The establishment of a new mouse model with orthotopic esophageal cancer showing the esophageal stricture

Ohara, Toshiaki; Takaoka, Munenori; Sakurama, Kazufumi; Nagaishi, Kaori; Takeda, Haruo; Shirakawa, Yasuhiro; Yamatsuji, Tomoki; Nagasaka, Takeshi; Matsuoka, Junji; Tanaka, Noriaki; Naomoto, Yoshio

doi:10.1016/j.canlet.2010.01.017

Cited by 21 publications

(20 citation statements)

References 8 publications

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“…19 As shown previously, this orthotopic mouse model shows a quick outcome from a lack of food intake due to esophageal stricture by the orthotopic tumor. Thus, we hypothesized that the inhibition of orthotopic tumor growth by temsirolimus would prolong the survival of this mouse model if the esophageal stricture could be retarded and normal food intake maintained.…”

Section: Resultssupporting

confidence: 64%

“…19 Briefly, a cell suspension of 5 × 10 6 TE-8 cells mixed with Matrigel (356234) was injected via the lumen into the esophagus of an anesthetized mouse (day 0) using a needle and barrel. The orthotopic tumorbearing mice were randomized into two groups and from day 7 the intraperitoneal administration of either 10 mg/kg of temsirolimus or PBS as a vehicle was given to each group.…”

Section: Methodsmentioning

confidence: 99%

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Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice

Nishikawa

Takaoka

Ohara

et al. 2013

Cancer Biology & Therapy

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Section: Resultssupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice

Nishikawa

Takaoka

Ohara

et al. 2013

Cancer Biology & Therapy

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“…67,68 Orthotopic transplantation as alternative mouse model seems to be possible, but also showed some drawbacks before. [69][70][71][72] For example, Gros and colleagues 69 injected primary EAC cells into the submucosa of the abdominal esophagus by an invasive surgery technique, but only peritoneal carcinomatosis without formation of primary tumors was observed in this model. Still, our study provides a first comprehensive in vitro approach and insight to show cancer cell-selectivity for the entity of esophageal cancer by comparing non-neoplastic esophageal Het-1A cells to five esophageal and one GEJ cancer cell lines, providing a proof of principle concept.…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine

Ahrens¹,

Timme

Hoeppner³

et al. 2015

Epigenetics

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Esophageal cancers are highly aggressive tumors with poor prognosis despite some recent advances in surgical and radiochemotherapy treatment options. This study addressed the feasibility of drugs targeting epigenetic modifiers in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells. We tested inhibition of histone deacetylases (HDACs) by SAHA, MS-275, and FK228, inhibition of DNA methyltransferases by Azacytidine (AZA) and Decitabine (DAC), and the effect of combination treatment using both types of drugs. The drug targets, HDAC1/2/3 and DNMT1, were expressed in normal esophageal epithelium and tumor cells of ESCC or EAC tissue specimens, as well as in non-neoplastic esophageal epithelial (Het-1A), ESCC (OE21, Kyse-270, Kyse-410), and EAC (OE33, SK-GT-4) cell lines. In vitro, HDAC activity, histone acetylation, and p21 expression were similarly affected in non-neoplastic, ESCC, and EAC cell lines post inhibitor treatment. Combined MS-275/AZA treatment, however, selectively targeted esophageal cancer cell lines by inducing DNA damage, cell viability loss, and apoptosis, and by decreasing cell migration. Non-neoplastic Het-1A cells were protected against HDACi (MS-275)/AZA treatment. RNA transcriptome analyses post MS-275 and/or AZA treatment identified novel regulated candidate genes (up: BCL6, Hes2; down: FAIM, MLKL), which were specifically associated with the treatment responses of esophageal cancer cells. In summary, combined HDACi/AZA treatment is efficient and selective for the targeting of esophageal cancer cells, despite similar target expression of normal and esophageal cancer epithelium, in vitro and in human esophageal carcinomas. The precise mechanisms of action of treatment responses involve novel candidate genes regulated by HDACi/AZA in esophageal cancer cells. Together, targeting of epigenetic modifiers in esophageal cancers may represent a potential future therapeutic approach.

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“…Nevertheless, tumors in this model have been slow to develop and appear with limited consistency (in less than 25% of mice). A third model involves explantation of esophageal cancer xenografts into immunodeficient mice (13, 14, 41, 42). Although this model produces consistent results, conclusions drawn from experimentation in immunodeficient hosts are not generalizable to the human population.…”

Section: Discussionmentioning

confidence: 99%

Adenoviral-Based Immunotherapy Provides Local Disease Control in an Orthotopic Murine Model of Esophageal Cancer

Quatromoni¹,

Predina²,

Bhojnagarwala³

et al. 2014

Journal of Immunotherapy

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Despite recent advances in the development of novel therapies, esophageal carcinoma remains an aggressive cancer associated with a poor prognosis. The lack a high throughput, reproducible syngeneic animal model that replicates human disease is partly responsible for the paucity of novel therapeutic approaches. In this report, we present the first successful syngeneic, orthotopic model for esophageal cancer. This model was used to test an established adenoviral-based tumor vaccine. We utilized a murine esophageal cancer cell line established from the EDL2-cyclin D1;p53−/− mouse that was transduced to express a viral tumor antigen, the Human Papilloma Virus (HPV) E7 protein. The tumor was established in its natural microenvironment at the gastroesophageal (GE) junction. Tumor growth was consistent and reproducible. An adenoviral vaccine to E7 (Ad.E7) induced an E7-specific population of functionally active CD8+ T cells which trafficked into the tumors and retained cytotoxicity. Ad.E7 vaccination reduced local tumor growth and prolonged overall survival. These findings suggest that orthotopic tumor growth is a reasonable preclinical model to validate novel therapies.

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The establishment of a new mouse model with orthotopic esophageal cancer showing the esophageal stricture

Cited by 21 publications

References 8 publications

Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice

Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice

Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine

Adenoviral-Based Immunotherapy Provides Local Disease Control in an Orthotopic Murine Model of Esophageal Cancer

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