Exploring the Mechanism of KLF15 on the Biological Activity and Autophagy of Gastric Cancer Cells based on PI3K/Akt/Mtor Signaling Pathway.

OBJECTIVE: To explore the mechanism of KLF15 on the biological activity and autophagy of gastric cancer cells based on the PI3K/Akt/mTOR signaling pathway. MATERIAL AND METHODS: The gastric cancer AGS cells were divided into the Con group, pcDNANC group, pcDNA-KLF15 group, LY294002 group and IGF-1 group. RT-PCR was used to detect the expression of KLF15 in human gastric mucosal cells and gastric cancer cells; MTT method to detect cell proliferation; Transwell method to detect cell invasion; flow cytometry to detect cell apoptosis; Western blotting to detect PI3K, Akt, mTOR in cells, LC3, Beclin1, p62 protein expression.P<0.05 was used to indicate statistical significance. RESULTS: Compared with the human gastric mucosal cell line GES-1 cells, the expression of KLF15 in human gastric cancer cell lines MKN-28, MFC, SCG-7901 and AGS cells was significantly decreased, And the expression of KLF15 in AGS cells, was the lowest (P=0.006). Compared with the Con group, The expression of KLF15 in the cells of the PCDNA-KLF15 group was significantly increased (P=0.018); There was no significant difference in the expression of KLF15 between the Con group and the PCDNA-NC group (P=0.225). Compared with the Con group, the proliferation and invasion abilities of the cells in the pcDNA-KLF15 group were significantly reduced, And the apoptosis ability was significantly increased (P=0.019). The ratio of LC3II/LC31 and the expression of Beclin1 Protein in the control group were significantly higher than those in the Con group (P=0.017). CONCLUSION: Overexpression of KLF15 can inhibit the proliferation and invasion of Gastric cancer cells and promote cell apoptosis and autophagy, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

Prognosis significance and potential association between ALDOA and AKT expression in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract and a leading cause of cancer-related death worldwide. Since many CRC patients are diagnosed already in the advanced stage, and traditional chemoradiotherapy is prone to drug resistance, it is important to find new therapeutic targets. In this study, the expression levels of ALDOA and p-AKT were detected in cancer tissues and paired normal tissues, and it was found that they were significantly increased in CRC tissues, and their high expression indicated poor prognosis. Moreover, a positive correlation between the expression of ALDOA and p-AKT was found in CRC tissues and paired normal tissues. In addition, the Kaplan-Meier analysis revealed that the group with both negative of ALDOA/p-AKT expression had longer five-year survival rates compared with the other group. Besides, the group with both high expression of ALDOA/p-AKT had a worse prognosis compared with the other group. Based on the expression of ALDOA and p-AKT in tumor tissues, we can effectively distinguish tumor tissues from normal tissues through cluster analysis. Furthermore, we constructed nomograms to predict 3-year and 5-year overall survival, showing that the expression of ALDOA/p-AKT plays a crucial role in predicting the prognosis of CRC patients. Therefore, ALDOA/p-AKT may act as a crucial role in CRC, which may provide new horizons for targeted therapies for CRC.

ITGB6 promotes pancreatic fibrosis and aggravates the malignant process of pancreatic cancer via JAK2/STAT3 signaling pathway.

Integrin ß6 (ITGB6) is upregulated in multiple tumor types and elevated ITGB6 levels have been detected in patients with chronic pancreatitis. However, the role of ITGB6 in pancreatic fibrosis and cancer remains to be elucidated. In the present study, ITGB6 expression was assessed using western blotting and qRT-PCR. Besides, cell proliferation, cycling, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays, respectively. The expression of fibrosis and JAK2/STAT3 signaling markers was detected by western blotting and immunofluorescence analysis. Moreover, nude mice were subcutaneously injected with co-cultured cell suspensions to establish an in vivo model. The results showed that ITGB6 was highly expressed in pancreatic cancer tissues and TGF-ß-induced pancreatic stellate cells (PSCs). Inhibition of ITGB6 expression in PSCs resulted in clear inhibition of activated PSC proliferation, migration, and fibrogenesis. Additionally, reduced ITGB6 expression inhibits the JAK2/STAT3 signaling pathway. Interestingly, activators of the JAK2/STAT3 signaling pathway reversed the effects of ITGB6 disruption on PSCs. Activated PSCs notably promoted the proliferation, invasion, and migration of pancreatic cancer cells in a co-culture assay. In contrast, activated PSCs with low ITGB6 expression failed to significantly affect the malignancy of pancreatic cancer cells. Moreover, in vivo results showed that interference with ITGB6 inhibited the activation of PSCs and promoted the development of pancreatic cancer. Silencing ITGB6 inhibited the proliferation, migration, and fibrosis-like effects of activated PSCs and indirectly inhibited the metastasis and malignant process of pancreatic cancer by inhibiting the JAK2/STAT3 signaling pathway. Therefore, ITGB6 is a potential candidate target for pancreatic cancer prevention and treatment.

Study on the application value of fluorescent laparoscopy in pancreatic tumor surgery.

Background: Fluorescent laparoscopy is rarely used in pancreatic surgery. The aim of this study was to investigate the value of fluorescent laparoscopy in pancreatic tumor surgery. Methods: A total of 19 patients with pancreatic tumors who were treated in the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to August 2022 were selected. Fluorescent laparoscopy was used intraoperatively, and the imaging characteristics of different tumors were recorded and analyzed. Results: Among the 19 participants, postoperative pathology confirmed 12 cases of pancreatic cancer (8 cases of moderately differentiated adenocarcinoma, 3 cases of moderately-poorly differentiated adenocarcinoma, and 1 case of acinar cell carcinoma), 4 cases of pancreatic cystic tumors (1 case of microcystic serous cystadenoma, 1 case of serous cystadenoma, 1 case of solid pseudopapillary tumor, and 1 case of solid-cystic pseudopapillary tumor), 1 case of pancreatic neuroendocrine tumor (G1 stage), and 2 cases of inflammatory lesions. There were 8 cases of pancreaticoduodenectomy, 6 cases of distal pancreatectomy, 3 cases of middle pancreatectomy, 1 case of local pancreatectomy, and 1 case of duodenum-preserving pancreatic head resection. One minute after intravenous injection of indocyanine green (ICG), 10 of the 12 patients with pancreatic cancer showed tumor peritumor imaging; 2 cases of pancreatic serous cystic tumors did not show imaging; 2 cases of solid pseudopapillary tumors had tumor body imaging; 1 case of neuroendocrine tumor had tumor body imaging, with complete fluorescence imaging after specimen dissection; there were 2 cases pathologically confirmed as inflammatory lesions, 1 case with tumor body imaging, and 1 case with capsule imaging. Conclusions: By reasonably controlling the administration time and dose of ICG during surgery, some pancreatic tumors can be fluorescently imaged, which is beneficial for intraoperative tumor localization and margin determination.

Application of a sectional U-shaped reinforcement combined with penetrating pancreaticojejunostomy (U-PPJ) for soft pancreas in laparoscopic pancreatic surgery.

Laparoscopic techniques have been widely used in pancreatic surgery, such as laparoscopic pancreaticoduodenectomy (LPD) and laparoscopic central pancreatectomy (LCP). Laparoscopic pancreaticojejunostomy (LPJ) is a common procedure for LPD and LCP, and is also the most critical. The quality of LPJ is associated with the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF). Although LPJ technology has been greatly improved, CR-POPF cannot be completely avoided especially to soft pancreas, which is an important reason for the high risk of laparoscopic pancreatic surgery. To date, there is a lack of standard LPJ approaches. Here, we report a U-shaped suture reinforcement for soft pancreatic section combined with penetrating pancreaticojejunostomy (PPJ) technique, called U-PPJ. Twenty-three patients with soft pancreas who underwent laparoscopic pancreatic surgery adopting U-PPJ method between 2017 and 2022 were enrolled (LPD = 19, LCP = 4). Preoperative, intraoperative and postoperative indexes were collected and analyzed. The results showed that all patients treated with U-PPJ were discharged without drainage tube or a small amount of exudate in the drainage tube does not require clinical treatment, but only needs to be removed after 2 days of observation. The average operation time was 417.35 min. The intraoperative blood loss was 171.74 ml. The pancreatic duct diameter was 3.41 mm. The average postoperative hospitalization days were 11.83 days. The average postoperative drainage tube removal time was 13.26 days. The incidence of postoperative B-grade pancreatic fistula was 4.3%, and no C-grade pancreatic fistula occurred. In our experience, U-PPJ can be completed by a skilled surgeon in less than 20 min. U-PPJ is safe, reliable, convenient and has a low incidence of CR-POPF in soft pancreas, which is worthy of clinical application. It also provides more options for laparoscopic pancreatic surgery. Since this is a retrospective study with a small number of cases, more prospective multicenter studies are needed to further verify its safety and efficacy.

Mixed neuroendocrine-nonneuroendocrine neoplasm of the ampulla: Four case reports.

BACKGROUND: Mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN) is a rare tumor that occurs in the gastrointestinal tract and pancreas, usually composed of adenocarcinoma and neuroendocrine carcinoma. MiNEN occurring in ampulla is even rarer. We report 4 cases of MiNEN in ampulla, combined with literature review to summarize the clinical features and treatment of the disease, in order to improve the understanding of the disease. CASE SUMMARY: A retrospective analysis was performed in 4 cases of MiNEN of the ampulla diagnosed by pathology from 2014 to 2021. The 4 patients were all male, aged 67-81 years (average 72.25 years). Among them, 2 patients had jaundice, 1 patient had abdominal pain, and 1 patient had jaundice with abdominal pain as the first symptom. All 4 patients underwent enhanced CT or MRI, which all indicated that the tumors were located in the ampulla. Two patients underwent duodenoscopy, and a biopsy revealed ampullary adenocarcinoma. All 4 patients underwent radical pancreaticoduodenectomy. Four cases were followed up: One patient developed severe complications after the operation, his condition deteriorated, and he survived for 1 mo. In the other 3 patients, tumor recurrence was observed during follow-up, and 2 of them survived for 29 mo and 22 mo respectively. One case survived and is still being followed up. CONCLUSION: MiNEN of the ampulla are extremely rare, lacking typical clinical symptoms and imaging features, and are usually diagnosed after postoperative histopathological and immunohistochemical examinations. The main treatment is radical surgical resection, which can be combined with chemotherapy. The best method of diagnosis and treatment needs further research.

Silencing of keratin 17 by lentivirus-mediated short hairpin RNA inhibits the proliferation of PANC-1 human pancreatic cancer cells.

Keratin 17 (KRT17) has been demonstrated to be a potential biological marker for the prediction of prognosis in particular types of cancer. The aim of the present study was to investigate the molecular mechanisms underlying the function of KRT17 in the pancreatic cancer (PAC) cell line PANC-1 and the potential of KRT17 as a therapeutic target for PAC. KRT17 expression levels were analyzed using quantitative PCR and compared with histological data using bioinformatics tools in PAC samples and three human PAC cell lines. Cell proliferation was determined using an MTT assay, in addition to cell cycle distribution and apoptosis analysis using flow cytometry, colony formation assay using Giemsa staining and cell motility analysis using a Transwell migration assay. Tumor growth was evaluated in vivo in nude mice. The expression levels of a number of signaling molecules were measured to establish the potential mechanism by which silencing KRT17 expression affected PAC PANC-1 cells. Increased levels of KRT17 expression were observed in human PAC compared with normal tissues, as well as in three human PAC cell lines (MIA PaCa-2, PANC-1 and KP-3 cells) compared with the H6c7 human immortal pancreatic duct epithelial cell line. High expression levels of KRT17 in PAC samples were associated with poor overall survival (P=0.036) and disease-free survival (P=0.017). Lentivirus-mediated KRT17 silencing inhibited cell proliferation, colony formation and migration, but promoted apoptosis and resulted in cell cycle arrest in the G0/G1 phase in PANC-1 cells. In addition, KRT17 knockdown inhibited in vivo tumor growth. KRT17 knockdown induced dysregulation of ERK1/2 and upregulation of the pro-apoptotic Bcl-2 protein Bad. In conclusion, the present study demonstrated that elevated KRT17 levels are positively associated with pancreatic cancer progression; KRT17 knockdown suppressed cell growth, colony formation, migration and tumor growth, and induced apoptosis and cell cycle arrest, affecting ERK1/2/Bad signaling. Therefore, the results of the present study suggested that KRT17 may be a potential target for the treatment of pancreatic cancer.