AKR1B1 Expression in the Colorectal Tumor Microenvironment Contributes Towards Its Prognostic Significance.

Background: AKR1B1, a member of the aldo-keto reductase enzyme family involved in the polyol pathway of aldehyde metabolism, is aberrantly expressed in colorectal cancer (CRC). Our previous studies demonstrated that AKR1B1 knockdown reduced the motility and proliferation of CRC cell lines, and its elevated expression was correlated with increased mesenchymal marker expression, inflammation, and poor prognosis in CRC patient cohorts. However, whether stromal cells also express AKR1B1 and whether stromal expression can affect clinical outcomes has not been examined.

A new CRISPR-mediated Apc knockout allele leads to pyloric gland adenoma-like gastric polyps in mice with C57BL/6;FVB/N mixed background.

Adenomatous polyposis coli (APC) mutations are the most frequently identified genetic alteration in sporadic colorectal cancer (CRC) cases, and a myriad of genetically engineered Apc-mutant CRC mouse models have been developed using various genetic manipulation techniques. The advent of the CRISPR/Cas9 system has revolutionized the field of genetic engineering and facilitated the development of new genetically engineered mouse models. In this study, we aimed to develop a novel Apc knockout allele using the CRISPR/Cas9 system and evaluate the phenotypic effects of this new allele in two different mouse strains.

Targeting LINC00152 activates cAMP/Ca/ferroptosis axis and overcomes tamoxifen resistance in ER+ breast cancer.

Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER+) breast cancer, constituting around 75% of all cases. However, emergence of resistance is common, necessitating the identification of novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen resistance via blocking tamoxifen-induced ferroptosis, an iron-mediated cell death.

Role of Reduced Bdnf Expression in Novel Apc Mutant Allele-induced Intestinal and Colonic Tumorigenesis in Mice.

Background/aim: Brain-derived neurotrophic factor (BDNF) is a growth factor of the neurotrophin family. Recent studies indicate that its expression is regulated by Wnt/β-catenin signaling. In this study, we aimed to examine the effects of reduced Bdnf levels in an Apc mutant intestinal/colonic tumor mouse model.

Characterization of the Subcellular Distribution of Phospho-β-catenin in Colorectal Cancer.

Background/aim: β-Catenin is a multifunctional protein, which is localized to different subcellular compartments of the normal colon epithelium. The hyperactivation of Wnt pathway results in the nuclear accumulation of β-catenin and induction of colorectal carcinogenesis. Although N-terminally hypo-phosphorylated β-catenin (active β-catenin) is known as the transcriptionally active form, phospho-S33/S37/T41-β-catenin (phospho-β-catenin) can also accumulate in the nucleus.

Prognostic and predictive value of tumor infiltrating lymphocytes in combination with systemic inflammatory markers in colon cancer.

Objective: Systemic inflammatory indices and CD8(+) tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are highly prognostic in colon cancer (CC) but combined assessment is less well studied. The purpose of this study was to investigate the prognostic and predictive value of CD8(+) TILs in combination with systemic inflammatory indices in patients with resected stage II-III colon cancer.

Patients And Methods: Patients with stage II-III CC (n = 304) diagnosed between 2008 and 2016 were included.

A Novel Gene List Identifies Tumors with a Stromal-Mesenchymal Phenotype and Worse Prognosis in Gastric Cancer.

Background: Molecular biomarkers that predict disease progression can help identify tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors.

Methods: Microarray, RNA sequencing, and single-cell RNA sequencing-based gene expression data from gastric tumors were obtained from public databases.

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer.

Objective: DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC.

Patients And Methods: Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved.

Gastric Carcinoma with Lymphoid Stroma: A Combination of Mismatch Repair Deficient Medullary Type and Epstein-Barr Virus-associated Gastric Carcinomas.

Gastric carcinomas consist of a heterogeneous group of neoplasms with broad cytological and architectural variations. Gastric carcinomas with lymphoid stroma show poor correlation between their histomorphology and biological behavior. This contrast causes a need for more detailed analysis and molecular exploration of lymphoid stroma-rich gastric carcinomas with medullary like features and lack of glandular differentiation.

Loss of CTNNB1 exon 3 in sclerosing angiomatoid nodular transformation of the spleen.

Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Although several hypotheses have been suggested, the etiopathogenesis of SANT remains unknown. It is also unclear whether SANT is a reactive or a neoplastic lesion.

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.

Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy.

Class III β-tubulin Expression in Colorectal Neoplasms Is a Potential Predictive Biomarker for Paclitaxel Response.

Background/aim: The challenges of cololorectal cancer (CRC) management include prediction of outcome and drug response or chemoresistance. This study aimed at examining whether βIII-tubulin (TUBB3), present in various types of normal tissues and cancer, is a biomarker for the response of colorectal neoplasms to paclitaxel.

Materials And Methods: Six tissue microarrays (TMAs) including 14 colon mucosa, 78 polyps and 202 CRCs were constructed.

An immunohistochemical approach to detect oncogenic CTNNB1 mutations in primary neoplastic tissues.

The Wnt/β-catenin signaling pathway is dysregulated in different types of neoplasms including colorectal cancer (CRC). Aberrant activation of this signaling pathway is a key early event in the development of colorectal neoplasms, and is mainly caused by loss of function mutations in Adenomatous Polyposis Coli (APC), and less frequently by β-catenin stabilization mutations via missense or interstitial genomic deletions in CTNNB1. In this study, we have defined an immunohistochemical algorithm to dissect Wnt pathway alterations in formalin-fixed and paraffin-embedded neoplastic tissues.

Morphologic and Immunohistochemical Appraisal of Primary Gastric Carcinomas.

Gastric carcinoma management requires adjustments answering their genetic and morphologic heterogeneity. We aim to assess the expression and significance of a myriad of biomarkers (p53, MLH1, MSH2, PMS2, MSH6, Epstein-Barr encoding region-RNA, c-erbB2, E-cadherin, CEA, chromogranin, Ki-67, CDX2, presenilin-1, cathepsin E, MUC5AC, cyclin-dependent kinase 1) in 117 gastric carcinomas, which we have morphologically subclassified with a simple algorithm. Immunohistochemical stains were applied to 3 tissue microarrays of primary gastric carcinomas (n=117) obtained from resection specimens of untreated patients.