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Helmut Friess

Publications and source records attributed to Helmut Friess.

178 records · Page 10Linked to original sources
PubMed2002

VEGF-RII influences the prognosis of pancreatic cancer.

OBJECTIVE: To evaluate whether the vascular endothelial growth factor (VEGF) pathway can be used as a target for effective treatment of pancreatic cancer. SUMMARY BACKGROUND DATA: VEGF and its receptors (VEGF-RI and -RII) are the predominant regulators of tumor neoangiogenesis, a key element for tumor growth and progression. However, VEGF receptor expression has been thought to be limited to endothelial cells, limiting the possibility of targeting it for therapy of pancreatic cancer. METHODS: Protein localization and mRNA were studied in pancreatic cancer specimens, normal pancreas, human pancreatic cancer cell lines, and an endothelial cell line. Cell proliferation was determined by [ H] thymidine uptake. Both VEGF receptors were genetically eliminated by antisense technology. The same approach was used in a murine model of pancreatic cancer in a therapeutic approach. RESULTS: VEGF-RI mRNA and VEGF-RII mRNA were expressed in 17 and 15 of 24 pancreatic cancer samples, respectively. VEGF receptors were found not only in blood vessels but also in pancreatic cancer cells. VEGF-RII expression correlated with poor tumor differentiation and was associated with poorer survival, while VEGF-RI expression did not correlate. VEGF treatment led to extensive growth stimulation in six of seven pancreatic cancer cell lines, which was completely inhibited by antisense treatment against VEGF-RII. Liposome-mediated gene transfer in nude mice with pancreatic tumors markedly reduced local tumor growth and decreased metastatic tumor spread. CONCLUSIONS: The VEGF/VEGF-RII pathway regulates angiogenesis and local tumor growth and spread in pancreatic cancer. Genetic targeting of VEGF-RII blocks local growth and metastatic spread of pancreatic cancer cells in vivo and therefore offers a potential new therapeutic option for patients with this disease.

Adenocarcinoma↗
PubMed2002

Differences in the expression of glutathione S-transferases in normal pancreas, chronic pancreatitis, secondary chronic pancreatitis, and pancreatic cancer.

INTRODUCTION: In our previous study, glutathione S-transferase-pi (GST-pi), a phase II drug metabolizing enzyme, was found to be expressed in pancreatic ductal and ductular cells but not acinar cells of the normal pancreas, chronic pancreatitis, and secondary pancreatitis caused by pancreatic cancer. A greater percentage of the cells expressing GST-pi was shown in the islets of chronic pancreatitis specimens compared with the normal pancreas and secondary pancreatitis. AIMS AND METHODOLOGY: To examine whether the increased number of islet cells expressing GST-pi and the absence in the acinar cells are compensated for by other GST isozymes, we investigated the expression of GST-alpha and GST-mu in the same specimens. RESULTS: Unlike the distribution of GST-pi, the distribution of GST-alpha and GST-mu in islets did not show marked differences between the three groups. However, in four of 18 primary chronic pancreatitis specimens, more islet cells (approximately 25%) expressed GST-alpha than in the normal pancreas and secondary chronic pancreatitis (both approximately 10%). The reactivity of cancer cells to GST-alpha, GST-mu, and GST-pi was similar to the ductal cells in the normal pancreas, chronic pancreatitis, and secondary chronic pancreatitis. Contrary to the expression of GST-pi, no statistically significant differences were found in the distribution of GST-alpha and GST-mu in the normal pancreas, chronic pancreatitis, and secondary chronic pancreatitis. CONCLUSION: The expression of the other GSTs does not compensate for the variation of expression of GST-pi. There was no specimen in each group that did not express at least one GST isozyme in islet, acinar, and ductal cells.

Adolescent↗
PubMed2002

Foreword.

Explore the source record for details and available documents.

Chronic Disease↗
PubMed2002

Surgical treatment and long-term follow-up in chronic pancreatitis.

In the past two decades our knowledge of the pathophysiology and surgical treatment options in chronic pancreatitis have improved substantially. Surgical treatment in chronic pancreatitis has evolved from radical to organ-preserving procedures. The classic Whipple resection is no longer indicated in chronic pancreatitis, and operations like the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple have replaced it as surgical standards. These procedures allow the preservation of exocrine and endocrine pancreatic function, provide pain relief in up to 90% of patients, and contribute to an improvement in the quality of life.

Chronic Disease↗
PubMed2002

The stem cell factor-c-kit system and mast cells in human pancreatic cancer.

Stem cell factor (SCF) and its receptor c-kit take part in the regulation of developmental processes of mast cells, hematopoietic stem cells, and melanocytes, as well as in the growth control of human malignancies. To explore the possible role of the SCF-c-kit system and of mast cells in pancreatic cancer, the concomitant expression and distribution of the two molecules were examined in 17 normal and 26 cancerous human pancreatic tissues and in 6 cultured pancreatic cancer cell lines. Mast cell distribution was also evaluated in the same tissue samples. In addition, the effects of SCF and of the c-kit tyrosine-kinase inhibitor STI571 on the growth of the cancer cell lines and of the normal pancreatic ductal cell line TAKA-1 were assessed. SCF immunoreactivity was absent in acinar, ductal, and islet cells of the normal pancreas and faint in pancreatic cancer tissues and cell lines. In contrast, c-kit was clearly present in some normal and hyperplastic ducts of the normal pancreas, in the cancer cells of 73% of the tumor samples, and in all the cell lines tested. Mast cells, identified by tryptase and chymase immunostaining on consecutive tissue sections, showed immunoreactivity for SCF and c-kit in both normal and cancerous specimens and their number was significantly increased (p = 0.03) in pancreatic cancer compared with the normal pancreas. SCF showed a dose-dependent growth inhibitory effect on TAKA-1 cells (p < 0.001), whereas pancreatic cancer cells were resistant to the SCF-induced growth inhibition. Nonetheless, the growth of TAKA-1 cells and pancreatic cancer cells was inhibited by the c-kit tyrosine kinase inhibitor STI571. In conclusion, the SCF-c-kit system, possibly with the contribution of mast cells, may have a growth-regulating role in the normal pancreas, which is altered during malignant transformation.

Adolescent↗
PubMed2002

Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemcitabine is associated with altered expression of apoptosis-regulating genes.

OBJECTIVES: Resistance to chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic cancer. Inasmuch as most effects of chemotherapeutic agents are mediated via the activation of apoptosis, the cytotoxic effects of gemcitabine and 5-fluorouracil (FU) in correlation with apoptosis-regulating genes in pancreatic cancer cell lines were analyzed. METHODS: The cytotoxic effects of 5-FU and gemcitabine in AsPC-1, Capan-1, Mia-PaCa-2 and T3M4 pancreatic cancer cell lines were assessed by growth assays, and mRNA expression levels of pro-apoptotic and anti-apoptotic genes of the Bcl-2 family were analyzed by RNAse protection assays. RESULTS: Pancreatic cancer cells displayed a wide range of responses towards 5-FU (IC(50) 0.22-4.63 microM) and gemcitabine (11.51-42.2 nM). After repeated treatment with 5-FU, the IC(50) values in Capan-1 and T3M4 cells increased 2.1- and 1.8-fold, respectively, compared to their parental cells. Following recurrent treatment with gemcitabine, the IC(50) values in Capan-1 cells increased significantly (1.5-fold, p < 0.01). RNase protection assay showed a negative correlation between bcl-x(L) and mcl-1 mRNA expression levels and the sensitivity to 5-FU and gemcitabine after 5-FU and gemcitabine treatment. The bax/bcl-2 ratio maintained relatively stable following 5-FU/gemcitabine treatment and reflected the chemotherapeutic sensitivity of these cell lines. CONCLUSIONS: These findings reveal that pancreatic cancer cell lines are generally resistant to 5-FU and are more sensitive towards gemcitabine. The bax/bcl-2 ratio is predictive of chemotherapy sensitivity, whereas bcl-x(L) and mcl-1 mRNA levels following repeated exposure to 5-FU or gemcitabine are associated with resistance to these drugs. These findings suggest that the activation of anti-apoptotic genes after repeated drug exposure contributes to chemoresistance of pancreatic cancer cells and that blockage of anti-apoptotic genes might enhance chemosensitivity in pancreatic cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Staging laparoscopy and its indications in pancreatic cancer patients.

BACKGROUND: Laparoscopy has become a popular and widespread surgical technique. An important goal in the treatment of patients with pancreatic cancer is to avoid any unnecessary procedure. Laparoscopy has been suggested as a routine tool for staging in order to prevent unnecessary laparotomies in these patients. METHODS: In this article we present our experience regarding the value of laparoscopic staging and review the literature on this topic. RESULTS AND CONCLUSION: A direct and conclusive comparison of the controversial literature is difficult because of different study designs. Inconsistent use of high-quality CT scans significantly affects the results. However, recent studies reveal that not more than 14% of the patients benefit from diagnostic laparoscopy when a state-of-the-art CT scan has been performed previously. Therefore, we conclude that routine diagnostic laparoscopy is not justified in all patients with pancreatic cancer. Rather, selective use is appropriate, especially in patients in whom ascites is an indirect sign of peritoneal metastases, or if liver metastases cannot be surely excluded preoperatively. This approach is cost-effective and limits diagnostic laparoscopy to a subgroup of patients in whom a laparotomy can be avoided.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2002

Surgical approaches for resection of pancreatic cancer: an overview.

OBJECTIVE: To overview the different surgical approaches for the resection of pancreatic cancer and our experience with these techniques. METHODS: Surgical procedures including the Whipple resection, Pylorus-preserving resection, total and subtotal panreatectomies, regional pancreatectomy and the extended lymph node resection were discussed. RESULTS: Studies have shown that no operation seems to produce significantly improved results in terms of survival, mortality and resection rates compared to the standard Whipple resection and pylorus-preserving duodenopancreatectomy. CONCLUSION: Despite the progress in the surgical treatment of pancreatic cancer, the overall prognosis after resection remains unsatisfied. Surgery is likely to be optional for the treatment of pancreatic cancer.

Humans↗
PubMed2001

NK-1 receptor gene expression is related to pain in chronic pancreatitis.

Recent theories of pathogenesis of pain in chronic pancreatitis (CP) are neuroimmune interactions of intrapancreatic nerves and inflammatory cells and increase in levels of pain neurotransmitters such as substance P (SP). This study analyzed the expression and localization of neurokinin 1 receptor (NK-1R), which binds SP, and its association with pain and inflammation in CP. Pancreatic tissues from 31 patients (22 males, nine females; mean age 45.9+/-9.4 years) with CP were evaluated. Nine normal pancreases (five males, four females; mean age 42.9+/-9.5 years) served as controls. Quantitative PCR was used to determine the NK-1R mRNA expression levels and in situ hybridization and immunohistochemistry were used to localize expression sites of NK-1R mRNA and protein, respectively. We also analyzed whether an association exists between NK-1R mRNA expression and pain and inflammation. In CP samples, in situ hybridization and immunohistochemistry localized NK-1R mRNA expression and protein mainly in the nerves, ganglia, blood vessels, inflammatory cells and occasionally in fibroblasts. In patients with mild to moderate and strong intensity of pain, NK-1R mRNA levels were increased 14- and 30-fold over controls, respectively. There was a significant relationship between NK-1R mRNA levels and intensity of pain (r=0.46, P=0.03), NK-1R mRNA and the frequency of pain (r=0.51, P=0.04), and NK-1 mRNA and duration of pain (r=0.46, P=0.01) in CP patients, but not with the degree of tissue inflammation. NK-1R signaling may be involved in the pain syndrome of CP. The expression of NK-1R in inflammatory cells and blood vessels also points to an interaction of immunoreactive substance P nerves, inflammatory cells and blood vessels, and further supports the existence of a neuroimmune interaction that probably influences the pain syndrome and chronic inflammatory changes so characteristic of CP.

Adult↗
PubMed2000

KAI1 gene is differently expressed in papillary and pancreatic cancer: influence on metastasis.

AIM:To compare KAI1 in cancer of papilla of Vater and pancreas to evaluate whether there are differences in biologic behavior which might account for prognosis.METHODS:We compared the expression in 24 papillay and 29 pancreatic cancers using Northern blot analysis, immunochemical assay and in situ hybridization, and investigated whether early diagnosis or molecular differences predict the outcome in these tumor entities.RESULTS:By Northern blot analysis there is no statistical difference of KAI1 levels in normal and cancerous papilla. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was found in the tumors. By immunohistochemical assay, KAI1 staining in cytoplasm of papillary cancer cells was similar to that of normal papillary cells. By in situ hybridization, the results of KAI1 mRNA expression in normal and cancerous papilla were similar to those with immunohistochemical assay. The normal and cancerous pancreas tissues were also analyzed by the methods used in papillary samples.CONCLUSION:Although the biologic roles of KAI1 have not been clarified, our results suggest that KAI1 may restrict the progression of malignant papillary cancer, but its expression might not have any effect on the characteristics of papillary tumor, whereas by the analysis of KAI1 gene, its reduced expression is closely related to the progression and metastases of pancreatic cancer.

Journal Article↗
PubMedDate not supplied

Pseudoaneurysms of the common hepatic artery following pancreaticoduodenectomy: successful emergency embolization.

We report a rare case of two communicating pseudoaneurysms of the common hepatic artery 1 month postoperatively following pylorus-preserving pancreaticoduodenectomy due an abscess formation. We describe the superselective transcatheteral embolization technique with deployment of interlocking detachable coils and Histoacryl-Lipiodol in this case and discuss the recent literature. Despite the technical success by achieving hemodynamic stability with initial preservation of liver function, the patient died 23 days postembolization due to multiorgan failure.

Abdominal Pain↗
PubMedDate not supplied

Synergistic cytotoxic effect of TRAIL and gemcitabine in pancreatic cancer cells.

BACKGROUND: Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a novel member of the TNF family and triggers apoptosis in a variety of malignant cells. MATERIALS AND METHODS: We assessed the antitumour activity of TRAIL in six human pancreatic cancer cell lines by measuring apoptosis with sulforhodamine B cytotoxicity assays, DAPI staining and FACScans. RESULTS: All six cell lines were sensitive to TRAIL-induced apoptosis. The expression levels of TRAIL receptors R1, R2, R3 and R4 did not correlate with TRAIL sensitivity. Simultaneous treatment with TRAIL and the chemotherapeutic agent gemcitabine had a synergistic effect. Caspase-8 and -3 activities were increased by TRAIL treatment and apoptosis was largely blocked by caspase-8 and -3 inhibitors. CONCLUSION: Apoptotic cell death can be induced in pancreatic cancer cells by TRAIL treatment and this may be mediated through activation of caspases-8 and -3. Gemcitabine significantly increased the antitumour effect of TRAIL, suggesting novel therapeutic approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Detection of circulating tumor cells by cytokeratin 20 and prostate stem cell antigen RT-PCR in blood of patients with gastrointestinal cancers.

BACKGROUND: Detection of circulating tumor cells in blood may be an important diagnostic and prognostic factor in the management of tumor patients. The present study aimed to examine whether cytokeratin 20 (CK-20) and prostate stem cell antigen (PSCA) are useful markers for the detection of disseminated cancer cells in the blood of tumor patients. MATERIALS AND METHODS: A nested RT-PCR assay was used to detect CK-20 and PSCA mRNA in blood samples from 18 healthy donors, 15 patients with non-malignant disease, 9 patients with benign tumors and 47 patients with malignant tumors (11 pancreatic carcinoma, 8 gastric cancer, 15 colorectal carcinoma and 13 miscellaneous tumors). RESULTS: CK-20 expression was observed in the peripheral blood of 19 out of 47 (40.4%) patients with malignant tumors, 2 out of 9 (22.2%) patients with benign tumors and 3 out of 15 (20%) patients with non-tumor diseases. PSCA expression was present in the blood of 22 out of 47 (46.8%) patients with malignant tumors and particularly in 7 out of 11 (63.6%) patients with pancreatic cancer. CK-20 and PSCA expression was not observed in blood samples from healthy donors. There was a relationship between PSCA expression and tumor stage. CONCLUSION: The present results demonstrate that it is possible to apply a simple and reliable method for the detection of circulating tumor cells based on CK-20 and PSCA RT-PCR assays.

Adult↗
PubMedDate not supplied

Novel method of pancreatojejunal reconstruction after spontaneous closure of previous lateral pancreatojejunostomy.

Lateral pancreatojejunostomy is a well-documented procedure for pain relief in chronic pancreatitis with a dilated main pancreatic duct. However, a number of patients develop recurrence of pain at variable intervals after a successful drainage procedure. A 40-year-old patient with tropical chronic pancreatitis developed recurrence of pain 13 years after a lateral pancreatojejunostomy. Investigation demonstrated a dilated main pancreatic duct. Re-exploration revealed a near complete closure of the previous lateral pancreatojejunostomy. A novel method of pancreatojejunal reconstruction was performed. Patient is pain-free after a follow-up of 18 months since surgery. The long-term status of lateral pancreatojejunostomy remains unclear. Our case documents, probably for the first time in published literature, a near total spontaneous closure of a previous lateral pancreatojejunostomy that was responsible for recurrence of pain. Our method of pancreatojejunal reconstruction adds to the armamentarium of the pancreatic surgeon.

Adult↗
PubMedDate not supplied

Silencing of X-linked inhibitor of apoptosis (XIAP) decreases gemcitabine resistance of pancreatic cancer cells.

BACKGROUND: The X-linked inhibitor of apoptosis (XIAP) belongs to a family of proteins that suppresses apoptosis by inhibition of caspases in some cancers. It confers resistance to apoptosis induction by chemotherapeutic agents. The aim of this study was to evaluate the influence of XIAP in pancreatic cancer. PATIENTS AND METHODS: Tissue samples from 43 patients with pancreatic adenocarcinoma (median age of 67 years, range from 39-81 years) were analyzed. Pancreatic samples from healthy organ donors (10) and chronic pancreatitis patients (10) served as controls. XIAP expression and localization analysis was carried out by quantitative RT-PCR and immunohistochemistry (IHC). XIAP silencing was achieved by transfection of specifically designed siRNA oligonucleotides. Proliferation and chemotherapy experiments were performed by MTT cell growth assays. RESULTS: There was a 2.1-fold increase of median XIAP mRNA levels in pancreatic cancers compared to controls. Kaplan-Meier analysis indicated a tendency for reduced patient survival with increasing levels of XIAP mRNA (higher levels: 13.4 months; lower levels: 16.1 months). IHC revealed strong XIAP staining in tubular complexes and pancreatic cancer cells. XIAP silencing resulted in a slight reduction of the proliferation of Capan-1 and T3M4 pancreatic cancer cells. In addition, XIAP silencing resulted in increased sensitivity of both cell lines to gemcitabine. CONCLUSION: XIAP is overexpressed in pancreatic cancer and contributes to chemoresistance. Interfering with this pathway may have potential therapeutic role in the treatment of this disease.

Adolescent↗