Yiqin Xiong

Endometrial cancer (EC), the most common gynecologic malignancy in the USA, has seen limited improvement in patient outcomes over recent decades, underscoring the need for relevant preclinical models. To address EC heterogeneity, we established an integrated platform of patient derived xenografts (PDXs) and matched patient derived primary cancer cells (PDCs) for disease modeling and systematic drug sensitivity testing. Fresh tumor specimens (n=103) were collected from EC patients to generate PDXs in immunodeficient mice and corresponding PDCs. Fifty-three PDX models were successfully established (52% engraftment rate), with higher success observed in high grade, recurrent, metastatic tumors (70%), compared with their low-grade counterparts (56%). Histopathologic and immunohistochemical analyses confirmed that PDX tumors faithfully preserved morphology, hormone receptor status, and intertumoral heterogeneity across multiple passages. Using 13 PDC models, we performed an unbiased screening of 179 FDA‑approved oncology drugs, revealing marked intertumoral variability in drug response. Almost all PDC models exhibited limited sensitivity to NCCN‑recommended therapies, highlighting the need for alternative treatment strategies. In contrast, multiple FDA-approved agents including epigenetic modulators, dual PI3‑kinase/HDAC inhibitors, topoisomerase II inhibitors, and proteasome inhibitors demonstrated potent antitumor activity. Importantly, a low‑dose combination of the DNA methyltransferase inhibitor 5‑azacytidine and the histone deacetylase inhibitor romidepsin significantly suppressed tumor growth across six independent PDX models. Together, these findings establish a comprehensive PDX and PDC platform as a robust translational resource. By capturing the histopathologic and molecular diversity of EC and identifying clinically actionable therapeutic advantages, including an epigenetic combination regimen, this study offers a translational resource for preclinical drug evaluation.

Background: Upper GI involvement is common in pediatric IBD, but the relative frequencies of specific endoscopic and histologic abnormalities at diagnosis remain poorly defined. Objective: To determine whether specific upper GI endoscopic and histologic features differ among pediatric Crohn disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) at diagnosis. Methods: We retrospectively analyzed 243 pediatric patients (P = .04), and eosinophilic esophagitis was more frequent in IC (20%, P = .03). CD showed more esophageal erosions/aphthae (12%, P < .01), gastric erosions/ulcers (24% vs UC 17%, P < .01), and duodenal erosions/ulcers (35%, P < .01). Histologically, lymphocytic esophagitis (29%, P < .001), epithelioid granulomas (14%, P < .001), and active duodenitis (28%, P = .007) were significantly more common in CD. Conclusions: Upper GI abnormalities are not limited to CD. Specific upper GI features—particularly lymphocytic esophagitis, epithelioid granulomas, and active duodenitis—are more strongly associated with CD at diagnosis and may assist subclassification in challenging pediatric IBD cases.

FABP5 mediates lipid incorporation

Obesity is strongly associated with triple-negative breast cancer (TNBC). A better understanding of the molecular mechanisms driving obesity-induced TNBC progression could facilitate the development of precision dietary intervention strategies. In this study, we used murine models of obesity induced by different high-fat diets (HFD) to examine their impact on TNBC progression. Compared with a low-fat diet, both cocoa butter and olive oil HFDs induced similar levels of obesity. However, only the olive oil HFD–induced obesity increased TNBC stemness and lung metastasis. Mechanistically, oleic acid (OA) in the olive oil HFD facilitated TNBC metastasis by activating the protein kinase C (PKC)–aldehyde dehydrogenase (ALDH) pathway. Furthermore, fatty acid–binding protein 5 (FABP5) in TNBC cells was identified as essential for OA-mediated PKC–ALDH pathway activation. FABP5 deficiency reduced TNBC metastasis in multiple mouse models, whereas higher FABP5 expression correlated with worse outcomes of TNBC in various human studies. These findings collectively suggest that the consumption of olive oil HFD promotes obesity-associated TNBC metastasis through OA/FABP5-driven oncogenic signaling.Significance:Comparison of obesity induced by different high-fat diets revealed that an olive oil-based diet promotes triple-negative breast cancer metastasis by activating FABP5/PKC/ALDH signaling, providing a target for the development of obesity-associated cancer therapeutics.

HFD-associated immunophenotypes

OA-induced tumor invasion in vitro