PubMed Health⌕ Search

Biomedical subjects

Helmut Friess

Publications and source records attributed to Helmut Friess.

At least 37 records · Page 2Linked to original sources
PubMed2003

Gene-expression analysis of single cells-nested polymerase chain reaction after laser microdissection.

AIM: The structural and functional characteristics of cells are dependent on the specific gene expression profile. The ability to study and compare gene expression at the cellular level will therefore provide valuable insights into cell physiology and pathophysiology. METHODS: Individual cells were isolated from frozen colon tissue sections using laser microdissection. DNA as well as RNA were extracted, and total RNA was reversely transcribed to complementary DNA (cDNA). Both DNA and cDNA were analyzed by nested polymerase chain reaction (PCR). The quality of isolated DNA and RNA was satisfactory. RESULTS: Single cells were successfully microdissected using an ultraviolet laser micromanipulator. Nested PCR amplification products of DNA and cDNA of single cells could clearly be visualized by agarose gel electrophoresis. CONCLUSION: The combined use of laser microdissection and nested-PCR provides an opportunity to analyze gene expression in single cells. This method allows the analysis and identification of specific genes which are involved in physiological and pathophysiological processes in a complex of variable cell phenotypes.

Colon↗
PubMed2003

[Gene expression analysis in liver tissue at a single cell level by nested polymerase chain reaction and laser microdissection].

OBJECTIVE: To investigate the measurements of gene expressing at a single hepatocyte level. METHODS: Individual hepatocyte was isolated from cryostat tissue section using laser microdissection technique. To detect the mRNA expressed by single hepatocyte, RNA was extracted, reversely transcribed to cDNA and amplified by nested polymerase chain reaction (PCR). RESULTS: Single cell was microdissected from cryostat tissue using an ultraviolet laser micromanipulator. The RNA could be extracted from the isolated cell(s), and the RT-PCR production could be observed after electrophoresis, whose quantitation was compatible with the number of cells. CONCLUSION: Combining laser microdissection and nested RT-PCR can monitor gene expression at a single cell level in vivo.

Dissection↗
PubMed2003

Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.

PURPOSE: Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer. EXPERIMENTAL DESIGN: STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry. RESULTS: STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2-10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors. CONCLUSIONS: These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis.

Aged↗
PubMed2003

[Preferential expression of cartilage oligomeric matrix protein in degenerating acinar cells in chronic pancreatitis and in chronic pancreatitis-like lesions].

OBJECTIVES: To study cartilage oligomeric matrix protein (COMP) mRNA and protein expression in normal pancreas, chronic pancreatitis (CP), and pancreatic cancer tissues. METHODS: Tissues from 15 cases of normal pancreas, 14 cases of chronic pancreatitis and 14 cases of pancreatic cancer were analyzed by Northern blot, Western blot, in situ hybridization and immunohistochemistry. RESULTS: COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. CONCLUSION: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this molecular in acinar cell dysfunction in CP.

Blotting, Northern↗
PubMed2002

Splenic tissue autotransplantation in rabbits: no restoration of host defense.

BACKGROUND: The loss of spleen may increase the incidence of overwhelming sepsis. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the effectiveness of regenerated splenic tissue in preventing infection. This study explored the effectiveness of splenic tissue autotransplantation in restoring host defense. MATERIALS AND METHODS: Rabbits were divided into three groups: splenic autotransplantation, sham operation, and total splenectomy. Histomorphology, T-lymphocyte count, serum lysozyme levels, hemolysin titers, and pneumococcal clearance were observed as read-out parameters over 24 weeks. RESULTS: Histological study showed that the white pulp was poorly developed and central arterioles were missing in the regenerated splenic tissue of the autotransplanted rabbits. The weight of regenerated spleens recovered 6 months later in the splenic autotransplantation group was 11% of that in the sham operation group and was significantly less than the weight at implantation. There was no significant difference in the number of T lymphocytes or level of serum lysozyme between the three groups. A poor antibody response by the rabbits in the splenic autotransplantation and total splenectomy groups was noted after the primary intravenous administration of sheep red blood cells compared to those of sham operation group. After the challenge with type 3 pneumococci intravenously, pneumococcal clearance from the bloodstream in the splenic autotransplantation group did not differ significantly from that in the total splenectomy group, but was markedly delayed compared with that in the sham operation group. CONCLUSIONS: The low quantity and poor quality of the regenerated splenic tissue contribute to the inferior immunoprotective ability of animals autotransplanted with one-third of the original spleen. This suggests that the regenerated spleen cannot compensate for the immunological function of the original one, especially host resistance to infection.

Animals↗
PubMed2002

Induction and expression of betaig-h3 in pancreatic cancer cells.

betaig-h3 (TGFBI, keratoepithelin) was first identified as a transforming growth factor-beta1 (TGF-beta1)-inducible gene in a human lung adenocarcinoma cell line. It encodes for a secreted extracellular matrix (ECM) protein, which is thought to act on cell attachment and ECM composition. Mutations of the betaig-h3 gene are involved in several corneal dystrophies. Pancreatic cancers display multiple alterations in the TGF-beta signaling pathway and in TGF-beta response genes, such as overexpression of all three TGF-beta isoforms and Smad4 mutations. In this report, we determined that betaig-h3 mRNA levels were induced by TGF-beta1 in two out of five examined pancreatic cancer cell lines (CAPAN-1, PANC-1). In CAPAN-1 cells, which harbor a Smad4 mutation, betaig-h3 but not PAI-1 was induced by TGF-beta1, whereas in PANC-1 cells that express wild-type Smad4, TGF-beta1 induced both PAI-1 and betaig-h3. In human pancreatic tissues, there was a 32.4-fold increase in betaig-h3 mRNA levels in pancreatic cancers in comparison to normal control tissues. In situ hybridization analysis revealed that betaig-h3 mRNA was expressed mainly in the cancer cells within the pancreatic tumor mass. These findings suggest that betaig-h3 is induced by TGF-betas in pancreatic cancer cells even in the presence of Smad4 mutations, which might explain, in part, the increased betaig-h3 mRNA levels observed in pancreatic cancer cells in vivo.

Adolescent↗
PubMed2002

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer.

The arylhydrocarbon receptor (AhR) was initially identified as a member of the adaptive metabolic and toxic response pathway to polycyclic aromatic hydrocarbons and to halogenated dibenzo-p-dioxins and dibenzofurans. In the present study, we sought to determine the functional significance of the AhR pathway in pancreatic carcinogenesis. AhR expression was analysed by Northern blotting. The exact site of AhR expression was analysed by in situ hybridization and immunohistochemistry. The effects of TCDD and four selective AhR agonists on pancreatic cancer cell lines were investigated by growth assays, apoptosis assays, and induction of the cyclin-dependent kinase inhibitor p21. There was strong AhR mRNA expression in 14 out of 15 pancreatic cancer samples, weak expression in chronic pancreatitis tissues, and faint expression in all normal pancreata. In pancreatic cancer tissues, AhR mRNA and protein expression were localized in the cytoplasm of pancreatic cancer cells. TCDD and the four AhR agonists inhibited pancreatic cancer cell growth in a dose-dependent manner, and decreased anchorage-independent cell growth. DAPI staining did not reveal nuclear fragmentation and CYP1A1 and was not induced by TCDD and AhR agonists. In contrast, TCDD and AhR agonists induced the expression of the cyclin-dependent kinase inhibitor p21. In conclusion, the relatively non-toxic AhR agonists caused growth inhibition in pancreatic cancer cells with high AhR expression levels via cell cycle arrest. In addition, almost all human pancreatic cancer tissues expressed this receptor at high levels, suggesting that these or related compounds may play a role in the therapy of pancreatic cancer in the future.

Adenocarcinoma↗
PubMed2002

Overexpression of Bax sensitizes human pancreatic cancer cells to apoptosis induced by chemotherapeutic agents.

PURPOSE: Bax plays an important role in the regulation of apoptosis induced by chemotherapy and other stimuli. We therefore investigated the role of Bax in drug-induced apoptosis in human pancreatic cancer cells. METHOD: A tetracycline-inducible retroviral expression vector bearing the human bax-alpha gene was constructed. ASPC-1 cells were stably infected with this vector. The sensitivity of the transformed cell line to gemcitabine and 5-Fu was assessed. RESULTS: Western blots revealed that Bax expression was enhanced in these cells by the tetracycline analogue doxycycline. Enhanced expression of Bax itself did not inhibit the growth rate of infected cells and did not influence expression of Bcl-2 and Bcl-xL. However, it significantly increased the sensitivity of cells to the chemotherapeutic drugs gemcitabine and 5-Fu. These drugs also activated caspase-8 and caspase-3 by up to ninefold. Caspase activation and/or an imbalance in Bax and Bcl-2/Bcl-xL expression may be the reasons for the augmentation of cytotoxicity by these drugs. CONCLUSIONS: The findings suggest that enhanced Bax expression may have therapeutic application in enhancing the efficacy of chemotherapy in pancreatic cancers.

Anti-Bacterial Agents↗
PubMed2002

Connective tissue growth factor gene expression alters tumor progression in esophageal cancer.

The ability of cancer cells to initiate specific fibroblast reactions may subsequently determine tumor evolution. In the present study we examined the coordinated expression of transforming growth factor-beta-1 (TGF-beta1), its signaling receptors, and its downstream mediator-connective tissue growth factor (CTGF)--and their impact on tumor progression and fibrogenesis in esophageal carcinomas. Messenger ribonucleic acid (mRNA) expression of TGF-beta1, CTGF, TGF-beta receptor subtype I ALK5 (TbetaR-IALK5), and TGF-beta receptor type II (TbetaR-II) was studied by Northern blot analysis in esophageal cancer and the normal esophagus. By means of immunohistochemistry and Western blot analysis, the respective proteins were localized in the tissue samples and the protein content was quantitated. Northern blot analysis revealed 3-fold and 4-fold increases (p < 0.05) in TGF-beta1 and CTGF mRNA levels, respectively, in esophageal cancer in comparison with normal controls, whereas TbetaR-I mRNA levels were significantly decreased and TbetaR-II mRNA levels were unchanged in the cancer samples. Immunostaining revealed results similar to those seen on the RNA level. TGF-beta1 and CTGF immunoreactivity were increased, TbetaR-II was unchanged, and TbetaR-IALK5 immunoreactivity was decreased. CTGF immunoreactivity was mainly present in the stroma surrounding the cancer cells but was also present in the cancer cells. The degree of fibrosis was different in squamous and adenocarcinomas and was significantly related to CTGF mRNA expression levels. The presence of CTGF in squamous cell carcinomas was associated with longer survival, whereas in adenocarcinomas it influenced survival negatively. The findings indicate that TGF-beta signaling is disturbed in esophageal cancer. CTGF, a downstream effector of TGF-beta action, differentially influences the composition of tumor microenvironment and distinct cell-matrix interactions in the two histological types of esophageal carcinoma, resulting in differences in tumor progression and patient survival.

Adenocarcinoma↗
PubMed2002

DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer.

To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis.

Adult↗
PubMed2002

Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma.

BACKGROUND: Lamps and Mac-2-BP are ligands of galectin-3, and they were suggested to influence tumor proliferation and metastasis formation. The authors studied the expression of Lamp-1, Lamp-2, and Mac-2-BP in pancreatic carcinoma and evaluated their influence on patient prognosis. METHODS: Northern blot analysis, in situ hybridization, and immunohistochemistry were performed in 12 normal and 28 pancreatic carcinoma tissue samples and in pancreatic carcinoma cell lines. The molecular findings in the tumor samples were correlated with the prognosis and histopathologic tumor characteristics. In addition, in Lamp-1 transfected CAPAN-1 pancreatic carcinoma cells, cell proliferation was analyzed. RESULTS: Lamp-1, Lamp-2, and Mac-2-BP were overexpressed in 61% (1.6-fold increase, not significant), 71% (3.0-fold increase, P < 0.01), and 93% (5.6-fold increase, P < 0.01) of the pancreatic carcinoma samples. Lamp-1 and Lamp-2 immunoreactivity was present at the luminal side of the ductal carcinoma cells whereas Mac-2-BP immunoreactivity was diffusely spread over the whole cytoplasm and the nucleolus of ductal carcinoma cells. Correlation of the molecular data with clinical patient parameters revealed that patients whose tumors exhibited high Lamp-1 mRNA expression lived significantly longer (median, 17 months) after tumor resection than patients whose tumors exhibited low to moderate Lamp-1 mRNA levels (median, 8 months; P < 0.02). No relation between Lamp-2 and Mac-2-BP mRNA expression and any of the histopathologic parameters was found. Lamp-1 transfected CAPAN-1 cells showed decreased cell growth compared with the nontransfected cells. CONCLUSIONS: Lamp-1 might influence local tumor progression rather than the formation of tumor metastasis in pancreatic carcinoma, whereas Mac-2-BP and Lamp-2 seem to have little influence on these parameters in pancreatic carcinoma.

Aged↗
PubMed2002

Adhesion molecules in human pancreatic cancer.

BACKGROUND AND OBJECTIVES: Adhesion molecules are cell surface glycoproteins that are important in cell-to-cell and cell-to-extracellular matrix interactions. In the present study, we analyzed the adhesion molecules ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and ELAM-1 (endothelial leukocyte adhesion molecule-1) in human pancreatic cancer. METHODS: ICAM-1, VCAM-1, and ELAM-1 were analyzed in 20 pancreatic cancer specimens and 20 normal pancreatic tissues. mRNA expression encoding ICAM-, VCAM-1, and ELAM-1 was assessed with Northern blot analysis. The distribution and localization of ICAM-1, VCAM-1, and ELAM-1 was determined in the pancreatic specimens by immunohistochemistry. RESULTS: Northern blot analysis revealed a 5.4-fold increase of ICAM-1 (P<0.01) and a 3.7-fold increase in VCAM-1 (P<0.01) mRNA expression in cancer samples in comparison with normal controls. In contrast, ELAM-1 mRNA levels did not show significant differences between the cancer and the normal tissues. Immunohistochemical analysis of cancer tissues showed strong immunostaining for ICAM-1 and VCAM-1, and faint immunostaining for ELAM-1 in the pancreatic cancer cells. Fibrotic or noncancerous pancreatic tissue adjacent to the cancer mass was devoid of any immunoreactivity for ICAM-1, ELAM-1, and VCAM-1. In contrast, the normal pancreas exhibited no immunoreactivity of ICAM-1, ELAM-1, and VCAM-1. CONCLUSIONS: Enhanced expression of ICAM-1 and VCAM-1 in human pancreatic cancers suggests a role in tumor pathogenesis. The increase of these adhesion molecules might influence the detachment of cancer cells in the primary tumor, might contribute to cancer cell migration and the spread of cancer cells to distant organs, or both.

Adenocarcinoma↗
PubMed2002

Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells.

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain non-neuronal tumors. In pancreatic cancer NGF is overexpressed, and this overexpression is associated with increased perineural invasion. NGF has the potential to stimulate the growth of some pancreatic cancer cell lines, and this effect is mediated by the phosphorylation of tyrosine kinase receptor A and mitogen-activated protein kinase activation; it is dependent on the expression levels of tyrosine kinase receptor A and p75 receptors. To determine whether cancer cell-derived NGF can participate in the regulation of pancreatic cancer cell proliferation, PANC-1 human pancreatic cancer cells were stably transfected with a full-length human beta-NGF expression vector. In vitro and in vivo growth characteristics were analyzed by proliferation assays and invasion assays and in a nude mouse tumor model. Stable transfection of NGF in PANC-1 cells resulted in enhanced anchorage-dependent growth, with a decrease in doubling times of up to 50%, and in an approximately twofold increase in anchorage-independent cell growth and cell invasion. Furthermore, stably transfected PANC-1 cells showed enhanced tumorigenicity in nude mice. These results suggest that NGF has the capacity to act in a paracrine and/or an autocrine manner in pancreatic cancer and that it enhances cancer cell growth and invasion in vivo, thereby contributing to the aggressiveness and poor prognosis of this disease.

Animals↗
PubMed2002

How to do a safe pancreatic anastomosis.

BACKGROUND/PURPOSE: Leakage of pancreaticojejunostomies has been associated with morbidity and mortality after pancreatic head resection. Different techniques have been described to perform a safe anastomosis to the left pancreatic remnant. METHODS: The pancreaticojejunostomy is preferably performed as an end-to-side anastomosis; drainage of the pancreatic duct by catheters or stents is not performed at our institution. RESULTS: Experience in more than 331 patients who underwent pancreaticojejunostomy indicates that a two-layer, single-stitch technique, with absorbable monofilament sutures and duct-to-mucosa adaptation, is a reliable method, with a pancreatic fistula rate of 2%. CONCLUSIONS: The results obtained with the described technique of pancreaticojejunostomy indicate that the pancreatic anastomosis is very safe when performed by experienced hands and does not necessarily contribute to morbidity and mortality after pancreatic head resection. The prevalence of pancreatic fistulae and intraabdominal abscesses may further decrease, and the prevalence of nonpancreatic complications may have a more important impact on the outcome in the future.

Anastomosis, Surgical↗
PubMed2002

Down-regulation of DOC-2 in colorectal cancer points to its role as a tumor suppressor in this malignancy.

PURPOSE: Colorectal cancer is the second most common cause of cancer death and the fourth most prevalent carcinoma in the Western world. Loss of tumor-suppressor gene function in colon cancer leads to ineffective negative growth regulation that is normally exerted by growth-suppressing factors. DOC-2/hDAB2 is a newly identified candidate tumor-suppressor gene in ovarian cancer and choriocarcinoma. In these tumors it negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In the present study we sought to determine the role of DOC-2 in colorectal cancer. METHODS: DOC-2 expression was analyzed by Northern blot analysis, hybridization, and immunohistochemistry in 27 primary and metastatic colorectal cancers and in 15 normal colon tissues in correlation with clinicopathologic data. RESULTS: Northern blot analysis demonstrated a decrease of DOC-2 messenger RNA levels in primary and metastatic colorectal cancers compared with normal controls. In normal colorectal tissues, DOC-2 immunoreactivity was strongly present on the surface columnar epithelial cells. In contrast, DOC-2 immunoreactivity was weak to moderate in the epithelium of colorectal cancers, and the intensity of the signals in colorectal cancer was greatly decreased compared with the normal colorectal tissues. In addition, DOC-2 immunoreactivity in lymph node and liver metastasis was weak to absent in the cancer cells and significantly decreased compared with their primary tumors. CONCLUSIONS: The expression of DOC-2 is down-regulated in primary tumors and metastases of colorectal cancer, which suggests that DOC-2 functions as a tumor suppressor in this malignancy.

Adaptor Proteins, Signal Transducing↗
PubMed2002

5-Lipoxygenase and leukotriene B(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue.

The 5-lipoxygenase (5-LOX) pathway is critical for pancreatic cancer cell growth and escape from apoptosis. Inhibition of 5-LOX blocks proliferation and induces apoptosis in human pancreatic cancer cells. However, the expression of 5-LOX and its downstream signaling pathway have not been investigated in human pancreatic adenocarcinoma. Reverse transcriptase-polymerase chain reaction revealed expression of 5-LOX mRNA in all pancreatic cancer cell lines tested including, PANC-1, AsPC-1, and MiaPaCa2 cells, but not in normal pancreatic ductal cells. The expression of 5-LOX protein in pancreatic cancer cell lines was demonstrated by Western blotting. Finally, 5-LOX up-regulation in human pancreatic cancer tissues was verified by intense positive staining in cancer cells by immunohistochemistry. Staining for the 5-LOX protein was particularly evident in the ductal components of the more differentiated tumors but not in ductal cells in normal pancreatic tissues from cadaver donors. Immunohistochemistry also revealed strong staining of cancer tissues with an antibody to the receptor of the downstream 5-LOX metabolite, leukotriene B(4). The current study demonstrated marked expression of 5-LOX and the leukotriene B(4) receptor in human pancreatic cancer tissues. These findings provide further evidence of up-regulation of this pathway in pancreatic cancer and that LOX inhibitors are likely to be valuable in the treatment of this dreadful disease.

Arachidonate 5-Lipoxygenase↗
PubMed2002

Glypican-3 expression is markedly decreased in human gastric cancer but not in esophageal cancer.

BACKGROUND: Deregulation of the expression of glypican-3, a heparan sulfate proteoglycan, has been demonstrated in several human cancers. METHODS: In the present study, glypican-3 mRNA expression was analyzed by Northern blotting and in situ hybridization in 20 normal and 41 cancerous esophageal specimens as well as in 15 normal and 32 cancerous gastric tissues. RESULTS: Glypican-3 mRNA was expressed in both normal and esophageal cancer tissues without a significant difference between normal and cancerous tissues, and without a correlation with histological type, tumor stage, tumor grade, or patient survival. Moderate to strong glypican-3 mRNA signals were found in the cytoplasm of squamous epithelial cells of the normal esophagus. In both squamous and adenocarcinomas of the esophagus glypican-3 mRNA signals were also moderately to strongly present in the cytoplasm of the cancer cells. In gastric tissues, glypican-3 mRNA was present in 53% of normal gastric tissue samples, but was below the detection level in all examined gastric cancer samples. Glypican-3 mRNA signals were moderately to strongly present in the cytoplasm of gastric mucosal epithelial cells, but were only very faintly present in some cancer cells. CONCLUSIONS: Glypican-3 may be involved in the growth control of normal esophageal and gastric epithelial cells. Furthermore, our results suggest that glypican-3 may play a tumor suppressor role in gastric but not in esophageal cancer.

Adult↗