Dataset Information

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts.

ABSTRACT: Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer. More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted. Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment. Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

SUBMITTER: Corso S

PROVIDER: S-EPMC5915970 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts.

Corso Simona S Cargnelutti Marilisa M Durando Stefania S Menegon Silvia S Apicella Maria M Migliore Cristina C Capeloa Tania T Ughetto Stefano S Isella Claudio C Medico Enzo E Bertotti Andrea A Sassi Francesco F Sarotto Ivana I Casorzo Laura L Pisacane Alberto A Mangioni Monica M Sottile Antonino A Degiuli Maurizio M Fumagalli Uberto U Sgroi Giovanni G Molfino Sarah S De Manzoni Giovanni G Rosati Riccardo R De Simone Michele M Marrelli Daniele D Saragoni Luca L Rausei Stefano S Pallabazzer Giovanni G Roviello Franco F Cassoni Paola P Sapino Anna A Bass Adam A Giordano Silvia S

Neoplasia (New York, N.Y.) 20180323 5

Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer. More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tum ...[more]

PMID: 29574251

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Project description:Patient-derived xenograft (PDX) models have been recognized as being more suitable for predicting therapeutic efficacy than cell-culture models. However, there are several limitations in applying PDX models in preclinical studies, including their availability-especially for cancers such as gastric cancer-that are not frequently encountered in Western countries. In addition, the differences in morphology between primary, PDX, and tumor cell line-derived xenograft (CDX) models have not been well established. In this study, we aimed to establish a series of gastric cancer PDXs and cell-lines from a relatively large number of gastric cancer patients. We also investigated the clinicopathological factors associated with the establishment of PDX and CDX models, and compared the histology between the primary tumor, PDX, and CDX that originated from the same patient. We engrafted 232 gastric cancer tissues into immune-deficient mice subcutaneously and successfully established 35 gastric cancer PDX models (15.1% success rate). Differentiated type adenocarcinomas (DAs, 19.4%) were more effectively established than poorly differentiated type adenocarcinomas (PDAs, 10.8%). For establishing CDXs, the success rate was less influenced by histological differentiation grade (DA vs. PDA, 12.1% vs. 9.8%). In addition, concordance of histological differentiation grade between primary tumors and PDXs was significant (p < 0.01), while concordance between primary tumors and CDXs was not. Among clinicopathological factors investigated, pathological nodal metastasis status (pN) was significantly associated with the success rate of PDX establishment. Although establishing cell lines from ascites fluid was more efficient (41.2%, 7/17) than resected tissues, it should be noted that all CDXs from ascites fluid had the PDA phenotype. In conclusion, we established 35 PDX and 32 CDX models from 249 gastric cancer patients; among them, 21 PDX/CDX models were established from the same patients. Our findings may provide helpful insights for establishing PDX and CDX models not only from gastric but from other cancer types, as well as select preclinical models for developing new therapeutics.

Dataset Information

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts.

Publications

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts.

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