Yongsheng Yang

Background: KANK2, a gene crucial for cell migration and movement, is implicated in neoplastic and non-neoplastic diseases. This study aimed to analyze KANK2's expression and its diagnostic and prognostic significance across 33 cancers using multiple online databases.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcitabine (GEM). However, the chemotherapy resistance to GEM is often overlooked in the clinical treatment of PDAC due to the lack of effective biological markers. Therefore, it is crucial to find new prognostic markers and therapeutic targets for patients with PDAC. In this study, we identified a novel regulatory mechanism in the development of resistance to GEM in PDAC. Here, we report that LINC01134 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that LINC01134 promotes PDAC resistance to GEM through facilitating stem cell features and modulating the cell cycle. Mechanistically, LINC01134 interactes with tumor suppressor miR-497-5p in PDAC cells. Increased LINC01134 downregulates miR-140-3p to promotes the oncogenic WNT5A expression. Moreover, m⁶A demethylase FTO participated in the upregulation of LINC01134 by maintaining LINC01134 mRNA stability through YTHDF2. Taken together, the present study suggested FTO-mediated LINC01134 stabilization to promote chemotherapy resistance to GEM through miR-140-3p/WNT5A/WNT pathway in PDAC. Our study identified new prognostic markers and new therapeutic targets for patients with PDAC.

The ADAMs (a disintegrin and metalloproteinase) are a family of cell surface proteins with crucial roles in the regulation of cell adhesion, cell proliferation to migration, proteolysis and cell signaling transduction pathways. Among these enzymes, the ADAM17 shows significant effects in the "ectodomain shedding" of its substrates such as cytokines (e.g., tumor necrosis factor α, TNFα), growth factors (e.g., epidermal growth factor, EGF), adhesion proteins (e.g., L-selectin), and their receptors (e.g., IL-6R and TNFα). Several studies focus on the underlying molecular mechanisms of ADAM17 in diseased conditions. Here, we took several different approaches to elucidate the function of ADAM17, the participation of ADAM17 in several human diseases, and the potential as targeted therapy reagents. As more and more studies verify the miRNA-mediated expression variation of ADAM17, the specific regulation network of miRNAs and ADAM17 was exploited in this review as well.

Laparoscopic pancreatic reconstruction is a challenging procedure and is considered the Achilles’ heel of laparoscopic pancreatectomy. Multiple techniques of laparoscopic pancreatic reconstruction ...

MiR-23a-3p has been shown to promote liver cancer cell growth and metastasis and regulate that of chemosensitivity. Protocadherin17 (PCDH17) is a tumor suppressor gene and plays an essential part in cell cycle of hepatocellular carcinoma (HCC). This study aimed at evaluating the effects of miR-23a-3p and PCDH17 on HCC cell cycle and underlining the mechanism. The level of miR-23a-3p was up-regulated, while PCDH17 level was down-regulated in HCC tissues compared to adjacent tissues. For the in vitro studies, high expression of miR-23a-3p down-regulated PCDH17 level; increased cell viability; promoted G1/S cell cycle transition; up-regulated cyclin D1, cyclin E, CDK2, CDK4, p-p27, and p-RB levels; and down-regulated the expression of p27. Dual luciferase reporter assay suggested PCDH17 was a target gene of miR-23a-3p. MiR-23a-3p inhibitor and PCDH17 siRNA led to an increase in cell viability and the number of cells in the S phase and up-regulated cyclin D1 and cyclin E levels, compared with miR-23a-3p inhibitor and NC siRNA group. For the in vivo experiments, high expression of miR-23a-3p promoted tumor growth and reduced PCDH17 level in the cytoplasm. These results indicated that high expression of miR-23a-3p might promote G1/S cell cycle transition by targeting PCDH17 in HCC cells. The miR-23a-3p could be considered as a molecular target for HCC detection.

The target of the current research was to investigate the anticancer activity of sitagliptin on diethylnitrosamine (DENA)‐induced cancer in the liver. Wistar rats were treated with or without sitagliptin before DENA treatment. We detected liver weight, blood glucose, and histopathology of the liver. Serum biochemical markers like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (SALP), gamma‐glutamyl transpeptidase (GGTP), total bilirubin (TBR), total protein (TPR), and albumin (ALB) were also evaluated. In addition, lipid profile parameters comprising total cholesterol (TC), triglycerides, and high‐density lipoprotein were also measured. Inflammatory mediators like interleukin‐6 (IL‐6), interleukin‐1beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) were determined in liver homogenate. Furthermore, the activity of nuclear factor (NF‐κB) was also measured. Our results showed that sitagliptin (10 and 20 mg/kg) in a dose‐dependent manner expressively decreased the DENA‐induced elevation of SGPT, SGOT, SALP, and GGTP. Whereas sitagliptin (10 and 20 mg/kg) in a dose‐dependent mode reduced the level of TBR and increased the TPR and ALB as well as improved the liver histopathology alterations in DENA‐exposed rats. Lipid profile was also restored by the sitagliptin (10 and 20 mg/kg) in a DENA‐treated rats. The level of IL‐1β, IL‐6, and TNF‐α were suggestively suppressed. Moreover, pretreatment with sitagliptin (10 and 20 mg/kg) prevented the activation of NF‐κB. In conclusion, sitagliptin (10 and 20 mg/kg) has a potential protective effect against DENA‐induced liver cancer by inhibition of inflammation and NF‐κB activation.

Sarcomatoid carcinoma (SC) is an extremely rare and complicated malignant neoplasm that consists of both malignant epithelial components and atypical spindle cells that express an epithelial phenotype. The presents study reported a case of SC of the pancreas (SCP), along with a brief review of the literature. A 63‑year‑old man was admitted to The Second Hospital of Jilin University hospital with complaints of epigastralgia and jaundice of one month in duration. Based on preoperative laboratory blood tests and radiography, a mass at the distal common bile duct was suspected. Intraoperative examination discovered a 2.5x2x1.8‑cm mass in the pancreatic head, with invasion of the distal bile duct. Pancreaticoduodectomy was performed. Histopathology and immunohistochemistry of the specimen confirmed the diagnosis of SCP. The patient succumbed 18 months after surgery due to multiple hepatic metastases.

Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances.