Detection of serum EphA2-EVs for pancreatic cancer diagnosis by light initiated chemiluminescent assay.

Pancreatic cancer has led to an extremely high mortality rate because of its insidious onset and lack of early clinical symptoms. Effective early diagnosis is essential to improve the treatment of pancreatic cancer. Tumor-secreted extracellular vesicles (EVs) have attracted great interest as potential tumor biomarkers. However, most of the methods for detecting serum EVs have some general problems such as cumbersome, time-consuming extraction steps, and high cost, which limit greatly the research on cancer detection based on EVs. Herein, we report a light-initiated chemiluminescent assay (LICA) method using photosensitive beads for direct detection of EVs in serum enriched with ephrin type-A receptor 2 (EphA2), which show high expression in pancreatic cancer patients. Combining with a serum biomarker CA19-9, pancreatic cancer patients could be distinguished rapidly by sensitive detection of EphA2-EVs from serum without any purification. This developed method could be extended to improve the diagnosis efficiency for other cancers and gain an insight into EV detection.

Laparoscopic ultrasonography-guided cryoablation of locally advanced pancreatic cancer: a preliminary report.

OBJECTIVE: To evaluate safety and feasibility of laparoscopic ultrasonography (LUS)-guided cryoablation of locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: From April 2018 to December 2018, ten patients (five women, five men; mean age 58.2 ± 9.4 years) with LAPC underwent the operation. LUS was used to guide the cryoablation. Computed tomography (CT) imaging, biochemical analysis and pain score analysis by numeric rating scale (NRS) were used to assess treatment outcomes at 1 week and 3 months after the operation. RESULTS: Cryoablation was performed by the operation in all cases. Seven patients received complete ablation and the success rate of operation was 70%. Two cryoablation cycles and an average of 1.4 ± 0.5 cryoprobes were used. The average freezing time and operation time were 23.8 ± 1.0 and 110.5 ± 24.7 min, respectively. The mean blood loss was 52.0 ± 16.6 ml. No major complications were observed after the operation. The mean maximum tumor diameter determined by CT decreased from 4.9 ± 0.7 cm before the operation to 4.7 ± 1.0 cm at 1 week and 4.6 ± 1.3 cm at 3 months, with P values of 0.53 and 0.51 (relative to the preoperative values), respectively. Postoperative CT imaging results suggested tumor necrosis in cryoablation-treated areas. The mean CA19-9 levels decreased from 347.5 ± 345.7 U/mL before operation to 190.4 ± 153.8 U/mL at 1 week and 182.7 ± 165.6 U/mL at 3 months, with P values of 0.15 and 0.14 (relative to the preoperative values), respectively. The average pain scores declined from 6.9 ± 1.1 before operation to 1.3 ± 1.2 at 1 week and 2.0 ± 0.8 at 3 months, with both P values of < 0.01 (relative to the preoperative values). CONCLUSION: This preliminary study suggested that LUS-assisted cryoablation was a safe and feasible treatment for LAPC.

Long Intergenic Nonprotein Coding RNA 173 Inhibits Tumor Growth and Promotes Apoptosis by Repressing Sphingosine Kinase 1 Protein Expression in Pancreatic Cancer.

Pancreatic cancer is a common malignant tumor worldwide. Extensive studies have been conducted on the functional role of long noncoding RNAs in pancreatic cancer. In this study, long intergenic nonprotein coding RNA 173 (LINC00173) was highly expressed in pancreatic cancer tissues. In vitro functional experiments showed that LINC00173 overexpression inhibited the proliferation and invasion of pancreatic cancer cells and promoted cell apoptosis in MIA PaCa-2 and PANC-1 cells. RNA sequencing analysis and Western blot assays demonstrated that LINC00173 reduced the expression of sphingosine kinase 1 (SPHK1) and then inhibited the protein expression of activated phospho-protein kinase B (AKT) and NF-κB. In vivo functional assays also revealed that LINC00173 inhibited the growth of pancreatic cancer xenografts, repressed cell proliferation, promoted cell apoptosis, and inhibited SPHK1 expression. The combined results of this study indicate that LINC00173 inhibits pancreatic cancer progression by repressing SPHK1 expression. Improving LINC00173 may represent a therapeutic strategy for pancreatic cancer in the future.

Metformin Increases the Chemosensitivity of Pancreatic Cancer Cells to Gemcitabine by Reversing EMT Through Regulation DNA Methylation of miR-663.

BACKGROUND: Pancreatic cancer is a devastating malignancy with poor prognosis. Metformin, a classic anti-diabetes drug, seems to improve survival of pancreatic cancer patients in some studies. METHODS: Cell counting kit-8 assay was used to detect the BxPC-3 and MIAPaCa-2 cell viability after treatment with gemcitabine only or with different concentrations of metformin. The methylation state and expression level of miR-663 were detected by methylation analysis and RT-PCR. Dual-luciferase reporter gene analysis, Western blot and RT-PCR were used to confirm the target of miR-663. Moreover, xenograft experiment was also performed to validate the role of metformin in chemosensitivity in vivo. RESULTS: We found that metformin increased the chemosensitivity of pancreatic cancer cells to gemcitabine, and epithelial-mesenchymal transition (EMT) progress caused by gemcitabine was suppressed by metformin. We further explored the possible molecular mechanisms and it was demonstrated that CpG islands of miR-663 were hypomethylated and relative expression level of miR-663 was up-regulated after treatment of metformin. miR-663, an important cancer suppressor miRNA, was confirmed to increase the chemosensitivity of pancreatic cancer cells by reversing EMT directly targeted TGF-ß1. Moreover, we identified that metformin increased the chemosensitivity through up-regulating expression of miR-663. CONCLUSION: We demonstrated that metformin increased the chemosensitivity of pancreatic cancer cells to gemcitabine by reversing EMT through regulation DNA methylation of miR-663.

Potential role of iodine excess in papillary thyroid cancer and benign thyroid tumor: A case-control study.

BACKGROUND AND OBJECTIVES: The relationship between nutritional status of iodine and thyroid tumor is unclear. We investigated the association between urinary iodine concentration and thyroid function in patients with papillary thyroid cancer, benign thyroid tumor and healthy individuals. METHODS AND STUDY DESIGN: We compared the biomarkers of thyroid function and urinary iodine concentration within and between each group. A regression analysis was used to identify risk factors for papillary thyroid cancer. Correlation analysis was performed to determine whether any significant correlation exists between urinary iodine concentration and thyroid function biomarkers. RESULTS: The iodine nutrition statuses of these three groups were adequate (median urinary iodine concentration= 100-199 µg/L). However, the median urinary iodine concentration of papillary thyroid cancer (174.7 µg/L) and benign thyroid tumor (165.04 µg/L) groups was significantly higher than that of the healthy control group (135.8 µg/L) (p<0.05). The regression analysis showed that thyroglobulin antibody was an independent risk factor for papillary thyroid cancer. After adjusting for age and gender, the association between thyroglobulin antibody and urinary iodine concentration was significant (ß: 0.002; p<0.05). In subgroup analyses, significant correlations was noted only in the papillary thyroid cancer group (adjusted ß: 0.002; 95% confidence interval: 0.000- 0.003). CONCLUSIONS: Excessive iodine in patients with thyroid tumors may affect thyroglobulin antibody, which may be an independent risk factor for papillary thyroid cancer.

Effects of active localization and vascular preservation of inferior parathyroid glands in central neck dissection for papillary thyroid carcinoma.

BACKGROUND: The purpose of present study is to assess the effects of active localization and vascular preservation of inferior parathyroid glands in central neck dissection (CND) for papillary thyroid carcinoma (PTC). METHODS: A classification of IPGs according to their location and vascular features was developed, and, based on this classification, a CND procedure was designed, and IPGs and their vascular were actively localized and strategically preserved. A total of 197 patients with PTC who underwent a total thyroidectomy and concomitant CND were enrolled. Eighty-nine patients with traditional meticulous fascia dissection were allocated to group A, and 108 patients with active location and vascular preservation of IPGs were allocated to group B. Those with inferior parathyroid glands auto-transplantation in each group were assigned as group At (18) and group Bt (12). Variables including serum intact parathyroid hormone (PTH), total calcium, the incidence of transient, and permanent hypoparathyroidism were studied. RESULTS: Compared with group A, serum intact PTH (P < 0.001) and total calcium levels (P < 0.05) in group B significantly improved on the first postoperative day, and the incidence of transient hypoparathyroidism significantly dropped in group B (P < 0.001). A total of 170 patients in the two groups had complete follow-up data. The incidence of permanent hypoparathyroidism significantly decreased in group B, from 8.8% to 1.0% (P = 0.017). However, there were no significant differences in all variables between group Bt and group At. CONCLUSION: Active location and vascular preservation of inferior parathyroid glands effectively protected the function of IPGs in CND for PTC.

Comparative peptidome profiling reveals critical roles for peptides in the pathology of pancreatic cancer.

BACKGROUNDS/AIMS: Pancreatic cancer is a digestive system tumour disease with a notably poor prognosis and a 5-year survival rate of less than 10 %. In recent years, peptide drugs have shown great clinical value in antitumour applications. We aim to identify differentially expressed peptides by using peptidomics techniques to explore the mechanisms involved in the development and pathology of pancreatic cancer. METHODS: We performed peptidomic analysis of pancreatic cancer and paired paracancerous tissues by using ITRAQ labelling technology and conducted in-depth bioinformatics analysis and functional studies on differentially expressed peptides. RESULTS: A total of 2,881 peptides were identified, of which 133 were differentially expressed (116 were upregulated and 17 were downregulated). By using GO analysis, the differentially expressed peptides were found to be closely related to the tumour microenvironment and extracellular matrix. KEGG enrichment analysis revealed that precursor proteins were closely related to the T2DM and RAS signalling pathways. The endogenous peptide P1DG can significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells. CONCLUSION: P1DG and its precursor GAPDH may be closely related to the proliferation, migration and invasion of pancreatic cancer. Peptidomics can aid in understanding the pathogenesis of pancreatic cancer more comprehensively.

Chronic pancreatitis with multiple pseudocysts and pancreatic panniculitis: A case report.

RATIONALE: Pancreatic pseudocyst can present single or multiple, inside or outside the pancreas. Pancreatic panniculitis is a rare skin lesion in pancreatic disease patients. The purpose of this study is to report a case of chronic pancreatitis coexisting with multiple pseudocysts and pancreatic panniculitis. PATIENT CONCERNS: A 46-year-old man with chronic pancreatitis presented multiple small cystic lesions inside the head of the pancreas and two large cystic lesions adjacent to the tail of the pancreas. The patient also developed subcutaneous nodules involving upper and lower limbs, hands, and lower abdomen bilaterally. DIAGNOSIS: The patient was diagnosed with pancreatic pseudocyst and pancreatic panniculitis resulted from chronic pancreatitis. INTERVENTIONS: Bile duct stent and pancreatic duct stent placement was performed endoscopicly. OUTCOMES: Panniculitis faded three weeks later and the pancreatic pseudocysts disappeared six weeks later. LESSONS: Clinicians should be aware of the manifestation of multiple pancreatic pseudocyst and pancreatic panniculitis, and endoscopic transpapillary drainage may be a effective way in this scenario.

High expression of long non-coding RNA ZEB1-AS1 promotes colorectal cancer cell proliferation partially by suppressing p15 expression.

This study aims to investigate the function of long non-coding RNA ZEB1-AS1, reveal its molecular mechanism in colorectal cancer cell growth, and evaluate its clinical significance in colorectal cancer patients. ZEB1-AS1 has reported in the development of several cancers, but the biological role of it in colorectal cancer has not been discussed. In this report, ZEB1-AS1 expression level was measured with quantitative real-time polymerase chain reaction in 63 pairs of colorectal cancer tissues and paired adjacent non-tumor colorectal tissues. The relationship between ZEB1-AS1 expression and overall survival was analyzed by virtue of Kaplan-Meier analysis. Subsequently, small interfering RNA or lentivirus vector-mediated lncRNA ZEB1-AS1 was transfected into colorectal cancer cell lines. Cell viability and apoptosis were examined. Later, nude mouse transplantation experiment was conducted to evaluate the effect of ZEB1-AS1 on colorectal cancer development in vivo. It turns out that ZEB1-AS1 is upregulated in colorectal cancer tissues and its expression is significantly associated with overall survival rate and recurrence-free survival. Upregulation of ZEB1-AS1 colorectal cancer promotes cell proliferation and inhibits cell apoptosis. In addition, cell cycle inhibitory protein p15 participates in the oncogenic function of ZEB1-AS1. Collectively, ZEB1-AS1 has asignificant effect on colorectal cancer pathological process and serves as a valuable prognostic biomarker for colorectal cancer.

Glucagonoma syndrome: A case report.

Necrolytic migratory erythema (NME), diabetes mellitus and glucagon-secreting tumors form the hallmarks of glucagonoma syndrome, and represent the major clinical manifestations of glucagonoma. NME is usually presented as the initial complaint of patients. Due to the rare incidence of glucagonoma, its diagnosis is often delayed, which leads to its progression. Here, we report a case of NME with a typical skin rash, which was misdiagnosed and treated with corticosteroids for two years. Removal of the tumor in the pancreatic body led to the rapid relief of the symptoms. The aim of the present study is to demonstrate the typical characteristics of glucagonoma syndrome to clinicians in order to improve its diagnosis and treatment.

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

BACKGROUND: Increasing 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. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: The 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.

Vasohibin 2 decreases the cisplatin sensitivity of hepatocarcinoma cell line by downregulating p53.

Hepatocellular carcinoma (HCC) is a prevalent problem worldwide. Chemotherapy, especially cisplatin (CDDP)-based systemic chemotherapy, is the best option for advanced liver cancer. However, CDDP resistance is becoming common and hindering the clinical application of CDDP. Meanwhile, no consensus has been reached regarding the chemotherapeutic use of vasohibin 2 (VASH2), which promotes the angiogenesis and proliferation of cancer cells. In this work, a tissue microarray was used to observe VASH2 and its possible role in cancer treatment. Results showed that VASH2 was highly expressed in HCC tissues and was significantly correlated with cancer differentiation. To further investigate the efficacy and mechanism of the combination of VASH2 with anti-cancer drugs in liver cancer cells, we stably built VASH2 overexpression and knockdown cell lines. We found that VASH2 can influence the CDDP sensitivity and that the cell overexpression of VASH2 had a higher cell viability and lower apoptosis rate after CDDP exposure. We also observed that VASH2 overexpression downregulated wild-type p53, as well as suppressed the expression of the pro-apoptotic protein BCL2-associated X protein (Bax) and cleaved caspase-3 (CC-3) after treatment by CDDP. Conversely, the knockdown of VASH2 significantly inhibited these effects. In an in vivo chemosensitivity study, nude mice were subcutaneously injected with tumor cells and received CDDP treatment through intraperitoneal administration every 3 days. We found that VASH2 knockdown markedly limited the tumor growth and enhanced the CDDP toxicity and apoptosis of tumor cells. Western blot analysis revealed that tumor cells with downregulated VASH2 had a higher expression of wild-type p53, Bax, and CC-3 than control cells. Overall, our results indicated the novel roles of VASH2 in the chemoresistance of hepatocarcinoma cells to CDDP and suggested that VASH2 may be a promising anticancer target.

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.

BACKGROUND: Digestive 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. METHODS: Percentage 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. RESULTS: Percentage 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. CONCLUSIONS: Altered 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.

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.

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.

[Establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ and research the relationship between SW1990/GZ and pancreatic cancer stem cell].

OBJECTIVES: To establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ, and to explore the relationship between drug-resistant cell line SW1990/GZ and pancreatic cancer stem cell. METHODS: Gemcitabine-resistant pancreatic cancer cell line SW1990/GZ was obtained by treating parental cell line SW1990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for 24 weeks. Stable cultures were obtained which were 77.2-fold increased in resistance relative to parental cells. Gene expressions of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP were determined by real-time PCR. Tumorigenic potential was performed by nude mice xenograft transplant experiments. Side population analysis and CD24CD44 positive cells explore were determined by flow cytometry to examine cancer stem cell proportion. RESULTS: Gemcitabine-resistant cell line SW1990/GZ underwent obvious morphological and functional changes. Compared with the parental cell line, SW1990/GZ cell was small and turned into round shape. SW1990/GZ had a higher gene expression level of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP than SW1990 (P < 0.01). Nude mice xenograft transplant experiments showed that only 1 × 10(5) SW1990/GZ cells were sufficient for tumor formation, whereas an injection of 1 × 10(5) SW1990 cells did not initiate tumors. Flow cytometry analysis showed that SP proportion in SW1990/GZ was (11.0 ± 1.0)%, whereas in parental SW1990 it was (4.6 ± 0.9)%, CD44CD24 positive cells was (8.73 ± 0.81)% in SW1990/GZ, whereas (1.1 ± 0.4)% in SW1990. CONCLUSIONS: Gemcitabine-resistant cell line SW1990/GZ has a higher proportion of pancreatic cancer stem cells compared to its parental cell line SW1990. CD44 is mainly responsible for acquired drug resistance, which can be a potential target to overcome acquired drug resistance in pancreatic cancer.

Roles of Smad3 and Smad7 in rat pancreatic stellate cells activated by transforming growth factor-beta 1.

BACKGROUND: Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor beta 1 (TGF-beta1) is a critical mediator of this process. This study aimed to determine the expression of the Smad3 and Smad7 genes in the process of PSC activation, and explore the mechanisms of chronic pancreatitis. METHODS: The expressions of Smad3 and Smad7 in PSCs before and after TGF-beta1 treatment were detected by reverse transcription-polymerase chain reaction and Western blotting analysis. Smad3 expression was detected in PSCs after treatment with 5 ng/ml of TGF-beta1 for 24 hours. RESULTS: Smad7 expression was decreased in TGF-beta1-activated PSCs (P<0.05) in a dose-dependent manner. When TGF-beta1 concentration reached 10 ng/ml, the expression of p-Smad3, Smad3, and Smad7 was inhibited (P<0.05). CONCLUSIONS: TGF-beta1 promotes the expression of Smad3 and inhibits the expression of Smad7 during the activation of PSCs. In contrast, high-dose TGF-beta1 downregulates the expression of Smad3 in completely activated PSCs.

Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells.

In this study, we first sought to determine the existence of side population (SP) cells in pancreatic cancer cell lines. Furthermore, we compared the biological characteristics of SP and non-SP cells. The presence of side population cells in pancreatic cancer cell lines was detected by Hoechst 33342 staining and FACS analysis. Cell cycle distribution was analyzed using flow cytometry. SP and non-SP cells were exposed to various concentrations of gemcitabine; drug sensitivity was examined using the MTT assay and flow cytometry using Annexin-V and PI staining. To compare the tumorigenic ability in vivo, groups of nude mice were orthotopically inoculated with varying numbers of SP and non-SP cells. The percentages of CD44+CD24+ and CD133+ in SP and non-SP cells were also detected by FACS analysis. The SP fraction was detected in BxPc-3, CFPAC-1, MIA PaCa-2, PANC-1 and SW1990 pancreatic cancer cell lines. Cell cycle analysis revealed that the SP cells contained more cells in the G1 phase and fewer cells in the S phase when compared with the non-SP cells. The SP cells exhibited increased tumorigenetic ability following in vivo transplantation into BALB/C nude mice and increased chemoresistance following in vitro exposure to gemcitabine. FACS analysis showed that the SP cells contained more CD44+CD24+ and CD133+ cells than the non-SP cells. In conclusion, these observations suggest that SP cells in the pancreatic cancer cell lines possess the property of cancer stem cells. SP cells may therefore be novel specific targets for the effective treatment of pancreatic cancer.

[Diagnosis and surgical treatment for non-functional islet cell tumor: a retrospective analysis of 44 cases].

OBJECTIVE: To evaluate the methods of diagnosis and surgical treatment for nonfunctional islet cell tumor (NICT). METHODS: Forty-four patients with non-functional islet cell tumor treated at the First Affiliated Hospital of Nanjing Medical University during January 1968 to June 2008 were analyzed retrospectively. There were 9 males and 35 females, aged from 7- to 70-years-old. Clinical manifestation: 15 cases (34.1%) of abdominal masses, 17 patients (38.6%) with epigastric or back pain, 5 cases of jaundice, 5 cases (11.4%) for upper abdominal fullness or vomiting, 10 cases (22.7%) of pancreatic tumor noticed by routine health checkups or imaging examinations. Imaging examination: CT scan, sonography, ERCP, MRI, upper GI series were performed in 33 (75.0%), 16 (36.4%), 6 (13.6%), 2 (4.5%), and 10 cases (22.7%) respectively. Operation methods: 39 patients (88.6%) underwent surgical resection and the other 5 patients did not. COMPLICATIONS: pancreatic fistula in 7 patients (15.9%), intra-abdominal bleeding in 4 (9.1%), gastrojejunal anastomosis outlet obstruction in 1 (2.3%), biliary fistula in 2 (4.5%) and incisional infection in 3 (6.8%). Surgery related mortality happened in 2 patients (4.5%), both treated before 1999. Twenty-five patients underwent operation between January 1999 and June 2008 were followed up for 6 to 108 months. All survive except one died 75 months after the surgery for unknown reason. CONCLUSIONS: No specific clinical manifestation is recognized for non-functional islet cell tumor. Spiral CT is an optimal diagnostic method, while surgery is the first choice for treatment. Middle segmental pancreatectomy has become an alternative surgical protocol for NICT.