Biomedical subjects

H Friess

Publications and source records attributed to H Friess.

At least 109 records · Page 6Linked to original sources

PubMed2001

Increased expression of glutathione S-transferase-pi in the islets of patients with primary chronic pancreatitis but not secondary chronic pancreatitis.

The mechanism of tissue alteration in chronic pancreatitis (CP) is still unclear. Different hypotheses have been discussed, including increasing oxidant stress in the acinar cells, often as a result of exposure to xenobiotics. To evaluate the role of oxidative stress in CP, the authors investigated the expression of the drug-metabolizing phase II enzyme, glutathione S-transferase-pi (GST-pi), in the pancreatic tissue of patients with CP and compared it with the healthy pancreatic tissue from age-matched donors. Pancreatic tissue from patients with secondary CP resulting from ductal obstruction by pancreatic cancer (PC) was also examined. The percentage of cells immunoreacting with anti-GST-pi was counted within 15 randomly selected islets in each slide of the three groups. In all specimens, ductal and ductular cells, and in PC, cancer cells, expressed GST-pi in a moderate intensity. Acinar cells did not stain. Various numbers of islet cells in each of the three groups were stained strongly. More islet cells expressed GST-pi in CP (42%) than in healthy pancreatic tissue (16%, p < 0.001) or PC (17%, p < 0.001). Our results imply an important role of islet cells in the metabolism of substances, which are the substrate for GST-pi, and lend support to the hypothesis of oxidative stress as the cause of CP.

Antibodies, Monoclonal↗

PubMed2001

Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer.

INTRODUCTION: ZO-1 is a tight junction membrane protein that plays a critical role in cell-cell interaction, proliferation, and differ entiation. AIM: To localize and evaluate the expression of ZO-1 in the normal human pancreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP). METHODOLOGY AND RESULTS: Northern and Western blot analysis revealed ZO-1 expression in all six tested pancreatic cancer cell lines. Expression of ZO-1 mRNA was increased sixfold in PDAC samples in comparison with normal samples (p = 0.04). Confocal microscopy revealed the presence of ZO-1 in the apical and apicolateral areas of ductular cells in the normal pancreas. Similarly, in CP, ZO-1 was localized at apical and apicolateral areas of small proliferating ductular cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed irrespective of whether the cancer cells formed duct-like structures or exhibited a diffuse infiltrating pattern. Metastatic pancreatic cancer cells within lymph nodes displayed variable staining patterns, ranging from apical and apicolateral to a diffuse membranous staining. CONCLUSION: These observations suggest that ZO-1 is overexpressed in PDAC and raise the possibility that this overexpression may confer a metastatic advantage to pancreatic cancer cells.

Adult↗

PubMed2001

Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumour worldwide, and its differential diagnosis from benign lesions of the liver is often difficult yet of great clinical importance. In the present study, we analysed whether glypican-3 is useful in differentiating between benign and malignant liver diseases and whether it influences the growth behaviour of HCC. METHODS: Northern blot analysis and in situ hybridisation. RESULTS: Northern blot analysis indicated that expression of glypican-3 mRNA was either low or absent in normal liver, in focal nodular hyperplasia (FNH), and in liver cirrhosis. In contrast, expression of glypican-3 mRNA was markedly increased in 20 of 30 and moderately increased in five of 30 HCC samples. The average increase in glypican-3 mRNA expression in HCC was significant compared with expression in normal liver (21.7-fold increase, p<0.01). In comparison with FNH or liver cirrhosis, glypican-3 mRNA expression in HCC was increased 7.2- (p<0.05) and 10.8-fold (p<0.01), respectively. In addition, pushing HCCs exhibited significantly higher glypican-3 mRNA expression than invading tumours (p<0.05). In situ hybridisation analysis demonstrated weak expression of glypican-3 mRNA in normal hepatocytes and bile ductular cells, and weak to occasionally moderate signals in hepatocytes forming nodules of liver cirrhosis and in regenerated hepatic nodules of FNH. In contrast, glypican-3 in situ hybridisation signals were intense in hepatic cancer cells with even higher levels in pushing HCCs than in invading HCCs. CONCLUSIONS: These findings suggest that glypican-3, in many cases, has the potential to differentiate between benign and malignant liver diseases.

Adult↗

PubMed2001

Cyclooxygenase 2 expression in chronic pancreatitis: correlation with stage of the disease and diabetes mellitus.

BACKGROUND: Fibrotic replacement of the exocrine pancreatic parenchyma and infiltration of inflammatory cells are the main characteristics of chronic pancreatitis (CP). Inflammation involves prostaglandin production in numerous inflammatory and noninflammatory cells, and cyclooxygenase 2 (COX-2) is the dominant regulator of prostaglandin synthesis. AIMS: In the present study, we analyzed the expression of COX-2, the key enzyme for prostaglandin synthesis in pancreatic tissues, and evaluated its relation to exocrine and endocrine tissue alterations in CP. PATIENTS AND METHODS: Pancreatic tissue specimens from 27 patients undergoing pancreatic head resection for CP were included in the study. Pancreatic tissues from 14 organ donors served as controls. The tissue specimens were analyzed histopathologically and for COX-2 immunoreactivity. RESULTS: In normal pancreatic tissue samples, COX-2 immunoreactivity was restricted to islet cells. In contrast, in early-stage CP, islets as well as ductal cells showed intense COX-2 immunoreactivity. In advanced-stage CP, ductal cells were still strongly positive for COX-2, yet islets displayed a variable COX-2 staining pattern which was associated with the distribution of insulin-positive cells and with the clinical diabetes mellitus status of the patient. Thus, patients with normal or latent diabetes mellitus status showed COX-2 immunoreactivity, whereas in diabetic patients the COX-2 immunoreactivity was decreased or absent in pancreatic islets. CONCLUSION: The presence of COX-2 in ductal cells of early and advanced CP, the relationship between COX-2 and insulin expression in the islets, and the diabetes mellitus status of CP patients suggest that this enzyme plays a role in the pathogenesis of exocrine and endocrine damage in CP.

Adult↗

PubMed2001

A modified technique of the Beger and Frey procedure in patients with chronic pancreatitis.

BACKGROUND: Resection of the pancreas requires control of tributaries of the superior mesenteric vein (SMV) inferior to the head of the pancreas as well as separation of the posterior surface of the pancreas from the SMV and from eventually existing collateral veins. This usually is the most tedious part when performing a resection of the pancreatic head, in particular if there are signs of portal hypertension. Portal vein pathology contributes to intra- and postoperative morbidity in pancreatic surgery. OPERATIVE TECHNIQUE: Instead of dissecting the pancreas along the anterior surface of the SMV our proposed technique allows resection of the head of the pancreas without division of the gland. This approach combines elements of Beger's duodenum-preserving pancreatic head resection and of Frey's limited local pancreatic head excision combined with a longitudinal pancreaticojejunostomy. This modified technique avoids the risk of a bleeding complication which is increased in the presence of portal hypertension and dilation. SUMMARY: The advantages of this modified technique over standard Beger and Frey procedures are: (1) the minimized risk of a bleeding complication in case of portal hypertension because pancreatic transsection does not need to be done, and (2) the considerably more radical excision as compared to local excision. Also, it represents the most minimal surgical trauma for resecting the head of the pancreas as compared to other commonly used techniques.

Anastomosis, Surgical↗

PubMed2001

Problems of reconstruction during pancreatoduodenectomy.

Pancreatoduodenectomy may be a difficult operation, not only during the resectional part of the procedure, but also during reconstruction. Usually, these problems are due to local conditions of the organs/tissues, such as small diameter of the common bile duct or pancreatic duct, friable soft pancreas, vascular anomalies, etc. Reconstruction may also be problematic because of the hemodynamic instability of the patient during surgery (subsequent to massive hemorrhage), and in those unusual cases, delayed reconstruction may be a life-saving, wise choice.

Anastomosis, Surgical↗

PubMed2001

Treatment of pancreatic cancer: the role of surgery.

Pancreatic cancer shows an aggressive growth behavior which results in an extremely poor prognosis. It is presently the 4th to 5th leading cause of cancer-related deaths in Western countries with an incidence of 8-10 new cases per 100,000 inhabitants. Since current conservative oncological therapies fail to influence the long-term outcome, curative resection remains the only possibility with a potential for cure. During the past decades, a considerable decrease in postoperative mortality after pancreatic resection and a significant increase in the resection rate have been achieved. Although several types of pancreatic resection have evolved, standard procedures are the classical Whipple resection for cancers of the pancreatic head and left resection for cancers of pancreatic body and tail. Since the pylorus-preserving Whipple resection and extended Whipple resection are still debated as better alternatives to the classical Whipple procedure, large, controlled clinical trials in patients need to be conducted to reach reliable conclusions. However, there is mounting evidence that the pylorus-preserving Whipple procedure offers a better postoperative outcome than the classical Whipple operation without compromising radicality and thereby the long-term prognosis. Despite the progress in surgical treatment of pancreatic cancer, the overall prognosis following resection remains unsatisfactory to date. It is hoped that progress in multimodality treatment and modern therapies, resulting from both clinical and advanced basic research, can improve the prognosis of this malignancy in the near future.

Combined Modality Therapy↗

PubMed2001

Activity of gemcitabine and continuous infusion fluorouracil in advanced pancreatic cancer.

BACKGROUND/OBJECTIVES: Gemcitabine has been shown to improve survival and quality of life parameters compared to fluorouracil alone in advanced pancreatic cancer [J Clin Oncol 1997;15:2403-2413]. However, fluorouracil was given as a weekly bolus in that study and other administration schedules might be more effective. The objective of this trial was to determine the activity and toxicity of gemcitabine in combination with continuous infusion (CI) fluorouracil in advanced pancreatic cancer. PATIENTS AND METHODS: Chemotherapy-naïve patients with measurable advanced adenocarcinoma of the pancreas were treated with gemcitabine 1,000 mg/m(2) intravenously weekly x 3 followed by 1 week of rest every 4 weeks and 200 mg/m(2)/day CI fluorouracil until disease progression or limiting toxicity. RESULTS: Twenty-five patients were evaluable for response and toxicity. Objective partial responses were documented in 5 patients (20%; 95% confidence interval 6.8-40.7%) and disease stabilization or minor responses in 13 patients (52%; 31.3-72.2%). Toxicity was mild with grade 2/3 leucopenia in 26%, stomatitis in 15%, nausea in 6%, diarrhea in 3%, and hand-foot syndrome in 2% of the treatment cycles. In 3 patients a catheter thrombus occurred and in 1 patient the treatment had to be stopped due to asthenia. The performance status improved in 39% of the patients and 65% benefitted in terms of a decrease in pain intensity or consumption of analgesics. CONCLUSION: This phase II trial confirms a significant antitumor activity and a beneficial clinical effect of gemcitabine plus CI fluorouracil in advanced pancreatic cancer. The combination is well tolerated and it will have to be shown whether oral fluoropyrimidines can increase the practicability of this treatment without impairing efficacy.

Adenocarcinoma↗

PubMed2001

Abnormal differentiation of islet cells in pancreatic cancer.

Pancreatic cancer in many patients is associated with altered glucose metabolism and abnormalities in pancreatic islet hormones at serum and tissue levels. Our previous studies have indicated a tendency of islet cells to differentiate toward ductal cell lineage, but the specificity of these findings for pancreatic cancer was not investigated. In the present study, we examined the immunoreactivity of pancreatic islets to antibodies against tumor-associated antigens DU-PAN-2, TAG-72 and CA19-9 in tissues from the normal pancreas, chronic pancreatitis and pancreatic cancer. Although no immunoreactive islet cells were found in the 12 normal pancreases and 20 chronic pancreatitis patients, 25 of 37 pancreatic cancer tissues showed the expression of these antigens, primarily CA19-9 and TAG-72, where the number of immunoreactive cells varied considerably from case to case. In 4 cases over 50% and in 2 of them more than 75% of the islets showed positive staining of 60-70% of islet cells within each islet. The presence of intrainsular ductular structures expressing the same antigen as the surrounding islet cells suggested transformation of antigen expressing islet cells to ductal cells. All but four islets were within or around the cancer favoring the notion that factors produced by cancer cells are responsible for the altered islet cell differentiation.

Antigens, Neoplasm↗

PubMed2001

Co-existent chronic pancreatitis and pancreatic neuroendocrine tumor. Case report and review of the literature.

BACKGROUND: Few reports exist in the literature regarding neuroendocrine tumors either presenting as, or associated with, chronic pancreatitis. We report a case of chronic pancreatitis with a coexisting neuroendocrine tumor (gastrinoma) of the body of the pancreas. The available literature is reviewed. METHODS: Patient data including history, surgical procedure, histology and radiology investigations were collected and summarized. A Medline search using the key words 'pancreatitis' and 'neuroendocrine tumors' was performed for the years 1966-1999. Cited references in the relevant papers not listed in Medline databases were also evaluated. RESULTS: A 64-year-old female patient was operated on for unclear cystic lesions in the head and tail of the pancreas. Intraoperatively, a gastrinoma was incidentally discovered in the body of the pancreas. It did not appear to be obstructing the main pancreatic duct. The patient underwent a distal pancreatectomy with pancreatico-jejunostomy. Four months postoperatively, she is doing well with no signs of tumor recurrence. The Medline search revealed 125 publications, of which only 17 dealt with either acute or chronic pancreatitis associated with neuroendocrine tumors. When all available data were included, there were 26 cases of neuroendocrine tumors associated with acute pancreatitis. Additionally, 11 cases were associated with chronic pancreatitis, of which only 3 appear to be merely coexistent with chronic pancreatitis without an apparent cause-and-effect relationship between these two entities. CONCLUSION: We report the rare co-existence of chronic pancreatitis and a neuroendocrine tumor (gastrinoma) of the pancreas. The cause-and-effect relationship between neuroendocrine tumors of the pancreas and chronic pancreatitis continues to be uncertain. However, when the etiology of chronic pancreatitis is unclear, rare neuroendocrine tumors of the pancreas might be considered. Questions remain with regard to the potential role of chronic pancreatitis in the pathogenesis of pancreatic neuroendocrine tumors.

Carcinoma, Neuroendocrine↗

PubMed2001

Growth factors in pancreatic health and disease.

In this article the role of different growth factors and their receptors in the pathogenesis of chronic pancreatitis and pancreatic cancer is discussed. The expression of members of the epidermal growth factor family, the fibroblast growth factor family, the transforming growth factor-beta family, the platelet-derived growth factor family, the nerve growth factor family, the insulin-like growth factor family and their signaling receptors is presented, and a correlation of the molecular data with clinical and pathological changes is performed. A number of these growth factors and their receptors are markedly overexpressed in chronic pancreatitis and pancreatic cancer. In chronic pancreatitis, overexpression of growth factors and their receptors contributes to tissue remodeling and fibrogenesis. In contrast to chronic pancreatitis, pancreatic cancer is associated with a variety of genetic alterations, including mutations in tumor suppressor genes and cell cycle regulators. In the presence of these genetic disturbances, enhanced expression of growth factors and their receptors contributes to cell proliferation and enhances the aggressiveness of pancreatic cancer cells. In summary, growth factors and their receptors are often altered in chronic pancreatitis and pancreatic cancer and contribute to various pathogenetic aspects in these disorders.

Animals↗

PubMed2001

Pancreatic cancer: factors regulating tumor development, maintenance and metastasis.

Pancreatic cancer has one of the poorest prognoses of all gastrointestinal malignancies. Today, it is the fourth or fifth leading cause of cancer-related deaths in Western industrialized countries, and the incidence has been increasing throughout the past decades. Insensitivity to growth-inhibitory and apoptotic signals as well as self-sufficiency of growth-promoting factors are hallmarks of the pathogenesis of this malignancy. In pancreatic cancer, a variety of growth factors and their receptors are expressed at increased levels. For example, the concomitant presence of the epidermal growth factor (EGF) receptor and its ligand EGF is associated with enhanced tumor aggressiveness and shorter survival following tumor resection. Furthermore, a number of other growth factors and their receptors, such as nerve growth factor and its receptor, are overexpressed in pancreatic cancer and contribute to its malignant phenotype. Besides factors which directly promote cell proliferation, a variety of other factors such as galectins are upregulated, which influences the tumor environment and the invasiveness of pancreatic cancer cells. In addition, tumor suppressor genes such as KAI1 are expressed at reduced levels, thereby enhancing the ability of pancreatic cells to form metastases. A complex disturbance of factors is present in pancreatic cancer, resulting in a distinct growth advantage which clinically results in rapid tumor progression and poor patient survival.

Genes, Tumor Suppressor↗

PubMed2001

Timing and extent of surgical intervention in patients from hereditary pancreatic cancer kindreds.

Our knowledge of the molecular and genetic etiology of hereditary pancreatic cancer has expanded considerably and is steadily increasing. However, there are only a few hard data available regarding the clinical and surgical management of these patients. Surgery is currently performed when we detect dysplastic changes in the pancreas or when cancer is suspected. Of the available diagnostic modalities, endoscopic ultrasonography has proven so far to be the most useful for detecting dysplastic changes in the pancreases of patients from hereditary pancreatic cancer kindreds. It seems reasonable, once dysplasia has been diagnosed in a high-risk patient, to proceed to total pancreatectomy. The multifocal nature of dysplastic lesions precludes any type of operation that would leave behind pancreatic tissue. Currently, prophylactic whole-organ resection in the absence of premalignant lesions cannot be recommended since we do not know the exact risk for the development of cancer.

Humans↗

PubMed2001

Comparative analysis of galectins in primary tumors and tumor metastasis in human pancreatic cancer.

Galectins are galactoside-binding proteins that exhibit an important function in tumor progression by promoting cancer cell invasion and metastasis formation. Using Northern blotting and Western blotting analysis, in situ hybridization (ISH), and immunohistochemistry (IHC), we studied galectin-1 and galectin-3 in tissue samples of 33 primary pancreatic cancers and in tumor metastases in comparison to 28 normal pancreases. Furthermore, the molecular findings were correlated with the clinical and histopathological parameters of the patients. Northern blotting and Western blotting analysis showed significantly higher galectin-1 and galectin-3 mRNA and protein levels in pancreatic cancer samples than in normal controls. For galectin-1, no ISH signals and immunoreactivity were observed in acinar or ductal cells in the normal pancreas and in pancreatic cancer cells, whereas fibroblasts and extracellular matrix cells around the cancer mass exhibited strong mRNA signals and immunoreactivity. Galectin-3 mRNA signals and immunoreactivity were strongly present in most pancreatic cancer cells, whereas in the normal controls only faint ISH and IHC signals were seen in some ductal cells. Metastatic pancreatic cancer cells exhibited moderate to strong galectin-3 immunoreactivity but were negative for galectin-1. No relationship between the galectin-1 and galectin-3 mRNA levels and the tumor stage or between the IHC staining score and the tumor stage was found. However, galectin-1 mRNA levels and the IHC staining score were significantly higher in poorly differentiated tumors compared with well/moderately differentiated tumors, whereas for galectin 3 no differences were found. The expression pattern of galectin-1 and galectin-3 in pancreatic cancer tissues indicates that galectin-1 plays a role in the desmoplastic reaction that occurrs around pancreatic cancer cells, whereas galectin-3 appears to be involved in cancer cell proliferation. High levels of galectin-3 in metastatic cancer cells suggest an impact on metastasis formation.

Adenocarcinoma↗

PubMed2001

Expression of nerve growth factors in pancreatic neural tissue and pancreatic cancer.

One of the characteristics of pancreatic cancer is its tendency to invade neural tissue. We hypothesized that the affinity of cancer cells for nerve tissue is related to the presence of growth factors in neural tissue and their receptors in cancer cells. Sections of pancreatic cancer and normal pancreatic tissue were examined by immunohistochemistry for the expression of the neurotrophins NGF, BDNF, NT-3, NT-4, and their receptors TrkA, TrkB, and TrkC, as well as the low-affinity receptor, p75NTR. TrkA expression was found in duct, islet, and cancer cells; TrkB was found in the alpha-cells of the islet only. The anti-pan-Trk antibody (TrkB3), which is presumed to recognize all three receptors, immunoreacted with duct and acinar cells in normal tissue and with cancer cells. The staining with TrkC was similar to that of TrkA. The low-affinity receptor p75NTR was expressed in the neural tissue and in scattered duct cells of the normal tissue only. Duct and acinar cells, as well as neural tissue and cancer cells, showed weak to strong immunoreactivity with NGF. NT-3 expression was noted in capillary endothelia and erythrocytes. NT-4 showed specific staining for ductule cells. The expression and distribution of neurotrophins and their receptors suggest their role in the potential of pancreatic cancer cells for neural invasion.

Humans↗

PubMed2001

Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells.

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription-PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa-2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time-dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy.

Blotting, Western↗

PubMed2001

Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance.

PURPOSE: Mucins are important biomolecules that frequently display an altered expression under pathological conditions. In a search for a unique and reliable marker(s) specific for pancreatic adenocarcinoma, we investigated the expression of different MUC genes in pancreatic tumors and tumor cell lines, in chronic pancreatitis, and in the normal pancreas. EXPERIMENTAL DESIGN: Total RNA from 16 pancreatic tumors, 10 chronic pancreatitis tissues, 7 normal pancreas tissues, and 15 pancreatic tumor cell lines were analyzed by reverse transcription-PCR with primers specific for MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes and by RNA slot blot analyses. RESULTS: Our results revealed that of all of the mucins examined, only MUC4 displayed a differential expression that was specific for pancreatic adenocarcinoma. Indeed, a substantial number of tumor tissue samples (12 of 16) and tumor cell lines (11 of 15) expressed MUC4 mRNA, whereas samples from chronic pancreatitis (0 of 10) and the normal pancreas (0 of 7) tissues failed to exhibit any detectable level of this mucin. In contrast, no significant alteration was observed in the expression of the other mucins relative to that in the normal pancreas samples. CONCLUSIONS: Overall, this work demonstrates that pancreatic mucin MUC4 is a tumor-associated mucin. Furthermore, the present study introduces a novel avenue to discriminate between pancreatic adenocarcinoma and pancreatitis. Future investigations of the role played by MUC4 in pancreatic adenocarcinoma may prove to be useful in the formulation of strategies for the diagnosis and therapeutic treatment of this malignancy.

Adenocarcinoma↗

PubMed2000

IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells.

IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene alpha (GROalpha). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROalpha mRNA and protein. Combination of IL-17 together with TNF-alpha resulted in an increased stability of GROalpha mRNA and synergistic release of GROalpha protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.

Animals↗