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Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 21, 2006; 12(3): 380-387
Published online Jan 21, 2006. doi: 10.3748/wjg.v12.i3.380
Gene therapy for gastric cancer: Is it promising?
Andreas P Sutter, Henry Fechner, Department of Gastroenterology/Infectious Diseases/Rheumatology and Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
Correspondence to: Dr. Andreas Sutter, Schering AG, Experimental Toxicology, Müllerstr. 178, 13342 Berlin, Germany.
Telephone: +49-30-468-18761 Fax: +49-30-468-15091
Received: June 22, 2005
Revised: June 28, 2005
Accepted: July 30, 2005
Published online: January 21, 2006


Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer, including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy. This review provides an update of the new developments in cancer gene therapy, new principles, techniques, strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.

Key Words: Gene therapy, Gastric cancer, Virotherapy


Gastric cancer is the fourth most common malignancy worldwide with an estimated 934 000 new cases that was reported in 2002 and the second most common cause of death from cancer (700 000 deaths annually). Almost two-thirds of the cases occur in developing countries and 42% in China alone[1]. The prognosis of gastric cancer is poor with an estimated relative 5-year survival rate of less than 20%[2]. The efficacy of current therapeutic approaches such as surgery, hormone, radio- and chemotherapy is limited. Thus, new therapeutic approaches are urgently needed. Cancer is an acquired genetic disease developing in a multi-step process. Mutations of genes related to growth control, apoptosis, invasion and metastasis form the molecular genetic basis of malignant transformation and tumor progression[3]. The characterization of dysregulated genes like the tumor suppressor p53, which are critical for carcinogenesis, and a better understanding of the molecular basis for tumor-host interaction led to significant progress in the development of new therapeutic agents. More than 15 years ago, gene therapy emerged as a new therapeutic approach and has meanwhile become an important strategy in cancer treatment. Cancer is by far the most frequent of all indications addressed by gene therapy (60% of all clinical trials[3]), underlining the expectations raised by this new therapeutic option. The original concept of cancer gene therapy was further developed into two branches as a result of different strategies of therapeutic benefit: molecular cancer therapy and virotherapy. Molecular cancer therapy can be defined as a therapeutic technique, which aims at the introduction of nucleic acids into cancer patients’ cells in order to modulate the gene expression profile of the target cells and thereby eradicate the tumor[4]. In contrast, virotherapy is a new concept of gene therapy that uses replication-competent oncolytic viral vectors (OVV) with viro-oncolytic potency for targeted tumor cell destruction[5].

There are different ways to modulate tumor growth by gene therapeutic strategies. These include direct destruction of tumor cells, inhibition of tumor angiogenesis and tumor cell spread and activation of the host immune response against the tumor. Although all these approaches showed promising anti-tumor effects in pre-clinical investigations, clinical trials have often been disappointing, since they demonstrated only slight therapeutic benefit. Thus, a major breakthrough is still needed in gene therapy of cancer. Nevertheless, clinical trials proved the relative safety of human cancer gene therapy. The application of vectors and the expression of transgenes are generally well tolerated and the low risk of severe side effects seems to be calculable.

The main problem of the relative inefficiency of cancer gene therapy continues to be the low in vivo efficiency of gene delivery into the target tumor cells, leading to low expression of therapeutic genes and thus limited curative effects. Several factors seem to be responsible for this, among them the presence of anatomic barriers inhibiting the efficient transfer of vectors from circulation to target cells and the low expression of vector-specific target receptors on the cancer cells causing reduced cellular uptake of viral vectors. Moreover, immunological responses of the host against the vectors and the rapid clearance of vectors from circulation after intravascular administration may be important factors preventing efficient gene transfer[6-8]. In the last few years, great efforts have been made to overcome these limitations. Especially the development of OVV[9] and vectors with enhanced tumor-specific targeting[10,11] together with improved vector application protocols have led to a significant enhancement of vector-mediated gene delivery. Furthermore, the use of new powerful molecular techniques like RNA interference (RNAi)[12] and the detection of new target genes are hopeful signs for improving human cancer by gene therapy. In the present paper, we review new trends in gene therapy and update their application in gastric cancer.


The most obvious way to target growth regulation in cancer cells is to introduce tumor suppressors that may be inactivated in tumors. The replacement of p53, which is the most commonly inactivated tumor suppressor and mutated in about 60% of human gastric cancers, has emerged as an attractive treatment option, both alone and combined with conventional chemotherapy[13,14]. Introduction of the p53 gene via a recombinant adenovirus has been shown to inhibit the growth of gastric cancer cells with mutated p53 in vitro and in vivo[15,16]. The pro-apoptotic function of p53 depends on the transactivation of genes such as Bax, Apaf-1, Fas, and PTEN, whose own expression or activity may be abnormal in tumor cells[17]. Consequently, the Bax gene may serve as a good alternative to p53 for cancer gene therapy, not only because it has been shown to kill cancer cells irrespective of their p53 status, but also because it may increase their sensitivity to other anti-tumor treatments[18]. Moreover, the adenoviral expression of the initiator caspase-8 leads to the selective induction of apoptosis in detached gastric tumor cells in vitro and in vivo, thus displaying anti-metastatic potential in gastric cancer[19]. All these signaling molecules work through a common pathway involving activation of the effector caspase 3. Thus, recombinant expression of caspase 3 leads to the induction of apoptosis in gastric cancer cells[20]. Moreover, the introduction of wild-type p16INK4A, another tumor suppressor and cell cycle regulator in gastric cancer cells harboring a p16 mutation, may also be a feasible approach to efficient tumor growth control and chemosensitization[21]. Finally, the replacement of Fhit, a tumor suppressor often inactivated in gastric cancer, decreases sensitivity to carcinogens and induces apoptosis in gastric tumor cells in vivo. Therefore, restoring Fhit expression by viral transduction may be a promising strategy for both the prevention and therapy of gastric tumors[22].


This strategy relies on the conversion of non-toxic substances (prodrugs) into physiologically active agents by means of non-mammalian enzymes. These suicide enzymes are over-expressed in neoplastic cells as a result of successful transfection with their genes[23]. The most widely used suicide gene/prodrug system is the herpes simplex virus (HSV) thymidine kinase (HSV-tk)/ganciclovir (GCV) system that can convert the prodrug GCV into phosphorylated GCV. The phosphorylated GCV inhibits cellular DNA synthesis and leads to the killing of cancer cells via apoptotic and non-apoptotic mechanisms[24,25]. One of the powerful features in these systems is the “bystander effect”, the mechanism by which the toxic metabolites are transferred from transduced cells to neighboring cancer cells via gap junctions or apoptotic vesicles. The bystander effect drastically enhances the tumor-killing capacity of the HSV-tk/GCV system[26,27]. Several studies were undertaken to evaluate the potential of suicide gene therapy in gastric cancer. In alpha-fetoprotein (AFP)-producing gastric tumors, the adenovirus-mediated expression of HSV-tk by an AFP enhancer/promoter element selectively eliminated AFP-positive, but not AFP-negative cell lines when treated with ganciclovir[28]. This approach may be a promising tumor-selective treatment option for AFP-positive gastric tumors with a very poor prognosis. A similar approach involves the expression of recombinant E. coli cytosine deaminase (CD) in gastric cancer cells together with the administration of 5-fluorocytosine (5-FC). 5-FC is given orally and converted to 5-fluorouracil in the tumor cells expressing CD. In attempts to increase the specificity of suicide gene therapy, CD expressed from gastric cancer cell-specific promoters SEL1L and TP1 was shown to cause efficient cytotoxic effects in combination with 5-FC[29]. An earlier attempt with tumor-specific and more efficient CD/5-FC gene therapy was carried out using the Cre/loxP regulation system. Ueda et al[30] constructed an adenovector-expressing Cre recombinase from a carcinoembryonic antigen (CEA) promoter and a second vector expressing CD under the control of the CAG promoter. The double infection with both vectors rendered CEA-producing gastric cancer cells 13 times more sensitive to 5-FC than the single infection with a vector expressing CD from the CEA promoter. Consequently, anti-tumor efficacy in vivo was also significantly enhanced by using the Cre/loxP system compared to the single infection with the vector directly expressing CD under the control of the CEA promoter. Finally, recombinant expression of the bacterial enzyme nitroimidazole reductase gene together with the administration of the prodrug CB1954 was evaluated in a phase I and pharmacokinetic study with the intention of treating gastric cancer[31].


Tumor angiogenesis plays an important role in the growth of solid tumors and the formation of metastases. Angiogenesis is a multi-level process including endothelial cell proliferation, migration, basement membrane degradation, and lumen reorganization. It is stimulated by several factors secreted from both host and tumor cells. The principal growth factors driving angiogenesis include, among others, the vascular endothelial growth factor (VEGF), the basic fibroblast growth factor, and the hepatocyte growth factor (HGF)[32]. Thus, there are various potential targets for anti-angiogenic cancer gene therapy. In contrast to other genetic treatments, anti-angiogenic gene therapy does not necessarily require direct and selective transduction of target genes into cancer cells, but rather transduction around the tumor to create an anti-angiogenic environment[33]. This advantage helps to overcome the limitations of the currently available vector systems, which often lack adequate transduction efficiency in cancer cells. Several studies were undertaken to evaluate the potential of anti-angiogenic gene therapy in gastric cancer. One study demonstrated that, if expressed from adenovector-transduced peritoneal mesothelial cells, the soluble VEGF receptor sFlt-1 is able to inhibit the peritoneal dissemination of gastric cancer in vivo and consequently prolong the survival of treated animals[33]. Another study evaluated the therapeutic efficacy of the HGF antagonist NK4, which is known for its inhibitory effects on several angiogenetic pathways. Application of an NK4-expressing adenovector inhibited the formation of both peritoneal metastases and intra-tumor vessels in gastric cancer in vivo[34]. New potential targets for anti-angiogenic gene therapy of gastric cancer were recently discovered. Meng et al[35] and Xue et al[36] showed that silencing Raf-1 and Rac1 GTPase, which are critical factors in hypoxia-induced gene activation of several angiogenesis factors, results in downregulation of the angiogenesis-promoting factors VEGF and Hif-1α and upregulation of the tumor suppressors and angiogenesis inhibitors p53 and VHL. Furthermore, downregulation of Raf-1 and Rac1 GTPase leads to tumor cell apoptosis and significantly inhibits cell proliferation. Similarly, Stoeltzing et al[37] showed that direct suppression of Hif-1α resulted in decreased secretion of VEGF, thereby impairing tumor growth, angiogenesis and vessel maturation in vivo.


Genetic immunotherapy aims at improving the host’s immune response to a particular tumor and is currently one of the most promising gene therapeutic options for cancer. The function of the immune system is very complex and its activation in gene therapeutic settings can be achieved by employing different strategies[38]. One of the most common strategies in immunotherapy of cancer is the use of mediators of the immune system. Among them, IL-2, IL-12, INF-γ, GM-CSF and TNF-α have raised special attention and several trials have proved their efficacy in cancer gene therapy[39-42]. New developments indicate further improvement of the benefit, if cytokine therapy is combined or used with other gene therapeutic options. For example, synergistic anti-tumor effects were achieved by simultaneous expression of IL-2 and INF-γ[40] or by combining an oncolytic adenovirus (oAdV) with IL-12 immunotherapy[43].

Based on this knowledge, studies were carried out in order to prove the efficacy of immunotherapy in combination with other gene therapeutic strategies in gastric cancer. Zhang et al[44-46] evaluated the anti-tumor effects of the HSV-tk/GCV system together with the expression of recombinant IL-2 or TNF-α in gastric cancer. In contrast to their disappointing results in vitro[46], they observed enhanced anti-tumor effects by HSV-tk/GCV suicide gene therapy combined with recombinant TNF-α expression in vivo[44]. Using a similar protocol, another group found strongly enhanced anti-tumor effects after coexpression of IL-2, GM-CSF and HSV-tk/GCV in a gastric cancer model in vivo[47]. These results strongly indicate the potential impact of combined cytotoxic and immunomodulatory gene therapy in gastric cancer. Other immunotherapeutics also demonstrated their potential efficacy in gastric cancer. For example, it was shown that the expression of recombinant intercellular adhesion molecule (ICAM)-2 prolonged the survival of mice with peritoneal metastases of gastric cancer[48]. Meng et al[49] tested the recently discovered gastric carcinoma-specific tumor-associated antigen MG7-Ag in a Salomonella typhimurium vaccine against gastric cancer. In detail, they constructed a recombinant gene vaccine consisting of the MG7-Ag mimotope fused with HBcAg, a protein from HBV enhancing the immunogenicity of its antigens. Oral application of the vaccine in vivo led to increased formation of MG7-Ag antibodies, reduced average tumor weight compared to the controls and prevented tumor growth in one of five immunized mice, thereby indicating some protective effects of the vaccine[50].


Inappropriately expressed genes are a major cause of uncontrolled cell growth. Thus, the specific downregulation of (onco)gene expression leading to tumor growth inhibition is a promising approach in cancer gene therapy[51]. Several years ago, double-strand RNA molecules homologous to the sequence of the target gene were shown to induce post-transcriptional gene silencing (PTGS) in a sequence-specific manner. This mechanism was designated as RNAi[52]. The process of PTGS is initiated by small interfering (si) RNA molecules, which have a length of 21-23 nucleotides[12]. In mammalian cells, siRNAs are incorporated into a large protein complex, the RNA-induced silencing complex, leading to precise degradation of complementary mRNA targets[53]. Due to its extraordinary efficiency, target gene specificity and simplicity of construction, siRNA technology has gained considerable attention as a new tool for gene knockdown and, hence, therapeutic use in cancer gene therapy. Chemically synthesized or in vitro-transcribed siRNAs are widely used for in vitro anti-cancer studies, while their use in vivo revealed several problems. Major limitations in vivo are the generally low transduction efficiency and short half-life. Furthermore, synthetic siRNAs preferentially transduce the liver after systemic application[54], rendering them useless for systemic cancer gene therapy. These obstacles may be overcome by the expression of siRNA from viral vectors. Currently, adenoviral, retroviral and adeno-associated virus vectors have been shown to efficiently express siRNAs resulting in strong downregulation of the target gene[55-57]. In this setting, vector-based expression systems were further developed, enabling tissue-specific and inducible siRNA expression by the use of tissue specific promoters[58] and pharmacologically regulated gene expression systems[55]. Furthermore, siRNA expressed from viral vectors seems to be more stable than synthetic siRNA[59]. Several studies were undertaken to evaluate siRNA technology in gastric cancer. Hong et al[60] constructed a eukaryotic vector expressing siRNA against new zinc ribbon (ZNRD1) gene, which promotes a multi-drug resistant phenotype in gastric cancer through the upregulation of permeability-glycoprotein. After transfection of a ZNRD1 siRNA, a dramatic reduction of ZNRD1 was observed accompanied by a significantly enhanced sensitivity to vincristine, adriamycin and etoposide. Further studies proved the high efficiency of siRNA-mediated gene silencing in gastric cancer cells in vitro[35,59,61-63]. Continuous development of siRNA technology warrants further investigations of its future therapeutic use in gastric cancer in vivo.

Further approaches for the downregulation of tumor genes in gastric cancer, including anti-sense-RNA[64], anti-sense oligonucleotides[65,66], ribozymes[67], and dominant negative forms of tumor proteins[37,68], have also been investigated and may be of potential clinical value in the gene therapy of gastric cancer. While anti-sense strategies preferentially aim at blocking the translation of a target mRNA by complementary binding to its specific mRNA, dominant negative mutant alleles compete with their endogenous homologs for binding in a protein complex, leading to the inhibition of protein function. For example, the insulin-like growth factor (IGF) I receptor is involved in carcinogenesis and proliferation. Its blockade by adenovector-mediated expression of a truncated dominant negative IGF was shown to sensitize gastric tumor cells for chemotherapy and to suppress their peritoneal dissemination in vivo[68]. In another study, Kim et al[66] showed that downregulation of anti-apoptotic protein bcl-2 by administering bcl-2 anti-sense oligonucleotides significantly increased the sensitivity of gastric cancer to chemotherapeutics in vivo.


The limited efficiency of replication-deficient viral vectors to transduce cancer cells and express effector genes in vivo led to the development of a new vector generation called OVV. In contrast to replication-deficient viral vectors, the primary replication cycle of OVV causes viro-oncolyis of initially infected tumor cells, resulting in the release of progeny virions followed by the infection of adjacent cells and the infection and destruction of further tumor mass[69]. Thus, OVV are intended to ultimately destroy a tumor although only a small percentage of tumor cells was initially infected. Furthermore, progeny virions can spread systemically by circulation[70] and infect tumor cells remote from the primary replication site of OVV, thus enhancing the potential therapeutic efficacy in metastatic cancer.

The restriction of OVV replication to cancer cells is a central concern of OVV development. This aim has been achieved by genetic engineering of viral vector genomes (e.g. in herpes- and adenoviruses) either by driving of viral genes essential for virus replication by tumor-specific promoters[71,72] or by inserting mutations into viral genes that abolish their function for viral replication in normal cells but not in tumor cells[73]. Other OVV with inherent oncolytic potency acquire tumor-selective replication competence through defects or dysregulation of cellular genes in cancer cells (e.g. Newcastle virus and vesicular stomatitis virus)[74,75].

Several studies have demonstrated that replication of OVV is 100- to 1 000-fold attenuated in normal cells compared to cancer cells. As shown in oAdVs, OVV safety can be further increased by pharmacological regulation of viral replication, using the rapamycin[76] or the Tet-On gene expression system[77,78] to regulate adenoviral E1A. This now opens the door to permanent external control of OVV during the treatment of patients. Various genetically engineered OVV and viruses with inherent oncolytic properties have recently been explored as anti-cancer agents, among them adenovirus[9,79,80], HSV[81-83], retroviruses[84], vaccinia virus[41], autonomous rodent parvovirus[85], vesicular stomatitis virus[86], Newcastle virus[87], and reoviruses[88-89]. Of these, HSV and adenovirus are the most widely studied ones. ONYX-015 was the first tested oAdV and is to date the most commonly used oAdV in clinical trials. Deletion of the adenoviral E1B-55kD enables the replication of ONYX-015 in cells with a defective p53 pathway and minimizes its replication in cells with a functionally active p53 pathway[9]. Thus, ONYX-015 is unable to replicate in normal cells, but strongly replicates in cancer cells. Several clinical trials have demonstrated the efficacy of ONYX-015 in patients with cancer. Strongest anti-tumor responses were observed in patients with squamous cell cancer of the head and neck[90,91], but responses to hepatocellular carcinoma[92], hepatobiliary tumors[93], and advanced pancreatic cancer[94] were reported, whereas no response was observed in patients with advanced ovarian cancer[95]. Two phase I/II clinical trials have provided evidence for the efficacy of ONYX-015 in metastatic gastrointestinal cancer[96,97]. Reid et al[96] administered ONYX-015 by hepatic artery infusion combined with 5-fluorouracil and leucoverin in 27 patients with both primary gastrointestinal carcinoma and liver metastases. The treatment was well tolerated showing only mild or moderate flu-like symptoms, including fever, myalgia, astenia and/or chills. Virus replication was demonstrated and three partial responses, four minor responses and nine stable diseases were documented as therapeutic outcome. In another study, patients with advanced sarcomas, among them patients with gastrointestinal stromal tumors, were given an intratumoral injection of ONYX-015 combined with MAP chemotherapy. The treatment was well tolerated and there was no significant toxicity. One of the six patients treated showed a partial response with an approximately 70% reduction of tumor size, and in four patients the disease stabilized[97]. Other oncolytic viruses like HSV, Newcastle virus and vaccinia virus also demonstrated their viro-oncolytic efficacy in clinical trials with cancer patients[41,98,99]. On the other hand, the studies revealed therapeutic limitations of the currently available OVV. Often, only a minority of patients shows a response, which is only partial and transient in most of the cases[5,97]. Obviously, there are several major limitations to the therapeutic potential of OVV. The key problems are low infectivity, replication rate and cytolytic activity of OVV. To overcome these limitations, measures have therefore been taken to further develop OVV. The low transduction efficiency of oAdV due to low coxsackie-adenovirus receptor (CAR) expression can be enhanced by modifying the fiber proteins. This can be achieved by adding foreign peptides to the HI loop or the C-terminus of the fiber knob[100,101] or by substituting fibers of adenoviral 2 and 5 with fibers derived from other adenoviruses, which bind to receptor molecules other than CAR[102,103]. These strategies seem to be promising for the treatment of gastric cancer as well, since gastric cancer cells express low amounts of CAR, making it resistant to adenoviral infection[100]. Recently published data demonstrate that oAdV with RGD motif in the HI-loop of the fiber-knob region or replacing its adenovirus type 5 knob by an adenovirus type 3 knob has a stronger anti-tumor effect than unmodified oAdV in a gastric cancer model in vivo[100]. Another study investigated re-targeting a doubly-ablated adenovector to the epithelial cell adhesion molecule (EpCAM) by introducing a bi-specific single-chain antibody to EpCAM. EpCAM is highly expressed in gastric cancer but not in gastric epithelium. Consequently, the vector was highly selective for primary gastric tumors, while transduction of normal gastric epithelium and liver was low[104].

Another way to improve the efficacy of OVV is combining OVV treatment with conventional and other gene therapeutic strategies. Preclinical and clinical data demonstrate that OVV-induced tumor cell killing can be strongly enhanced by the expression of therapeutic transgenes from OVV like anti-angiogenetic factors, suicide genes, or tumor suppressor genes and simultaneous treatment with conventional chemo- and radiotherapy[43,96,105-110].


Gene therapy has become a generally accepted new therapeutic tool in the treatment of cancer. More and more cancer patients profit from its use due to the progress made in the development of vector systems and gene therapeutic strategies. Thus, cancer gene therapy will increase its importance as a therapeutic tool even though many problems still need to be solved. One of the most important issues affecting the possible clinical application of gene therapy is the need to ensure the highest possible safety levels. Many clinical investigations have demonstrated that the currently available vector systems are well tolerated and side effects are acceptable. However, the use of retroviral vectors is discussed controversially, since 3 of 11 children with X-linked severe combined immunodeficiency, who were treated with a retrovirus, developed uncontrolled T-lymphocyte proliferation in a French gene therapy trial.

The major problem of cancer gene therapy that still remains is the relatively poor therapeutic outcome. This problem is not restricted to a specific tumor entity, but is rather a general problem. There may be many reasons for this, but it is widely agreed that this is mainly due to the relative resistance of cancer cells to introduce foreign material combined with low transgene expression in vivo. Thus, improved vector systems and application protocols will continue to be the biggest issues to be dealt with in cancer gene therapy in the next few years. However, important progress to overcome these limitations has already been made by the development of OVVs and vectors with increased tumor cell tropism.

Great progress has also been made in the development of gene therapeutic strategies in gastric cancer. New vector systems as well as the evaluation of new target genes and gene therapeutic strategies have substantially improved the chances for successful treatment of gastric cancer by gene therapy. The next challenge will be to test the results gained thus far in clinical studies.


S- Editor Xia HHX L- Editor Elsevier HK E- Editor Liu WF

1.  Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13286]  [Cited by in F6Publishing: 13414]  [Article Influence: 706.0]  [Reference Citation Analysis (1)]
2.  Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997;349:1498-1504.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4227]  [Cited by in F6Publishing: 3995]  [Article Influence: 148.0]  [Reference Citation Analysis (1)]
3.  Gottesman MM. Cancer gene therapy: an awkward adolescence. Cancer Gene Ther. 2003;10:501-508.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 50]  [Cited by in F6Publishing: 52]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
4.  Heo DS. Progress and limitations in cancer gene therapy. Genet Med. 2002;4:52S-55S.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
5.  Lin E, Nemunaitis J. Oncolytic viral therapies. Cancer Gene Ther. 2004;11:643-664.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 101]  [Cited by in F6Publishing: 108]  [Article Influence: 5.7]  [Reference Citation Analysis (0)]
6.  Fechner H, Haack A, Wang H, Wang X, Eizema K, Pauschinger M, Schoemaker R, Veghel R, Houtsmuller A, Schultheiss HP. Expression of coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers. Gene Ther. 1999;6:1520-1535.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 239]  [Cited by in F6Publishing: 243]  [Article Influence: 9.7]  [Reference Citation Analysis (0)]
7.  Okegawa T, Li Y, Pong RC, Bergelson JM, Zhou J, Hsieh JT. The dual impact of coxsackie and adenovirus receptor expression on human prostate cancer gene therapy. Cancer Res. 2000;60:5031-5036.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Alemany R, Suzuki K, Curiel DT. Blood clearance rates of adenovirus type 5 in mice. J Gen Virol. 2000;81:2605-2609.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996;274:373-376.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1264]  [Cited by in F6Publishing: 1172]  [Article Influence: 41.9]  [Reference Citation Analysis (0)]
10.  Mizuguchi H, Hayakawa T. Targeted adenovirus vectors. Hum Gene Ther. 2004;15:1034-1044.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 129]  [Cited by in F6Publishing: 135]  [Article Influence: 7.1]  [Reference Citation Analysis (0)]
11.  Grandi P, Spear M, Breakefield XO, Wang S. Targeting HSV amplicon vectors. Methods. 2004;33:179-186.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 9]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
12.  Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494-498.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6971]  [Cited by in F6Publishing: 6867]  [Article Influence: 298.6]  [Reference Citation Analysis (0)]
13.  Yen N, Ioannides CG, Xu K, Swisher SG, Lawrence DD, Kemp BL, El-Naggar AK, Cristiano RJ, Fang B, Glisson BS. Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type. P53 (Ad-p53). Cancer Gene Ther. 2000;7:530-536.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 54]  [Cited by in F6Publishing: 55]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
14.  Horio Y, Hasegawa Y, Sekido Y, Takahashi M, Roth JA, Shimokata K. Synergistic effects of adenovirus expressing wild-type p53 on chemosensitivity of non-small cell lung cancer cells. Cancer Gene Ther. 2000;7:537-544.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 29]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
15.  Tatebe S, Matsuura T, Endo K, Teramachi K, Nakamura T, Sato K, Ito H. Adenovirus-mediated transfer of wild-type p53 gene results in apoptosis or growth arrest in human cultured gastric carcinoma cells. Int J Oncol. 1999;15:229-235.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Ohashi M, Kanai F, Ueno H, Tanaka T, Tateishi K, Kawakami T, Koike Y, Ikenoue T, Shiratori Y, Hamada H. Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo. Gut. 1999;44:366-371.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 31]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
17.  Wolf BB, Schuler M, Li W, Eggers-Sedlet B, Lee W, Tailor P, Fitzgerald P, Mills GB, Green DR. Defective cytochrome c-dependent caspase activation in ovarian cancer cell lines due to diminished or absent apoptotic protease activating factor-1 activity. J Biol Chem. 2001;276:34244-34251.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 90]  [Cited by in F6Publishing: 91]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
18.  Tsunemitsu Y, Kagawa S, Tokunaga N, Otani S, Umeoka T, Roth JA, Fang B, Tanaka N, Fujiwara T. Molecular therapy for peritoneal dissemination of xenotransplanted human MKN-45 gastric cancer cells with adenovirus mediated Bax gene transfer. Gut. 2004;53:554-560.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 29]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
19.  Nishimura S, Adachi M, Ishida T, Matsunaga T, Uchida H, Hamada H, Imai K. Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells. Cancer Res. 2001;61:7009-7014.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Fu YG, Qu YJ, Wu KC, Zhai HH, Liu ZG, Fan DM. Apoptosis-inducing effect of recombinant Caspase-3 expressed by constructed eukaryotic vector on gastric cancer cell line SGC7901. World J Gastroenterol. 2003;9:1935-1939.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Jeong YW, Kim KS, Oh JY, Park JC, Baek WK, Suh SI, Suh MH, Lee JC, Cho JW. Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions. Int J Mol Med. 2003;12:61-65.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Ishii H, Zanesi N, Vecchione A, Trapasso F, Yendamuri S, Sarti M, Baffa R, During MJ, Huebner K, Fong LY. Regression of upper gastric cancer in mice by FHIT gene delivery. FASEB J. 2003;17:1768-1770.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Kirn D, Niculescu-Duvaz I, Hallden G, Springer CJ. The emerging fields of suicide gene therapy and virotherapy. Trends Mol Med. 2002;8:S68-S73.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 56]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
24.  Wei SJ, Chao Y, Hung YM, Lin WC, Yang DM, Shih YL, Ch'ang LY, Whang-Peng J, Yang WK. S- and G2-phase cell cycle arrests and apoptosis induced by ganciclovir in murine melanoma cells transduced with herpes simplex virus thymidine kinase. Exp Cell Res. 1998;241:66-75.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 65]  [Cited by in F6Publishing: 67]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
25.  Kwon GY, Jeong J, Woo JK, Choi HY, Lee MJ, Ko JK, Shim YH, Kim CW. Co-expression of bfl-1 enhances host response in the herpes simplex virus-thymidine kinase/ganciclovir gene therapy system. Biochem Biophys Res Commun. 2003;303:756-763.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 6]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
26.  Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL, Abraham GN. The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res. 1993;53:5274-5283.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Tanaka T, Yamasaki H, Mesnil M. Induction of a bystander effect in HeLa cells by using a bigenic vector carrying viral thymidine kinase and connexin32 genes. Mol Carcinog. 2001;30:176-180.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 19]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
28.  Nakaya H, Ishizu A, Ikeda H, Tahara M, Shindo J, Itoh R, Takahashi T, Asaka M, Ishikura H, Yoshiki T. In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer. Anticancer Res. 2003;23:3795-3800.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Aberle S, Schug N, Mathlouthi R, Seitz G, Küpper JH, Schröder K, Blin N. Promoter selection for the cytosine deaminase suicide gene constructs in gastric cancer. Eur J Gastroenterol Hepatol. 2004;16:63-67.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
30.  Ueda K, Iwahashi M, Nakamori M, Nakamura M, Matsuura I, Yamaue H, Tanimura H. Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model. Cancer Res. 2001;61:6158-6162.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  Chung-Faye G, Palmer D, Anderson D, Clark J, Downes M, Baddeley J, Hussain S, Murray PI, Searle P, Seymour L. Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954. Clin Cancer Res. 2001;7:2662-2668.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Tandle A, Blazer DG, Libutti SK. Antiangiogenic gene therapy of cancer: recent developments. J Transl Med. 2004;2:22.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 76]  [Cited by in F6Publishing: 79]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
33.  Sako A, Kitayama J, Koyama H, Ueno H, Uchida H, Hamada H, Nagawa H. Transduction of soluble Flt-1 gene to peritoneal mesothelial cells can effectively suppress peritoneal metastasis of gastric cancer. Cancer Res. 2004;64:3624-3628.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 46]  [Cited by in F6Publishing: 52]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
34.  Ueda K, Iwahashi M, Matsuura I, Nakamori M, Nakamura M, Ojima T, Naka T, Ishida K, Matsumoto K, Nakamura T. Adenoviral-mediated gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice. Eur J Cancer. 2004;40:2135-2142.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 25]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
35.  Meng F, Ding J, Liu N, Zhang J, Shao X, Shen H, Xue Y, Xie H, Fan D. Inhibition of gastric cancer angiogenesis by vector-based RNA interference for Raf-1. Cancer Biol Ther. 2005;4:113-117.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 16]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
36.  Xue Y, Bi F, Zhang X, Pan Y, Liu N, Zheng Y, Fan D. Inhibition of endothelial cell proliferation by targeting Rac1 GTPase with small interference RNA in tumor cells. Biochem Biophys Res Commun. 2004;320:1309-1315.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 24]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
37.  Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, Bucana CD, Semenza GL, Ellis LM. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 2004;96:946-956.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 187]  [Cited by in F6Publishing: 202]  [Article Influence: 10.1]  [Reference Citation Analysis (0)]
38.  Larin SS, Georgiev GP, Kiselev SL. Gene transfer approaches in cancer immunotherapy. Gene Ther. 2004;11 Suppl 1:S18-S25.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 15]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
39.  Narvaiza I, Mazzolini G, Barajas M, Duarte M, Zaratiegui M, Qian C, Melero I, Prieto J. Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy. J Immunol. 2000;164:3112-3122.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Kircheis R, Küpcü Z, Wallner G, Wagner E. Cytokine gene-modified tumor cells for prophylactic and therapeutic vaccination: IL-2, IFN-gamma, or combination IL-2 + IFN-gamma. Cytokines Cell Mol Ther. 1998;4:95-103.  [PubMed]  [DOI]  [Cited in This Article: ]
41.  Mastrangelo MJ, Maguire HC, Eisenlohr LC, Laughlin CE, Monken CE, McCue PA, Kovatich AJ, Lattime EC. Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 1999;6:409-422.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 267]  [Cited by in F6Publishing: 279]  [Article Influence: 11.2]  [Reference Citation Analysis (0)]
42.  Liu Y, Saxena A, Zheng C, Carlsen S, Xiang J. Combined alpha tumor necrosis factor gene therapy and engineered dendritic cell vaccine in combating well-established tumors. J Gene Med. 2004;6:857-868.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 13]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
43.  Motoi F, Sunamura M, Ding L, Duda DG, Yoshida Y, Zhang W, Matsuno S, Hamada H. Effective gene therapy for pancreatic cancer by cytokines mediated by restricted replication-competent adenovirus. Hum Gene Ther. 2000;11:223-235.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 64]  [Cited by in F6Publishing: 62]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
44.  Zhang JH, Wan MX, Pan BR, Yu B. Cytotoxicity of HSVtk and hrTNF-alpha fusion genes with IRES in treatment of gastric cancer. Cancer Biol Ther. 2004;3:1075-1080.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 6]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
45.  Zhang JH, Wan MX, Yuan JY, Pan BR. Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901. World J Gastroenterol. 2004;10:26-30.  [PubMed]  [DOI]  [Cited in This Article: ]
46.  Zhang JH, Wan MX, Yuan JY, Pan BR. Do there exist synergistic antitumor effects by coexpression of herpes simplex virus thymidine kinase with cytokine genes on human gastric cancer cell line SGC7901. World J Gastroenterol. 2004;10:147-151.  [PubMed]  [DOI]  [Cited in This Article: ]
47.  Guo SY, Gu QL, Zhu ZG, Hong HQ, Lin YZ. TK gene combined with mIL-2 and mGM-CSF genes in treatment of gastric cancer. World J Gastroenterol. 2003;9:233-237.  [PubMed]  [DOI]  [Cited in This Article: ]
48.  Tanaka H, Yashiro M, Sunami T, Sakate Y, Kosaka K, Hirakawa K. ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma. Clin Cancer Res. 2004;10:4885-4892.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 20]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
49.  Meng FP, Ding J, Yu ZC, Han QL, Guo CC, Liu N, Fan DM. Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer. World J Gastroenterol. 2005;11:1833-1836.  [PubMed]  [DOI]  [Cited in This Article: ]
50.  Schödel F, Moriarty AM, Peterson DL, Zheng JA, Hughes JL, Will H, Leturcq DJ, McGee JS, Milich DR. The position of heterologous epitopes inserted in hepatitis B virus core particles determines their immunogenicity. J Virol. 1992;66:106-114.  [PubMed]  [DOI]  [Cited in This Article: ]
51.  Ryther RC, Flynt AS, Phillips JA, Patton JG. siRNA therapeutics: big potential from small RNAs. Gene Ther. 2005;12:5-11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 223]  [Cited by in F6Publishing: 222]  [Article Influence: 11.7]  [Reference Citation Analysis (0)]
52.  Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806-811.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10522]  [Cited by in F6Publishing: 9701]  [Article Influence: 373.1]  [Reference Citation Analysis (1)]
53.  Tuschl T. Expanding small RNA interference. Nat Biotechnol. 2002;20:446-448.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 300]  [Cited by in F6Publishing: 320]  [Article Influence: 14.5]  [Reference Citation Analysis (0)]
54.  Lewis DL, Hagstrom JE, Loomis AG, Wolff JA, Herweijer H. Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat Genet. 2002;32:107-108.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 427]  [Cited by in F6Publishing: 445]  [Article Influence: 20.2]  [Reference Citation Analysis (0)]
55.  Hosono T, Mizuguchi H, Katayama K, Xu ZL, Sakurai F, Ishii-Watabe A, Kawabata K, Yamaguchi T, Nakagawa S, Mayumi T. Adenovirus vector-mediated doxycycline-inducible RNA interference. Hum Gene Ther. 2004;15:813-819.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 41]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
56.  Sumimoto H, Yamagata S, Shimizu A, Miyoshi H, Mizuguchi H, Hayakawa T, Miyagishi M, Taira K, Kawakami Y. Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference. Gene Ther. 2005;12:95-100.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 58]  [Cited by in F6Publishing: 62]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
57.  Xu D, McCarty D, Fernandes A, Fisher M, Samulski RJ, Juliano RL. Delivery of MDR1 small interfering RNA by self-complementary recombinant adeno-associated virus vector. Mol Ther. 2005;11:523-530.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 66]  [Cited by in F6Publishing: 64]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
58.  Song J, Pang S, Lu Y, Yokoyama KK, Zheng JY, Chiu R. Gene silencing in androgen-responsive prostate cancer cells from the tissue-specific prostate-specific antigen promoter. Cancer Res. 2004;64:7661-7663.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 25]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
59.  Shinomiya N, Gao CF, Xie Q, Gustafson M, Waters DJ, Zhang YW, Vande Woude GF. RNA interference reveals that ligand-independent met activity is required for tumor cell signaling and survival. Cancer Res. 2004;64:7962-7970.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 84]  [Cited by in F6Publishing: 87]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
60.  Hong L, Ning X, Shi Y, Shen H, Zhang Y, Lan M, Liang S, Wang J, Fan D. Reversal of multidrug resistance of gastric cancer cells by down-regulation of ZNRD1 with ZNRD1 siRNA. Br J Biomed Sci. 2004;61:206-210.  [PubMed]  [DOI]  [Cited in This Article: ]
61.  Liu N, Bi F, Pan Y, Sun L, Xue Y, Shi Y, Yao X, Zheng Y, Fan D. Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA expression and activity. Clin Cancer Res. 2004;10:6239-6247.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 73]  [Cited by in F6Publishing: 80]  [Article Influence: 4.2]  [Reference Citation Analysis (0)]
62.  Nieth C, Priebsch A, Stege A, Lage H. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi). FEBS Lett. 2003;545:144-150.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 142]  [Cited by in F6Publishing: 154]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
63.  Guo C, Ding J, Yao L, Sun L, Lin T, Song Y, Sun L, Fan D. Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. Int J Cancer. 2005;116:155-160.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 48]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
64.  Tong QS, Zheng LD, Wang L, Zeng FQ, Chen FM, Dong JH, Lu GC. Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells. Cancer Gene Ther. 2005;12:509-514.  [PubMed]  [DOI]  [Cited in This Article: ]
65.  Ye J, Wu YL, Zhang S, Chen Z, Guo LX, Zhou RY, Xie H. Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype. World J Gastroenterol. 2005;11:2230-2237.  [PubMed]  [DOI]  [Cited in This Article: ]
66.  Kim R, Emi M, Tanabe K, Toge T. Preclinical evaluation of antisense bcl-2 as a chemosensitizer for patients with gastric carcinoma. Cancer. 2004;101:2177-2186.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 29]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
67.  Bi F, Fan D, Hui H, Wang C, Zhang X. Reversion of the malignant phenotype of gastric cancer cell SGC7901 by c-erbB-2-specific hammerhead ribozyme. Cancer Gene Ther. 2001;8:835-842.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 11]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
68.  Min Y, Adachi Y, Yamamoto H, Imsumran A, Arimura Y, Endo T, Hinoda Y, Lee CT, Nadaf S, Carbone DP. Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts. Gut. 2005;54:591-600.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 60]  [Cited by in F6Publishing: 65]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
69.  Bauerschmitz GJ, Barker SD, Hemminki A. Adenoviral gene therapy for cancer: from vectors to targeted and replication competent agents (review). Int J Oncol. 2002;21:1161-1174.  [PubMed]  [DOI]  [Cited in This Article: ]
70.  Sauthoff H, Hu J, Maca C, Goldman M, Heitner S, Yee H, Pipiya T, Rom WN, Hay JG. Intratumoral spread of wild-type adenovirus is limited after local injection of human xenograft tumors: virus persists and spreads systemically at late time points. Hum Gene Ther. 2003;14:425-433.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 95]  [Cited by in F6Publishing: 98]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
71.  Nettelbeck DM, Rivera AA, Balagué C, Alemany R, Curiel DT. Novel oncolytic adenoviruses targeted to melanoma: specific viral replication and cytolysis by expression of E1A mutants from the tyrosinase enhancer/promoter. Cancer Res. 2002;62:4663-4670.  [PubMed]  [DOI]  [Cited in This Article: ]
72.  Huang TG, Savontaus MJ, Shinozaki K, Sauter BV, Woo SL. Telomerase-dependent oncolytic adenovirus for cancer treatment. Gene Ther. 2003;10:1241-1247.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 101]  [Cited by in F6Publishing: 103]  [Article Influence: 4.9]  [Reference Citation Analysis (0)]
73.  Heise C, Hermiston T, Johnson L, Brooks G, Sampson-Johannes A, Williams A, Hawkins L, Kirn D. An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med. 2000;6:1134-1139.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 431]  [Cited by in F6Publishing: 416]  [Article Influence: 17.3]  [Reference Citation Analysis (0)]
74.  Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med. 2000;6:821-825.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 607]  [Cited by in F6Publishing: 615]  [Article Influence: 25.6]  [Reference Citation Analysis (0)]
75.  McKie EA, MacLean AR, Lewis AD, Cruickshank G, Rampling R, Barnett SC, Kennedy PG, Brown SM. Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours--evaluation of a potentially effective clinical therapy. Br J Cancer. 1996;74:745-752.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 83]  [Cited by in F6Publishing: 87]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
76.  Chong H, Ruchatz A, Clackson T, Rivera VM, Vile RG. A system for small-molecule control of conditionally replication-competent adenoviral vectors. Mol Ther. 2002;5:195-203.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 34]  [Cited by in F6Publishing: 38]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
77.  Fechner H, Wang X, Srour M, Siemetzki U, Seltmann H, Sutter AP, Scherübl H, Zouboulis CC, Schwaab R, Hillen W. A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication. Gene Ther. 2003;10:1680-1690.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 32]  [Cited by in F6Publishing: 33]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
78.  Hurtado Picó A, Wang X, Sipo I, Siemetzki U, Eberle J, Poller W, Fechner H. Viral and nonviral factors causing nonspecific replication of tumor- and tissue-specific promoter-dependent oncolytic adenoviruses. Mol Ther. 2005;11:563-577.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 21]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
79.  Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR. Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res. 1997;57:2559-2563.  [PubMed]  [DOI]  [Cited in This Article: ]
80.  Toth K, Djeha H, Ying B, Tollefson AE, Kuppuswamy M, Doronin K, Krajcsi P, Lipinski K, Wrighton CJ, Wold WS. An oncolytic adenovirus vector combining enhanced cell-to-cell spreading, mediated by the ADP cytolytic protein, with selective replication in cancer cells with deregulated wnt signaling. Cancer Res. 2004;64:3638-3644.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 41]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
81.  Kambara H, Okano H, Chiocca EA, Saeki Y. An oncolytic HSV-1 mutant expressing ICP34.5 under control of a nestin promoter increases survival of animals even when symptomatic from a brain tumor. Cancer Res. 2005;65:2832-2839.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 164]  [Cited by in F6Publishing: 180]  [Article Influence: 9.5]  [Reference Citation Analysis (0)]
82.  Reinblatt M, Pin RH, Fong Y. Carcinoembryonic antigen directed herpes viral oncolysis improves selectivity and activity in colorectal cancer. Surgery. 2004;136:579-584.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 7]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
83.  Walker JR, McGeagh KG, Sundaresan P, Jorgensen TJ, Rabkin SD, Martuza RL. Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207. Hum Gene Ther. 1999;10:2237-2243.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 118]  [Cited by in F6Publishing: 108]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
84.  Wang WJ, Tai CK, Kasahara N, Chen TC. Highly efficient and tumor-restricted gene transfer to malignant gliomas by replication-competent retroviral vectors. Hum Gene Ther. 2003;14:117-127.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 64]  [Cited by in F6Publishing: 70]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
85.  Olijslagers S, Dege AY, Dinsart C, Voorhoeve M, Rommelaere J, Noteborn MH, Cornelis JJ. Potentiation of a recombinant oncolytic parvovirus by expression of Apoptin. Cancer Gene Ther. 2001;8:958-965.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 43]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
86.  Shinozaki K, Ebert O, Woo SL. Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. Hepatology. 2005;41:196-203.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 46]  [Cited by in F6Publishing: 48]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
87.  Phuangsab A, Lorence RM, Reichard KW, Peeples ME, Walter RJ. Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett. 2001;172:27-36.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 106]  [Cited by in F6Publishing: 112]  [Article Influence: 4.9]  [Reference Citation Analysis (0)]
88.  Coffey MC, Strong JE, Forsyth PA, Lee PW. Reovirus therapy of tumors with activated Ras pathway. Science. 1998;282:1332-1334.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 555]  [Cited by in F6Publishing: 545]  [Article Influence: 21.0]  [Reference Citation Analysis (0)]
89.  Norman KL, Coffey MC, Hirasawa K, Demetrick DJ, Nishikawa SG, DiFrancesco LM, Strong JE, Lee PW. Reovirus oncolysis of human breast cancer. Hum Gene Ther. 2002;13:641-652.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 124]  [Cited by in F6Publishing: 125]  [Article Influence: 5.7]  [Reference Citation Analysis (0)]
90.  Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C. a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med. 2000;6:879-885.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 820]  [Cited by in F6Publishing: 753]  [Article Influence: 31.4]  [Reference Citation Analysis (0)]
91.  Nemunaitis J, Khuri F, Ganly I, Arseneau J, Posner M, Vokes E, Kuhn J, McCarty T, Landers S, Blackburn A. Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol. 2001;19:289-298.  [PubMed]  [DOI]  [Cited in This Article: ]
92.  Habib NA, Mitry RR, Sarraf CE, Jiao LR, Havlík R, Nicholls J, Jensen SL. Assessment of growth inhibition and morphological changes in in vitro and in vivo hepatocellular carcinoma models post treatment with dl1520 adenovirus. Cancer Gene Ther. 2002;9:414-420.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 23]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
93.  Makower D, Rozenblit A, Kaufman H, Edelman M, Lane ME, Zwiebel J, Haynes H, Wadler S. Phase II clinical trial of intralesional administration of the oncolytic adenovirus ONYX-015 in patients with hepatobiliary tumors with correlative p53 studies. Clin Cancer Res. 2003;9:693-702.  [PubMed]  [DOI]  [Cited in This Article: ]
94.  Hecht JR, Bedford R, Abbruzzese JL, Lahoti S, Reid TR, Soetikno RM, Kirn DH, Freeman SM. A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin Cancer Res. 2003;9:555-561.  [PubMed]  [DOI]  [Cited in This Article: ]
95.  Vasey PA, Shulman LN, Campos S, Davis J, Gore M, Johnston S, Kirn DH, O'Neill V, Siddiqui N, Seiden MV. Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer. J Clin Oncol. 2002;20:1562-1569.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 103]  [Cited by in F6Publishing: 99]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
96.  Reid T, Galanis E, Abbruzzese J, Sze D, Wein LM, Andrews J, Randlev B, Heise C, Uprichard M, Hatfield M. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res. 2002;62:6070-6079.  [PubMed]  [DOI]  [Cited in This Article: ]
97.  Galanis E, Okuno SH, Nascimento AG, Lewis BD, Lee RA, Oliveira AM, Sloan JA, Atherton P, Edmonson JH, Erlichman C. Phase I-II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas. Gene Ther. 2005;12:437-445.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 114]  [Cited by in F6Publishing: 124]  [Article Influence: 6.5]  [Reference Citation Analysis (0)]
98.  Bennett JJ, Delman KA, Burt BM, Mariotti A, Malhotra S, Zager J, Petrowsky H, Mastorides S, Federoff H, Fong Y. Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer. Cancer Gene Ther. 2002;9:935-945.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 66]  [Cited by in F6Publishing: 70]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
99.  Pecora AL, Rizvi N, Cohen GI, Meropol NJ, Sterman D, Marshall JL, Goldberg S, Gross P, O'Neil JD, Groene WS. Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol. 2002;20:2251-2266.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 265]  [Cited by in F6Publishing: 272]  [Article Influence: 12.4]  [Reference Citation Analysis (0)]
100.  Ono HA, Davydova JG, Adachi Y, Takayama K, Barker SD, Reynolds PN, Krasnykh VN, Kunisaki C, Shimada H, Curiel DT. Promoter-controlled infectivity-enhanced conditionally replicative adenoviral vectors for the treatment of gastric cancer. J Gastroenterol. 2005;40:31-42.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 30]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
101.  Jacob D, Bahra M, Schumacher G, Neuhaus P, Fang B. Gene therapy in colon cancer cells with a fiber-modified adenovector expressing the TRAIL gene driven by the hTERT promoter. Anticancer Res. 2004;24:3075-3079.  [PubMed]  [DOI]  [Cited in This Article: ]
102.  Mizuguchi H, Hayakawa T. Adenovirus vectors containing chimeric type 5 and type 35 fiber proteins exhibit altered and expanded tropism and increase the size limit of foreign genes. Gene. 2002;285:69-77.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 92]  [Cited by in F6Publishing: 92]  [Article Influence: 4.2]  [Reference Citation Analysis (0)]
103.  Denby L, Work LM, Graham D, Hsu C, von Seggern DJ, Nicklin SA, Baker AH. Adenoviral serotype 5 vectors pseudotyped with fibers from subgroup D show modified tropism in vitro and in vivo. Hum Gene Ther. 2004;15:1054-1064.  [PubMed]  [DOI]  [Cited in This Article: ]
104.  Heideman DA, van Beusechem VW, Offerhaus GJ, Wickham TJ, Roelvink PW, Craanen ME, Pinedo HM, Meijer CJ, Gerritsen WR. Selective gene transfer into primary human gastric tumors using epithelial cell adhesion molecule-targeted adenoviral vectors with ablated native tropism. Hum Gene Ther. 2002;13:1677-1685.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 17]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
105.  Rein DT, Breidenbach M, Kirby TO, Han T, Siegal GP, Bauerschmitz GJ, Wang M, Nettelbeck DM, Tsuruta Y, Yamamoto M. A fiber-modified, secretory leukoprotease inhibitor promoter-based conditionally replicating adenovirus for treatment of ovarian cancer. Clin Cancer Res. 2005;11:1327-1335.  [PubMed]  [DOI]  [Cited in This Article: ]
106.  Kim SH, Wong RJ, Kooby DA, Carew JF, Adusumilli PS, Patel SG, Shah JP, Fong Y. Combination of mutated herpes simplex virus type 1 (G207 virus) with radiation for the treatment of squamous cell carcinoma of the head and neck. Eur J Cancer. 2005;41:313-322.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 32]  [Cited by in F6Publishing: 32]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
107.  Lamfers ML, Grill J, Dirven CM, Van Beusechem VW, Geoerger B, Van Den Berg J, Alemany R, Fueyo J, Curiel DT, Vassal G. Potential of the conditionally replicative adenovirus Ad5-Delta24RGD in the treatment of malignant gliomas and its enhanced effect with radiotherapy. Cancer Res. 2002;62:5736-5742.  [PubMed]  [DOI]  [Cited in This Article: ]
108.  Li Y, Yu DC, Chen Y, Amin P, Zhang H, Nguyen N, Henderson DR. A hepatocellular carcinoma-specific adenovirus variant, CV890, eliminates distant human liver tumors in combination with doxorubicin. Cancer Res. 2001;61:6428-6436.  [PubMed]  [DOI]  [Cited in This Article: ]
109.  Zhang Z, Zou W, Wang J, Gu J, Dang Y, Li B, Zhao L, Qian C, Qian Q, Liu X. Suppression of tumor growth by oncolytic adenovirus-mediated delivery of an antiangiogenic gene, soluble Flt-1. Mol Ther. 2005;11:553-562.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 44]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
110.  Geoerger B, Vassal G, Opolon P, Dirven CM, Morizet J, Laudani L, Grill J, Giaccone G, Vandertop WP, Gerritsen WR. Oncolytic activity of p53-expressing conditionally replicative adenovirus AdDelta24-p53 against human malignant glioma. Cancer Res. 2004;64:5753-5759.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 55]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]