Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

Ding, Lin; Zaatari, Mohamad El; Merchant, Juanita L.

doi:10.1007/978-3-319-41388-4_22

Cited by 10 publications

(10 citation statements)

References 198 publications

(195 reference statements)

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“…Nitrosamines are indirect dietary byproducts implicated in the pathogenesis of gastric premalignancy 10 and carry carcinogenic properties that increase the risk of cancer 11 , 12 . Indeed, rodent models have incorporated environmental exposures into the study of gastric adenocarcinoma 10 , 13 - 15 . Mouse models that incorporate the SS1 strain of Helicobacter pylori ( H. pylori ) and H. felis can recapitulate chronic inflammation, resultant gastritis and metaplasia, and eventually dysplasia 13 , 16 - 18 .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, rodent models have incorporated environmental exposures into the study of gastric adenocarcinoma 10 , 13 - 15 . Mouse models that incorporate the SS1 strain of Helicobacter pylori ( H. pylori ) and H. felis can recapitulate chronic inflammation, resultant gastritis and metaplasia, and eventually dysplasia 13 , 16 - 18 . By contrast, carcinogen exposure gives rise to a distinct model of gastric cancer by promoting dysplastic lesions and adenocarcinoma with relatively little to no metaplasia.…”

Section: Introductionmentioning

confidence: 99%

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Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model

et al. 2020

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Somatic alterations in cancer genes are being detected in normal and premalignant tissue, placing greater emphasis on gene-environment interactions that enable disease phenotypes. By combining early genetic alterations with disease-relevant exposures, we developed an integrative mouse model to study gastric premalignancy. Deletion of Trp53 in gastric cells confers a selective advantage and promotes the development of dysplasia in the setting of dietary carcinogens. Organoid derivation from dysplastic lesions facilitated genomic, transcriptional, and functional evaluation of gastric premalignancy. Cell cycle regulators, most notably Cdkn2a , were upregulated by p53 inactivation in gastric premalignancy, serving as a barrier to disease progression. Co-deletion of Cdkn2a and Trp53 in dysplastic gastric organoids promoted cancer phenotypes but also induced replication stress, exposing a susceptibility to DNA damage response pathway inhibitors. These findings demonstrate the utility of mouse models that integrate genomic alterations with relevant exposures and highlight the importance of gene-environment interactions in shaping the premalignant state.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model

et al. 2020

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“…Animal models have been extensively used to study the pathogenesis and metastatic mechanisms of gastric cancer and play an extremely important role in the evaluation of the efficacy and toxicity of therapeutic drugs [8][9][10]. At present, gastric cancer animal models mainly include the following: the induction model, the transplantation model, and the genetic engineering model [11].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Human Gastric Cancer Xenograft Model in Immunocompetent Mice Using the Microcarrier-6

Wang

Yang

et al. 2020

BioMed Research International

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Gastric cancer is among the most common malignant tumors of the digestive tract. Establishing a robust and reliable animal model is the foundation for studying the pathogenesis of cancer. The present study established a mouse model of gastric carcinoma by inoculating immunocompetent mice with MKN45 cells using microcarrier. Sixty male C57BL/6 mice were randomly divided into three groups: a 2D group, an empty carrier group, and a 3D group, according to the coculture system of MKN45 and the microcarrier. The mouse models were established by hypodermic injection. Time to develop tumor, rate of tumor formation, and pathological features were observed in each group. In the 3D group, the tumorigenesis time was short, while the rate of tumor formation was high (75%). There was no detectable tumor formation in either the 2D or the empty carrier group. Both H&E and immunohistochemical staining of the tumor xenograft showed characteristic evidence of human gastric neoplasms. The present study successfully established a human gastric carcinoma model in immunocompetent mice, which provides a novel and valuable animal model for the cancer research and development of anticancer drugs.

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“…However, maintaining genetic models presents practical challenges. Several models have an average age of onset between 40 weeks and 20 months ( Ding et al, 2016 ). Furthermore, as the number of transgenic alleles in a model increases, the cost-effectiveness and breeding efficiency decrease, making them expensive and time-consuming.…”

Section: Animal Models Of Cancer-related Painmentioning

confidence: 99%

Animal Models of Cancer-Related Pain: Current Perspectives in Translation

2020

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The incidence of pain in cancer patients during diagnosis and treatment is exceedingly high. Although advances in cancer detection and therapy have improved patient prognosis, cancer and its treatment-associated pain have gained clinical prominence. The biological mechanisms involved in cancer-related pain are multifactorial; different processes for pain may be responsible depending on the type and anatomic location of cancer. Animal models of cancer-related pain have provided mechanistic insights into the development and process of pain under a dynamic molecular environment. However, while cancer-evoked nociceptive responses in animals reflect some of the patients’ symptoms, the current models have failed to address the complexity of interactions within the natural disease state. Although there has been a recent convergence of the investigation of carcinogenesis and pain neurobiology, identification of new targets for novel therapies to treat cancer-related pain requires standardization of methodologies within the cancer pain field as well as across disciplines. Limited success of translation from preclinical studies to the clinic may be due to our poor understanding of the crosstalk between cancer cells and their microenvironment (e.g., sensory neurons, infiltrating immune cells, stromal cells etc.). This relatively new line of inquiry also highlights the broader limitations in translatability and interpretation of basic cancer pain research. The goal of this review is to summarize recent findings in cancer pain based on preclinical animal models, discuss the translational benefit of these discoveries, and propose considerations for future translational models of cancer pain.

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Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

Cited by 10 publications

References 198 publications

Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model

Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model

Establishment of a Human Gastric Cancer Xenograft Model in Immunocompetent Mice Using the Microcarrier-6

Animal Models of Cancer-Related Pain: Current Perspectives in Translation

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