Abstract
The incidence of pancreatic cancer has been rising worldwide, and its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical ...diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Association, the Chinese Society of Surgery, Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China (2014) after reviewing evidence-based and problem-oriented literature published during 2015–2021, mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer, conversion strategies for locally advanced pancreatic cancer, treatment of pancreatic cancer with oligo metastasis, adjuvant and neoadjuvant therapy, standardized processing of surgical specimens and evaluation of surgical margin status, systemic treatment for unresectable pancreatic cancer, genetic testing, as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues, and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation, Assessment, Development, and Evaluation system. This guideline aims to standardize the clinical diagnosis and therapy, especially surgical treatment of pancreatic cancer in China, and further improve the prognosis of patients with pancreatic cancer.
Abstract
Objective:
The aim of this study is to investigate the current status of pancreatic cancer patients undoing surgical treatment in China and to find ways to improve the survival of these ...patients in the future.
Methods:
This study is a national, multicenter, cross-sectional study in China. Information regarding pancreatic cancer patients undergoing surgical treatment from 34 high-volume tertiary IIIA level hospitals was collected and analyzed from the March 1, 2016 to the February 28, 2017.
Results:
In total, 2200 pancreatic cancer patients were enrolled from 34 tertiary IIIA level hospitals in 16 provinces across China. The male-to-female ratio was 1.5. More than 80% of the patients were between 50 and 70 years old. The top 4 symptoms were epigastric discomfort, abdominal pain, jaundice, and weight loss. Carbohydrate antigen 19-9 and carcinoembryonic antigen were elevated in 70.9% and 27.1% of patients, respectively. A multidisciplinary team (MDT) discussion was carried out for 35.0% of patients before surgery. The proportion of minimally invasive pancreatic surgeries was approximately 20%. A total of 83.4% of the operations achieved R0 resection, and the incidence of grade 3/4 postoperative complications was 7.7%. Only 13.4% of the patients received postoperative adjuvant chemotherapy. The percentage of pathological stage I tumors was only 24.5%.
Conclusion:
The majority of pancreatic cancer patients undergoing surgical resection in China are in an advanced stage. The MDT consultations for pancreatic cancer have not been widely carried out. R0 resection has been achieved in most cases, with relatively low incidence of serious complications, but minimally invasive pancreatic surgery should be further promoted. The application of postoperative chemotherapy remains low. This national, multicentre, cross-sectional study comprehensively presents the current status of pancreatic cancer patients undergoing surgical treatment and shows the road to improve survival of these patients in the future.
Although the upregulation of Neuropilin-1 (NRP-1) is associated with many solid tumors, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The aim of this study was ...to investigate the role of NRP-1 in improving treatment and determining the prognosis of pNEN. In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analyzed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with small interfering RNAs against NRP-1 or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The expression of NRP-1 in pNEN tissues was markedly increased compared with adjacent normal pancreatic tissues. High NRP-1 expression was strongly correlated with tumor grades (P = .026), lymph node metastasis (P = .025), and tumor-node-metastasis stages (P = .012). Furthermore, NRP-1 downregulation notably inhibited the metastatic capacity of pNEN cells, and STAT3 knockdown was found to downregulate the expression of NRP-1. BON1 cells upregulated NRP-1 expression upon stimulation with IL-6. This was accompanied by activation/phosphorylation of the AKT and STAT3 signaling pathways. Western blot of extracts of human pNENs confirmed increased NRP-1 expression, as well as AKT/STAT3 phosphorylation in tissue of pNENs with elevated expression levels of IL-6. In conclusion, our findings suggest that NRP-1 is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with the IL-6/STAT3 signaling pathway.
•IL-6/STAT3 signaling upregulated NRP-1 expression in pNEN•NRP-1 and STAT3 affect the invasion capacity of pNEN cell line BON1•NRP-1 may be a direct target of STAT3 in pNEN
Objective:
The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms (pNENs) undergoing surgery in China.
Methods:
...This is a multicenter cross-sectional study performed in China. Data from patients with pNENs undergoing surgery at 33 high-volume medical centers, where the number of pancreatectomies exceeds 20 cases per year, were collected and analyzed between March 1, 2016 and February 28, 2017.
Results:
In total, 392 patients with pNENs were enrolled. The male to female ratio was 1.4. The majority of patients were aged between 40 and 70 years. 65.6% of the patients had non-functional tumors. Among those with functional tumors, the percentages of insulinomas, gastrinomas, glucagonomas, and vasoactive intestinal peptide-secreting tumors were 94.8%, 1.5%, 2.2%, and 1.5%, respectively. Multidisciplinary team (MDT) discussion was conducted for 39.0% of the patients. Minimally invasive surgery was performed on 31.1% of the 392 patients. The incidence of grade B/C pancreatic fistula formation was 4.4%. A total of 89.0% of the surgeries achieved R0 resection, and 41.6% of the tumors were well differentiated. Lymph node metastasis was present in 8.9% of the patients. The percentages of patients with grades G1, G2, and G3 disease were 49.2%, 45.7%, and 5.1%, respectively.
Conclusion:
This multicenter cross-sectional study systematically presents the current status of the diagnosis and treatment of patients with pNENs undergoing surgery in China. MDT consultation for pNENs has not been widely implemented in China. Although the incidence of surgical complications is relatively low, minimally invasive procedures should be further promoted. This study shows us how to improve the outcomes of these patients.
Pancreatic cancer (PC) has a high mortality rate in all cancers worldwide. According to recent studies, long noncoding RNA‐CASC2 is involved in the development and progression of many malignant ...tumors; in the present study, we demonstrated that lncRNA‐CASC2 was specifically downregulated in PC tissues and cell lines, and a lower CASC2 expression in PC was related with a poorer prognosis. CASC2 suppressed PC cell proliferation. Hepatocyte nuclear factor 1 alpha (HNF1A) is a transcription factor known to regulate pancreatic differentiation and maintain the homeostasis of the endocrine pancreas. Recently, HNF1A is considered to be a possible tumor suppressor in PC. In the present study, we observed that HNF1A positively regulated CASC2 expression. Through luciferase assays, we demonstrated that CASC2 gene possessed an HNF1A‐responsive element (CASC2‐HNF1A RE); HNF1A could promote CASC2 expression through direct binding to CASC2‐HNF1A RE. Further, PTEN/Akt signaling was involved in HNF1A regulation of CASC2. Finally, we evaluated the expression level of HNF1A in PC tissues; lower HNF1A expression was correlated with shorter overall survival in patients with PC. Taken together, these findings will shed light on the role and mechanism of HNF1A/CASC2 in regulating PC cells proliferation through PTEN/Akt signaling. CASC2 may serve as a potential therapeutic target in PC in the future.
Sex-determining region Y-related high-mobility group box 4 (SOX4) has been proven to serve as a critical role in cancer progression. However, the pathological role of SOX4 in colorectal cancer (CRC) ...remains unknown. The aim of this study was to investigate the role of SOX4 in CRC. In this study, we investigated the expression of SOX4 in CRC tissues by immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. We also evaluated the effect of SOX4 on cell proliferation and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and transwell assay. The SOX4 messenger RNA (mRNA) and protein expression were markedly higher in CRC tissues compared with adjacent normal mucosa tissues. Inhibition of SOX4 could suppress CRC cell proliferation, and invasion in vitro. Our findings indicate that targeting SOX4 might provide a new therapeutic modality for the treatment of CRC patients.
The transcription factor Krüppel-like factor 8 (KLF8) plays an important role in tumor development and growth, but its role in pancreatic cancer (PC) is not clear.
KLF8 expression in human PC cell ...lines and tumor tissues was measured by quantitative real-time polymerase chain reaction and Western blot analyses. The effects of lentivirus mediated knockdown of KLF8 on proliferation and growth in Panc-1 pancreatic cancer cells were examined.
KLF8 was overexpressed in 5 pancreatic cancer cell lines and in samples from patients with PC. In Panc-1 cells, KLF8 knockdown inhibited cell proliferation, tumorigenicity, and induced G2/M phase arrest. KLF8 knockdown suppressed PC tumor growth in nude mice model. Western blot analysis showed that KLF8 knockdown in Panc-1 cells down-regulated the expression of CDK1/CDC2, cyclin B1, and cyclin D1 and up-regulated the expression of p21, and p27.
Overexpression of KLF8 may contribute to the progression of pancreatic cancer, and downregulation of KLF8 expression by lentivirus-delivered shRNA is a novel therapeutic approach for PC.
•KLF8 was overexpressed in pancreatic cancer tissues and cell lines.•KLF8- knockdown resulted in cell proliferation suppression both in vitro and in vivo.•KLF8-knockdown influence expression of CDC2, p21, p27, resulted in G2/M arrest.•KLF8 may play an important role in PC progression.
The roles of M2 macrophages on promoting tumor progression and chemotherapy resistance have been well studied in many cancers, such as pancreatic cancer, kidney cancer and so on, but its linkage to ...HCC cells still remains unclear. Here we found that M2 macrophages could alter miR-149-5p to increase MMP9 expression in HCC cells and mechanism dissection revealed that miR-149-5p might directly target the 3'UTR of MMP9-mRNA to suppress its translation. The in vivo orthotopic xenografts mouse model with oemiR-149-5p also validated in vitro data. Together, these findings suggest that M2 macrophages may through altering the miR-149-5p to promote HCC progression and targeting the M2 macrophages/miR149-5P/MMP9 signaling may help in the development of the novel therapies to better suppress the HCC progression.
Display omitted
•miR-125a-3p is reduced in PDAC.•Rescue of miR-125a-3p level increases cancer cells’ sensitivity to gemcitabine.•miR-125a-3p inhibits EMT programs in PDAC.•miR-125a-3p regulates EMT ...process via directly targeting Fyn.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and resistance to cytotoxic chemotherapy is the major cause of mortality in PDAC patients. miR-125a-3p was found to be down-regulated in PDAC cells; however, the function of miR-125a-3p in PDAC has been elusive. Here, we explored the role of miR-125a-3p in chemosensitivity in PDAC cells.
We used qRT-PCR to detect miR-125a-3p expression in two PDAC cell lines. And we measured cell viability and apoptosis by MTT assay and flow cytometry, respectively. Scratch wound healing assay and transwell invasion assay were used to test the effects of miR-125a-3p and Fyn on cell EMT process. In addition, we validated the interaction of miR-125a-3p and Fyn by dual luciferase reporter assay. qRT-PCR and western blot were used to detect the mRNA and protein expressions of E-cadhrein, N-cadhrein, Snail and Fyn.
We found that miR-125a-3p was down-regulated in a time-dependent manner following treatment with gemcitabine in PDAC cells. Meanwhile, we found that overexpression of miR-125a-3p significantly increased chemosensitivity to gemcitabine and suppressed epithelial-mesenchymal transition (EMT) of PDAC cells. Mechanistically, miR-125a-3p directly targeted Fyn and decreased the expression of Fyn that functions to promote EMT process in PDAC. Furthermore, overexpression of Fyn could partially reverse the effects of miR-125a-3p on chemosensitivity to gemcitabine.
Our study is the first to show that miR-125a-3p is responsible for chemosensitivity in PDAC and could inhibit epithelial-mesenchymal transition by directly targeting Fyn. This provides a novel potential therapeutic strategy to overcome chemoresistance in PDAC.
PDF
