High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

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.

Recent advances in targeted therapy for pancreatic adenocarcinoma

Pancreatic adenocarcinoma(PDAC)is a fatal disease with a 5-year survival rate of 8%and a median survival of 6 mo.In PDAC,several mutations in the genes are involved,with Kirsten rat sarcoma oncogene(90%),cyclin-dependent kinase inhibitor 2A(90%),and tumor suppressor 53(75%–90%)being the most common.Mothers against decapentaplegic homolog 4 represents 50%.In addition,the selfpreserving cancer stem cells,dense tumor microenvironment(fibrous accounting for 90%of the tumor volume),and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC.Molecular targeted therapy is widely utilized and effective in several solid tumors.In PDAC,targeted therapy has been extensively evaluated;however,survival improvement of this aggressive disease using a targeted strategy has been minimal.There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC–erlotinib,but the absolute benefit of erlotinib in combination with gemcitabine is also minimal(2 wk).In this review,we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process,analyze possible reasons for the lack of positive results in clinical trials,and suggest ways to improve them.We also discuss emerging trends in targeted therapies for PDAC:combining targeted inhibitors of multiple pathways.The PubMed database and National Center for Biotechnology Information clinical trial website(www.clinicaltrials.gov)were queried to identify completed and published(PubMed)and ongoing(clinicaltrials.gov)clinical trials(from 2003-2022)using the keywords pancreatic cancer and targeted therapy.The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.

Rare ROS1-CENPW gene in pancreatic acinar cell carcinoma and the effect of crizotinib plus AG chemotherapy:A case report

BACKGROUND This is the first report of an ROS1-CENPW fusion gene in pancreatic malignancies.CASE SUMMARY A 77-year-old woman with a pancreatic tumor and multiple liver metastases was admitted to our hospital.Genetic testing revealed the presence of the ROS1-CENPW fusion gene,a rare fusion gene that has not been previously reported in the field of pancreatic cancer.The patient received crizotinib plus AG(albumin paclitaxel plus gemcitabine)chemotherapy.After treatment,the patient’s condition stabilized,and her prognosis was good.CONCLUSION The ROS1-CENPW gene treatment regimen used in this case is an excellent treatment option that provides new hope for patients with advanced pancreatic cancer and similar genetic mutations.To date,owing to the rarity of the ROS1-CENPW fusion gene,our team has encountered only a single case.Therefore,the efficacy of crizotinib plus AG chemotherapy in patients with pancreatic acinar cell carcinoma harboring the ROS1-CENPW fusion gene requires further validation.

Rapid transformation of branched pancreatic duct-derived intraductal tubulopapillary neoplasm into an invasive carcinoma: A case report

BACKGROUND Intraductal tubulopapillary neoplasm(ITPN)is a rare disease accounting for approximately 3%of all intraductal pancreatic tumors,with intraductal papillary mucinous neoplasm(IPMN)being one of the most common differential diagnoses.Both ITPN and IPMN display slow growth.A branched pancreatic duct type is commonly observed in IPMN,whereas ITPN derived from the branched pancreatic duct has been reported in a limited number of cases;hence,its pathogenesis remains unclear.CASE SUMMARY Here,we present the case of a patient with ITPN localized in a branched pancreatic duct,with poorly controlled irritable bowel syndrome.A contrastenhanced computed tomography scan of the abdomen incidentally revealed a 5-mm oligemic nodule-like change in the body of the pancreas.Endoscopic ultrasound(EUS)indicated a 10-mm hypoechoic mass without any cystic structures that had grown within 2 mo.EUS-guided fine needle aspiration was performed for definitive diagnosis,and the findings suggested ductal papillary carcinoma.Distal pancreatectomy was performed,and the tumor was pathologically diagnosed as ITPN with an invasive cancerous component,pT3N1aM0,pStage IIB(International Cancer Control,8^(th) edition).The patient underwent treatment with postoperative adjuvant chemotherapy(S-1 monotherapy);however,relapse was observed 1 year and 10 mo after surgical resection,and subsequent treatment involving a combination of chemotherapy and radiotherapy was administered.Maintenance therapy has since facilitated a stable disease state.CONCLUSION Regardless of the microscopic size of the neoplasm,early diagnosis of ITPN with EUS-guided fine needle aspiration and surgical resection are crucial.

Advancements of molecular imaging and radiomics in pancreatic carcinoma

Despite the recent progress of medical technology in the diagnosis and treatment of tumors,pancreatic carcinoma remains one of the most malignant tumors,with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation.This paper focuses on the research progress of magnetic resonance imaging,nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma.We also briefly described the achievements of our team in this field,to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients

BACKGROUND Pancreatic mucinous cystic neoplasms(MCNs)represent one of the precursor lesions of pancreatic ductal adenocarcinoma,and their detection has been facilitated by advances in preoperative imaging.Due primarily to the rarity of MCNs,however,there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation.A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes.AIM To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma(MCNAIC).METHODS All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed.Only cases with ovarian-type stroma verified by progesterone receptor staining were included.Preoperative features,histological findings and postoperative course were documented.Multivariate logistic regression was employed to investigate variables related to malignancy.Survival analysis was performed using the Kaplan-Meier curve,and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC.RESULTS Among the 48 patients,36 had benign MCNs,and 12 had malignant MCNs(1 high-grade atypical hyperplasia and 11 MCN-AIC).Age,tumour size,presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy.The follow-up period ranged from 12 mo to 120 mo,with a median overall survival of 58.2 mo.Only three patients with MCN-AIC died,and the 5-year survival rate was 70.1%.All 11 cases of MCN-AIC were stage I,and extracapsular invasion was identified as a prognostic factor for poorer outcomes.CONCLUSION The risk factors independently associated with malignant transformation of MCNs included age,tumour size,presence of solid components or mural nodules,and pancreatic duct dilatation.Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.

Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

AIM: To evaluate the utility of carbohydrate antigen19-9(CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis.METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis.Pooled analysis was performed using random-effects models, and receiver operating characteristic(ROC) curves were generated.Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools.RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included.Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81(95%CI: 0.80-0.83); specificity, 0.81(95%CI: 0.79-0.82); positive likelihood ratio, 4.08(95%CI: 3.39-4.91); negative likelihood ratio, 0.24(95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31(95%CI: 14.40-25.90).The area under the ROC curve was 0.88.No significant publication bias was detected.CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy.

FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: A meta-analysis

AIM: To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC). METHODS: A systematic review of relevant literatures in PubMed, Embase and Cochrane Library was performed. The sensitivity and specificity of diagnostic and staging studies, and HRs for prognosis predicting studies were pooled. The bivariate model was used for diagnostic studies and the random-effect model for prognostic studies. Heterogeneity between included studies was tested using χ 2 test, and subgroup analysis was performed to explain the heterogeneities. All of the calculations were performed using Stata version 11.0.RESULTS: A total of 39 studies were included. The pooled sensitivity of PET in diagnosing PC (30 studies, 1582 patients), evaluating N stating (4 studies, 101 patients) and liver metastasis (7 studies, 316 patients) were 0.91 (95%CI: 0.88-0.93), 0.64 (95%CI: 0.50-0.76), and 0.67 (95%CI: 0.52-0.79), respectively; and the corresponding specificity was 0.81 (95%CI: 0.75-0.85), 0.81 (95%CI: 0.25-0.85), and 0.96 (95%CI: 0.89-0.98), respectively. In prognosis analysis (6 studies, 198 patients), significant difference of overall survival was observed between high and low standardized uptake value groups (HR = 2.39, 95%CI: 1.57-3.63). Subgroup analysis showed that PET/CT was more sensitive than PET alone in evaluating liver metastasis of PC, 0.82 (95%CI: 0.48-0.98) and 0.67 (95%CI: 0.52-0.79), respectively. CONCLUSION: PET can be used as a valuable diagnostic and predictive tool for PC, but its effect in the staging of PC remains indeterminate.

Pancreatic head carcinoma:clinical analysis of 189 cases

BACKGROUND: Pancreatic cancer is a lethal disease with an increasing incidence. We retrospectively reviewed the clinical data on diagnosis and treatment of pancreatic head carcinoma, and analyzed the factors affecting prognosis of the disease. METHODS: The data of 189 patients with pancreatic head carcinoma treated from September 1, 1995 to August 31, 2005 were reviewed retrospectively. Ninety-four patients treated from September 1, 2000 to August 31, 2005 were followed up in April 2008. The median survival time (MST) and 1- to 5-year cumulative survival rates of the patients were calculated by the life table method and the Kaplan-Meier method. Cox regression was used to screen out significant risk factors. RESULTS: 96.9% of the patients were more than 40 years old, and the male/female ratio was 1.63. The detection rate of transabdominal ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), and serum tumor marker CA19-9 were 82.0%, 93.1%, 94.7% and 79.8%, respectively. The MST of patients with pancreatic head carcinoma was 360 +/- 60 days. The 1- to 5-year cumulative survival rates were 50.0%, 19.2%, 12.1%, 9.4% and 4.7%, respectively. However, patients with unresectable tumor survived for a shorter time (183 +/- 18 days). Their 1- to 2-year cumulative survival rates were 28.3% and 0.0%. Cox regression analysis showed that in pancreatic head carcinoma, the independent predictors for prognosis included tumor size, invasion of the superior mesenteric vessel, and radical resection. The MST of patients with pancreatic head carcinoma after radical resection was 510 days, significantly longer than that of patients undergoing non-specific treatment and palliative therapy (225 days). In addition, patients with slight jaundice survived for the longest time (533 +/- 51 days), compared with patients with severe jaundice (236 +/- 43 days) and without jaundice (392 +/- 109 days). CONCLUSIONS: Pancreatic head carcinoma is easily misdiagnosed, and is usually found to be advanced when tumor size is too large (above 4 cm in diameter) with local spread or metastatic disease. In these cases, surgical resection is usually not feasible, and its prognosis is usually very poor. Therefore, careful attention should be paid to these high-risk patients, especially, males, more than 40 years old, and presenting slight jaundice. Then imaging examination (US, CT and EUS) and serum tumor marker examination (CA19-9) are used to detect this disease earlier, and perform curative resection earlier. In this way, it is possible to cure the patients with a longer survival time and better quality of life.

Predictors of long-term survival after pancreaticoduodenectomy for peri-ampullary adenocarcinoma: A retrospective study of 5-year survivors

Background: Pancreaticoduodenectomy(PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival( ≥ 5 years) after PD. Methods: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group(I) patients who survived less than 5 years and group(II) patients who survived ≥ 5 years. Results: There were 47(20.6%) long-term survivors( ≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31(66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age < 60 years old, serum CEA < 5 ng/mL, serum CA 19-9 < 37 U/mL, non-cirrhotic liver, tumor size < 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 < 37 U/mL [OR(95% CI) = 1.712(1.24 8–2.34 8), P = 0.001], smaller tumor size [OR(95% CI) = 1.335(1.032–1.726), P = 0.028] and R0 resection [OR(95% CI) = 3.098(2.095–4.582), P < 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. Conclusions: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 < 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years.

CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part Ⅱ):Imaging of pancreatic carcinoma nerve invasion

Computed tomography (CT) and magnetic resonance imaging (MRI) are excellent modalities which have the ability to detect,depict and stage the nerve invasion associated with pancreatic carcinoma.The aim of this article is to review the CT and MR patterns of pancreatic carcinoma invading the extrapancreatic neural plexus and thus provide useful information which could help the choice of treatment methods.Pancreatic carcinoma is a common malignant neoplasm with a high mortality rate.There are many factors influencing the prognosis and treatment options for those patients suffering from pancreatic carcinoma,such as lymphatic metastasis,adjacent organs or tissue invasion,etc.Among these factors,extrapancreatic neural plexus invasion is recognized as an important factor when considering the management of the patients.

Comparison of pancreatic acinar cell carcinoma and adenocarcinoma using multidetector-row computed tomography

AIM:To distinguish acinar cell carcinoma(ACC)from pancreatic adenocarcinoma(AC)by comparing their computed tomography findings.METHODS:Patients with ACC and AC were identified on the basis of results obtained using surgically resected pancreatectomy specimens.The preoperative computer tomographic images of 6 acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4 phases(non-contrast,arterial,portal venous,and delayed phase)were compared.The scan delay times were 40,70,and 120 s for each contrast-enhanced phase.The visual pattern,tomographic attenuation value,and time attenuation curve were assessed and compared between AC and ACC cases using the 2test,Wilcoxon signed-rank test,and Mann Whitney U test.RESULTS:The adenocarcinomas tended to be hypodense in all 4 phases.The acinar cell carcinomas also tended to be hypodense in the 3 contrast-enhancedphases,although their computed tomographic attenuation values were higher.Further,5 of the 6 acinar cell carcinomas(83%)were isodense in the non-contrast phase.The time attenuation curve of the adenocarcinomas showed a gradual increase through the 4 phases,and all adenocarcinomas showed peak enhancement during the delayed phase.The time attenuation curve of the acinar cell carcinomas showed peak enhancement during the portal venous phase in 4 cases and during the arterial phase in 2 cases.None of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase.CONCLUSION:The tumor density in the non-contrast phase and time attenuation curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas,and multidetector-row computed tomography can thus distinguish these tumors.

Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis:Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging

AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-Ⅲ (n = 13) or Ⅳ (n = 20) TIC. Tumor-forming pancreatitis showed type-Ⅱ (n = 5) or Ⅲ (n = 3) TIC. All islet cell tumors revealed type-Ⅰ. The type-Ⅳ TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis.CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.

Value of three-dimensional reconstructions in pancreatic carcinoma using multidetector CT:Initial results

AIM:To evaluate the use of three-dimensional imaging of pancreatic carcinoma using multidetector computed tomography(CT)in a prospective study.METHODS:Ten patients with suspected pancreatic tumors were examined prospectively using multidetec-tor CT(Somatom Sensation 16,Siemens,Erlangen,Germany).The images were evaluated for the pres-ence of a pancreatic carcinoma and invasion of the peripancreatic vessels and surrounding organs.Using the isotropic CT data sets,a three-dimensional image was created with automatic vascular analysis and semi-automatic segmentation of the organs and pancreatic tumor by a radiologist.The CT examinations and the three-dimensional images were presented to the sur-geon directly before and during the patient's operation using the Medical Imaging Interaction Toolkit-based software "ReLiver".Immediately after surgery,the value of the two images was judged by the surgeon.The operation and the histological results served as the gold standard.RESULTS:Nine patients had a pancreatic carcinoma(all pT3),and one patient had a serous cystadenoma.One tumor inf iltrated the superior mesenteric vein.The inf iltration was correctly evaluated.All carcinomas were resectable.In comparison to the CT image with axial and coronal reconstructions,the three-dimensional image was judged by the surgeons as better for operation planning and consistently described as useful.CONCLUSION:A 3D-image of the pancreas repre-sents an invaluable aid to the surgeon.However,the 3D-software must be further developed in order to be integrated into daily clinical routine.

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Analysis of gene expression profiles in pancreatic carcinoma by using cDNA microarray

OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarray and detect target genes for further study. METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 cases of moderate-differentiated pancreatic carcinoma were studied by means of cDNA microarray consisting of 18 000 genes. RESULTS: 1484 and 1353 different expressed genes were observed in two cancer samples respectively. We identified 455 genes altered with the same tendency in both samples, including 102 up-regulated and 353 down-regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and 52.0% genes respectively had an expression level in cancer that was 2-fold higher or lower than that in normal samples. Tumor suppressor genes, growth factors and receptor genes, signal conduction genes, transcription factor genes were identified. CONCLUSIONS: cDNA microarray is an efficient and high-throughout method to investigate gene expression profiles in pancreatic carcinoma. MBD1, EDG1 and gene hypermethylation mechanism would play an important role in the pathogenesis of pancreatic carcinoma.

Apoptosis of human pancreatic carcinoma cell-1 cells induced by Yin Chen Hao Decoction

AIM: To evaluate human pancreatic carcinoma cell line(PANC-1) cells apoptosis and Bcl-2 and Bax expression induced by Yin Chen Hao Decoction(YCHD).METHODS: The cell growth inhibitory rate was determined by MTT assay. Apoptosis of PANC-1 cells before and after treatment with YCHD was determined by TUNEL staining. Expression of the apoptosisassociated genes, Bcl-2 and Bax, was detected by immunohistochemical staining and reverse transcription-PCR.RESULTS: YCHD inhibited the growth of PANC-1 cells. Following treatment with YCHD for 24-96 h, the apoptotic rate of PANC-1 cells increased with time. In addition, the positive rate of Bcl-2 protein expression decreased in a time-dependent manner, whereas the positive rate of Bax protein expression increased in a time-dependent manner. Following treatment of with YCHD for 24-96 h, expression of BAX m RNA increased gradually and BCL-2 m RNA reduced gradually with time.CONCLUSION: YCHD induces apoptosis of PANC-1 cells mediated in part via up-regulation of BAX and down-regulation of BCL-2.

Effects of integrin-targeted photodynamic therapy on pancreatic carcinoma cell

AIM:To investigate the effects of photodynamic therapy with quantum dots-arginine-glycine-aspartic acid(RGD)probe as photosensitizer on the proliferation and apoptosis of pancreatic carcinoma cells.METHODS:Construction of quantum dots-RGD probe as photosensitizer for integrin-targeted photodynamic therapy was accomplished.After cells were treated with photodynamic therapy(PDT),the proliferation of SW1990 cells were measured by methyl thiazolyl tetrazolium assay.Morphologic changes,cell cycle retardance and apoptosis were observed under fluoroscope and flow cytometry.The expression of myeloid cell leukemia-1(Mcl-1),protein kinase B(Akt)and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)mRNA were detected by reverse transcriptionpolymerase chain reaction.The amount of reactive oxygen species were also evaluated by fluorescence probe.RESULTS:The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibited cell proliferation(P<0.01).Apoptotic cells and morphologic changes could be found under optical microscope.The FCM revealed PDT group had more significant cell apoptosis rate compared to control cells(F=130.617,P<0.01)and cell cycle G0/G1and S retardance(P<0.05)compared to control cells.The expression of Mcl-1 and Akt mRNA were down-regulated,while expression of TRAIL mRNA was up-regulated after cells treated with PDT.PDT group had more significant number of cells producing reactive oxygen species compared to control cells(F=3262.559,P<0.01).CONCLUSION:The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibits cell proliferation and increases apoptosis in SW1990 cells.

Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice

AIM: To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechanism. METHODS: A surgical orthotopic implantation (SOI) model was established by suturing small pieces of SW1990 pancreatic carcinoma into the tail of pancreas in nude male mice. Mice then received either single therapy (n = 24) or combined therapy (n = 32). Mice receiving single therapy were randomly divided into control group, G100 group receiving 100 mg/kg gemcitabine IP on d O, 3, 6 and 9 after transplantation, and T30 group receiving 30 mg/kg TNP-470 s.c on alternate days for 8 wk. Mice receiving combined therapy were randomly divided into control group, T15 group, G50 group and combination group (TNP-470 30 mg/kg and gemcitabine 50 mg/kg). Animals were killed 8 wk after transplantation. Transplanted tumors, liver, lymph node and peritoneum were removed. Weight of transplanted tumors, the T/C rate (the rate of mean treated tumor weight to mean control tumor weight), change of body weight, metastasis rate, and 9-wk survival rate were investigated. Tumor samples were taken from the control group, T30 group, G100 group and combination group. PCNA index (PI) and microvessel density (MVD) were investigated by immunohistochemical staining for PCNA and factor VIII, respectively. RESULTS: There was a significant inhibitory effect on primary tumor growth of pancreatic carcinoma in G100 group, compared to T30 group, whereas tumor metastasis was significantly inhibited in T30 group compared to G100 group. There was no significant improvement in survival rate in these two groups. No significant inhibitory effect on tumor growth and metastasis in T15 group and G50 group. However, significant anti-tumor and anti-metastatic effects were observed in the combination group with a significant improvement in survival rate. The inhibitory effect on tumor growth in combination group enhanced 2 times in comparison with G50 group and 5 times in comparison with T15 group. Moreover, 25% of the animals hearing tumors were cured by the combination therapy. The levels of MVD and PI were 14.50±5.93 and 0.41±0.02,12.38±1.60 and 0.30±0.07, 7.13±2.99 and 0.37±0.03, and 5.21±1.23 and 0.23±0.02 respectively in the control group, G100 group, T30 group and combination group. A significant inhibitory effect on PI level and MVD level was observed in G100 group and T30 group respectively whereas both MVD and PI levels were significantly inhibited in the combination group (P<0.05). CONCLUSION: Antiangiogenic therapy shows significant anti-tumor and anti-metastatic effects, and is helpful to reduce the dosage of cytotoxic drugs and the side effects. These effects are related to the antiangiogenic effect of TNP-470 and cytotoxic effect of gemcitabine.