Frailty and coronary plaque characteristics on optical coherence tomography.

The relationship between frailty and plaque characteristics is unclear and was investigated by optical coherence tomography (OCT) in this study. One hundred and four patients undergoing OCT before percutaneous coronary intervention were evaluated. Frailty was defined as a clinical frailty scale score of ≧6. Frailty was found in 16% of the patients (17/104). Compared with the nonfrail patients, frail patients showed significantly lower body mass index (BMI; 20.8 ± 4.0 kg/m2 vs. 25.0 ± 3.9 kg/m2, P < 0.001), less dyslipidemia [47% (8/17) vs. 75% (65/87), P = 0.023], lower triglycerides levels (95 ± 42 mg/dL vs. 147 ± 81 mg/dL, P < 0.001), less use of statin [29% (5/17) vs. 60% (52/87), P = 0.021], more lipid-rich plaque [82% (14/17) vs. 46% (40/87), P = 0.006] on OCT, more thin-cap fibroatheromas [TCFAs; 71% (12/17) vs. 26% (23/87), P < 0.001], more plaque rupture [53% (9/17) vs. 25% (22/87), P = 0.023], and significantly higher adverse clinical outcomes (death, acute myocardial infarction, acute heart failure, acute coronary syndrome, or target lesion revascularization) [24% (4/17) vs. 6% (5/87), P = 0.007]. The multivariable analysis showed that frailty was one of the independent predictors of TCFAs (odds ratio 8.95, 95% CI 2.40-33.32, P = 0.001). In conclusion, frailty was associated with high plaque vulnerability due to more lipid-rich plaque, TCFAs and plaque rupture on OCT regardless of low BMI, less dyslipidemia and low triglycerides levels, and frail patients had higher adverse clinical outcomes.

Plaque characteristics and slow flow during percutaneous coronary intervention of irregular protrusion by optical coherence tomography.

Irregular protrusion on optical coherence tomography (OCT) is associated with clinical events and target lesion revascularization. We investigated clinical and procedure characteristics, plaque characteristics, slow flow after stent implantation, and clinical outcomes with irregular protrusion using OCT. Eighty-four lesions in 76 patients undergoing OCT before percutaneous coronary intervention were evaluated. Irregular protrusion was defined as protrusion of material with an irregular surface into the lumen between stent struts with a maximum height of ≥100 µm. Lesions with irregular protrusion were found in 56% (47/84). Compared with lesions without irregular protrusion, those with irregular protrusion had significantly higher low-density lipoprotein cholesterol (LDL-C) levels (108 ± 31 mg/dl vs. 95 ± 25 mg/dl, P = 0.044); a tendency toward decreased use of statins [44% (19/43) vs. 67% (22/33), P = 0.065]; significantly larger reference vessel diameter (3.12 ± 0.53 mm vs. 2.74 ± 0.63 mm, P = 0.004); more frequent slow flow after stent implantation [38% (18/47) vs. 11% (4/37), P = 0.006]; higher incidence of thin-cap fibroatheromas [TCFAs; 49% (23/47) vs. 5% (2/37), P < 0.001]; plaque rupture [40% (19/47) vs. 16% (6/37), P = 0.018]; and a tendency higher incidence of 1-year adverse clinical outcomes (death, acute myocardial infarction, acute coronary syndrome, or target lesion revascularization) [12% (5/43) vs. 0% (0/33), P = 0.075]. In conclusion, irregular protrusion on OCT was associated with high plaque vulnerability, higher LDL-C, less frequent use of statin, larger vessel diameter, slow flow after stent implantation, and 1-year adverse clinical outcomes.

Comparison of Coronary Intimal Plaques by Optical Coherence Tomography in Arteries With Versus Without Internal Running Vasa Vasorum.

It has been reported that the internal running vasa vasorum (VV) was associated with plaque vulnerability, and microchannels in optical coherence tomography (OCT) are consistent pathologically with VV. We investigated plaque vulnerability and incidence of slow flow during percutaneous coronary intervention of the internal longitudinal running VV. Subjects were 71 lesions that underwent OCT before percutaneous coronary intervention. Internal running VV was defined as intraplaque neovessels running from the adventitia to plaque. Lesions with internal running VV were found in 47% (33 of 71). Compared with lesions without internal running VV, lesions with internal running VV showed significantly higher incidence of intimal laceration (64% [21 of 33] vs 16% [6 of 38], p <0.001), lipid-rich plaque (79% [26 of 33] vs 26% [10 of 38], p <0.001), plaque rupture (52% [17 of 33] vs 13% [5 of 38], p <0.001), thin-cap fibroatheroma (58% [19 of 33] vs 11% [4 of 38], p <0.001), macrophage accumulation (61% [20 of 33] vs 26% [10 of 38], p = 0.004), intraluminal thrombus (36% [12 of 33] vs 3% [1 of 38], p <0.001), and slow flow after stent implantation (42% [14 of 33] vs 13% [5 of 38], p = 0.007). The multivariable analysis showed that internal running VV was an independent predictor of slow flow after stent implantation (odds ratio 4.23, 95% confidence interval 1.05 to 17.01, p = 0.042). In conclusion, compared with those without, plaques with internal running VV in OCT had high plaque vulnerability with more intimal laceration, lipid-rich plaque, plaque rupture, thin-cap fibroatheroma, macrophage accumulation, and intraluminal thrombus, and they had high incidence of slow flow after stent implantation.

Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations.

The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET. Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F-positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F-positive patients. Our findings suggest that JAK2V617F-positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future.

Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in human umbilical vein endothelial cells.

AIM: Vascular senescence, which is accelerated in individuals with chronic kidney disease (CKD), contributes to the development of cardio-renal syndrome, and various uremic toxins may play important roles in the mechanisms underlying this phenomenon. We recently reported that indoxyl sulfate (IS), a uremic toxin, directly activates aryl hydrocarbon receptor (AhR) and generates oxidative stress through NADPH oxidase-4 in human umbilical vein endothelial cells (HUVECs). In the current study, we sought to examine whether IS regulates sirtuin 1 (Sirt1) and affects endothelial senescence via AhR activation. METHODS: HUVECs were incubated with 500 µmol/L of IS for the indicated time periods. In order to evaluate changes in the senescence of the HUVECs, the number of senescence-associated ß-galactosidase (SA ß-gal)-positive cells was determined using an image analysis software program. The intracellular nicotinamide phosphoribosyltransferase (iNampt) activity, cellular NAD(＋)/NADPH ratio and Sirt1 activity were analyzed according to a colorimetric assay to determine the mechanism of cellular senescence. Furthermore, we evaluated the involvement of AhR in the senescence-related changes induced by IS using AhR antagonists. RESULTS: IS decreased the iNampt activity, NAD(＋)/NADPH ratio and Sirt1 activity, resulting in an increase in the percentage of SA ß-gal-positive cells. On the other hand, the AhR antagonists restored the IS-induced decrease in the NAD(＋) content in association with an improvement in the iNampt activity and ameliorated the senescence-related changes. Taken together, these results indicate that IS impairs the iNampt-NAD(＋)-Sirt1 system via AhR activation, which in turn promotes endothelial senescence. CONCLUSIONS: The IS-AhR pathway induces endothelial senescence. Therefore, blocking the effects of AhR in the endothelium may provide a new therapeutic tool for treating cardio-renal syndrome.

Is 18F-FDG PET/CT useful for distinguishing between primary thyroid lymphoma and chronic thyroiditis?

PURPOSE: This study aims to investigate the usefulness of (18)F-FDG PET/CT for distinguishing between primary thyroid lymphoma (PTL) and chronic thyroiditis. METHODS: We retrospectively reviewed the data of 196 patients with diffuse (18)F-FDG uptake of the thyroid gland and enrolled patients who were diagnosed as having PTL or chronic thyroiditis based on the medical records, pathological findings, and laboratory data. The enrolled patients comprised 10 PTL patients (M/F = 4:6) and 51 chronic thyroiditis patients (M/F = 8:43). Images had been acquired on a PET/CT scanner at 100 minutes after intravenous injection of (18)F-FDG. RESULTS: The PTL group consisted of 7 patients with diffuse large B-cell lymphoma (DLBCL) and 3 with mucosa-associated lymphoid tissue (MALT) lymphoma. The maximum standardized uptake value (SUV(max)) was significantly higher in the PTL group than that in the chronic thyroiditis group (25.3 ± 8.0 and 7.4 ± 3.2, P < 0.001). On the other hand, the CT density (Hounsfield unit: HU) was significantly lower in the PTL group than that in the chronic thyroiditis group (46.1 ± 7.0 HU and 62.1 ± 6.9 HU, P < 0.001). Within the PTL group, the SUV(max) was significantly higher in the cases of DLBCL than in those of MALT lymphoma (29.0 ± 6.4 and 16.7 ± 2.3, P = 0.017). CONCLUSIONS: The SUV(max) was significantly higher and the CT density was significantly lower in PTL as compared with those in chronic thyroiditis. Thus, (18)F-FDG PET/CT may be useful for distinguishing between PTL and chronic thyroiditis.

Activation of aryl hydrocarbon receptor mediates indoxyl sulfate-induced monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells.

BACKGROUND: Indoxyl sulfate (IS) is a uremic toxin that causes renal injury, but little is known about its adverse effects on the cardiovascular system. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor that mediates adaptive and toxic responses in cells. Recent studies identified IS as an endogenous agonist for AhR, as well as other tryptophan metabolites. The aim of the study was to investigate whether IS activates AhR, with subsequent inflammatory responses contributing to the development of atherogenesis, in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: We demonstrated that IS stimulates the expression of AhR target genes, including cytochromes P450 1A1 and 1B1 mRNA, in a time-dependent manner, as well as translocation of AhR into the nucleus from the cytoplasm, indicating AhR activation. IS-stimulated AhR activation was accompanied by an increase in oxidative stress, proven by enhanced NADPH oxidase 4 expression and dihydroethidium staining. Additionally, AhR inhibitors abolished the IS-induced increase in monocyte chemoattractant protein-1 (MCP-1) expression in a dose-dependent manner. Taken together, these results suggest that IS activates AhR as an endogenous agonist and induces MCP-1 expression through reactive oxygen species production in HUVECs. CONCLUSIONS: Our findings give a novel understanding of the physiological effect of IS on the cardiovascular system and indicate possibilities for preventing cardiorenal syndrome by regulating serum IS levels.

First case report of acquired pure red cell aplasia associated with micafungin.

A 70-year-old Japanese man with chronic kidney disease under treatment with oral prednisolone for organizing pneumonia developed pulmonary aspergilloma. The patient was started on micafungin (MCFG), with no addition of any other new drug. About 5 weeks later, aggravation of his normocytic anemia associated with a low reticulocyte count was observed. Bone marrow puncture and biopsy revealed intense hypoplasia of the erythroblasts. As there was no evidence of malignancy, human parvovirus B19 infection, autoimmune diseases or hemorrhage, the patient was diagnosed as having acquired pure red cell aplasia (PRCA). The anemia improved along with an increase of the reticulocyte count to the normal level within 12 weeks of discontinuation of the MCFG therapy. The patient showed no evidence subsequently of any recurrence of the normocytic normochromic anemia or relapse of the PRCA. This is the first reported case of PRCA associated with MCFG.

The expression and function of glucose-dependent insulinotropic polypeptide in the embryonic mouse pancreas.

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is a member of a structurally related group of hormones that also includes glucagon, glucagon-like peptides, and secretin. GIP is an incretin, known to modulate glucose-induced insulin secretion. Recent studies have shown that glucagon is necessary for early insulin-positive differentiation, and a similar role for incretins in regulating embryonic insulin-positive differentiation seems probable. Here we studied the role of GIP signaling in insulin-positive differentiation in the embryonic mouse pancreas. RESEARCH DESIGN AND METHODS: The ontogeny of the GIP ligand and GIP receptor in the embryonic pancreas was investigated by immunohistochemistry and RT-PCR. GIP signaling was inhibited in cultured embryonic pancreata using morpholine-ring antisense against GIP ligand and receptor, or small interfering RNA (siRNA) for GIP ligand and receptor. Markers of endocrine cells and their progenitors were studied by immunohistochemistry and RT-PCR. RESULTS: GIP and GIP receptor mRNA were both detected in the embryonic pancreas by embryonic day 9.5 and then persisted throughout gestation. GIP was generally coexpressed with glucagon by immunostaining. The GIP receptor was typically coexpressed with insulin. Morpholine-ring antisense or siRNA against either GIP ligand or GIP receptor both inhibited the differentiation of insulin-positive cells. Inhibition of GIP or its receptor also led to a decrease in the number of Pdx-1-positive and sox9-positive cells in the cultured embryonic pancreas. The number of Pax6- and Nkx2.2-positive cells, representative of developing pancreatic endocrine cells and ß-cells, respectively, was also decreased. CONCLUSIONS: GIP signaling may play a role in early embryonic pancreas differentiation to form insulin-positive cells or ß-cells.

Adenoendocrine cell carcinoma of the extrahepatic bile duct: a case report and review of the literature.

Extrahepatic bile duct cancer with an endocrine cell component has rarely been reported. We report here on a case of adenoendocrine cell carcinoma in the middle bile duct. An 82-year-old man was admitted to hospital for jaundice and anorexia. Computed tomography and magnetic resonance imaging examination showed a papillary low-density mass in the middle bile duct. Endoscopic retrograde cholangiography showed obstruction of the bile duct, and blushing cytology of the bile duct revealed an adenocarcinoma. We resected the extrahepatic bile duct with regional lymph node dissection. A pathological examination revealed a neuroendocrine component showing small cytoplasmic cells with hyperchromatic nuclei and a rosette-like structure in the middle of the tumor. In the peripheral mucosal region, there was a well-differentiated adenocarcinoma composed of columnar and cuboidal epithelial cells with clear and slightly granular eosinophilic cytoplasm. Immunohistochemical analysis showed positive staining for CD56, following the diagnosis of adenoendocrine cell carcinoma. The Ki-67 rate was >30% suggesting a small-cell endocrine carcinoma. The adenocarcinoma component infiltrated into the endocrine component, and some of the endocrine component was positive for cytokeratin, suggesting transdifferentiation of the adenocarcinoma into the endocrine component rather than originating from the common precursor cell. The patient experienced liver metastasis 3 months after the operation and died 6 months after the operation. Adenoendocrine tumor of the bile duct is extremely rare and adjuvant chemotherapy is necessary according to the malignant potential of the neuroendocrine tumor rather than the adenocarcinoma.

The distribution of atypical epithelium in main-duct type intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND/PURPOSE: The purpose of this study was to obtain the fundamental data necessary to discuss the appropriate operative mode for the resection of main-duct type intraductal papillary mucinous neoplasms (mIPMNs) of the pancreas. METHODS: In 23 patients who underwent total pancreatectomy with preoperative and postoperative diagnoses of mIPMN, the imaging studies and clinicopathological data were collected. The whole pancreatic specimen was histologically evaluated, and the distribution of atypical epithelium was mapped on a schema. RESULTS: Pathological examination of the specimens revealed that 18 patients had carcinoma in the pancreas; 8 patients had invasive lesions and one patient had lymph node metastasis. Specimens from 5 patients did not bear carcinoma lesions but had widespread borderline lesions in the pancreas. The mapping of lesions in the pancreatic specimens revealed that, at least, borderline or higher lesions were present both in the head and distal pancreas in all patients. In the majority of the specimens, lesions from adenoma to carcinoma co-existed on the same slide, and there were normal cell intervals between the malignant lesions. CONCLUSION: We conclude that total pancreatectomy should be performed for mIPMN when dilatation of the main duct suggests possible spread of the lesion to the whole pancreas.

Noninvasive intraductal papillary mucinous neoplasm with para-aortic lymph node metastasis: report of a case.

Intraductal papillary mucinous neoplasms (IPMNs) with an invasive carcinoma component are categorized as minimally invasive or invasive. The prognosis after resection of minimally invasive IPMNs has been reported to be similar to that after resection of noninvasive IPMNs. We report a case of noninvasive branchduct IPMN with multiple lymph node metastases, including para-aortic node involvement, treated successfully by distal pancreatectomy with lymph node dissection. The patient, a 72-year-old man, had two multilocular cysts in the pancreatic body, 22 mm and 14 mm in diameter, respectively, communicating with the main pancreatic duct. The primary tumor and nodal metastases had similar patterns of mucin expression. The primary tumor contained a region of carcinoma in situ (CIS) without histological evidence of stromal invasion; thus, it was diagnosed as minimally invasive carcinoma. We report this case to emphasize two important points: first, even small branch-duct IPMNs without any indications for resection can have a component of CIS or more advanced disease; and second, even branch-duct IPMNs without any apparent invasive component can be aggressive and spread to the lymph nodes. Therefore, nodal status should be assessed carefully in every patient, even if the primary IPMN is not advanced.

Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine.

The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status.

Preoperative assessment of para-aortic lymph node metastasis in patients with pancreatic cancer.

BACKGROUND: Para-aortic lymph node (PALN) metastasis is an important prognostic factor in patients with pancreatic cancer, but accurate preoperative diagnosis is difficult. The objective of this study was to assess the accuracy of diagnosis of PALN by computed tomography (CT), magnetic resonance imaging (MRI), and (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET). METHODS: From August 2005 to July 2008, 119 patients with invasive ductal adenocarcinoma of the pancreas were included in this study. PALNs with a longer diameter >10 mm on CT or MRI were suspected of being involved by metastasis, whereas FDG uptake exceeding that of the adjacent normal tissue was considered to be positive for metastasis on FDG-PET studies. The imaging findings were compared with the pathological diagnosis of PALN metastasis. RESULTS: PALN dissection was performed in 71 patients (60.0%). Although histopathological examination revealed metastasis in 6 patients (8.5%), none of these patients was positive in any of the preoperative imaging studies. The longer diameter, the shorter diameter, the ratio of the two diameters, and the calculated lymph node volume showed no significant differences between patients with and without PALN metastasis. CONCLUSIONS: Preoperative detection of PALN metastasis in patients with pancreatic cancer is very difficult. Intraoperative histopathological examination of frozen sections is necessary if radical resection is contemplated.

Single-institution validation of the international consensus guidelines for treatment of branch duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The international consensus guidelines (the guidelines) for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of branch duct IPMNs with any of the following features: cyst size >30 mm, mural nodules, main pancreatic duct diameter >6 mm, positive cytology, and symptoms. The aim of this study was to evaluate the usefulness of these guidelines for resection of branch duct IPMNs. METHODS: We reviewed 84 consecutive patients with branch duct IPMNs who underwent surgical resection at our hospital between January 1984 and December 2007. RESULTS: Sixty-nine patients had indications for resection according to the guidelines. Malignant IPMNs had significantly larger cysts than benign tumors (P = 0.026). Patients with malignant IPMNs had significantly more indications for resection than those with benign IPMNs (2.6 +/- 1.0 vs. 1.7 +/- 0.9, P < 0.001), and 36 of the 37 patients with malignant IPMNs had indications. The sensitivity of the guidelines for predicting malignancy was 97.3%. One of 15 patients without indications had malignancy, and the specificity was low (29.8%). CONCLUSIONS: The guidelines show a high sensitivity for predicting malignancy of branch duct IPMNs, but the specificity is low. The cyst size and the total number of indications in each patient should be taken into account when predicting the risk of malignancy for branch duct IPMNs.

Prognostic value of metastin expression in human pancreatic cancer.

BACKGROUND: KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. METHODS: We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay. RESULTS: Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%), while strong expression of GPR54 was detected in 30 tumors (56.6%). Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047). Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04). Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02). Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1-4.7; p = 0.03), and the patients with a high plasma metastin level (n = 6) did not die after surgical resection. CONCLUSION: Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.

Adenovirus vectors with chimeric type 5 and 35 fiber proteins exhibit enhanced transfection of human pancreatic cancer cells.

Adenovirus (Ad) vectors are widely used for gene transfer. Efficient gene transfer into malignant cells is an important requirement for anticancer gene therapy, but transgene expression after transfer with adenoviral vectors varies among different cancer cell lines. Recently, Ad vectors containing chimeric type 5 and 35 fiber proteins have been developed. We evaluated the expression of coxsackie and adenovirus receptor (CAR), as well as integrins alphaV, beta3 and beta5, in seven human pancreatic cancer cell lines and assessed the relationship between expression of these molecules and Ad transfection efficiency. We compared the transfection efficiency of a conventional type 5 Ad vector (Ad5GFP) with that of an Ad vector containing chimeric type 5 and 35 fiber proteins (Ad5/35GFP), which expressed green fluorescent protein (GFP) driven by the cytomegalovirus promoter. There was strong CAR expression by AsPC-1, CFPAC-1 and PANC-1 cells, whereas the other cell lines showed weak expression. There was strong integrin beta3 expression by MIAPaCa-2, PANC-1 and Suit-2 cells, but expression by AsPC-1, BxPC-3, CFPAC-1 and HPAC cells was weak. Transfection efficiency of the vectors for human pancreatic cancer cell lines was not directly related to the CAR or integrin expression. However, transfection by Ad5/35GFP was significantly greater than by Ad5GFP at MOIs of 10 and 25 in all five human pancreatic cell lines. In conclusion, the Ad5/35GFP vector mediates more efficient gene transfer to human pancreatic cancer cells. These results may have implications for improving the efficiency of Ad-mediated gene transfer and developing adenoviral vectors.