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Helmut Friess

Publications and source records attributed to Helmut Friess.

At least 91 records · Page 5Linked to original sources
PubMed2004

Cell wounding in early experimental acute pancreatitis.

It is well established that damage to the outer membrane of cells is a common phenomenon allowing abnormal transmission of substances into the cytosol. Penetration of albumin into acinar cells has been detected in experimental acute pancreatitis, raising the possibility that membrane damage is a very early event, potentially representing the first changes leading to pancreatitis. To determine if direct damage to the cell membrane is a key factor during induction of acute pancreatitis, thus altering the balance of extra- and intracellular substances, fluorescein-dextran was administered with supramaximal doses of caerulein via the jugular vein or by injection directly into the pancreas. This tracer rapidly penetrates into cells. Two patterns of tracer penetration are observed: cytosolic and vesicular/vacuolar. Fluorescein-dextran administered intravenously with caerulein penetrates into the cytosol of acinar cells within 10 min. Strong cytoplasmic fluorescence occurs within 5 min after direct injection. It may be concluded that supramaximal caerulein, administered in vivo, damages the cell membrane of acinar cells, allowing large molecules to enter the cytosol. Thus Ca(2+) and other substances may enter the cells in abnormally high concentrations, initiating the cellular changes characteristic of pancreatitis. The results raise the question whether membrane wounding may play a role in the initiation of human pancreatitis.

Acute Disease↗
PubMed2004

Heidelberg's first experiences in establishing a living-donation liver transplantation programme.

BACKGROUND: Since indications for liver transplantation (LTx) have increased and the shortage of brain dead transplant organs continues, an increase in deaths related to extended waiting periods can be documented. Living-related LTx (LRLTx) is a good alternative that can help compensate the shortness of organs for transplantation and can reduce waiting periods and deaths related to a long waiting list. We started a LRLTx programme at the transplantation centre, Department of Surgery at the University of Heidelberg to increase our transplantation activities. In this article we present our primary experiences and protocol. METHODS: From September 2002 to June 2003, three LRLTx were performed. Indications in recipients were hepatocellular carcinoma in two cases and liver cirrhoses due to hepatitis B in one patient. Two patients received the right liver (segments V-VIII) of their donors. One patient received the complete liver collected as a Domino LTx. All liver transplants were performed without the use of a venous bypass. RESULTS: The peri- and post-operative courses of our donors were without complications, except for an infected intraabdominal bilioma, which was drained interventionally. The donors were fully able to work after the operation. The coordinative and logistical work should not be underestimated. CONCLUSIONS: This therapy should only be offered and performed in centres with excellent expert knowledge in liver and transplantation surgery.

Adult↗
PubMed2004

Adenovirus-mediated transfer of a truncated fibroblast growth factor (FGF) type I receptor blocks FGF-2 signaling in multiple pancreatic cancer cell lines.

Pancreatic ductal adenocarcinomas (PDACs) overexpress several members of the fibroblast growth factor (FGF) family of ligands and the type I FGF receptor (FGFR-1), and enhanced FGF-2 protein levels correlate with shorter postoperative survival of patients with PDAC. In this study, we investigated the effects of FGF-2 on cell proliferation and mitogen-activated protein kinase (MAPK) activation before and after abrogation of FGFR-1-dependent signaling in 4 pancreatic cancer cell lines (ASPC-1, COLO-357, MIA-PaCa-2, and PANC-1). Signaling was blocked by infecting the cells with an adenoviral vector encoding for a truncated FGFR-1 (AdtrFGFR-1). FGF-2 enhanced the growth of all 4 cell lines and activated MAPK in 3 of these cell lines. Infection with the AdtrFGFR-1 virus resulted in abundant expression of the truncated FGFR-1 at the RNA and protein level, markedly attenuated FGF-2-induced proliferation in all 4 tested cell lines, and decreased FGF-2-dependent MAPK activation in the 3 cell lines in which FGF-2 activated this pathway. These findings suggest that FGFR-1-mediated mitogenesis in multiple pancreatic cancer cells can be efficiently blocked with an adenoviral vector encoding a truncated FGFR-1, raising the possibility that AdtrFGFR-1 may ultimately have a therapeutic role in PDAC.

Adenoviridae↗
PubMed2004

Epstein-Barr virus-associated lymphoepithelial carcinoma in the pancreas.

Lymphoepithelial carcinoma is a relatively common malignancy in the nasopharyngeal region, but it rarely occurs at other sites. We report a lymphoepithelial carcinoma in the pancreas of a 65-year-old male patient operated on for a gastric stump carcinoma 7 years previously. The solitary tumor in the pancreas presented as a circumscribed lesion and measured 5.5 cm in diameter. The tumor was densely infiltrated by lymphocytes, and the neoplastic cells fulfilled all criteria for a lymphoepithelial carcinoma. Several peripancreatic lymph node metastases were observed. Marked reactivity for Epstein-Barr virus (EBV) early RNA (EBER) was detected in the majority of tumor cells using in situ hybridization. Nuclear EBER signals were also detected in the previously operated gastric stump adenocarcinoma, which also exhibited focal lymphocytic infiltration but otherwise displayed a histology different from lymphoepithelial carcinoma and did not show local recurrence. Even though an unusually late metastasis of the gastric carcinoma cannot be ruled out, we favor the hypothesis that this patient developed an EBV-related pancreatic lymphoepithelial carcinoma as a second primary tumor, based on the considerable delay of this tumor manifestation, the unusual site, the pathologic presentation, the exclusively peripancreatic nodal spread, and the different histology of the lesion.

Aged↗
PubMed2004

Cartilage oligomeric matrix protein expression in hepatocellular carcinoma and the cirrhotic liver.

BACKGROUND: Cartilage oligomeric matrix protein (COMP) is the fifth member of the thrombospondin family of extracellular, calcium-binding proteins. It was initially isolated and characterized in cartilage tissue, where it is thought to contribute to the extracellular matrix composition and cell-extracellular matrix interaction. In the present study the expression of COMP was investigated in normal liver (n=19), liver cirrhosis (n=14) and hepatocellular carcinoma (HCC; n=16) tissues, both at the mRNA and protein level. METHODS AND RESULTS: By northern blot and western blot analysis, COMP was absent or rarely expressed in the normal liver and liver cirrhosis tissues, but significantly overexpressed in HCC tissue samples. The COMP mRNA overexpression in HCC was not related to the clinical stage or tumor grade. By in situ hybridization and immunohistochemistry analysis, COMP mRNA and protein expression were localized within the cytoplasm of the tumor cells. CONCLUSION: COMP is highly expressed within the tumor cells of HCC, suggesting that COMP might play a role in the pathophysiology of this disease.

Adult↗
PubMed2004

Surgical treatment of oesophageal cancer.

Various reconstructive conduits and routes of reconstruction have an impact on operative morbidity and foregut function in patients undergoing oesophagectomy. Advantages of a fundus rotation gastroplasty are the better blood supply and the greater length of the gastric tube and its possible impact on anastomotic complications. For a subgroup of patients with oesophageal carcinoma limited to the lamina propria vagal-sparing oesophagectomy seems to be a good alternative in terms of quality of life to preserve gastric secretory, motor, and reservoir function. Posterior mediastinal reconstruction is usually preferred when complete resection (R0) has been accomplished. Anterior mediastinal reconstruction may secondary prevent dysphagia after incomplete resections due to tumour recurrence (R0, R1). However, for all presently available surgical approaches in the treatment of oesophageal cancer qualified studies (prospective randomised) are needed. In addition, randomized trials are needed to identify the specific subgroups of patients who benefit from neoadjuvant or adjuvant radiochemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Pathogenesis of pain in chronic pancreatitis.

The pathophysiology of pain in chronic pancreatitis (CP) is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. The existence of different hypotheses to explain the genesis of pain in CP also reflects the different therapeutic approaches to pain in these patients. Increased intraductal pressure as a result of single or multiple strictures and/or calculi is believed to be a common cause of pain in CP patients with a dilated main pancreatic duct. Other suggested causes include pancreatic fibrosis, interstitial hypertension and pancreatic ischemia. Additionally, extrapancreatic causes like duodenal and common bile duct stenosis with scarring due to pancreatic inflammation are suggested as factors causing pain in CP. The 'neurogenic inflammation' hypothesis is a fascinating theory which is supported by different studies. Immunohistological reports have shown that the amount of neurotransmitters, such as substance P and its receptor, calcitonin gene-related peptide and other neurotransmitters, are increased in afferent pancreatic nerves and a correlation between pain and immune cell infiltration of the nerves has been reported in CP. In this review we will discuss the different pain hypotheses and will present the perspective that neuroimmune interaction is an important factor for pain generation in CP.

Animals↗
PubMed2004

Gefitinib ('Iressa', ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits pancreatic cancer cell growth, invasion, and colony formation.

Pancreatic cancer is a devastating malignancy, characterized by low responsiveness to conventional chemotherapies. Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has shown clinical activity against EGFR-expressing tumors. Since pancreatic cancers frequently overexpress EGFR (ErbB-1) and its ligands, our aim was to investigate the potential role of gefitinib in this disease. The GI50 of gefitinib as well as the effects of gefitinib on growth factor actions in pancreatic cancer cell lines were analyzed using MTT assays. FACS analysis using Annexin and propidium iodide (PI) staining were performed to study cell cycle, apoptosis and cell death. Western blot analysis was carried out to investigate expression levels of the 4 members of the ErbB family of receptors in pancreatic cancer cell lines, as well as MAP kinase and EGFR phosphorylation. Soft agar assays were used to measure colony formations. Invasiveness of cancer cells was analyzed using Matrigel-coated filters. gefitinib inhibited cell proliferation of pancreatic cancer cell lines with GI50 concentrations ranging from 2.5 to over 10 micro M. Gefitinib completely inhibited EGF-induced cell proliferation, but did not significantly influence insulin-like growth factor (IGF)-induced mitogenesis. Gefitinib also completely abolished EGF-induced phosphorylation of EGFR and MAP kinase. Furthermore, gefitinib inhibited basal and EGF-induced anchorage-independent cell growth and invasion. Our data demonstrate that gefitinib inhibits pancreatic cancer cell growth through EGFR-dependent pathways. Gefitinib also inhibits anchorage-independent growth and invasiveness, suggesting that gefitinib may offer a new approach for the treatment of pancreatic cancer.

Animals↗
PubMed2003

Cancer cachexia.

In recent years many efforts of researchers and clinicians were made to improve our knowledge of cachexia syndrome. Not only cancer, but also many chronic or end-stage diseases such as AIDS, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, tuberculosis and Crohn's disease are associated with cachexia, a condition of abnormally low weight, weakness, and general bodily decline which deteriorates quality of life and reduces the prognosis of the patients who suffer from it. In the present editorial we will focus cachexia related on cancer and provide some insight into this prognosis-limiting syndrome.

Cachexia↗
PubMed2003

Reverse transcription-PCR analysis of laser-captured cells points to potential paracrine and autocrine actions of neurotrophins in pancreatic cancer.

PURPOSE: Neurotrophins (NTs) can stimulate cell proliferation and differentiation in various cell types, and play a role in certain human cancers. In this study we analyzed the expression and localization of NTs and their receptors in microdissected pancreatic cancer tissue samples, and studied their ability to stimulate cell growth. EXPERIMENTAL DESIGN: The expression of nerve growth factor, brain-derived neurotrophic factor, NT-3, and NT-4/5, and the receptors tropomyosin receptor kinase A, B, and C, and P75 was studied in pancreatic cancer cell lines, and normal and pancreatic ductal adenocarcinoma (PDAC) tissue samples by quantitative reverse transcription-PCR. Laser capture microdissection was performed in 21 PDAC samples, and mRNA levels were determined in cancer cells, acinar cells, desmoplastic stroma areas, and nerve fibers. Cell growth assays with NTs and in coculture with dorsal root ganglia were performed. RESULTS: NT receptors were differentially expressed in the cancer cell lines, whereas tropomyosin receptor kinase C was not detectable. NTs modulated pancreatic cancer cell growth. Analysis of nonmicrodissected samples revealed that all of the receptors and tested ligands were overexpressed in PDAC when compared with normal pancreas. Analysis of laser captured samples revealed that NTs and their receptors were expressed in the cancer cells but were especially abundant in the intratumoral nerves. Coculture of dorsal root ganglia with T3M4 cells significantly enhanced the proliferation of this cell line. CONCLUSION: The abundance of NTs in the intratumoral nerves in PDAC and the presence of NT receptors in the cancer cells, in conjunction with the ability of NTs to modulate pancreatic cancer cell growth, point to potential paracrine and autocrine effects of NTs in PDAC. Thus, our findings provide additional evidence that blocking NT actions may have a therapeutic potential in PDAC.

Adenocarcinoma↗
PubMed2003

Effects of STI571 (gleevec) on pancreatic cancer cell growth.

BACKGROUND: Pancreatic cancer is an aggressive malignancy characterized by low responsiveness to chemotherapy and radiotherapy. This resistance is partly due to the overexpression of several tyrosine kinase receptors and their ligands. STI571 has specific activity in inhibiting c-kit, PDGF and Abl receptor tyrosine kinases and has proven successful in the treatment of CML and GIST patients. Here, we investigated the potential role of STI571 in pancreatic cancer. RESULTS: The GI50 of STI571 as well as the effects of STI571 on growth factor actions in pancreatic cell lines were analyzed using the MTT assay. FACS analysis using Annexin and PI staining was performed to study cell cycle, apoptosis, and cell death. Western blot analysis was carried out to investigate MAP kinase and receptor tyrosine kinase phosphorylation. STI571 inhibited cell proliferation in pancreatic cancer cell lines with GI50 concentrations ranging from 17 to 31.5 microM. EGF, IGF-1, and FGF-2 but not PDGF exerted growth stimulatory effects in pancreatic cancer cell lines. STI571 only partly blocked these effects on cell growth, and did not abrogate growth factor-induced receptor and MAPK phosphorylation. CONCLUSION: Our data demonstrate that STI571 inhibits pancreatic cancer cell growth with high GI50 concentrations through tyrosine-kinase receptor independent pathways. The clinical application of STI571 in pancreatic cancer is therefore rather doubtful.

Antineoplastic Agents↗
PubMed2003

Risk of malignancy in serous cystic neoplasms of the pancreas.

BACKGROUND: In contrast to mucinous cystic neoplasms of the pancreas, which are known to have considerable malignant potential, the serous variant is generally thought to be benign. There are, however, several reports of malignancy in serous cystic neoplasms of the pancreas. AIMS: To assess the risk of malignancy of serous cystic tumors of the pancreas and to investigate specific clinical and histological features. METHODS: Clinical and pathological characteristics of benign and malignant serous cystic neoplasms of the pancreas were investigated by a review of the literature and documented by a case of a serous cystadenocarcinoma and immunohistochemical analysis of a series of serous cystadenomas. Reviewing the literature prevalence, age and sex distribution of serous cystic neoplasms were analyzed. RESULTS: The prevalence of cancer among serous cystic neoplasms reported since 1989 was 3%. Serous cystadenoma of the pancreas present at an earlier age (61 years) than serous cystadenocarcinoma (66 years; p = 0.056) and are symptomatic in the majority of patients. Pathological examination of the primary tumor was not able to distinguish cystadenoma from cystadenocarcinoma in 38% of cases. In 25% the diagnosis of cancer was established only after growth of metachronous metastases. In the present case, nuclear atypia, papillary structures, proliferation marker Ki-67 and p53 protein were increased in the primary tumor and/or metachronous metastasis. CONCLUSION: Serous cystic neoplasms of the pancreas do have malignant potential with a risk of malignancy of 3% and should be surgically treated if the operative risk is acceptable. Routine analysis of genetic and proliferation markers may improve diagnosis of malignancy in these tumors.

Cystadenocarcinoma, Serous↗
PubMed2003

Evidence-based surgery in chronic pancreatitis.

BACKGROUND: In the past two decades our knowledge of the pathophysiology and surgical treatment options in chronic pancreatitis has improved substantially. Surgical treatment in chronic pancreatitis has evolved from extending to organ-preserving procedures. DISCUSSION: The classical Whipple resection is no longer a standard procedure in chronic pancreatitis, and is continuously being replaced by operations such as the duodenum-preserving pancreatic head resection and pylorus-preserving Whipple. These procedures allow the preservation of exocrine and endocrine pancreatic function, provides pain relief in up to 90% of patients, and contributes to an improvement in life quality. CONCLUSIONS: In addition to presently available results from randomized controlled trials, new studies comparing available surgical approaches in chronic pancreatitis are needed to determine which procedure is the most effective in the treating chronic pancreatitis.

Chronic Disease↗
PubMed2003

Invasion and metastasis in pancreatic cancer.

Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate below 1%. The process of cancer initiation, progression and metastasis is still not understood well. Invasion and tumor metastasis are closely related and both occur within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate cell migration, and promote cell proliferation and tumor cell survival. During the last decade considerable progress has been made in understanding genetic alterations of genes involved in local and systemic tumor growth. The most important changes occur in genes which regulate cell cycle progression, extracellular matrix homeostasis and cell migration. Furthermore, there is growing evidence that epigenetic factors including angiogenesis and lymphangiogenesis may participate in the formation of tumor metastasis. In this review we highlight the most important genetic alterations involved in tumor invasion and metastasis and further outline the role of tumor angiogenesis and lymphangiogenesis in systemic tumor dissemination.

Animals↗
PubMed2003

Changes in morbidity after pancreatic resection: toward the end of completion pancreatectomy.

HYPOTHESIS: Advances in specialized centers for pancreatic diseases have improved surgical morbidity and outcome. In the past, postoperative local complications (pancreatic fistulae) were causing most of the mortality. Now, more patients experience postoperative complications related to their comorbidity. DESIGN: To report a prospective audit of a single center's experience with pancreatic resection during an 8-year period. SETTING: Tertiary referral center focused on pancreatic diseases. PATIENTS AND INTERVENTIONS: Six hundred seventeen consecutive patients underwent pancreatectomy between November 1, 1993, and August 31, 2001. The series included 468 pancreatic head resections (76%), 25 total pancreatectomies (4%), 88 left-sided resections (14%), and 36 others (6%). MAIN OUTCOME MEASURES: Morbidity after pancreatic resection. RESULTS: Postoperative in-hospital mortality was 1.6%, and the additional operation rate was 4.1%. Four patients died of surgical complications and 6 of systemic complications. Systemic morbidity was 18% and consisted primarily of cardiopulmonary complications (13%). The most frequent postoperative complication was delayed gastric emptying (14%), which caused significant prolongation of the hospital stay. No patients died of a postoperative pancreatic fistula, which occurred in 3.2%, and no completion pancreatectomies were necessary. CONCLUSIONS: Pancreatic resections can be performed with considerable safety and a low rate of pancreatic complications. More patients die of systemic complications than in the past, which increases the demand for precise preoperative patient selection. Completion pancreatectomy should no longer be considered in patients with a pancreatic fistula.

Adolescent↗
PubMed2003

Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal of all the common malignancies and markers for early detection or targets for treatment of this disease are urgently required. The disease is characterised by a strong stromal response, with cancer cells usually representing a relatively small proportion of the cells in the tumor mass. We therefore performed laser capture microdissection (LCM) to enrich for both normal and malignant pancreatic ductal epithelial cells. Proteins extracted from these cells were then separated by two-dimensional gel electrophoresis (2-DE). The limited amounts of protein in the LCM procured samples necessitated the detection of 2-DE resolved proteins by silver staining. Consequently, loading equivalent amounts of protein onto gels was essential. However, we found that conventional means of measuring total protein in the samples were not sufficiently accurate. We therefore adopted a strategy in which the samples were first separated by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis, stained with silver stain and subjected to densitometry. Evaluation of the staining intensity was then used to normalise the samples. We found that the protein profiles from undissected normal pancreas and LCM-acquired non-malignant ductal epithelial cells from the same tissue block were different, underpinning the value of LCM in our analysis. The comparisons of protein profiles from nonmalignant and malignant ductal epithelial cells revealed nine protein spots that were consistently differentially regulated. Five of these proteins showed increased expression in tumor cells while four showed diminished expression in these cells. One of the proteins displaying enhanced expression in tumor cells was identified as the calcium-binding protein, S100A6. To determine the incidence of S100A6 overexpression in pancreatic cancer, we carried out immunohistochemical analysis on sections from a pancreas cancer tissue array containing 174 duplicate normal and malignant pancreatic tissue samples, from 46 pancreas cancer patients. Normal pancreatic ductal epithelia were either devoid of detectable S100A6 or showed weak expression only. Moderately or poorly differentiated tumors, by contrast, showed a higher incidence and a higher level of S100A6 expression. These observations indicate that the combination of LCM with 2-DE provides an effective strategy to discover proteins that are differentially expressed in PDAC.

Annexin A3↗