degree of malignancy， and rapid progression， and it is difficult to make an early diagnosis. Gallstones and gallbladder polyps are considered the most common risk factors for gallbladder carcinoma. Ultrasound is the preferred examination， while CT， MRI， and PET also have their own advantages. There is a lack of radical treatment methods for gallbladder carcinoma， and surgical operation remains the preferred treatment method for gallbladder carcinoma； however， due to the rapid progression of this disease， most patients have lost the opportunity for surgery at the time of diagnosis. A combination of various treatment modalities， such as radiochemotherapy， targeted therapy， and immunotherapy， has improved the prognosis of patients to a certain extent， but with an unsatisfactory long-term therapeutic effect. Therefore， it is of particular importance to give priority to prevention rather than treatment and emphasize early identification and treatment.

OBJECTIVETo study the injection of NKG5SV gene to inhibit growth and metastasis of hepatocellular carcinoma (HCC).

METHODSNKG5SV gene was inserted into retroviral vector pLXSN by normal methods. LacZ gene was used as control. LCI-D20 tumor together with saline, pLXSN-LacZ DNA or pLXSN-NKG5SV was subcutaneously inoculated to the nude mice. Tumor formation rate and tumor size were noted 35 days after inoculation. LCI-D20 tumor was inoculated subcutaneously. Saline, pLXSN-LacZ DNA or pLXSN-NKG5SV was intratumorally injected respectively 10 days after inoculation. Tumor growth was observed 35 days after inoculation. Liver cancer was resected 22 days after intrahepatic inoculation. Saline, pLXSN-LacZ DNA or pLXSN-NKG5SV was respectively injected at incisal margin or intraspleen. Mice were killed 35 days after inoculation to observe tumor recurrence at incisal margin, intrahepatic metastasis and extrahepatic metastasis.

RESULTSTumor formation rate and tumor diameter(cm) were 1.76 +/- 0.11, 1.51 +/- 0.34, 0.33 +/- 0.04 in the control group, LacZ group, NKG5SV group respectively when tumor and different cDNA were inoculated together. Tumor diameter(cm) and weight(g) were 0.87 +/- 0.08, 0.83 +/- 0.05, 0.26 +/- 0.04; 0.43 +/- 0.06, 0.38 +/- 0.04, 0.08 +/- 0.06 in the control group, LacZ group, NKG5SV group respectively when different cDNA were injected into the LCI-D20 tumor. Sites with extrahepatic metastasis nidi, incisal margin recurrence tumor size(cm), intrahepatic metastasis nidi, metastasis involved hepatic lobes in the control group, LacZ group, NKG5SV group were 4.25 +/- 1.48, 4.25 +/- 1.04, 0.63 +/- 0.51; 1.51 +/- 0.27, 1.35 +/- 0.17, 0.81 +/- 0.17; 2.50 +/- 1.41, 2.38 +/- 1.06, 1.25 +/- 0.71; 2.13 +/- 0.99, 2.00 +/- 0.75, 1.38 +/- 0.74 respectively when NK cells were injected at incise margin. They were 4.38 +/- 1.85, 4.25 +/- 1.48, 1.00 +/- 0.75; 1.13 +/- 0.23, 0.97 +/- 0.29, 0.76 +/- 0.16; 2.50 +/- 1.41, 2.05 +/- 1.12, 0; 2.13 +/- 0.83, 1.75 +/- 0.88, 0 respectively when NK cell were injected intrasplenicly.

CONCLUSIONSNKG5SV gene can inhibit HCC growth and postoperative metastasis and recurrence.

Animals ; Antigens, Differentiation, T-Lymphocyte ; Cell Division ; drug effects ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; genetics ; Humans ; Injections ; Liver Neoplasms, Experimental ; genetics ; pathology ; therapy ; Male ; Mice ; Mice, Nude ; Neoplasm Metastasis ; prevention & control ; Receptors, Immunologic ; genetics ; physiology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays

OBJECTIVETo develop a new kind of vector system called gene-viral vector, which combines the advantages of gene and virus therapies.

METHODSUsing recombinant technology, an anti-tumor gene was inserted into the genome of replicative virus specific for tumor cells. The cell killing effect, reporter gene expression of the green fluorescence protein, anti-tumor gene expression of mouse interleukin-12 (mIL-12) and replication of virus were observed by the methods of cell pathology, fluorescence microscopy, ELISA and electron microscopy, respectively.

RESULTSA new kind of gene-viral vector system of adenovirus, in which the E1b-55 kD gene was deleted but the E1a gene was preserved, was constructed. The vector system, like the replicative virus ONYX-015, replicated and proliferated in tumor cells but not in normal ones. Our vector had an advantage over ONYX-015 in that it carried different kinds of anti-tumor genes to enhance its therapeutic effect. The reporter gene expression of the green fluorescence protein in tumor cells was much better than the adenovirus vector employed in conventional gene the rapy, and the expression in our vector system was as low as or even less than that in the conventional adenovirus gene therapy system. Similar results were observed in experiments with this vector system carrying the anti-tumor gene mIL-12. Replication and proliferation of the virus carrying the mIL-12 gene in tumor cells were confirmed by electron microscopy.

CONCLUSIONSGene-viral vectors are new vectors with an anti-tumor gene inserted into the genome of replicative virus specific for tumor cells. Because of the specific replication and proliferation of the virus in tumor cells, expression of the anti-tumor gene is increased hundreds to thousands of times. This approach takes full advantages of gene therapy and virus therapy to enhance the effect on the tumor. It overcomes the disadvantages of conventional gene therapy, such as low transfer rate, low gene expression, lack of target tropism, and low anti-tumor activity. We believe that this is a promising means for future tumor treatment.

Adenoviridae ; genetics ; Adenovirus E1A Proteins ; genetics ; Adenovirus E1B Proteins ; genetics ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; Humans ; Interleukin-12 ; genetics ; Neoplasms ; therapy ; Recombination, Genetic ; Tumor Cells, Cultured ; Virus Replication

We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ ₂) receptor ligands. Two ligands with high σ ₂ receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [¹⁸F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[¹⁸F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ ₂ receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [¹⁸F]9 to σ ₂ receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [¹⁸F]9 in the brain that is consistent with the distribution pattern of σ ₂ receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [¹⁸F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [¹⁸F]9 as the first highly specific and promising imaging agent for σ ₂ receptors in the brain.