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H Friess

Publications and source records attributed to H Friess.

At least 91 records · Page 5Linked to original sources
PubMed2001

Heparanase expression in primary and metastatic pancreatic cancer.

The human endoglycosidase heparanase (hpa) degrades heparan-sulfate proteoglycans, which constitute prominent components of basement membranes and extracellular matrix. Due to the critical function of hpa in cancer cell invasion and metastasis, we have analyzed the expression of hpa in human primary and metastatic pancreatic cancer as well as in the normal pancreas and in chronic pancreatic inflammation. By real-time quantitative PCR, there was a 7.9- and 30.2-fold increase of hpa mRNA in chronic pancreatitis and pancreatic cancer tissue samples, respectively, in comparison with normal pancreatic tissues. There was a significant correlation between enhanced hpa mRNA expression and shorter postoperative patient survival. hpa mRNA and protein localized in the cancer cells of primary and metastatic pancreatic cancer, with a preferentially higher expression at the primary tumor site. Cultured pancreatic cancer cells transfected with a full-length hpa construct displayed enhanced invasiveness in an invasion chamber assay. These results suggest that hpa overexpression in human pancreatic cancers facilitates cancer cell invasion, thereby enhancing the metastatic potential of the tumors.

Adult↗
PubMed2001

Determination of 5-fluorouracil and 5-fluoro-2'-deoxyuridine-5'-monophosphate in pancreatic cancer cell line and other biological materials using capillary electrophoresis.

Capillary zone electrophoresis (CZE) was used for the rapid determination of 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) in pancreatic cancer cell line (PANC-1), culture medium, plasma and pancreatic tissue. The assay is based upon protein precipitation with acetonitrile followed by a 9-min CZE analysis of the supernatant in an uncoated fused-silica capillary employing a borate buffer and on-column absorbance detection at 265 nm. Using 50 microl of sample, 5-FU levels between 4.12 and 132 microg/ml (31.7-1000 microM) were found to provide linear calibration graphs. Intra-day and inter-day RSD values evaluated from peak height ratios (n=5) were <7.6 and <8.8%, respectively. Corresponding RSD values of detection times (n=7) were <1 and <1.5%, respectively. The limits of detection for 5-FU and FdUMP were 1.72 and 5.29 microg/ml, respectively. As application, the accumulation of 5-FU by PANC-1 cells over a 4-h time period was investigated. Having a culture medium concentration of 100 microg/ml, the 5-FU cell content was estimated to become equal to that of the surrounding medium (i.e., 100 microg/ml or 3.61 fmol per cell with a volume of 4.7 pl) within that time period. The sensitivity of the assay was sufficient for the determination of 5-FU in all cell samples. FdUMP, however, could not be detected in these samples. Furthermore, the data obtained in uncoated capillaries are compared to those measured in a fused-silica capillary whose inner surface was coated with linear polyacrylamide (about 10-fold reduction of electroosmosis). The latter capillary format was found to be useless for simultaneous analysis of 5-FU and FdUMP in pancreatic cells but could be potentially useful for analysis of these compounds in plasma.

Antimetabolites, Antineoplastic↗
PubMed2001

Differential expression of metastasis-associated genes in papilla of vater and pancreatic cancer correlates with disease stage.

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.

Adolescent↗
PubMed2001

Effects and expression of TRAIL and its apoptosis-promoting receptors in human pancreatic cancer.

Pancreatic cancer cells are usually resistant to apoptosis mediated by tumor necrosis factor (TNF)-alpha or FasL, and their toxicity towards normal cells hampers their application for therapeutic use. TNF-related apoptosis-inducing ligand (TRAIL), a novel member of the TNF family, triggers apoptosis in a variety of malignant cells, but exhibits less cytotoxicity in normal cells. To investigate the therapeutic potential of TRAIL, we analyzed the expression of TRAIL and its apoptosis-inducing receptors (DR4 and DR5) in the normal and cancerous human pancreas, and the sensitivity of pancreatic cancer cells to TRAIL cytotoxicity. TRAIL, DR4 and DR5 mRNA levels were concomitantly increased in pancreatic cancers compared with normal controls (P<0.01), and there were positive correlations between the expression levels of TRAIL and DR4, TRAIL and DR5 and between DR4 and DR5 mRNA (r=0.85, r=0.87, r=0.91; P<0.01). Immunostaining revealed the presence of the corresponding proteins frequently within the same cancer cells. In five pancreatic cancer cell lines, TRAIL, DR4 and DR5 mRNA expression was detectable at various levels. However, independent of the presence of DR4 and DR5, TRAIL cytotoxicity assays revealed that pancreatic cancer cells showed a significantly lower sensitivity (LD(50)>85 ng/ml) to TRAIL treatment than Jurkat T lymphoma cells (LD(50)=7.2 ng/ml). These findings show that pancreatic cancers are insensitive towards TRAIL-mediated apoptosis despite expression of TRAIL and its receptors, suggesting the presence of mediators which inhibit the TRAIL cell-death-inducing pathway in pancreatic cancer cells.

Adult↗
PubMed2001

Growth factors and their receptors in pancreatic cancer.

Pancreatic cancer has an incidence of approximately 8 to 10 cases per 100,000 citizens in Western industrialized countries, and the incidence has been increasing throughout the last decades. Insensitivity to antigrowth and apoptotic signals as well as self-sufficiency in growth signals are hallmarks of malignant growth. Pancreatic cancers often exhibit alterations in growth inhibitory pathways such as Smad4 mutations and Smad6 and Smad7 overexpression, and evade apoptosis through p53 mutations and aberrant expression of apoptosis regulating genes. In addition, in pancreatic cancer a variety of growth factors are expressed at increased levels. For example, the concomitant presence of the EGF-receptor and its ligands EGF, TGF-alpha, and/or amphiregulin is associated with enhanced tumor aggressiveness and shorter survival periods following tumor resection. Furthermore, a number of other growth factors and their receptors, such as fibroblast growth factors, nerve growth factor, platelet-derived growth factors, and insulin-like growth factors and their respective receptors are expressed at increased levels in pancreatic cancer and are thought to contribute to its malignant phenotype. Taken together, the disturbance of growth inhibitory and apoptotic pathways and the abundance of growth promoting factors give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival prognosis.

Adenocarcinoma↗
PubMed2001

The patterns of extrainsular endocrine cells in pancreatic cancer.

Abnormal glucose tolerance and frank diabetes mellitus develop in up to 80% of pancreatic cancer patients. Islets within these tumors show a decreased number of beta cells and increased number of alpha cells. The reduced number of beta cells could induce beta cell neogenesis in extrainsular tissue to compensate for the loss of insulin in islets. On the other hand, because the beta cell depletion in pancreatic cancer seems to be the effect of substances released by cancer cells, suppression of extrainsular endocrine cells is expected. We compared the pattern of extrainsular endocrine cells in pancreatic cancer patients with normal pancreas as well as chronic pancreatitis, which is known to be associated with impaired glucose tolerance or frank diabetes. As in the normal tissue, extrainsular endocrine cells were found in chronic pancreatitis and pancreatic cancer. However, in the chronic pancreatitis specimens insulin cells were the predominant cell type, whereas in pancreatic cancer specimens more glucagon than insulin cells were found, although the differences were statistically insignificant. Thus, our results indicate that the alteration of beta cells in pancreatic cancer patients is mainly restricted to the endocrine cells within the islets and that there is no compensatory proliferation of beta cells.

Adenocarcinoma↗
PubMed2001

Carcinogenesis of cancer of the papilla and ampulla: pathophysiological facts and molecular biological mechanisms.

BACKGROUND: Ampullary cancer has one of the highest resectability rates and best prognoses among neoplasms arising in the periampullary region. DISCUSSION: Early diagnosis due to early symptoms can partially explain the better prognosis as compared to other cancers of the periampullary region, but biologic factors should also be taken in account. In the past few years, the molecular mechanisms underlying this disease have been investigated and alterations of genes that regulate different cell functions have been described. Mutations of K-ras and of the tumor suppressor genes APC, p16 and p53 indicate a major disturbance in cell cycle regulation. CONCLUSIONS: If the molecular profile of ampullary cancer is examined in terms of rate and type of molecular changes, it seems to be more similar to intestinal than to pancreatic cancer. Furthermore, the fact that many ampullary carcinomas arise from adenomas and the frequent finding of ampullary tumors in patients affected by polyposis syndromes also suggest that ampullary and colon cancers share common molecular mechanisms of carcinogenesis.

Ampulla of Vater↗
PubMed2001

Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy.

BACKGROUND: The role of preoperative biliary drainage in patients with biliary obstruction undergoing pancreatoduodenectomy remains controversial. Several authors failed to show any effect of preoperative biliary drainage, whereas others even reported an increased morbidity following pancreatoduodenectomy. METHODS: Retrospective analysis was performed in a consecutive series of 257 patients undergoing pancreatoduodenectomy between November 1993 and November 1999. RESULTS: Ninety-nine patients (38%) underwent preoperative biliary drainage for a median time period of 10 days (range 1 to 41) prior to resection. Cumulative postoperative morbidity was 47% (120 patients), the reoperation rate was 4.3% (11 patients), and mortality was 2.3% (6 patients). There was no difference in total morbidity, infectious complications, reoperation rate, mortality, or long-term survival between patients with or without preoperative biliary drainage. CONCLUSIONS: Preoperative biliary instrumentation and biliary drainage do not affect early or late outcome in patients undergoing pancreatoduodenectomy.

Aged↗
PubMed2001

Brain-derived neurotrophic factor (BDNF) is upregulated and associated with pain in chronic pancreatitis.

Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate its association with pain. By immunohistochemistry, in the normal pancreas BDNF immunoreactivity was moderately present in the cytoplasm of most ductal cells and weakly present in most acinar cells, islet cells, nerve fibers (including perineurium), and ganglia cells. In contrast, in CP intense immunostaining of BDNF was present in most cells of ductular complexes and in the perineurium of enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar cells and islet cells. In addition, moderate immunoreactivity of BDNF was also detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP samples (P < 0.01) compared with normal pancreas samples. The expression level of BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r = 0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF is increased in CP. Its association with pain suggests that it functions as a peripheral and central pain modulator, as reported previously in other inflammatory disorders.

Adolescent↗
PubMed2001

Doc-2/hDab2 expression is up-regulated in primary pancreatic cancer but reduced in metastasis.

SUMMARY: DOC-2/hDab2 (DOC-2) has tumor suppressive functions in ovarian cancer and choriocarcinoma. In these tumors, it negatively influences mitogenic signal transduction of growth factors and blocks ras activity. Pancreatic cancer exhibits a high frequency of K-ras gene mutations; however, it is not known whether DOC-2 expression is altered in these tumors. Therefore, we investigated DOC-2 expression in 22 pancreatic adenocarcinomas and in 6 pancreatic cancer cell lines. Findings in human tumors were compared with normal controls and correlated with clinicopathological data. Additionally, the influence of K-ras on DOC-2 transcription was investigated. Northern blot and Western blot analyses both demonstrated an increase of DOC-2 mRNA and protein levels in primary pancreatic cancers in comparison with normal controls. In situ hybridization showed DOC-2 mRNA expression in the majority of cancer cells of primary tumors, as well as in chronic pancreatitis-like lesions surrounding the cancer mass. Immunohistochemistry mirrored the in situ hybridization findings. In contrast, levels of expression of DOC-2 in lymph node metastases were markedly decreased in comparison with levels in primary tumors. In addition, in 5 metastatic pancreatic cancer cell lines, DOC-2 mRNA and protein levels were low, whereas quantitative RT-PCR demonstrated relatively higher levels in a nonmetastatic pancreatic cancer cell line. In conclusion, DOC-2 is overexpressed in primary pancreatic adenocarcinoma but down-regulated in metastatic disease, suggesting a tumor suppressor function of DOC-2 in the late steps of pancreatic carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Surveillance of pre-malignant disease of the pancreatico-biliary system.

Technical advancements in ultrasonography, contrast-enhanced computed tomography and magnetic resonance imaging, as well as the wider availability of these ultramodern imaging techniques, have resulted in the early detection and a better classification of various asymptomatic and symptomatic pancreatico-biliary lesions. Pre-malignant biliary and pancreatic lesions are rare disorders, and no clear data are available to define their malignant potential. Because of the lack of controlled epidemiological data, the time span for malignant transformation and its frequency cannot be defined in the majority of these lesions. Adenomyomatosis of the gallbladder and gallbladder polyps larger than 10 mm should be treated by cholecystectomy even in asymptomatic patients because of an increased risk of malignant transformation. Chronic cholangitis, primary sclerosing cholangitis and choledochal cysts are also pre-malignant conditions. The timing of surgery, once it is advised for a pre-malignant condition that is still benign, should, however, be individualized to the particular patient situation. In patients with chronic pancreatitis, surgery may be indicated for disease-related complications. In as much as chronic pancreatitis predisposes to a higher risk of pancreatic cancer, any suspicion of malignancy should warrant a surgical exploration. Intraductal papillary tumours and mucin-producing pancreatic tumours are other pre-malignant pancreatic lesions whose malignant potential cannot be precisely determined pre-operatively. They should be resected in situations where there is a high degree of suspicion even without a clear objective diagnosis. In conclusion, pre-malignant hepato-biliary and pancreatic lesions of uncertain pathology should undergo early resection in view of treatment limitations and the dismal prognosis of established cancers. While hepato-biliary and pancreatic surgery is nowadays performed in specialized centres, with a low post-operative morbidity and mortality, it is equally important to understand that observation alone with regular computed tomography or magnetic resonance imaging control can no longer be recommended in the management of these lesions.

Biliary Tract Neoplasms↗
PubMed2001

Mast cell distribution and activation in chronic pancreatitis.

Chronic pancreatitis (CP) is characterized by mononuclear inflammatory cell infiltration and replacement of the destroyed parenchyma by fibrous tissue. Recently, mast cells have been implicated in chronic inflammatory processes with fibrous tissue deposition. Therefore, the number and distribution of mast cells and their state of activation were evaluated in 12 normal specimens and in 46 specimens of CP with different causes (alcoholic, tropical, and idiopathic). Furthermore, the presence of stem cell factor (SCF), the main mast cell growth factor, and of its receptor, c-kit, was also assessed. In CP tissues, mast cells were localized both in the fibrotic areas and in the residual acinar parenchyma. The total number of mast cells was significantly higher in CP than in the normal pancreas (P < .0001) and correlated positively with the extent of fibrosis and the intensity of inflammation. Immunoglobulin E (IgE)-dependent mast cell activation was higher in CP than in the normal pancreas. No differences in mast cell number or IgE positivity were found among the 3 causes of CP. SCF-and c-kit immunoreactive mast cells were mostly localized in fibrous tissue and around regenerating ducts, which were also positive for c-kit but were negative for SCF. These results suggest that mast cells, activated by an IgE-dependent mechanism and/or by an SCF-c-kit autocrine loop, are a relevant component of the inflammatory infiltrate in CP, independent of the underlying cause. Their localization near degenerating acini and regenerating ducts might indicate that they play a crucial role in tissue destruction and remodeling in CP.

Adolescent↗
PubMed2001

Molecular mechanisms in chronic pancreatitis.

The pathogenesis of chronic pancreatitis (CP) is still controversial. None of the proposed models has been able to provide a convincing link between the known etiological factors - alcohol abuse, metabolic disturbances, congenital or acquired obstruction of the duct system - and the complex morphological and pathophysiological aspects of the disease. Molecular and cell biology research during the last years, however, has elucidated that a dysregulated immune response, together with an active involvement of pancreatic parenchymal cells, contributes to tissue destruction, fibrosis and remodeling in CP. Infiltration of the pancreas by particular subsets of immune effector cells, aberrant and enhanced expression of MHC molecules, and overexpression of growth factors and their receptors have all recently been found to play a role in CP. In addition, genetic analysis has led to the discovery of genes that predispose their carriers to the development of the disease, and has shed new light on the relation between CP and pancreatic cancer.

Animals↗
PubMed2001

Phospholipase A2 isoforms in acute pancreatitis.

OBJECTIVE: To assess phospholipase A2 isoforms during human and experimental acute necrotizing pancreatitis. Phospholipase A2 isoforms (group I, II, and IV) were examined in acute pancreatitis tissues in humans and rats to determine whether the exocrine pancreas itself is a source of these mediators. SUMMARY BACKGROUND DATA: Phospholipase A2 has important regulatory functions, especially in inflammation. METHODS: Using Northern blot analysis and immunohistochemistry, the expression and localization of phospholipase A2 isoforms were analyzed in pancreatic tissue obtained from 21 patients with acute necrotizing pancreatitis and in pancreatic tissues of rats with acute edematous and necrotizing pancreatitis. Rat samples were examined daily for 1 week. RESULTS: In human acute pancreatitis, phospholipase A2-I mRNA expression was 8.9-fold decreased. By contrast, phospholipase A2-II (7.8-fold) and phospholipase A2-IV (8.1-fold) mRNA levels were increased. By in situ hybridization, phospholipase A2-IV was found to be expressed in remaining acinar and ductal cells adjacent to the necrotic areas. Immunostaining revealed moderate to intense phospholipase A2-II immunoreactivity in remaining acinar and ductal cells next to the necrosis. In rat pancreatitis, phospholipase A2-II mRNA levels in the pancreas were unchanged in the early phase (8 hours) but markedly increased after 24 hours, with a fluctuating pattern until day 7. CONCLUSIONS: Enhanced expression of phospholipase A2-II and A2-IV isoenzymes in human and experimental acute pancreatitis suggests that these enzymes play a role in modulating the inflammatory reaction in the pancreas. Because phospholipase A2-II and A2-IV mRNA was strongly present in remaining viable pancreatic acinar and ductal cells, the pancreas itself seems to be at least partly a source and a regulator of phospholipase A2-II- and A2-IV-dependent inflammatory reactions in acute pancreatitis.

Adolescent↗
PubMed2001

Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial.

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Adenocarcinoma↗
PubMed2001

Identification of disease-specific genes in chronic pancreatitis using DNA array technology.

OBJECTIVE: To use DNA arrays to analyze the differential gene expression patterns in the normal pancreas and in pancreatic diseases. SUMMARY BACKGROUND DATA: Genome-wide gene expression analysis will provide new insights into gene function and cause of disease. METHODS: RNA was extracted from eight normal pancreatic specimens, eight specimens with chronic pancreatitis (CP), and eight pancreatic cancer (PCa) tissues. Poly A(+) RNA was purified, reverse-transcribed, and converted into cRNA using biotinylated nucleotides. The HuGeneFL DNA array containing 5,600 full-length human genes was used for analysis. RESULTS: First, normal pancreatic tissues were analyzed in comparison with a panel of other normal tissues (colon, liver, prostate, lung, lymph node). This analysis revealed 11 signature genes that were selectively expressed in the pancreas (e.g., pancreatic elastase-IIA). Comparison of the expression of 5,600 genes between the normal pancreas, CP, and PCa specimens showed that the expression of 34 genes was decreased in CP tissues compared with normal pancreatic tissues, and that the expression of all of these genes was simultaneously decreased in PCa. In addition, the expression of 157 genes was increased in CP tissues compared with the normal pancreas. Of those, 152 genes were simultaneously increased in PCa. Thus, only 5 of 5,600 genes were significantly overexpressed in CP compared with both normal pancreas and PCa. CONCLUSIONS: The majority of alterations observed in CP are present in PCa, and the number of genes whose expression is selectively deregulated in CP is surprisingly small. These results may provide new insight into the pathobiology of CP and help identify certain molecular alterations that might serve as targets for new diagnostic tools and disease-specific therapy.

Adult↗
PubMed2001

Real-time quantitative PCR of telomerase mRNA is useful for the differentiation of benign and malignant pancreatic disorders.

The presence of telomerase activity has been proposed as a specific and sensitive marker for malignant tissue, and positivity rates of up to 95% have been reported in pancreatic cancer. In the present study telomerase activity analysis was reevaluated in 29 pancreatic cancer tissues compared with 36 chronic pancreatitis tissues and 21 normal controls, and a study was made of whether malignant and benign pancreatic disorders can be better differentiated using a novel technique real-time quantitative PCR analysis-analyzing telomerase mRNA expression. Telomerase activity was present in 35% (10 of 29) of pancreatic cancer samples, 3% (one of 36) of chronic pancreatitis samples, and none of the normal pancreatic tissue samples in the TRAP assay. Real-time quantitative PCR analysis revealed the presence of telomerase mRNA expression in 50% (10 of 20) of normal, 86% (31 of 36) of chronic pancreatitis, and 90% (26 of 29) of pancreatic cancer samples. However, quantification of the expression data revealed that the relative increase above normal was 5.5 (range, 3.5-8.6) for chronic pancreatitis and 23.9 (range, 18.6-30.7) for pancreatic cancer samples (p < 0.01). No relationship was found between telomerase activity and the fold increase of telomerase mRNA above normal and gender, patient age, tumor stage, or tumor grade. These data indicate that detection of telomerase activity using the TRAP assay has limitations in differentiating benign and malignant pancreatic disorders. However, telomerase mRNA analysis by real-time quantitative PCR analysis allows a highly sensitive detection and differentiation of pancreatic cancer from normal pancreas and chronic pancreatitis and thereby may serve as a new reliable, easy, and effective diagnostic tool for cancer diagnosis.

Adult↗