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Targeted Next-Generation Sequencing in Succinate Dehydrogenase-Deficient GI Stromal Tumor Identifies Actionable Alterations in the PI3K/mTOR Pathway.
JCO Precis Oncol
January 2025
Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Purpose: Less than 5% of GI stromal tumors (GISTs) are driven by the loss of the succinate dehydrogenase (SDH) complex, resulting in a pervasive DNA hypermethylation pattern that leads to unique clinical features. Advanced SDH-deficient GISTs are usually treated with the same therapies targeting KIT and PDGFRA receptors as those used in metastatic GIST. However, these treatments display less activity in the absence of alternative therapeutic options.
View Article and Find Full Text PDFRAD51 testing in patients with early HER2-negative breast cancer and homologous recombination deficiency: post-hoc analysis of the GeparOla trial.
Clin Cancer Res
December 2024
Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Purpose: The randomized GeparOla trial reported comparable pathological complete response (pCR) rates with neoadjuvant containing olaparib vs. carboplatin treatment. Here, we evaluate the association between functional homologous repair deficiency (HRD) by RAD51 foci and pCR, and the potential of improving patient selection by combining RAD51 and stromal tumor infiltrating lymphocytes (sTILs).
View Article and Find Full Text PDFCD4+ T helper 2 cell-macrophage crosstalk induces IL-24-mediated breast cancer suppression.
JCI Insight
January 2025
Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
CD4+ T cells contribute to antitumor immunity and are implicated in the efficacy of cancer immunotherapies. In particular, CD4+ T helper 2 (Th2) cells were recently found to block spontaneous breast carcinogenesis. However, the antitumor potential of Th2 cells in targeting established breast cancer remains uncertain.
View Article and Find Full Text PDFVariant Pseudocystic Desmoplastic Small Round Cell Tumor With Heterologous Mullerian Cysts.
Pediatr Dev Pathol
January 2025
Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University Medical Center, St. Louis, MO, USA.
A desmoplastic small round cell tumor (DSRCT) presented in a 13-year-old female with an acute abdomen due to torsion of a fallopian tube cyst. She was found to have an incidental 2 cm pedunculated, solid, and multicystic mass attached to the pelvic floor on laparoscopy. The neoplasm had a variably myxoid and spindle cell pattern with nests and cords of small cells, forming pseudocysts, and true cysts lined by ciliated epithelium which were PAX-8+ and ER+/PR+.
View Article and Find Full Text PDFHuman collagen type I‑based scaffold retains human‑derived fibroblasts in a patient‑derived tumor xenograft mouse model.
Exp Ther Med
February 2025
Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
The present study aimed to investigate the role of a recombinant protein based on human collagen type I (RCPhC1) as a scaffold in maintaining the human tumor microenvironment within a patient-derived tumor xenograft (PDTX) model. RCPhC1, synthesized under animal component-free conditions, was explored for its potential to support the human-specific stroma associated with tumor growth. PDTX models were established using resected colorectal cancer liver metastasis specimens, and stromal cell populations from humans and mice were compared using three scaffolds: No scaffold (control), Matrigel and recombinant human collagen type I, across two passages.
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