2.Proposal of novel staging system CNM (Crohn’s primary site, nodes, mesentery) to predict postoperative recurrence of Crohn’s disease
Guduru Venkat RAO ; Partha PAL ; Anuradha SEKARAN ; Pradeep REBALA ; Manu TANDAN ; D. Nageshwar REDDY
Intestinal Research 2023;21(2):196-204
After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn’s disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn’s primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.
4.Mutations in foregut SOX2 cells induce efficient proliferation via CXCR2 pathway.
Tomoaki HISHIDA ; Eric VAZQUEZ-FERRER ; Yuriko HISHIDA-NOZAKI ; Ignacio SANCHO-MARTINEZ ; Yuta TAKAHASHI ; Fumiyuki HATANAKA ; Jun WU ; Alejandro OCAMPO ; Pradeep REDDY ; Min-Zu WU ; Laurie GERKEN ; Reuben J SHAW ; Concepcion RODRIGUEZ ESTEBAN ; Christopher BENNER ; Hiroshi NAKAGAWA ; Pedro GUILLEN GARCIA ; Estrella NUÑEZ DELICADO ; Antoni CASTELLS ; Josep M CAMPISTOL ; Guang-Hui LIU ; Juan Carlos IZPISUA BELMONTE
Protein & Cell 2019;10(7):485-495
Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2 foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2 cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.