Sequential Histopathological Changes in vivo after Suicide Gene Therapy of Gastric Cancer Induced by N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine in Rats

Okino, Tetsuya; Onda, Masahiko; Matsukura, Norio; Inada, Ken Iti; Tatematsu, Masae; Shimada, Takashi

doi:10.1111/j.1349-7006.2001.tb01147.x

Cited by 7 publications

(2 citation statements)

References 23 publications

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“…The distribution and expression level of Ron in normal human gastrointestinal organs was examined by immunohistochemistry, and a comparison was made of expression between adult and fetal tissue (Okino et al, 2001). High level expression was seen in the esophagus, small intestine and colon, but gall bladder was negative.…”

Section: H Gastrointestinal Tumorsmentioning

confidence: 99%

Met‐Related Receptor Tyrosine Kinase Ron in Tumor Growth and Metastasis

Wagh

Peace

Waltz

2008

Advances in Cancer Research

143

168

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The Ron receptor is a member of the Met family of cell surface receptor tyrosine kinases and is primarily expressed on epithelial cells and macrophages. The biological response of Ron is mediated by binding of its ligand, hepatocyte growth factor-like protein/macrophage stimulatingprotein (HGFL). HGFL is primarily synthesized and secreted from hepatocytes as an inactive precursor and is activated at the cell surface. Binding of HGFL to Ron activates Ron and leads to the induction of a variety of intracellular signaling cascades that leads to cellular growth, motility and invasion. Recent studies have documented Ron overexpression in a variety of human cancers including breast, colon, liver, pancreas, and bladder. Moreover, clinical studies have also shown that Ron overexpression is associated with both worse patient outcomes as well as metastasis. Forced overexpression of Ron in transgenic mice leads to tumorigenesis in both the lung and the mammary gland and is associated with metastatic dissemination. While Ron overexpression appears to be a hallmark of many human cancers, the mechanisms by which Ron induces tumorigenesis and metastasis are still unclear. Several strategies are currently being undertaken to inhibit Ron as a potential therapeutic target; current strategies include the use of Ron blocking proteins, siRNA, monoclonal antibodies, and small molecule inhibitors. In total, these data suggest that Ron is a critical factor in tumorigenesis and that inhibition of this protein, alone or in combination with current therapies, may prove beneficial in the treatment of cancer patients.

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Section: H Gastrointestinal Tumorsmentioning

confidence: 99%

Met‐Related Receptor Tyrosine Kinase Ron in Tumor Growth and Metastasis

Wagh

Peace

Waltz

2008

Advances in Cancer Research

143

168

View full text Add to dashboard Cite

show abstract

“…The most common gene-editing strategies to treat GC are "tumor-suppressor actions," by which an irreversible gene KO leads to cell growth inhibition or to lose metastatic ability, "suicide gene therapy," i.e., the transduction of a gene processing a non-toxic "pro-drug" into a toxic one and the "immunomodulation" by which we can potentiate the host immune response against cancer cells. Being p53 one of the master regulator of the genome integrity and resulting mutated in about 60% of gastric cancer, its replacement with a wildtype version is fascinating and in 1999, Ohashi M et al reported that such reintroduction, through AVs, led to a significant growth inhibition showing to be of clinical interest [109], while the two most common suicide gene therapies are based on the conversion of 5-fluorocytosine to 5-fluorouracil (5-FU), through expression of cytosine deaminase and the phosphorylation of ganciclovir, throughout the herpes simplex virus thymidine kinase, both used in combination with a CEA promoter to make their expression cancer-specific [110,111]. It is our opinion that currently, molecular research needs to take several steps forward to use gene therapy constantly in clinical practice, especially by uncovering specific surface molecular targets to make such therapies more selective and avoiding any off-target effects.…”

Section: Discussionmentioning

confidence: 99%

Update on gastric cancer treatments and gene therapies

Biagioni

Skalamera

Peri

et al. 2019

Cancer Metastasis Rev

144

100

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Gastric cancer is an active topic of clinical and basic research due to high morbidity and mortality. To date, gastrectomy and chemotherapy are the only therapeutic options for gastric cancer patients, but drug resistance, either acquired or primary, is the main cause for treatment failure. Differences in development and response to cancer treatments have been observed among ethnically diverse GC patient populations. In spite of major incidence, GC Asian patients have a significantly better prognosis and response to treatments than Caucasian ones due to genetic discordances between the two populations. Gene therapy could be an alternative strategy to overcome such issues and especially CRISPR/Cas9 represents one of the most intriguing gene-editing system. Thus, in this review article, we want to provide an update on the currently used therapies for the treatment of advanced GC.

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Reversal of adriamycin resistance of hepatocellular carcinoma by targeting with recombined adenovirus carring antisense mdr1 RNA

Ding

Mei

Shi

et al. 2006

Chin. J. Clin. Oncol.

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OBJECTIVE Chemotherapy is an important therapy for hepatocellular carcinoma (HCC). However, it is not effective in many cases due to recurrence and metastasis even if the initial treatment produces a response. Multidrug resistance (MDR) is considered to be one of the considerable causes. The aim of this study was to reverse MDR of HepG2/ADM cells by blocking mdrl with an adenovirus vector carrying antisense mdrl in a tumor transplantated in athymic mice. METHODS Pcuv ~E was removed from the pshuttle vector. A 0.3 kb AFP promoter was inserted into the pshuttle vector and pCMV changed into pAFP. The pAFP and asmdrl PCR products were doubly digested with Kpnl and Apal, the digested products were ligated by T4 ligase, the asmdrl gene was inserted into pAFP and a flewly plasmid pAFP-asmdrl was constructed. Following digestion with PI-Scel/I-Ceu I, pAFP-asmdrl was ligated with Adeno-X genome DNA and amplified in E.cofi XL1-Blue. The HEK293 cells were transfected and virus collected. The HepG2MDR cells (HepGJADM) were induced by graded resistance to ADM and were inoculated into athymic mice. After adeno-asmdrl was injected, the expression of mdrl-mRNA and the volume of the transplantated tumor and its cells were observed. RESULTS Following injection with Adeno-asmdrl, the tumor volume in the ADM+Adeno-asmdrl group did not increase. However the tumor volume in the PBS plus ADM group did significantly increase (P<0.05). In the tumor xenograft cells, mdrl mRNA in the xenografts was assessed by RT-PCR and was found to be reduced at 1 week and 4 weeks in the ADM+asmdrl group, but it was stable in the ADM group. It was only 20% in the ADM+asmdrl group compared to the ADM group at the 4th week (P<0.05). Evidence of apoptosis was observed in the tumor xenograft cells treated with Adeno-asmdrl, but there was rare or no apoptosis in the group treated with ADM and PBS. CONCLUSION Adenovirus carrying antisense mdrl RNA can partially reverse the MDR of HepGJADM cells and inhibit tumor growth by downregulating mdrl mRNA resulting in tumor cell apoptosis.

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Sequential Histopathological Changes in vivo after Suicide Gene Therapy of Gastric Cancer Induced by N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine in Rats

Cited by 7 publications

References 23 publications

Met‐Related Receptor Tyrosine Kinase Ron in Tumor Growth and Metastasis

Met‐Related Receptor Tyrosine Kinase Ron in Tumor Growth and Metastasis

Update on gastric cancer treatments and gene therapies

Reversal of adriamycin resistance of hepatocellular carcinoma by targeting with recombined adenovirus carring antisense mdr1 RNA

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