Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

A cluster of mutagenesis revealed an osmotic regulatory role of the OsPIP1 genes in enhancing rice salt tolerance

Aquaporins play important regulatory roles in improving plant abiotic stress tolerance.To better understand whether the Os PIP1 genes collectively dominate the osmotic regulation in rice under salt stress,a cluster editing of the Os PIP1;1,Os PIP1;2 and Os PIP1;3 genes in rice was performed by CRISPR/Cas9 system.Sequencing showed that two mutants with Cas9-free,line 14 and line 18 were successfully edited.Briefly,line 14 deleted a single C base in both the Os PIP1;1 and Os PIP1;3 genes,and inserted a single T base in the Os PIP1;2 gene,respectively.While line 18 demonstrated an insertion of a single A base in the Os PIP1;1gene and a single T base in both the Os PIP1;2 and Os PIP1;3 genes,respectively.Multiplex editing of the Os PIP1 genes significantly inhibited photosynthetic rate and accumulation of compatible metabolites,but increased MDA contents and osmotic potentials in the mutants,thus delaying rice growth under salt stress.Functional loss of the Os PIP1 genes obviously suppressed the expressions of the Os PIP1,Os SOS1,Os CIPK24 and Os CBL4 genes,and increased the influxes of Na+and effluxes of K^(+)/H^(+)in the roots,thus accumulating more Na+in rice mutants under salt stress.This study suggests that the Os PIP1 genes are essential modulators collectively contributing to the enhancement of rice salt stress tolerance,and multiplex editing of the Os PIP1 genes provides insight into the osmotic regulation of the PIP genes.

High-resolution genetic mapping and identification of candidate genes for the wheat stem rust resistance gene Sr8155B1

Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is the best strategy for controlling the disease.In this study,we performed fine mapping and characterization of the all-stage stem rust resistance(Sr)gene Sr8155B1 from the durum wheat line 8155-B1.In seedling tests of biparental populations,Sr8155B1 was effective against six Chinese Pgt races tested.In a segregating population of 5060 gametes,Sr8155B1 was mapped to a 0.06-cM region flanked by markers Pku2772 and Pku43365,corresponding to 1.5-and 2.7-Mb regions in the Svevo and Chinese Spring reference genomes.Both regions include several typical nucleotide-binding leucine-rich repeat(NLR)and protein kinase genes that represent candidate genes.Among them,three NLR genes and three receptor-like protein kinases were highly polymorphic between the parental lines and their transcripts were upregulated in the homozygous resistant line TdR2 relative to its susceptible sister line TdS4.Four markers(Pku2772,Pku43365,Pku2950,and Pku3721)developed in this study,together with seedling resistance responses,correctly predicted Sr8155B1 absence or presence in 78 tetraploid wheat genotypes tested.The presence of Sr8155B1 in tetraploid wheat accessions CItr 14916,PI 197492,and PI 197493 was confirmed by mapping in three F_(2)populations.The genetic map and linked markers developed in this study may accelerate the deployment of Sr8155B1-mediated resistance in wheat breeding programs.

Regulatory role of NFAT1 signaling in articular chondrocyteactivities and osteoarthritis pathogenesis

Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartilage remains themajor hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding orreversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development isa critical barrier to progress in OA therapy. Recent studies by the current authors’ group and others have revealedthat the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulatesthe expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. Thisreview mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities ofarticular chondrocytes and its implication in the pathogenesis of OA.

Changes of p53 and Waf1p21 and cell proliferation in esophageal carcinogenesis

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大鼠Neurogenesin-1基因真核表达载体的构建及在cos-7细胞中的表达

目的克隆大鼠海马中Neurogenesin-1(Ng1)基因片段,构建pSecTag2/HygroB-Ng1真核表达载体,并检测其在cos-7细胞中的表达,为进一步研究该基因对脊髓神经干细胞分化的影响提供实验依据。方法在无RNA酶污染的条件下提取出大鼠海马总RNA。利用逆转录聚合酶链反应扩增出Ng1基因片段。将该基因片段连接到真核表达载体pSecTag2/HygroB,聚合酶链反应初步筛选,双酶切鉴定后送测序。将构建成功的重组真核表达载体转染入cos-7细胞,Westernblot鉴定重组Ng1蛋白的表达。结果逆转录聚合酶链反应成功获得大鼠Ng1cDNA。随机挑选10个重组真核表达载体的克隆,聚合酶链反应筛选出阳性克隆2个,经双酶切鉴定、测序及Blast分析鉴定重组质粒构建成功。脂质体介导转染cos-7细胞48h后,Westernblot鉴定重组Ng1蛋白在cos-7细胞中的表达,在46ku处出现阳性条带。结论大鼠海马Ng1基因的真核表达载体pSecTag2/HygroB-Ng1构建成功,转染cos-7细胞后能够表达重组Ng1蛋白。

New perspectives in prognostication of hepatocellular carcinoma:The role and clinical implications of transient receptor potential family genes

The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.

NS特异性干扰载体pGenesil-1-NS的构建及鉴定

目的核干细胞因子(nucleostemin,NS)是维持干细胞和癌细胞增殖所必需的蛋白质,可能成为肿瘤基因治疗的潜在靶点.本文旨在构建靶向NS干扰载体p Genesil-1-NS,为后续实验奠定基础.方法基于已发布的NS mRNA序列(NM_206825),选取5'-AAGCCTA GGAAAGACCCAGG-3'(397-416)作为候选靶序列,按shRNA载体设计原则,设计合成两条互补DNA链,退火后插入载体,并以酶切和测序鉴定重组转化子.结果经酶切及测序鉴定证实合成序列正确插入载体.结论成功构建NS特异性干扰载体p Genesil-1-NS,可用于NS在肿瘤中的功能研究.

Study on the Function of ORF Genes of Porcine Circovirus-like Virus P1

[Objectives]This study was conducted to determine the functions of eight ORF genes of porcine circovirus-like virus P1.[Methods]The double-copy tandem molecular cloning of porcine circovirus-like virus P1 genome was used to construct molecular clones with eight ORFs deleted by DNA site-directed mutagenesis technology.After transfected into PK15 cells for a certain period of time,RNA were extracted and was used to verify whether the eight ORFs were deleted or not and used for gene microarry analysis.The GO functions and KEGG pathway enrichment of differentially expressed genes were analyzed.[Results]P1 ORF1 is mainly involved in the biological processes of defense response to virus,signal transduction,regulation of Rab GTPase activity,and lipid metabolic process,and involved in the molecular functions of protein phosphatase inhibitor activity,phosphatidylinositol phospholipase C activity,2 iron,2 sulfur cluster binding,phosphoric diester hydrolase activity,and Rab GTPase activator activity,and in the KEGG pathways of secretion of digestive gland and nervous system development.P1 ORF2 is mainly involved in the biological processes of positive regulation of leukocyte chemotaxis,positive regulation of cell proliferation,positive regulation of cell migration,defense response to virus,regulation of cell growth,and involved in the molecular functions of insulin-like growth factor binding,and chemokine activity,and in the KEGG pathways of cytosolic DNA-sensing pathway,RIG-I-like receptor signaling pathway,toll-like receptor signaling pathway,chemokine signaling pathway,and cytokines,cytokine-cytokine receptor interaction.The biological processes,molecular functions and related pathways involving P1 ORF3 and ORF5 are basically similar to those of ORF2.P1 ORF8 is mainly involved in the biological processes of purine ribonucleotide biosynthetic process,amino acid transport,defense response to virus,amino acid transmembrane transport,and involved in molecular functions of N6-(1,2-dicarboxyethyl)AMP AMP-lyase(fumarate-forming)activity,iron-sulfur cluster binding,amino acid transmembrane transporter activity.[Conclusions]The analysis of the ORF functions of P1 virus lays a foundation for the study of its pathogenicity and pathogenesis.

The Effects of Dwarfing Genes (Rht-B1b, Rht-D1b, and Rht8) with Different Sensitivity to GA_3 on the Coleoptile Length and Plant Height of Wheat

Understanding the effects of wheat dwarfing genes on the coleoptile length and plant height is crucial for the proper utilization of dwarfing genes in the improvement of wheat yield. Molecular marker analysis combined with pedigree information were used to classify wheat cultivars widely planted in major wheat growing regions in China into different categories based on the dwarfing genes they carried. The effects of the dwarfing genes with different sensitivity to gibberellins （GA3） on the coleoptile length and plant height were analyzed. Screening of 129 cultivars by molecular marker analysis revealed that 58 genotypes of wheat contained the dwarfing gene Rht-B1b, 24 genotypes of wheat contained Rht-D1b gene and 73 genotypes of wheat possessed Rht8 gene. In addition, among these 129 cultivars, 35 genotypes of wheat cultivars contained both Rht-B1b and Rht8 genes and 16 genotypes of wheat cultivars contained both Rht-D1b and Rht8 genes. Wheat cultivars with the dwarfing genes Rht-B1b or Rht-D1b were insensitive to GA3, while the cultivars with the dwarfing gene Rht8 were sensitive to GA3. Most of the wheat genotypes containing combination of Rht8 gene with either Rht-B1b or Rht-D1b gene were insensitive to GA3. The plant height was reduced by 24.6, 30.4, 28.2, and 32.2%, respectively, for the wheat cultivars containing Rht-B1b, Rht-D1b, Rht-B1b ＋ Rht8, and Rht-D1b ＋ Rht8 genes. The plant height was reduced by 14.3% for the wheat cultivar containing GA3-sensitive gene Rht8. The coleoptile length was shortened by 25.4, 31.3, 28.4 and 31.3%, respectively, in the wheat cultivars containing Rht-B1b, Rht-D1b, Rht-B1b ＋Rht8 and Rht-D1b ＋ Rht8 genes, while the coleoptile length was shortened only by 6.2% for the wheat cultivar containing Rht8 gene. We conclude that GA3-insensitive dwarfing genes （Rht-B1b and Rht-D1b） are not suitable for the wheat improvement in dryland because these two genes have effect on reducing both plant height and coleoptile length. In contrast, GA3- sensitive dwarfing gene （Rht8） is a relatively ideal candidate for the wheat improvement since it significantly reduces the plant height of wheat, but has less effect on the coleoptile length.

EMP-1 Promotes Tumorigenesis of NSCLC through PI3K/AKT Pathway

This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and immunohis to chemically detected to evaluate the correlation of EMP-1 expression to the clinical features of NSCLC. Recombinant adenovirus was constructed to over-express EMP-1 and then infect PC9 cells. Cell proliferation was measured by Ki67 staining. Western blotting was performed to examine the effect of EMP-1 on the PI3K/AKT signaling. Moreover, tumor xeno-grafts were established by subcutaneous injection of PC9 cell suspension (about 5×107/mL in 100 μL of PBS) into the right hind limbs of athymic nude mice. The results showed EMP-1 was significantly up-regulated in NSCLC patients as compared with those with benign lung diseases. Over-expression of EMP-1 promoted proliferation of PC9 cells, which coincided with the activation of the PI3K/AKT pathway. EMP-1 promoted the growth of xenografts of PC9 cells in athymic nude mice. It was concluded that EMP-1 expression may contribute to the development and progress of NSCLC by activating PI3K/AKT pathway.

Systemic acquired resistance, NPR1, and pathogenesis-related genes in wheat and barley

In Arabidopsis, systemic acquired resistance （SAR） is established beyond the initial infection by a pathogen or is directly induced by treatment with salicylic acid （SA） or its functional analogs, 2,6-dichloroisonicotinic acid （INA） and benzothiadiazole （BTH）. NPR1 protein is considered the master regulator of SAR in both SA signal sensing and transduction. In wheat （Triticum aesfivum） and barley （Hordeum vulgare）, both pathogen infection and BTH treatment can induce broad-spectrum resistance to various diseases, including powdery mildew, leaf rust, Fusarium head blight, etc. However, three different types of SAR-like responses including acquired resistance （AR）, systemic immunity （SI）, and BTH-induced resistance （BIR） seem to be achieved by activating different gene pathways. Recent research on wheat and barley NPR1 homologs in AR and SI has provided the initial clue for understanding the mechanism of SAR in these two plant species. In this review, the specific features ofAR, Si, and BIR in wheat and barley were summarized and compared with that of SAR in model plants of Arabidopsis and rice. Research updates on downstream genes of SAR, including pathogenesis-related （PR） and BTH-induced genes, were highlighted.

Characterization of NPR1 Genes from Norton and Cabernet Sauvignon Grapevine

Non-expressor of pathogenesis-related genes 1 （NPR1） plays a significant role in the defense responses of plants to pathogens by regulating the expression of defense-related genes. In the present study, we isolated two NPR1 genes from Vitis aestivalis cv. Norton and Vitis vinifera cv. Cabernet Sauvignon, which were referred to as VaNPR1.1 and VvNPR1. 1-CS, respectively. They encode a protein of 584 amino acids with a predicted molecular weight of 64.8 kDa and a theoretical isoelectric point （pI） of 5.74. The predicted amino acid sequences of VaNPR1.1 and VvNPR1.1-CS differ by only one amino acid. Over-expression of VaNPR1.1 gene in Arabidopsis npr1-1 mutant plants restores the transcriptional expression of AtPR-1 gene, though not to the full scale. This result demonstrated that a grapevine VaNPR1.1 possesses a similar function to the Arabidopsis NPR1 in the regulation of defense-related genes. Over-expression of VaNPR1.1 in transgenic Arabidopsis plant increased tolerance to salinity, but had no effect on the drought tolerance. We conclude that VaNPR1.1 is a functional ortholog of AtNPR1 and also involved in grapevine＇s response to the salt stress.

TfR1 Extensively Regulates the Expression of Genes Associated with Ion Transport and Immunity

Transferrin receptor 1(TfR1),encoded by the TFRC gene,is the gatekeeper of cellular iron uptake for cells.A variety of molecular mechanisms are at work to tightly regulate TfR1 expression,and abnormal TfR1 expression has been associated with various diseases.In the current study,to determine the regulation pattern of TfR1,we cloned and overexpressed the human TFRC gene in HeLa cells.RNA-sequencing(RNA-seq)was used to analyze the global transcript levels in overexpressed(OE)and normal control(NC)samples.A total of 1669 differentially expressed genes(DEGs)were identified between OE and NC.Gene ontology(GO)analysis was carried out to explore the functions of the DEGs.It was found that multiple DEGs were associated with ion transport and immunity.Moreover,the regulatory network was constructed on basis of DEGs associated with ion transport and immunity,highlighting that TFRC was the node gene of the network.These results together suggested that precisely controlled TfR1 expression might be not only essential for iron homeostasis,but also globally important for cell physiology,including ion transport and immunity.

PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

Host markers and correlated mutations in the overlapping genes of influenza viruses: M1, M2;NS1, NS2;and PB1, PB1-F2

The influenza A viruses have three gene segments, M, NS, and PB1, which code for more than one protein. The overlapping genes from the same segment entail their interdependence, which could be reflected in the evolutionary constraints, host distinction, and co-mutations of influenza. Most previous studies of overlapping genes focused on their unique evolutionary constraints, and very little was achieved to assess the potential impact of the overlap on other biological aspects of influenza. In this study, our aim was to explore the mutual dependence in host differentiation and co-mutations in M, NS, and PB1 of avian, human, 2009 H1N1, and swine viruses, with Random Forests, information entropy, and mutual information. The host markers and highly co-mutated individual sites and site pairs (P values < 0.035) in the three gene segments were identified with their relative significance between the overlapping genes calculated. Further, Random Forests predicted that among the three stop codons in the current PB1-F2 gene of 2009 H1N1, the significance of a mutation at these sites for host differentiation was, in order from most to least, that at 12, 58, and 88, i.e., the closer to the start of the gene the more important the mutation was. Finally, our sequence analysis surprisingly revealed that the full-length PB1-F2, if the three stop codons were all mutated, would function more as a swine protein than a human protein, although the PB1 of 2009 H1N1 was derived from human H3N2.

Expansion and expression diversity of FAR1/FRS-like genes provides insights into flowering time regulation in roses

Roses are important horticultural plants with enormous diversity in flowers and flowering behavior.However,molecular regulation of flowering time variation in roses remains poorly characterized.Here,we report an expansion of the FAR1/FRS-like genes that correlates well with the switch to prostrate-toerect growth of shoots upon flowering in Rosa wichuraiana‘Basye's Thornless'(BT).With the availability of the high-quality chromosome-level genome assembly for BT that we developed recently,we identified 91 RwFAR1/FRS-like genes,a significant expansion in contrast to 52 in Rosa chinensis‘Old Blush’(OB),a founder genotype in modern rose domestication.Rose FAR1/FRS-like proteins feature distinct variation in protein domain structures.The dispersed expansion of RwFAR1/FRS-like genes occurred specifically in clade I and II and is significantly associated with transposon insertion in BT.Most of the RwFAR1/FRS-like genes showed relatively higher expression level than their corresponding orthologs in OB.FAR1/FRS-like genes regulate light-signaling processes,shade avoidance,and flowering time in Arabidopsis thaliana.Therefore,the expansion and duplication of RwFAR1/FRS-like genes,followed by diversification in gene expression,might offer a novel leverage point for further understanding the molecular regulation of the variation in shoot-growth behavior and flowering time in roses.

Cigarette smoking, dietary habits and genetic polymorphisms in GSTT1, GSTM1 and CYP1A1 metabolic genes: A case-control study in oncohematological diseases

AIM To analyze the association between oncohematological diseases and GSTT1 /GSTM1 /CYP1A1 polymorphisms, dietary habits and smoking, in an argentine hospitalbased case-control study.METHODS This hospital-based case-control study involved 125 patients with oncohematological diseases and 310 control subjects. A questionnaire was used to obtain sociodemographic data and information about habits. Blood samples were collected, and DNA was extracted using salting out methods. Deletions in GSTT1 and GSTM1 (null genotypes) were addressed by PCR. CYP1A1 MspI polymorphism was detected by PCR-RFLP. Odds ratio(OR) and 95%CI were calculated to estimate the association between each variable studied and oncohematological disease.RESULTS Women showed lower risk of disease compared to men(OR 0.52, 95%CI: 0.34-0.82, P = 0.003). Higher levels of education(> 12 years) were significantly associated with an increased risk, compared to complete primary school or less(OR 3.68, 95%CI: 1.82-7.40, P < 0.001 adjusted for age and sex). With respect to tobacco, none of the smoking categories showed association with oncohematological diseases. Regarding dietary habits, consumption of grilled/barbecued meat 3 or more times per month showed significant association with an increased risk of disease(OR 1.72, 95%CI: 1.08-2.75, P = 0.02). Daily consumption of coffee also was associated with an increased risk(OR 1.77, 95%CI: 1.03-3.03, P = 0.03). Results for GSTT1, GSTM1 and CYP1A1 polymorphisms showed no significant association with oncohematological diseases. When analyzing the interaction between polymorphisms and tobacco smoking or dietary habits, no statistically significant associations that modify disease risk were found. CONCLUSION We reported an increased risk of oncohematological diseases associated with meat and coffee intake. We did not find significant associations between genetic polymorphisms and blood cancer.

Effects of adenoviral vector-mediated transduction of human p53,B7-1 and GM-CSF genes on liver cancer cells

The potential efficacy and clinical feasibility of gene therapy for liver cancer were tested through therecombinant adenovirus-mediated (Ad-multigenes ) co-transfer of human wild-type p53, B7-l co-stimulation(CD8o) and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes into human hepatocellular carcinoma cell lines. The treated cells underwent apoptosis with specific DNA fragmentation and became more sensitiveto cisplatin, a chemotherapeutic drug. Their growth was partly inhibited. Efficient proliferation and generation ofCTLs and cytokine production were induced in mixed lymphocytes through tumor cell reaction (MLTR) using peripheral blood T lymphocytes from donors as effector cells and Ad-multigenes or Ad-p53-transfected human hepatocellular carcinoma cells (HepG2 or BEL7402) as stimulator cells. Ad-multigenes-transfected rat carcinosarcomaWalker 256 cells were inoculated subcutaneously into normal rats. Fourteen days later, the activity of spleen cellsin rats inoculated with Ad-multigenes-transduced Walker 256 cells was higher than that in Ad-p53-transducedones. These findings suggest that adenovirus-mediated multigenes p53, B7-1 and GM-CSF can induce apoptosis ofliver cancer cells and initiate a potent antitumor immune response against them.