Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.
Age and the extent of gastrectomy were revealed as the prognostic factors for overall complications and the complications of grade IIIa or over according to the Clavien-Dindo classification following gastrectomy for gastric cancer.
Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic spread of primary tumor to regional lymph nodes in clinical practice. In this research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was developed. The NIR-emitting polymer nanoprobes were designed and synthesized by conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer nanogels. The NIR-PNG nanoprobes were found to be photostable compared with the IRDye800-free dye at room temperature. Upon intradermal injection of the NIR-PNG into the front paw of a mouse, the nanoprobes entered the lymphatic system and migrated to the axillary lymph node within 2 min. The NIR fluorescence signal intensity and retention time of NIR-PNG in the lymph node were superior to the corresponding properties of the IRDye800-free dye. A immunohistofluorescence study of the SLN resected under NIR imaging revealed that the NIR-PNG nanoprobes were predominantly co-localized with macrophages and dendritic cells. Intradermal injection of NIR-PNG nanoprobes into the thigh of a pig permitted real-time imaging of the lymphatic flow toward the SLN. The position of the SLN was identified within 1 min with the help of the NIR fluorescence images. Taken together, the experimental results demonstrating the enhanced photostability and retention time of the NIR-PNG provide strong evidence for the potential utility of these polymer probes in cancer surgery such as SLN mapping.
Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract and is most frequently developed in the stomach in the form of submucosal tumor. The incidence of gastric gastrointestinal stromal tumor is estimated to be as high as 25% of the population when all small and asymptomatic tumors are included. Because gastric gastrointestinal stromal tumor is not completely distinguished from other submucosal tumors, a surgical excisional biopsy is recommended for tumors >2 cm. The surgical principles of gastrointestinal stromal tumor are composed of an R0 resection with a normal mucosa margin, no systemic lymph node dissection, and avoidance of perforation, which results in peritoneal seeding even in cases with otherwise low risk profiles. Laparoscopic surgery has been indicated for gastrointestinal stromal tumors <5 cm, and the indication for laparoscopic surgery is expanded to larger tumors if the above mentioned surgical principles can be maintained. A simple exogastric resection and various transgastric resection techniques are used for gastrointestinal stromal tumors in favorable locations (the fundus, body, greater curvature side). For a lesion at the gastroesophageal junction in the posterior wall of the stomach, enucleation techniques have been tried preserve the organ's function. Those methods have a theoretical risk of seeding a ruptured tumor, but this risk has not been evaluated by well-designed clinical trials. While some clinical trials are still on-going, neoadjuvant imatinib is suggested when marginally unresectable or multiorgan resection is anticipated to reduce the extent of surgery and the chance of incomplete resection, rupture or bleeding.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.