Meiotic nuclear divisions 1 suppresses the proliferation and invasion of pancreatic cancer cells via regulating H2A.X variant histone

Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.

Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

Circulating tumor cells in pancreatic cancer:The prognostic impact in surgical patients

Pancreatic cancer is associated with a poor prognosis,even in the early stages,mainly due to metastatic progression.New diagnostic techniques that predict unfavorable outcomes are needed in order to improve treatment strategies.Circulating tumor cells(CTCs)are showing promising results as a predictive biomarker for various tumors.In this editorial we comment on the article by Zhang et al,who published the first systematic review and meta-analysis evaluating the prognostic value of CTCs as biomarkers in early-stage pancreatic cancer patients undergoing surgery.CTCs were detected in peripheral or central venous system blood,before or during surgery.Positive CTCs showed a correlation with decreased overall survival and decreased relapse-free,disease-free and progression-free survival in this meta-analysis.However,the heterogeneity was significant.The authors suggest that this result was related to the separation methods used between studies,but other differences such as the margin status or the neoadjuvant and adjuvant treatments used are also important to consider.CTCs may be a potential prognostic biomarker in pancreatic cancer patients,but it is necessary to compare and standardize the platforms used to isolate CTCs,to compare different biomarkers from liquid biopsy and to determine the impact on prognosis when therapeutic changes are made based on CTCs levels.

Circulating tumor cells as prognostic marker in pancreatic cancer

In this editorial we comment on the article by Zhang et al published in the recent issue of the World Journal of Clinical Oncology.Pancreatic cancer is the fourth most common cause of cancer-related mortality and has the lowest survival rate among all solid cancers.It causes 227000 deaths annually worldwide,and the 5-year survival rate is very low due to early metastasis,which is 4.6%.Cancer survival increases with better knowledge of risk factors and early and accurate diagnosis.Circulating tumor cells(CTCs)are tumor cells that intravasate from the primary tumor or metastasis foci into the peripheral blood circulation system spontan-eously or during surgical operations.Detection of CTC in blood is promising for early diagnosis.In addition,studies have associated high CTC levels with a more advanced stage,and more intensive treatments should be considered in cases with high CTC.In tumors that are considered radiologically resectable,it may be of critical importance in detecting occult metastases and preventing unnecessary surgeries.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Mesenchymal stem cells help pancreatic islet transplantation to control type 1 diabetes

Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.

Antioxidant activity of chito-oligosaccharides on pancreatic islet cells in streptozotocin-induced diabetes in rats

AIM:To investigate the antioxidant activity of chitooligosaccharides(COSs)on pancreatic islet cells in diabetic rats induced by streptozotocin. METHODS:The antioxidant effect of COSs on pancreatic islet cells was detected under optical microscopy and with colorimetric assay and gel electrophoresis.The activities of glutathione peroxidase and superoxide dismutase,total antioxidant capacity,and content of malondialdehyde in serum and tissue slices of pancreas were examined after 60 d to determine the effect of COSs in streptozotocin-induced diabetes in rats. RESULTS:COSs can prohibit the apoptosis of pancreatic islet cells.All concentrations of COSs can improve the capability of total antioxidant capacity and activity of superoxide dismutase and decrease the content of malondialdehyde drastically.Morphological investigation in the pancreas showed that COSs have resulted in the reduction of islets,loss of pancreatic cells,and nuclear pyknosis of pancreatic cells. CONCLUSION:COSs possess various biological activities and can be used in the treatment of diabetes mellitus.

Differentiation of fetal pancreatic stem cells into neuron-like and islet-like cells in vitro

Pancreatic stem cells were isolated and cultured from aborted human fetal pancreases of gestational age 14-20 weeks. They were seeded at a density of 1 × 104 in serum-free media for differentiation into neuron-like cells, expressing β-tubulin III and glial fibrillary acidic protein. These neuron-like cells displayed a synapse-like morphology and appeared to form a neuronal network. Pancreatic stem cells were also seeded at a density of 1 × 105 for differentiation into islet-like cells, expressing insulin and glucagon, with an islet-like morphology. These cells had glucose-stimulated secretion of human insulin and C-peptide. Results suggest that pancreatic stem cells can be differentiated into neuron-like and islet-like cells.

Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats

AIM: To investigate the effect of chitooligosaccharides on proliferation of pancreatic islet cells, release of insulin and 2 h plasma glucose in streptozotocin-induced diabetic rats.METHODS: In vitro, the effect of chitooligosaccharides on proliferation of pancreatic islet cells and release of insulin was detected with optical microscopy, colorimetric assay, and radioimmunoassay respectively. In vivo, the general clinical symptoms, 2 h plasma glucose, urine glucose, oral glucose tolerance were examined after sixty days of feeding study to determine the effect of chitooligosaccharides in streptozotocin-induced diabetic rats. RESULTS: Chitooligosaccharides could effectively accelerate the proliferation of pancreatic islet cells. Chitooligosaccharides (100 mg/L) had direct and prominent effect on pancreastic β cells and insulin release from islet cells. All concentrations of chitooligosaccharides could improve the general clinical symptoms of diabetic rats, decrease the 2 h plasma glucose and urine glucose, and normalize the disorders of glucose tolerance.CONCLUSION: Chitooligosaccharides possess various biological activities and can be used in the treatment of diabetes mellitus.

Ca^(2+) signals induced from calcium stores in pancreatic islet β cells

In single rat pancreatic βcells, using fura-2 microfluorometry to measure [Ca2+] response upon different stimuli, the ways of calcium regulation have been studied. When the extracellular calcium concentration was 2.5 mmol/L, either 60 mmol/L KCI, 20 mmol/L D-glucose or 0.1 mmol/L tolbutamide induced increase in [Ca2+]. Such increase in [Ca2+] was absent when the same stimuli were applied under zero extracellular calcium. These results indicate that the increase of [Ca2+] is induced by the activation of voltage-dependent calcium channels in p celis. The manifold forms of [Ca2+] change induced by glucose imply that the effects of glucose are complex. 5 mmol/L caffeine or 5 mmol/L MCh increase the [Ca2+], which is independent of the external calcium, suggesting that [Ca2+] can be regulated by Ca2+ release from not only the IP3-sensitive but also the ryanodine sensitive calcium stores in p celis. The latency of Ca responses for IP3 pathway (5 s) is faster than that for ryanodine pathway (30 s), it is

Imaging pancreatic islet cells by positron emission tomography

It was estimated that every year more than 30000 persons in the United States- approximately 80 people per day- are diagnosed with type 1 diabetes(T1D). T1 D is caused by autoimmune destruction of the pancreatic islet(β cells) cells. Islet transplantation has become a promising therapy option for T1 D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography(PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells.

STUDIES OF EFFECTS OF PORTASYSTEMIC SHUNT ON THE FUNCTION OF HEPATIC AND PANCREATIC ISLET CELLS

The present study was aimed at dynamic observation of the ef fects of end to side portacaval shunt (PCS) and end to side mesocaval shunt (MCS) in dogs on the functions of the liver and pancreatic islet cells. According to correlation between the changes of plasma insulin level in the portal vein and hepatic flow and liver morphology after PCS and MCS, we conclude that the depletion of hepatic flow is the major factor in the deterioration of liver functions. The levels of insulin and glucagon in both the peripheral vein and the portal vein were decreased after PCS and MCS. There was also depletion of pancreatic islet A and B cells and vacuolar degeneration of the pancreas. These changes were more signifcant in PCS than in MCS, suggesting that portasystemic shunt, especially total portasystemie shunt, might damage pancreatic endocrine functions.

Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.

Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells

AIM:To investigate the effects of ginsenoside Rh2 on the human pancreatic cancer cell line Bxpc-3.METHODS:The human pancreatic cancer cell line Bxpc-3 was cultured in vitro and treated with or without ginsenoside Rh2.Growth rates for Bxpc-3 cells were assessed by methyl thiazolyl tetrazolium(MTT) and colony formation assays.Cell cycle changes were analyzed by flow cytometry.Apoptosis was measured by flow cytometry and Hoechst 33258 fluorescence staining.A scratch assay and a Matrigel invasion assay were used to detect cell migration and invasion.Expression of Bax,Bcl-2,survivin,cyclin D1,matrix metalloproteinase(MMP)-2,MMP-9,cleaved caspase-3,caspase-8,and caspase-9 mRNA were determined by reverse transcriptase-polymerase chain reaction(RT-PCR).Bax,Bcl-2,survivin,cyclin D1,cleaved caspase-3,caspase-8 and caspase-9 protein levels were examined by western blotting.Expression of MMP-2 and MMP-9 proteins in culture supernatants were determined by enzymelinked immunosorbent assay(ELISA).RESULTS:Rh2 significantly inhibited Bxpc-3 cell proliferation in a dose-and time-dependent manner,as evaluated by the MTT(P < 0.05) and colony formation assays(P < 0.05).Compared to the control group,Rh2 significantly increased the percentage of Bxpc-3 cells in the G 0 /G 1 phase from 43.32% ± 2.17% to 71.32% ± 1.16%,which was accompanied by a decrease in S phase(from 50.86% ± 1.29% to 28.48% ± 1.18%) and G 2 /M phase(from 5.81% ± 1.19% to 0.20% ± 0.05%) in a dose-dependent manner(P < 0.05),suggesting that Rh2 arrested cell cycle progression at the G 0 /G 1 phase,as measured by flow cytometry.Compared to the control group,cells treated with Rh2 showed significantly higher apoptosis ratios in a dosedependent manner(percentage of early apoptotic cells:from 5.29% ± 2.28% to 38.90% ± 3.42%(F = 56.20,P < 0.05);percentage of late apoptotic cells:from 4.58% ± 1.42% to 36.32% ± 2.73%(F = 86.70,P < 0.05).Rh2 inhibited Bxpc-3 cell migration and invasion,as detected by scratch wound healing assay and Matrigel invasion assay [percentages of scratch wound healing for 12 h,24 h and 48 h(control vs experimental group):37.3% ± 4.8%vs 18.30% ± 1.65%,58.7% ± 3.5% vs 38.00% ± 4.09% and 93.83% ± 4.65% vs 65.50% ± 4.09%,respectively;t = 6.489,t = 6.656 and t = 7.926,respectively,P < 0.05;the number of cells invading at various concentrations(0 μmol/L,35 μmol/L,45 μmol/L and 55 μmol/L):81.10 ± 9.55,46.40 ± 6.95,24.70 ± 6.88 and 8.70 ± 3.34,respectively(F = 502.713,P < 0.05)].RT-PCR,western blotting or ELISA showed that mRNA and protein expression of Bax,cleaved caspase-3 and caspase-9 were upregulated(P < 0.05),while mRNA and protein expression of Bcl-2,survivin,cyclin D1,MMP-2 and MMP-9 were downregulated(P < 0.05).CONCLUSION:Ginsenoside Rh2 inhibits proliferation,migration and invasion and induces apoptosis of the human pancreatic cancer cell line Bxpc-3.

Circulating tumor cells in pancreatic cancer patients:Enrichment and cultivation

AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device.

Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients:Potential role in clinical practice

AIM To evaluate the clinical properties of three subpopulations of circulating tumor cells(CTCs) undergoing epithelial-mesenchymal transition(EMT) in pancreatic ductal adenocarcinoma(PDAC) patients.METHODS We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule(EpCAM)(E-CTC), the mesenchymal cell markers vimentin and twist(M-CTC), or both(E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and classification were correlated with patient clinicopathological features and outcomes.RESULTS CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio(NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage(P < 0.01) and distant metastasis(P < 0.01). Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation(P < 0.01).CONCLUSION Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.

Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells

Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induced pluripo- tent stem （iPS） cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDXl-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insuIin-producing ceils. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.

Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis

AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation were evaluated.Peritoneal and alveolar macrophages were obtained and the expression of tumor necrosis factor α was determined.Myeloperoxidase activity was measured to evaluate the effect of mast cell inhibition on the progression of the inflammatory process.Finally,the effect of plasma on cultured mast cells or macrophages was evaluated in vitro.RESULTS:The mast cell stabilizer signif icantly reduced inflammation in the pancreas and lung and the activation of alveolar macrophages but had no effect on peritoneal macrophages.Mast cell degranulation was observed in the pancreas during pancreatitis but no changes were observed in the lung.Plasma from rats with pancreatitis could activate alveolar macrophages but did not induce degranulation of mast cells in vitro.CONCLUSION:Pancreatic mast cells play an important role in triggering the local and systemic inflammatory response in the early stages of acute pancreatitis.In contrast,lung mast cells are not directly involved in the inflammatory response related to pancreatic damage.

Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids

Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.