Publication

Epidermal growth factor receptor (EGFR) is overexpressed in many human colorectal cancers and anti-EGFR agents are employed as immunotherapies. However, KRAS, EGFR, and BRAF gene mutations can influence the activity of the anti-EGFR agents. We evaluated EGFR expression at protein and mRNA levels in canine intestinal adenocarcinomas using immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH). We also investigated the mutation status of EGFR, KRAS, and BRAF to aid the development of anti-EGFR agents for canine intestinal adenocarcinoma.

The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell.

Heightened aggressive behavior is considered as one of the central symptoms of many neuropsychiatric disorders including autism, schizophrenia, and dementia. The consequences of aggression pose a heavy burden on patients and their families and clinicians. Unfortunately, we have limited treatment options for aggression and lack mechanistic insight into the causes of aggression needed to inform new efforts in drug discovery and development. Levels of proinflammatory cytokines in the periphery or cerebrospinal fluid were previously reported to correlate with aggressive traits in humans.

Diffuse large B‑cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism.

Background and aims Liver lobules are typically subdivided into three metabolic zones: zones 1, 2, and 3. However, the contribution of zonal differences in hepatocytes to liver regeneration, as well as to carcinogenic susceptibility, remains unclear. Methods We developed a new method for sustained genetic labeling of zone 3 hepatocytes and performed fate tracing to monitor these cells in multiple mouse liver tumor models. Results We first examined changes in the zonal distribution of the Wnt target gene Axin2 over time using Axin2-CreERT2;Rosa26-Lox-Stop-Lox-tdTomato mice (Axin2;tdTomato).

Aberrant NOTCH3 signaling and overexpression is oncogenic, associated with cancer stem cells and drug resistance, yet therapeutic targeting remains elusive. Here, we develop NOTCH3-targeted antibody drug conjugates (NOTCH3-ADCs) by bioconjugation of an auristatin microtubule inhibitor through a protease cleavable linker to two antibodies with differential abilities to inhibit signaling. The signaling inhibitory antibody rapidly induces ligand-independent receptor clustering and internalization through both caveolin and clathrin-mediated pathways.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma and of which the prognosis of activated B-cell-like (ABC) subtype is poor. Although R-CHOP significantly improves the survival of patients with DLBCL, 20% to 40% of patients were resistant to R-CHOP therapy. Thus, screening for candidate therapeutic targets for R-CHOP resistant patients is urgent. The previous researches have shown that CD24 is related to the development, invasion, and metastasis of cancer. Our project aims to clarify the relationship between CD24 and ABC-DLBCL.

Background & Aim: T cells therapies have revolutionized cancer treatment for many patients. However, for the majority of patients with advanced solid tumors, sustained clinical benefit has not been achieved. Unlike T cells, myeloid cells readily accumulate in tumors, in some cases contributing up to 50% of the tumor mass.

In a multi-level ‘deconstruction’ of omental metastases, we previously identified a prognostic matrisome gene expression signature in high-grade serous ovarian cancer (HGSOC) and twelve other malignancies. Here, our aim was to understand how six of these extracellular matrix, ECM, molecules, COL11A1, COMP, FN1, VCAN, CTSB and COL1A1, are up-regulated in cancer. Using biopsies, we identified significant associations between TGFβR activity, Hedgehog signalling and these ECM molecules and studied the associations in mono-, co- and tri-culture.

Background: Oral cancer pain is debilitating and understanding mechanisms for it is critical to develop treatment strategies. Brain-derived neurotrophic factor (BDNF) signaling is elevated in oral tumor biopsies and has been reported to promote tumor progression. However, whether BDNF signaling in oral tumors contributes to cancer-induced pain is not known. Therefore, the current study evaluates a novel peripheral role of BDNF/TrkB signaling in oral cancer pain.