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Helmut Friess

Publications and source records attributed to Helmut Friess.

At least 73 records · Page 4Linked to original sources
PubMed2005

Role of mononuclear cells and inflammatory cytokines in pancreatic cancer-related cachexia.

BACKGROUND AND PURPOSE: The mechanism behind aggressive development of cachexia in patients suffering from pancreatic cancer is not well understood. In this study, we investigated which factors are associated with the cachectic status of the patients and evaluated cachexia-promoting capacity of cancer and inflammatory cells. EXPERIMENTAL DESIGN: DNA microarray analysis and quantitative reverse transcription-PCR were used to screen for cachexia-associated factors in pancreatic specimens obtained from noncachectic and cachetic patients diagnosed with pancreatic ductal adenocarcinoma. The expression pattern of the most prominently altered cachexia-associated factor, interleukin-6 (IL-6), was further analyzed in patients sera by ELISA, in pancreatic specimens by immunohistochemistry, and in a coculture system by quantitative reverse transcription-PCR using pancreatic cancer cell lines T3M4 (IL-6 positive) and Panc-1 (IL-6 negative) and peripheral blood mononuclear cells (PBMC) obtained from donors and noncachectic and cachectic patients. RESULTS: Among numerous analyzed factors, IL-6 was significantly overexpressed in pancreatic specimens and elevated in serum of cachectic patients. The coculture system revealed that pancreatic cancer T3M4 cells but not Panc-1 cells were able to stimulate IL-6 exclusively in cachectic PBMC (by 14-fold) and this triggering was reduced by half in the presence of IL-6-neutralizing antibodies. CONCLUSION: IL-6 represents a prominent cachexia-associated factor in pancreatic cancer. IL-6 overexpression in cachectic patients is related to the ability of certain tumors to sensitize PBMC and induce cytokine expression in cachectic PBMC.

Adult↗
PubMed2005

Aberrant gata-3 expression in human pancreatic cancer.

Gata-3 has been shown to specifically alter its expression patterns in different types of cancers. Recent evidence suggests that an interference of Gata-3 exists in the TGF-beta signaling pathway. To determine the role of Gata-3 in pancreatic cancer, pancreatic cancer samples were analyzed in comparison to normal pancreatic tissues. Furthermore, four different pancreatic cancer cell lines with different alterations of the TGF-beta pathway were studied. To evaluate if a potential relationship with TGF-beta signaling pathway exists, we correlated mRNA expression levels with the expression of TGF-betas, TGF-beta receptors, and Smad-3. Finally, we analyzed the influence of TGF-beta on Gata-3 expression in vitro. All pancreatic cancer samples demonstrated a marked overexpression of Gata-3 mRNA and protein. Immunohistochemical staining revealed strong and persistent cytoplasmic Gata-3 immunoreactivity in cancer cells. In an electrophoretic mobility shift assay, a disturbed nuclear translocation was confirmed. The expression of Gata-3 showed a significant correlation with the expression of TGF-betas, TGF-beta receptors, and Smad-3. TGF-beta responsive cell lines showed a downregulation of Gata-3 mRNA upon TGF-beta exposure, whereas in TGF-beta-unresponsive cell lines, Gata-3 mRNA expression persisted at high levels. Furthermore, strong specific upregulation of Gata-3 impaired nuclear translocation and its cooperative action with the TGF-beta pathway, suggesting that Gata-3 plays a central role in human pancreatic cancer.

Adult↗
PubMed2005

Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase.

The extracellular matrix (ECM) facilitates pancreatic cancer cells survival, which is of central importance for pancreatic adenocarcinoma that is highly fibrotic. Here, we show that reactive oxygen species (ROS) mediate the prosurvival effect of ECM in human pancreatic cancer cells. Fibronectin and laminin stimulated ROS production and NADPH oxidase activation in pancreatic cancer cells. Both pharmacological and molecular approaches show that fibronectin stimulated ROS production through activation of NADPH oxidase and NADPH oxidase-independent pathways and that 5-lipoxygenase (5-LO) mediates both these pathways. Analyses of the mechanisms of ROS production by ECM proteins and growth factors indicate that activation of NADPH oxidase (Nox4) is a common mechanism employed both by ECM proteins and growth factors to increase ROS in pancreatic cancer cells. We also found that Nox4 is present in human pancreatic adenocarcinoma tissues and that these tissues display membrane NADPH oxidase activity. ECM proteins and growth factors activate NADPH oxidase through different mechanisms; in contrast to ECM proteins, growth factors activate NADPH oxidase through 5-LO-independent mechanisms. Inhibition of 5-LO or NADPH oxidase with pharmacological inhibitors of these enzymes and with Nox4 or 5-LO antisense oligonucleotides markedly stimulated apoptosis in cancer cells cultured on fibronectin. Our results indicate that ROS generation via 5-LO and downstream NADPH oxidase mediates the prosurvival effect of ECM in pancreatic cancer cells. These mechanisms may play an important role in pancreatic cancer resistance to treatments and thus represent novel therapeutic targets.

Adenocarcinoma↗
PubMed2005

5-Lipoxygenase, a marker for early pancreatic intraepithelial neoplastic lesions.

Pancreatic cancer has an abysmal prognosis because of late diagnosis. Therefore, it is important to identify risk factors if we are to be able to prevent and detect this cancer in an early, noninvasive stage. Pancreatic intraepithelial neoplasias (PanIN) are the precursor lesions which could be an ideal target for chemoprevention. This study shows up-regulation of 5-lipoxygenase (5-LOX) in all grades of human PanINs and early lesions of pancreatic cancer in two different animal models (EL-Kras mice and N-nitrosobis(2-oxopropyl)amine-treated hamsters) by immunohistochemistry. The results were consistent in all tissues examined, including seven chronic pancreatitis patients, four pancreatic cancer patients, one multiorgan donor, nine EL-Kras mice, and three N-nitrosobis(2-oxopropyl)amine-treated hamsters, all with PanINs. Overexpression of 5-LOX in NIH3T3 cells resulted in greater sensitivity of these cells to the growth inhibitory effects of the 5-LOX inhibitor Rev5901. These findings provide evidence that 5-LOX plays a key role in the development of pancreatic cancer. Furthermore, the lipoxygenase pathway may be a target for the prevention of this devastating disease.

Adenocarcinoma↗
PubMed2005

Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis.

Altered expression of apoptosis-regulating genes plays an important role in the aggressive growth behavior and chemoresistance of pancreatic ductal adenocarcinoma. In the present study, the hypoxia-inducible proapoptotic gene, BNIP3, was analysed in terms of expression, effect on patient survival, and chemo-responsiveness in pancreatic cancer cell lines. cDNA microarray, real-time light cycler quantitative polymerase chain reaction, laser-capture microdissection, and immunohistochemistry analyses were used to evaluate BNIP3 expression in normal and diseased pancreatic specimens. Modulation of BNIP3 expression was achieved using specific siRNA molecules. The effect of chemotherapeutic agents on pancreatic cancer cells was assessed utilizing 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide assays. BNIP3 mRNA levels were 3.0- and 6.3-fold lower in chronic pancreatitis and pancreatic cancer compared to the normal pancreas, respectively. Microdissection analysis confirmed the reduction of BNIP3 expression in pancreatic cancer cells compared to normal duct cells. By immunohistochemistry, BNIP3 was predominantly expressed in the acinar cells of the normal and diseased pancreas. Interestingly, while BNIP3 was undetectable in the cancer cells of 59% of the cases, 75-100% of PanIN2/3 lesions displayed BNIP3 immunoreactivity. Loss of BNIP3 expression correlated with poorer survival of patients (8 vs 14 months for BNIP3 negative vs positive tumors). Hypoxia induced BNIP3 expression in four out of eight pancreatic cancer cell lines, while it was absent under normoxic and hypoxic conditions in the remaining four. Downregulation of BNIP3 resulted in increased resistance to 5-fluoro-uracil and gemcitabine. In conclusion, loss of BNIP3 expression occurs late in pancreatic cancer, contributes to resistance to chemotherapy, and correlates with a worsened prognosis.

Cell Line, Tumor↗
PubMed2005

The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour.

BACKGROUND: The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. METHODS: Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. RESULTS: The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. CONCLUSION: Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy.

Adult↗
PubMed2005

Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma.

Pancreatic ductal adenocarcinoma is among the top 10 causes of death from cancer in industrialized countries. In comparison with other gastrointestinal malignancies, pancreatic cancer is one of the tumors most resistant to chemotherapy. An important mechanism of tumor multidrug resistance is increased drug efflux mediated by several transporters of the ABC superfamily. Especially BCRP (ABCG2), MDR1 P-glycoprotein (ABCB1) and members of the MRP (ABCC) family are important in mediating drug resistance. The MRP family consists of 9 members (MRP1-MRP9) with MRP1-MRP6 being best characterized with respect to protein localization and substrate selectivity. Here, we quantified the mRNA expression of BCRP and of all MRP family members in normal human pancreas and pancreatic carcinoma and analyzed the mRNA level of the transporters most abundantly expressed in pancreatic tissue, BCRP, MRP1, MRP3, MRP4 and MRP5, in 37 tissue samples. In addition, we determined the localization of the 4 MRP proteins in normal human pancreas and in pancreatic carcinoma. The expression of BCRP, MRP1 and MRP4 mRNA did not correlate with tumor stage or grading. On the other hand, the expression of MRP3 mRNA was upregulated in pancreatic carcinoma samples and was correlated with tumor grading. The MRP5 mRNA level was significantly higher in pancreatic carcinoma tissue compared to normal pancreatic tissue. These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer.

Adult↗
PubMed2005

Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment.

Heme oxygenase-1 (HO-1) is believed to represent a key enzyme for the protection of cells against "stress." Its overexpression in different types of human cancers supports the notion that HO-1 provides a growth advantage and contributes to cellular resistance against chemotherapy and radiotherapy. Given the poor survival rates of patients with pancreatic cancer due to its aggressive growth behavior and its exceptional resistance to all known forms of anticancer treatment, we have investigated the expression of HO-1 in human pancreatic cancer cells growth behavior and prognosis. Expression of HO-1 was analyzed in human pancreatic cancer samples in comparison with normal pancreas by quantitative PCR, Western blot, and confocal microscopy. The influence of radiotherapy and chemotherapy on HO-1 expression in pancreatic cancer cell lines was evaluated. Furthermore, HO-1 expression was specifically suppressed by small interfering RNA transfection and subsequently the alterations of growth behavior and resistance to anticancer treatment were tested. Human pancreatic cancer showed a 6-fold and 3.5-fold HO-1 up-regulation in comparison to normal pancreas based on mRNA and protein level, respectively (P < 0.05). Cancer tissues revealed marked HO-1 immunoreactivity in tumor cells and in tumor associated immunocytes. Treatment of the pancreatic cancer cell lines with gemcitabine or radiation strongly induced HO-1 expression. Targeted knockdown of HO-1 expression led to pronounced growth inhibition of the pancreatic cancer cells and made tumor cells significantly more sensitive to radiotherapy and chemotherapy. Therefore, specific inhibition of HO-1 expression may be a new option in pancreatic cancer therapy and may be used as sensitizer to chemotherapy and radiotherapy.

Adult↗
PubMed2005

Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer.

UNLABELLED: Hsulf-1 is a newly identified enzyme, which has the ability to decrease the growth of hepatocellular, ovarian, and head and neck squamous cell carcinoma cells by interfering with heparin-binding growth factor signaling. Since pancreatic cancers over-express a number of heparin-binding growth factors and their receptors, the expression and function of this enzyme in pancreatic cancer was analyzed. RESULTS: Pancreatic cancer samples expressed significantly (22.5-fold) increased Hsulf-1 mRNA levels compared to normal controls, and Hsulf-1 mRNA was localized in the cancer cells themselves as well as in peritumoral fibroblasts. 4 out of 8 examined pancreatic cancer cell lines expressed Hsulf-1, whereas its expression was below the level of detection in the other cell lines. Stable transfection of the Hsulf-1 negative Panc-1 pancreatic cancer cell line with a full length Hsulf-1 expression vector resulted in increased sulfatase activity and decreased cell-surface heparan-sulfate proteoglycan (HSPG) sulfation. Hsulf-1 expression reduced both anchorage-dependent and -independent cell growth and decreased FGF-2 mediated cell growth and invasion in this cell line. CONCLUSION: High expression of Hsulf-1 occurs in the stromal elements as well as in the tumor cells in pancreatic cancer and interferes with heparin-binding growth factor signaling.

Adult↗
PubMed2005

A case of methicillin-resistant Staphylococcus aureus infection following bile duct stenting.

AIM: To present a case of methicillin-resistant Staphylococcus aureus (MRSA) infection following bile duct stenting in a patient with malignant biliary obstruction. METHODS: A 78-year-old male patient was admitted to a community hospital with progredient painless jaundice lasting over two weeks, weight loss and sweating at night. Whether a stent should be implanted pre-operatively in jaundiced patients or whether these patients should directly undergo surgical resection, was discussed. RESULTS: ERC and a biopsy from the papilla of Vater revealed an adenocarcinoma. In addition, a 7-Ch plastic stent was placed into the common bile duct. Persistent abdominal pain, increasing jaundice, weakness and indigestion led to the transfer of the patient to our hospital. A pylorus-preserving pancreatoduodenectomy was performed. Intraoperatively, bile leaked out of the transected choledochus and the stent was found to be dislocated in the duodenum. A smear of the bile revealed an infection with MRSA, leading to post-operative isolation of the patient. CONCLUSION: As biliary stents can cause severe infection of the bile, the need for pre-operative placement of biliary stents should be carefully evaluated in each individual case.

Adenocarcinoma↗
PubMed2005

Melanoma Inhibitory Activity (MIA) increases the invasiveness of pancreatic cancer cells.

BACKGROUND: Melanoma inhibitory activity (MIA) is a small secreted protein that interacts with extracellular matrix proteins. Its over-expression promotes the metastatic behavior of malignant melanoma, thus making it a potential prognostic marker in this disease. In the present study, the expression and functional role of MIA was analyzed in pancreatic cancer by quantitative real-time PCR (QRT-PCR), immunohistochemistry, immunoblot analysis and ELISA. To determine the effects of MIA on tumor cell growth and invasion, MTT cell growth assays and modified Boyden chamber invasion assays were used. RESULTS: The mRNA expression of MIA was 42-fold increased in pancreatic cancers in comparison to normal pancreatic tissues (p < 0.01). In contrast, MIA serum levels were not significantly different between healthy donors and pancreatic cancer patients. In pancreatic tissues, MIA was predominantly localized in malignant cells and in tubular complexes of cancer specimens, whereas normal ductal cells, acinar cells and islets were devoid of MIA immunoreactivity. MIA significantly promoted the invasiveness of cultured pancreatic cancer cells without influencing cell proliferation. CONCLUSION: MIA is over-expressed in pancreatic cancer and has the potential of promoting the invasiveness of pancreatic cancer cells.

Journal Article↗
PubMed2005

Effect of antecolic reconstruction on delayed gastric emptying after the pylorus-preserving Whipple procedure.

HYPOTHESIS: Antecolic duodenojejunostomy prevents delayed gastric emptying (DGE) after a pylorus-preserving Whipple (ppW) procedure better than retrocolic duodenojejunostomy. DESIGN: A single operation team's experience with antecolic and retrocolic duodenojejunostomy in ppW is analyzed on a prospective database using univariate and multivariate models. SETTING: Tertiary referral center that focuses on pancreatic diseases. PATIENTS AND INTERVENTIONS: One hundred consecutive patients undergoing a ppW procedure with retrocolic reconstruction between January 1, 1996, and December 31, 2001, and 100 consecutive patients undergoing a ppW procedure with antecolic reconstruction between January 1, 2002, and December 31, 2003. Characteristics such as median age, median hospital stay, sex, diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists risk groups, stent implantation, and especially DGE were matched for the comparison groups. MAIN OUTCOME MEASURES: We compared DGE, characteristics, and perioperative variables in patients with antecolic vs retrocolic reconstruction after ppW. RESULTS: The DGE occurred significantly more often in patients with retrocolic reconstruction than in those with antecolic reconstruction (P < .001). The antecolic and retrocolic study groups were comparable in age (P = .25), sex (P = .48), and postoperative surgical (P = .19) and medical (P = .054) complications. The univariate analysis between patients with and without DGE did not show significant differences regarding diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists classification, or stent implantation. In the multivariate analysis, only the type of reconstruction (P = .006) and sex (P = .04) seemed to affect DGE. CONCLUSION: We recommend antecolic duodenjejunostomy in patients undergoing a ppW procedure regardless of their diagnosis.

Aged↗
PubMed2005

Localization of the human hedgehog-interacting protein (Hip) in the normal and diseased pancreas.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Previously, it has been shown that Indian hedgehog (Ihh) and its two signaling receptors patched (Ptc) and smoothened (Smo) are involved in the pathogenesis of chronic pancreatitis (CP) and PDAC. In the current study we analyzed the expression, distribution, and function of another component of this signaling pathway, the human hedgehog-interacting protein (Hip), in the normal pancreas, CP and PDAC utilizing real-time quantitative reverse transcription-polymerase chain reaction (QRT-PCR), immunohistochemistry, immunofluorescence, Hip siRNA transfection, cell growth assays, and cell cycle analysis. By QRT-PCR, Hip mRNA levels were fifteenfold and fourteenfold increased in CP (n = 22) and PDAC (n = 31) tissues, respectively, compared to normal pancreatic tissues (n=20) and correlated with glioma associated antigen (Gli1) but not Ptc or Protein kinase A (PKA) mRNA levels. Only SU-8686 and BxPC-3 pancreatic cancer cells expressed Hip mRNA, whereas expression was below the level of detection in the other six pancreatic cancer cell lines tested. As shown by immunohistochemistry, Hip was expressed in normal pancreatic tissues mainly in the cytoplasm of islet cells and in smooth muscle cells of blood vessels. In contrast, in CP and PDAC there was a different distribution and staining intensity within the islets. Moreover, Hip immunoreactivity was observed in the tubular complexes, PanIN 1-3 lesions, as well as in pancreatic cancer cells. Incubation of pancreatic cancer cell lines with recombinant Hip revealed a growth inhibitory effect in SU-8686 and Capan-1 pancreatic cancer cells and no effect on cell growth in the other tested cell lines. In addition, silencing of Hip expression using specific siRNA molecules increased the growth of SU-8686 cells. In conclusion, Hip is expressed in the normal pancreas, CP and PDAC tissues. The different pattern of Hip expression and abnormal localization in the diseased pancreas suggest that the enhanced activation of hedgehog signaling in CP and PDAC is-at least in part-due to the aberrant responsiveness and expression of Hip in these diseases.

Adenocarcinoma↗
PubMed2005

DE-310, a macromolecular prodrug of the topoisomerase-I-inhibitor exatecan (DX-8951), in patients with operable solid tumors.

BACKGROUND: DE-310 is composed of the topoisomerase-I-inhibitor DX-8951 (exatecan) and a biodegradable macromolecular carrier, which are covalently linked by a peptidyl spacer. In pre-clinical studies, high levels and prolonged retention of conjugated DX-8951 (carrier-bound DX-8951) have been observed in tumor tissues following DE-310 administration. This phenomenon is explained as the enhanced permeability and retention (EPR) effect. DX-8951 and G-DX-8951 (glycyl-DX-8951) exerting anti-tumor activity in vivo are released from DE-310 by enzymatic cleavage of the spacer. METHODS: To quantify the concentration of conjugated DX-8951, DX-8951 and G-DX-8951 in human tissues, six patients with different solid tumor types received 6.0 mg/m(2) of DE-310 (as equivalent of DX-8951) as a single three-hour infusion administered 7 days (+/-2 days) prior to scheduled tumor resection. Drug concentrations were then determined in the resected tissues. To evaluate the plasma PK of DE-310, plasma samples were taken up to 42 days post dosing. RESULTS: There were no severe side effects of the DE-310 infusion. Concentrations of conjugated DX-8951, DX-8951 and G-DX-8951 were in general similar in tumor and relevant normal tissue samples and preferential accumulation of DE-310, DX-8951 and G-DX-8951 in human tumor tissues was not observed. CONCLUSIONS: These data indicate that there is distribution of DE-310 into tissue and that DX-8951 and G-DX-8951 are released slowly over an extended period from DE-310 providing prolonged exposure similar to a continuous infusion. However, the similarity in the concentrations in tumor and relevant normal tissues does not support the EPR concept in the studied human cancers.

Aged↗
PubMed2005

Isolated left ventricular noncompaction of the myocardium as a cause of embolic superior mesenteric artery occlusion.

Isolated noncompaction of the left ventricular (LV) myocardium is a rare congenital disorder resulting from an arrest of the compaction process of the myocardial trabeculae during normal embryogenesis. It is characterized by the presence of prominent LV myocardial trabeculations and deep intertrabecular recesses that are in continuity with the LV cavity. The most common clinical presentation includes progressive LV dysfunction, life-threatening tachyarrhythmias, and the risk for severe cardioembolic events. We describe a case where isolated noncompaction of the LV myocardium was diagnosed after an embolic occlusion of the superior mesenteric artery in a 40-year-old Caucasian woman.

Adult↗
PubMed2005

The segments of the hepatic veins-is there a spatial correlation to the Couinaud liver segments?

PURPOSE: To investigate and describe the volume, position and shape of venous segments within the human liver and define their spatial correlation to the Couinaud segments (CS) and to the portal vein segments (PVS). MATERIAL AND METHODS: This study was based on 64 routinely acquired CT scans of patients undergoing hepatic surgery. The final analysis included 19 patients. All 19 CT data sets were transformed into 3D liver models. Three venous segments were postulated reflecting the left, middle, and right hepatic vein. Each venous segment was furthermore divided in two venous subsegments. Volume, position and shape of these venous segments/subsegments were calculated and, finally, compared with the volume, position and shape of the Couinaud segments and the portal vein segments. RESULTS: The right hepatic vein covers with 539.8 +/- 119.5 ml (47.1%) the largest part of total liver volume followed by the middle hepatic vein 372.7 +/- 151.1 ml (32.5%) and the left hepatic vein 248 +/- 75.9 ml (20.4%). The Couinaud liver segments and portal vein segments 2, 3, 5, 7, and 8 have consistent positional assignments within the three venous segments. Only the CS 4a, 4b, and 6 showed significantly different positions compared to the PVS 4a, 4b, and 6 (P < 0.03). The venous subsegments have a broad volumetric distribution reaching from 79 to 337 ml. There is no positional correlation of venous subsegments compared to Couinaud segments or portal vein segments at all (kappa < 0.75). In contrast, the venous segments/subsegments which can be assigned to either liver halve and either liver lobe have an identical volume, shape and position compared to the corresponding Couinaud liver segments (kappa > 0.75). CONCLUSION: The venous segments distinguish liver areas divided by the left and middle hepatic vein in exactly the same pattern as Couinaud segments and portal vein segments do. However, the comparison of shape and position of venous subsegments showed no correlation with both liver segmental approaches.

Adult↗
PubMed2005

Secretin receptors in normal and diseased human pancreas: marked reduction of receptor binding in ductal neoplasia.

Receptors for gut hormones, which are often overexpressed in cancer, are clinically relevant for receptor-targeted tumor imaging and therapy. Because the receptors for the gut hormone secretin are poorly characterized, we assessed secretin receptor expression in the main secretin target, the human pancreas. We investigated 58 non-neoplastic pancreases and 55 pancreatic tumors for receptor localization and density by in vitro receptor autoradiography using [(125)I]Tyr(10) rat secretin and for secretin receptor mRNA by reverse transcriptase-polymerase chain reaction. Secretin receptors were highly expressed in non-neoplastic ducts and lobuli and also in lower amounts in ductal neoplasias, including ductal adenocarcinoma, intraductal papillary mucinous tumors, and pancreatic intraepithelial neoplasia. Reverse transcriptase-polymerase chain reaction revealed wild-type receptor mRNA in the non-neoplastic pancreas and both wild-type and spliced variant receptor transcripts in ductal adenocarcinomas. Serous cystic tumors were highly positive for secretin receptors, whereas mucinous cystic tumors were negative. This study is the first to describe the precise secretin receptor distribution in human non-neoplastic pancreas and various pancreatic tumors. High secretin receptor expression in the non-neoplastic ducts reflects the major role of secretin in bicarbonate secretion. Reduced secretin binding in pancreatic ductal tumors may relate to (alternatively spliced) secretin receptor isoforms. Thus, secretin receptors in pancreatic tumors may represent potential clinical targets.

Adenocarcinoma↗