Colorectal cancer (CRC) remains a major global health burden, being one of the most prevalent cancers with high mortality rates. Despite advances in conventional treatment modalities, patients with metastatic CRC often face limited options and poor outcomes. Chimeric antigen receptor-T (CAR-T) cell therapy, initially successful in hematologic malignancies, presents a promising avenue for treating solid tumors, including CRC.
View Article and Find Full Text PDFEnteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the parasite Heligmosomoides polygyrus bakeri (Hpb) reprograms the intestinal epithelium into a fetal-like state marked by the emergence of Clusterin-expressing revival stem cells (revSCs). Organoid-based studies using parasite-derived excretory-secretory products reveal that Hpb-mediated revSC generation occurs independently of host-derived immune signals and inhibits type 2 cytokine-driven differentiation of secretory epithelial lineages that promote their expulsion.
View Article and Find Full Text PDFDespite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades.
View Article and Find Full Text PDFColorectal cancer liver metastases (CRCLM) that receive their blood supply via vessel co-option are associated with a poor response to anti-angiogenic therapy. Angiopoietins (Ang1 and Ang2) with their Tyrosine-protein kinase receptor (Tie2) have been shown to support vessel co-option. We demonstrate significantly higher expression of Ang1 in hepatocytes adjacent to the tumor region of human chemonaïve and treated co-opting (replacement histopathological growth patterns: RHGP) tumors.
View Article and Find Full Text PDFThe turnover of the intestinal epithelium is driven by multipotent LGR5 crypt-base columnar cells (CBCs) located at the bottom of crypt zones. However, CBCs are lost following injury, such as irradiation, but the intestinal epithelium is nevertheless able to recover. Thus, a second population of quiescent '+4' cells, or reserve stem cells (RSCs), has previously been proposed to regenerate the damaged intestine.
View Article and Find Full Text PDFSolitary fibrous tumors (SFTs) are rare mesenchymal neoplasms, displaying variable morphological and clinicopathological features. Supportive immunohistochemical markers such as CD34, CD99, BCL2 and LSD1 are commonly applied in the differential diagnosis of SFTs, although none is sufficiently sensitive or specific enough. The aim of the present study was to examine the most differential markers for the reliable distinction of SFTs from histological mimics.
View Article and Find Full Text PDFObjective: Recent studies have reported that antioxidant status, including serum selenium concentrations, is altered in women who develop preeclampsia. We wished to examine the effects of selenium supplementation in the prevention of preeclampsia in high-risk pregnant women.
Design: We carried out a randomized, double-blind, placebo-controlled pilot trial.
Objective: We assessed the impact of selenium, a trace element with antioxidant properties on a simple measure of oxidative stress in pregnant women.
Study Design: A novel assay of prooxidant-antioxidant balance (PAB) was applied in a double-blind, placebo-controlled study of selenium supplementation in pregnancy. We measured the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby calculating a redox index.