Cuncai Dai

Comprehensive analysis of the percentage of surface receptors and cytotoxic granules positive natural killer cells in patients with pancreatic cancer, gastric cancer, and colorectal cancer

BackgroundDigestive malignancies, especially pancreatic cancer (PC), gastric cancer (GC), and colorectal cancer (CRC), still occur at persistently high rates, and disease progression in these cancers has been associated with tumor immunosurveillance escape. Natural killer (NK) cell dysfunction may be responsible for this phenomenon, however, the exact relationship between tumor immunosurveillance escape in digestive malignancies and NK cell dysfunction remains unclear.MethodsPercentage of the surface receptors NKG2A, KIR3DL1, NKG2D, NKp30, NKp44, NKp46, and DNAM-1, as well as the cytotoxic granules perforin and granzyme B positive NK cells were determined in patients with pancreatic cancer (n = 31), gastric cancer (n = 31), and CRC (n = 32) prior to surgery and healthy controls (n = 31) by multicolor flow cytometry. Independent t-tests or Mann-Whitney U-tests were used to compare the differences between the patient and healthy control groups, as well as the differences between patients with different pathologic features of cancer.ResultsPercentage of NKG2D, NKp30, NKp46, and perforin positive NK cells was significantly down-regulated in patients with PC compared to healthy controls, as well as GC and CRC; reduced levels of these molecules was associated with indicators of disease progression in each malignancy (such as histological grade, depth of invasion, lymph node metastasis). On the contrary, percentage of KIR3DL1 positive NK cells was significantly increased in patients with PC, as well as GC and CRC, but was not associated with any indicators of disease progression.ConclusionsAltered percentage of surface receptors and cytotoxic granules positive NK cells may play a vital role in tumor immunosurveillance escape by inducing NK cell dysfunction in patients with PC, GC, and CRC.

Galectin-1 secreted by activated stellate cells in pancreatic ductal adenocarcinoma stroma promotes proliferation and invasion of pancreatic cancer cells: an in vitro study on the microenvironment of pancreatic ductal adenocarcinoma.

Objectives: This study aimed to clarify that the activated pancreatic stellate cells (PaSCs) are the origin of the highly expressed galectin-1 in the stroma of pancreatic ductal adenocarcinoma (PDAC) tissue and to evaluate the effect of the secreted galectin-1 on proliferation and invasion ability of pancreatic cancer cell line CFPAC-1 in vitro. Methods: Different kinds of PaSCs were isolated from the normal or cancerous pancreatic tissues and cultured. Immunohistochemistry study, quantitative polymerase chain reaction, and Western blot were carried out to check the cellular origin of galectin-1 in PDAC tissue. By using modified Boyden chambers, in vitro coculture system of PaSCs was established with the pancreatic cancer cell line CFPAC-1 and based on which we assessed the proliferation and invasion ability of CFPAC-1 with or without galectin-1 antagonists. Results: We identified PaSCs as the primary source of the highly expressed galectin-1 in PDAC stroma. Galectin-1 secreted by PaSCs increased CFPAC-1 proliferative rate in the proliferation assay and facilitated CFPAC-1 infiltration in the invasion assay. Conclusions: Under malignant circumstances, PaSCs express and secret galectin-1, which could further promote the proliferation and invasion of cancer cells.

RNA interference‐mediated silencing of the polo‐like kinase 1 gene enhances chemosensitivity to gemcitabine in pancreatic adenocarcinoma cells

Gemcitabine is the first‐line chemotherapeutic agent for advanced adenocarcinoma of the pancreas; however, chemoresistance to gemcitabine remains a major cause of failure for the clinical treatment of this disease. Polo‐like kinase 1 (Plk‐1) is highly expressed in pancreatic cancer cell lines and pancreatic tumour tissues, and is involved in a wide variety of cell cycle processes. Nevertheless, its biological role and implication for gemcitabine resistance are not clearly defined. In this study, we used RNA‐interference (RNAi)‐mediated depletion of Plk‐1 to determine its potential for sensitizing pancreatic tumour cells to gemcitabine. We showed that the level of Plk‐1 protein was correlated significantly with gemcitabine resistance in human pancreatic adenocarcinoma cells and that overexpression of Plk‐1 reduced sensitivity to gemcitabine in these cells. In addition, small interfering RNA (siRNA)‐mediated knockdown of Plk‐1 caused cell cycle arrest at G2/M and the reduction of cellular proliferation. More importantly, the treatment of pancreatic cancer cells with Plk‐1 siRNA followed by exposure to gemcitabine dramatically decreased cell viability and increased cellular apoptosis, as compared with treatment with either agent alone. These observations indicate that down‐regulation of Plk‐1 expression by RNAi enhances gemcitabine sensitivity and increases gemcitabine cytotoxicity in pancreatic tumour cells. This is the first demonstration that the combination of Plk‐1 gene therapy and gemcitabine chemotherapy has synergistic anti‐tumour activity against pancreatic carcinoma in vitro. This combination treatment warrants further investigation as an effective therapeutic regimen for patients with resistant pancreatic cancer and other tumours.

Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism

BackgroundIncreasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified.MethodsIn this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software.ResultsWe found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.ConclusionsThe present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.

CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer.

Pancreatic cancer is a disease with an extremely poor prognosis. The acquisition of invasion properties in pancreatic cancer is accompanied by the process of epithelial-mesenchymal transition (EMT). Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is emerging as an important determinant of the malignant phenotype in a range of cancers, including pancreatic cancer. Therefore, the aim of this study was to evaluate the potential involvement of CEACAM6 in the invasion and metastasis of pancreatic cancer cells via EMT regulation. The results of our study showed a positive association between CEACAM6 expression and poor prognosis of pancreatic cancer, differentiation and lymph node metastasis. Elevated levels of CEACAM6 in pancreatic cancer cells promoted EMT, migration and invasion in vitro and metastasis in animal models, whereas shRNA-mediated CEACAM6 knockdown had the opposite effect. Furthermore, we demonstrated that miR-29a/b/c specific for CEACAM6 could regulate its expression at the post-transcriptional level. Collectively, our findings identified CEACAM6, which is regulated by miR-29a/b/c, as an important positive regulator of EMT in pancreatic cancer offering an explanation for how elevated levels of CEACAM6 are likely to contribute to the highly metastatic phenotype of pancreatic cancer.

Comparison of patency rates and clinical impact of different reconstruction methods following portal/superior mesenteric vein resection during pancreatectomy

INTRODUCTION Few studies have compared patency rates of the different methods of venous reconstruction (VR) during a pancreatectomy. This study aimed to evaluate the patency rates and the clinical impact of various reconstruction methods. METHODS For the meta-analysis, databases were systematically searched to identify studies reporting the outcomes of patients who underwent PVR/SMVR. For the retrospective study, clinical data were retrospectively analyzed from patients who underwent a pancreatectomy and VR between Feb. 2009 and Oct. 2015. Patency was assessed by CT and/or ultrasound. RESULTS For the meta-analysis, the long-term patency rates of the primary repair group and the autologous graft group were significantly higher than that of the synthetic graft group. For the retrospective study, the reconstruction consisted of primary repair in 62 cases (89.8%) and synthetic grafting in 7 cases (10.1%). Synthetic grafting was more likely to cause acute thrombosis compared with primary repair for PVR/SMVR (85.7% versus 16.7%). Acute thrombosis was associated with decreased median survival (12 versus 6 months) and increased hazard of death. Late thrombosis and stenosis were not associated with survival or serious clinical impact. Median survival for the primary repair group and the synthetic grafting group was 12 and 7 months, respectively. CONCLUSION Primary repair following PVR/SMVR is preferred and can be achieved in most situations. Stenosis should be noted when with risk factors (long segmental and tension), but it produced little clinical impact. Synthetic grafting was associated with a higher thrombosis rate. Acute thrombosis is associated with increased mortality and decreased survival.

Acute Pancreatitis as a Long-term Complication of Pancreatectomy

To the Editor: Acute pancreatitis (AP) is a common digestive disorder with a broad spectrum of etiologies.[1] Apart from gallstones and alcohol abuse which are two of most common etiologies of AP, all of other potential causes need to be considered. Pancreatectomy is the surgical removal of all or part of the pancreas, which includes pancreaticoduodenectomy (PD), distal pancreatectomy, segmental pancreatectomy, and total pancreatectomy. These procedures are used in the management of several diseases involving the pancreas, ampulla, extrahepatic bile duct, and duodenum. Based on the previous researches and studies, it was well accepted that pancreatectomy is associated with a series of common complications such as pancreatic fistula, postsurgical hemorrhage, and delayed gastric emptying.[2] As a less frequent immediate surgical complication, postoperative AP occasionally appears just after the surgery on the pancreas. The mechanism involves direct trauma to the pancreatic parenchyma caused by pancreatectomy. To date, there has been little work on AP as a long‐term complication following any pancreatectomy procedure.

Application of intraoperative transluminal core-biopsy for diagnosis of pancreatic head mass: A single center 15-year experience

BACKGROUND Pathology is the gold standard for diagnosis of pancreatic cancer. Preoperative endoscopic ultrasound-guided biopsy is an expensive procedure that is not routine in developing countries, hence a cheap, reliable alternative is required. AIM To evaluate the effectiveness and safety of a new technique of intraoperative biopsy from pancreatic head mass. METHODS Patients undergoing intraoperative transluminal core-biopsy (TLCB) for pancreatic head mass from January 2000 to June 2015 were included in this study. Following Kochers maneuver, a biopsy was taken from the mass through the duodenum transluminally, using a commercial 16G automatic core-biopsy needle. Multiple tissue specimens were obtained for intraoperative frozen section examination. Depending on the pathological results, a decision was taken to either perform pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, bypass surgery, or to just terminate the operation. The malignancy status of the lesion was confirmed by postoperative pathological examination and/or long-term follow-up of the patients. RESULTS A total of 525 patients were included. Intraoperative pathological reports revealed 436 malignant cases and 89 cases without evidence of malignancy. The sensitivity, specificity, false positive rate, and false negative rate were 97.7%, 100%, 0%, and 2.3%, respectively. Complications occurred in 2 patients. CONCLUSION TLCB is a quick, safe, effective, and accurate method for intraoperative diagnosis method in patients with pancreatic head mass; it can provide reliable evidence for surgical decision-making.

Black pleural effusion due to pancreatic pseudocyst: A case report

Rationale: Black pleural effusion (BPE) is an extremely uncommon type of pleural fluid, which can be due to infection, primary or metastatic malignancy, and hemorrhage. As reported in previous studies, BPE is also observed in some patients with pancreatic pseudocyst. Patient concerns: We herein reported a case of a 14-year-old female patient who was admitted to our center with a history of cough for 1 and a half months and right chest pain for 1 month. Before this, she was consecutively hospitalized in 3 different hospitals due to the same symptoms. However, the previous treatments were ineffective due to the lack of a definitive diagnosis. Laboratory examination of the pleural effusion showed BPE with a high amylase concentration. Chest x-ray and computed tomography (CT) showed massive pleural effusion, more prominent in the right chest. CT and MRCP of the abdomen showed a cystic lesion located in the tail of the pancreas, which entered the chest cavity via an esophageal hiatal hernia. Diagnoses: pancreatic pseudocyst. Interventions: After confirming that the tumor was a pancreatic pseudocyst by intraoperative biopsy, internal drainage to the jejunum was performed. Outcomes: The postoperative recovery was rapid and without complications, and the final discharge diagnosis was idiopathic pancreatic pseudocyst (without history of pancreatitis or pancreatic injuries) with BPE of the right chest. Lessons: This case demonstrates that massive BPE could present as a rare complication of pancreatic pseudocyst, and surgery is a potential treatment for such patients.

Small amounts of tissue preserve pancreatic function: Long-term follow-up study of middle-segment preserving pancreatectomy

AbstractMiddle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires.Our case series included 3 women and 2 men, with median age of 50 (37–81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250–615) min and 800 (400–5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4 preoperatively euglycemic patients. Beta-cell function parameters in this group of patients were quite comparable to those after Whipple procedure, and seemed better than those after total pancreatectomy. No symptoms of hypoglycemia were identified in any patient, although half of the patients reported symptoms of exocrine insufficiency.In conclusion, MPP is a feasible and effective procedure for middle-segment sparing multicentric lesions in the pancreas, and patients exhibit satisfied endocrine function after surgery.