Biomedical subjects

Hans Lippert

Publications and source records attributed to Hans Lippert.

At least 19 recordsLinked to original sources

PubMed2007

Localization of TFF3 peptide in human esophageal submucosal glands and gastric cardia: differentiation of two types of gastric pit cells along the rostro-caudal axis.

TFF3 (trefoil factor family 3), which is a major secretory product of the gastric antrum and the intestine, but which is nearly absent in the gastric corpus, plays a key role in the maintenance of mucosal integrity. Here, we have systematically investigated TFF3 expression in the esophagus and gastric cardia by the use of reverse transcription/polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Synthesis of TFF3, but not TFF1 or TFF2, is detectable in esophageal submucosal glands. The stratified squamous epithelium is devoid of TFF synthesis. Prominent TFF3 expression starts at the Z-line with a sharply decreasing gradient toward the cardia. Immunohistochemistry has localized TFF3 to surface mucous cells of the proximal cardia. TFF3 distribution differs characteristically from that of TFF1 (secreted primarily by superficial surface mucous cells), whereas TFF3, together with the mucin MUC5AC, is also found in deeper lying cells toward the isthmus. This is the first report of TFF3 as a typical secretory peptide of esophageal submucosal glands and gastric cardia. The different expression patterns of TFF3 and TFF1 in the cardia suggest a stepwise maturation of surface mucous cells from TFF3/MUC5AC-positive cells close to the isthmus to TFF1/TFF3/MUC5AC-positive cells at the pit. The gradient of TFF3 expression along the gastric rostro-caudal axis defines two types of gastric pit cells: those secreting TFF3 in the cardia and the antrum and those nearly devoid of TFF3 synthesis in the corpus. This indicates the special requirement, particularly of the esophagogastric junction, for TFF3-triggered protection and repair.

Adult↗

PubMed2006

No prognostic impact of isolated lymphovascular invasion after radical resection of rectal cancer--results of a multicenter observational study.

BACKGROUND: The prognostic impact of isolated lymphovascular invasion (LVI) after radical resection of rectal cancer is controversially discussed. However, it could be relevant to decide for an adjuvant treatment. AIM: The aim of the analysis was, based on the data of an observational study, to determine the prognostic relevance of the isolated LVI. MATERIALS AND METHODS: Patients after radical resection of rectal cancer with no hemangioinvasion were subdivided in three groups: I-no LVI, no lymph node metastases (LNM); II-positive LVI, no LNM; III-positive LNM. Five-year local recurrence rate, distant metastases-free and disease-free survival were determined uni- and multivariate. RESULTS: Patients, n = 846, were studied (I, n = 471; II, n = 75; III, n = 300). The univariate comparison between the groups revealed the following 5-year results: local recurrence rate: 9.4 vs 10.0 vs 14.0%; distant metastases-free survival: 84.1 vs 82.5 vs 49.3%; disease-free survival: 83.2 vs 80.7 vs 45.5%. The differences between groups I and III were significant, but not between groups I and II. The determined higher disease-free survival rate in group II vs group III was significant (P = 0.041), but the differences in local recurrence rate and rate of distant metastases did not reach statistical significance. The multivariate analysis revealed no impact of the isolated LVI on the oncological outcome. CONCLUSION: The isolated LVI has no independent prognostic impact on the local recurrence rate and long-term survival after radical resection of rectal cancer. Based on this finding, no indication for an adjuvant treatment in these patients can be derived.

Aged↗

PubMed2006

Laparoscopic cholecystectomy and gallbladder cancer.

Heightened awareness of the possible presence of gallbladder cancer (GBC) and the knowledge of appropriate management are important for surgeons practising laparoscopic cholecystectomy (LC). Long-term effects of initial LC versus open cholecystectomy (OC) on the prognosis of patients with GBC remain undefined. Patients who are suspected to have GBC should not undergo LC, since it is advantageous to perform the en-bloc radical surgery at the initial operation. Since preoperative diagnosis of early GBC is difficult, preventive measures, such as preventing bile spillage and bagging the gallbladder should be applied for every LC. Many port-site recurrences (PSR) have been reported after LC, but the incidence of wound recurrence is not higher than after OC. No radical procedure is required after postoperative diagnosis of incidental pT1a GBC. It is unclear if patients with pT1b GBC require extended cholecystectomy. In pT2 GBC, patients should have radical surgery (atypical or segmental liver resection and lymphadenectomy). In advanced GBC (pT3 and pT4), radical surgery can cure only a small subset of patients, if any. Additional port-site excision is recommended, but the effectiveness of such measure is debated.

Catheters, Indwelling↗

PubMed2006

Dynamic patchplasty--a tension-free reconstruction of incisional hernias.

BACKGROUND AND AIMS: An anatomical and physiological reconstruction of the abdominal wall after incisional hernia must include reconstruction of the linea alba to restore the physiological function of the vertebral column and respiration. Against this background, a special reconstruction method employing a mesh, which is performed in our department, is presented. MATERIALS AND METHODS: In the period between 1 January 2000 and 1 June 2004, a total of 106 patients with incisional hernias after median laparotomy of the upper and lower abdomen were operated on in our department using this tension-free technique with one or two meshes. We have now evaluated the outcomes after a median follow-up of 25.8 months (6.5-53.3). RESULTS: In one patient (0.9%), the peritoneal sac was inadvertently opened, resulting in injury to the small bowel serosa. Surgical complications were observed in 14 patients (13.2%) after dynamic patchplasty. In seven cases (6.6%), wound healing disorders were seen. Overall, 6 out of 106 (5.5%) patients needed revision surgery. In the follow-up period, 92 patients (follow-up 86.8%) could be contacted and re-examined. Four patients (3.8%) had died. There were four recurrences (4.3%), which had already been repaired, and one chronic seroma, which caused no symptoms and which was detected in ultrasound and computed tomography. CONCLUSION: In view of the possibility of achieving physiological reconstruction and in the light of a tolerable morbidity rate, dynamic patchplasty is a suitable method for incisional hernias. Long-term results hold out promise of an acceptable low recurrence rate.

Abdomen↗

PubMed2006

Incurable stenosing colorectal carcinoma: endoscopic stent implantation or palliative surgery?

BACKGROUND: Palliative surgery for the treatment of incurable obstructive colorectal carcinoma is associated with a considerable perioperative morbidity and mortality but no substantial improvement of the prognosis. The aim of the present study was to study the effectiveness of colorectal stenting compared with palliative surgery in incurable obstructive colorectal carcinoma. PATIENTS AND METHODS: From April 1999 to April 2005, data of consecutive patients with incurable stenosing colorectal carcinoma, either treated with stent implantation or palliative surgical intervention, were prospectively recorded with respect to age, sex, tumor location (including metastases), ASA-score, peri-interventional morbidity, mortality, rates of complications, and re-interventions as well as survival. RESULTS: Of 40 patients, 38 (95%) were successfully treated with a stent. Two patients (5%) underwent surgical intervention after stent dislocation. In contrast, 38 patients primarily underwent palliative surgical intervention. Stent patients were significantly older (P=0.020), had a higher ASA-score (P=0.012), and had more frequently distant metastases (P=0.011). After successful stent implantation, no early complications were observed, but late complications occurred in 11 subjects (29%). Following palliative surgical intervention, postoperative complications occurred in 12 individuals (32%) . Postoperative mortality was 5% in the surgery group, whereas no patient died following stent implantation. There was no significant differences in the survival of both groups (9.9 vs. 7.8 months, respectively; log rank: 0.506). CONCLUSIONS: Palliative treatment of incurable obstructive colorectal carcinoma using stents is an effective and suitable alternative to palliative surgery with no negative impact on the survival but less peri-interventional morbidity and mortality as well as comparable overall morbidity.

Aged↗

PubMed2006

Intraperitoneal versus intravenous CPT-11 given intra- and postoperatively for peritoneal carcinomatosis in a rat model.

PURPOSE: Peritoneal recurrence after resection of colorectal carcinoma is still a major concern. We investigated whether the novel cytostatic drug, CPT-11 (Irinotecan), delivered intraperitoneally (i.p.) and intravenously (i.v.), could inhibit intraperitoneal tumor spread in a rat model. METHODS: We induced intraperitoneal tumor growth using a tumor cell transfer model (10(6) cells) and divided the rats into the following five groups of eight: group IP1, given CPT-11 i.p. immediately after intraperitoneal tumor cell transfer; group IV1, given CPT-11 i.v. immediately after intraperitoneal tumor cell transfer; group IP2, given CPT-11 i.p. on postoperative days (PODs) 5, 10, and 15; group IV2, given CPT-11 on PODs 5, 10, and 15; and a control group. The rats were killed 30 days after tumor cell transfer, and the tumor weight, number of nodes in the greater omentum and peritoneum, presence of metastases in the liver and lungs, and ascites volume were determined. RESULTS: CPT-11 inhibited peritoneal tumor growth significantly. The direct intraoperative intraperitoneal application induced a more pronounced effect than the early postoperative intraperitoneal application, but both these application modes were superior to the intravenous route, which had no significant effect. CONCLUSION: CPT-11 was highly efficacious against peritoneal carcinomatosis in this experimental model. The combination of CPT-11 with other cytostatic agents and drugs generating different effector mechanisms may diminish or even prevent intraperitoneal tumor growth.

Animals↗

PubMed2006

Results of regional chemotherapy using the aortic stop-flow technique in advanced pancreatic carcinoma.

PURPOSE: Systemic palliative chemotherapy provides only a disappointing response and almost no prolongation of the survival time in patients with pancreatic carcinoma. Isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects. The aim of the study was to investigate the feasibility of the aortic stop-flow technique using commercially available tools in patients with advanced pancreatic carcinoma. METHODS: Seventeen patients with either unresectable or metastasized pancreatic carcinoma (diagnosed by histologic investigation) were enrolled in the study. In total, a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 of mitomycin C (Medac, Hamburg, Germany) was carried out 22 times. The cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. The tumor response was assessed using computed tomography and a tumor marker (CA19-9) every 4 weeks. RESULTS: While 12 patients underwent one cycle, in 5 patients two complete perfusions were performed. Mitomycin C concentration was 10-fold higher within the regional compared with the systemic compartment at its maximum. The area under the curve (AUC) was 4.02 times larger. The degree of toxicity was considerable: World Health Organization grade I/II in 8/17, III/IV in 9/17 cases. Three treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission [CR], 2 partial remissions [PR]). In 3 subjects, a stable disease (SD) and in 11 individuals tumor progression (PD) was registered. The median survival was 4.1 months. CONCLUSION: The aortic stop-flow technique was associated with a high toxicity rate but no improvement in the tumor response and survival was seen in comparison to the systemic chemotherapy of the historical group. Despite detectable pharmacokinetic advantages, the aortic stop-flow technique is therefore not considered to be feasible for palliative chemotherapy in patients with pancreatic carcinoma for routine use.

Adolescent↗

PubMed2005

Sealing of the hepatic resection area using fibrin glue reduces significant amount of postoperative drain fluid.

AIM: To investigate whether the routine use of fibrin glue applied onto the hepatic resection area can diminish postoperative volume of bloody or biliary fluids drained via intraoperatively placed perihepatic tubes and can thus lower the complication rate. METHODS: Two groups of consecutive patients with a comparable spectrum of recent hepatic resections were compared: (1) 13 patients who underwent application of fibrin glue immediately after resection of liver parenchyma; (2) 12 patients who did not. Volumes of postoperative drainage fluid were determined in 4-h intervals through 24 h indicating the intervention caused bloody and biliary segregation. RESULTS: Through the first 8 h postoperatively, there was a tendency of higher amounts of fluids in patients with no additional application of fibrin glue while through the following intervals, a significant increase of drainage volumes was documented in comparison with the first two 4-h intervals, e.g., after 12 h, 149.6 mL +/-110 mL vs 63.2 mL +/-78 mL. Using fibrin glue, postoperative fluid amounts were significantly lower through the postoperative observation period of 24 h (851 mL +/-715 mL vs 315 mL +/-305 mL). CONCLUSION: For hepatic resections, the use of fibrin glue appears to be advantageous in terms of a significant decrease of surgically associated segregation of blood or bile out of the resection area. This might result in a better outcome.

Adult↗

PubMed2005

Solid-pseudopapillary tumor of the pancreatic tail.

We report a case of the rare solid-pseudopapillary tumor of the pancreas. In contrast to other pancreatic tumors, the solid-pseudopapillary tumor has a favorable prognosis. The 60-year-old female patient we report on here was treated by left pancreatic resection combined with splenectomy for a non-metastasizing tumor of the pancreas. A solid-pseudopapillary tumor was found on histology. The patient had no signs of metastases at present. Since a microscopically invasive tumor growth is assumed, oncologically curative resection should be preferred vs the less radical enucleation. The rare solid-pseudopapillary tumor of the pancreas has a good prognosis after successful oncological resection.

Carcinoma, Papillary↗

PubMed2005

Pharmacokinetics of the antineoplastic drug mitomycin C in regional chemotherapy using the aortic stop flow technique in advanced pancreatic carcinoma.

BACKGROUND: An isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects in comparison with systemic palliative chemotherapy. The aim of the present study was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop flow technique with commercially available tools in patients with advanced pancreatic carcinoma. METHODS: Seventeen patients with unresectable or metastasized pancreatic carcinoma (diagnosed by histological investigation) underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 mitomycin C (Mitomedac, medac, Hamburg, Germany) 22 times. Cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. RESULTS: The mitomycin C concentration was 10 times higher within the regional compared with the systemic compartment at its maximum. The area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission, 2 partial remissions). In 3 subjects, stable disease was registered, and in 11 individuals, tumor progression. The median survival was 4.1 months. CONCLUSION: Though high concentrations of the cytostatic drug were achieved within the regional compartment, the aortic stop flow technique was associated with a high toxicity rate but no improvement of tumor response and survival in comparison with systemic chemotherapy. Despite its pharmacokinetic advantages, the aortic stop flow technique is currently not recommendable for routine use.

Adult↗

PubMed2005

Vascular graft infections: in vitro and in vivo investigations of a new vascular graft with long-term protection.

We investigated a polyester vascular prosthesis (PET) coated with elemental silver (SC). Measurement of silver release over a period of 52 weeks by means of inductively coupled plasma atomic emission spectrometry of PET with (PET-G) and without (PET-N) gelatine impregnation revealed a silver release on the first day of 1.2 +/- 0.2 microg (PET-N) and 1.2 +/- 0.1 microg (PET-G) (calculated for 1 g of prosthesis); from the 90th day onward, it was between 0.22 +/- 0.14 microg (PET-N) and 0.18 +/- 0.12 microg (PET-G) per day. The prostheses were incubated with Staphylococcus aureus (S.a.), Staphylococcus epidermidis (S.e.), or Escherichia coli (E.c.) to investigate in vitro antibacterial efficacy. After 6 h of incubation, no colony-forming units were to be seen for any of the bacterial suspensions for PET with SC (p < 0.001). To investigate in vivo antibacterial efficacy, PET-G rings with and without SC contaminated with S.a., S.e., or E.c. were implanted in 18 albino rabbits and examined 7 days after agar culture for 48 h. The silver coating was associated with a significant reduction in bacterial growth (S.a., p = 0.001; S.e., p < 0.005; E.c., p < 0.001). The silver-coated prosthesis, with and without gelatine impregnation, had a significantly antibacterial effect with continuous release of silver.

Animals↗

PubMed2005

Web-based data warehouse on gene expression in human colorectal cancer.

Based on biomedical literature databases, we tried a first step for constructing a gene expression "data warehouse" specific to human colorectal cancer (CRC). Results of genome-wide transcriptomic research were available from 12 studies, using various technologies, namely, SAGE, cDNA and oligonucleotide arrays, and adaptor-tagged amplification. Three studies analyzed CRC cell lines and nine studies of human samples. The total number of patients was 144. Out of 982 up- or down-regulated genes, 863 (88%) were found to be differentially expressed in a single study, 88 in two studies, 22 in three studies, 7 in four studies, and only 2 genes in six studies. Eight large-scale proteomics studies were published in CRC, using 2-D-, SDS- or free-flow electrophoresis, involving only 11 patients. Out of 408 differentially expressed proteins, 339 (83%) were found to be differentially expressed only in a single study, 16 in three studies, 10 in four studies, 3 in five, and 1 in eight studies. Confirmation at proteome level of results obtained with large-scale transcriptomics studies was possible in 25%. This proportion was higher (67%) for reproducing proteome results using transcriptomics technologies. Obviously, reproducibility and overlapping between published gene expression results at proteome and transcriptome level are low in human CRC. Thus, the development of standardized processes for collecting samples, storing, retrieving, and querying gene expression data obtained with different technologies is of central importance in translational research.

Colorectal Neoplasms↗

PubMed2005

Effect of intraperitoneal application of an endotoxin inhibitor on survival time in a laparoscopic model of peritonitis in rats.

Gram-negative sepsis due to fecal peritonitis is a hazardous disease with a high percentage having a lethal course. The inflammatory effects are induced by endotoxin release. We performed this study to evaluate the potential of direct intraperitoneal application of an endotoxin inhibitor in a laparoscopic peritonitis model in rats. The human feces specimen was prepared, and a standard fecal specimen (0.5 ml/kg b.w.) was applied via minilaparotomy. The rats were randomized to two studies. First, rats were randomized to three groups to define the survival time: (1) rats without further manipulation; (2) rats with laparoscopic lavage using NaCl; (3) rats with laparoscopic lavage using endotoxin inhibitor. Second, rats underwent the same procedure used in the first part of the study and an additional group with only NaCl lavage without peritonitis was randomized. To evaluate the immunologic or biochemical effects, animals were killed at a standard time of 20 hours until the postmortem examination was established. Interleukins 6 and 10 (IL-6, IL-10), malondialdehyde, and protein carbonyl group levels in plasma and particularly in peritoneal fluid were assayed. The first part of the experiment showed significantly increased survival after endotoxin inhibitor lavage. In the second part, administration of endotoxin inhibitor intraperitoneally caused a significant reduction of IL-6 in the peritoneal fluid, in contrast to that in the other groups. Laparoscopic application of endotoxin inhibitor intraperitoneally thus produced a beneficial effect on survival and reduction of IL-6 in peritoneal fluid. Hence, it is possible to influence the inflammation cascade by causing intraperitoneal endotoxin inhibition.

Animals↗

PubMed2005

The impact of the risk factor "age" on the early postoperative results of surgery for colorectal carcinoma and its significance for perioperative management.

The risks and benefits of surgery for colorectal cancer in old patients have not been unequivocally defined. The present investigation was carried out in 309 hospitals as a prospective multicenter study. In the period between 1 January 2000 and 31 December 2001, a total of 19,080 patients were recruited for the study; 16,142 (84.6%) patients were younger than 80 years (<80) and 2932 (15.4%) were 80 years and older (> or =80). Significant differences between the age groups were observed for general postoperative complications (22.3% for <80 years; 33.9% for > or =80). Specific postoperative complications were identical in both groups. Overall, significantly elevated morbidity and mortality rates were found with increasing age (morbidity: 33.9% vs. 43.5%; mortality: 2.6% vs. 8.0%). The distribution of tumor stages revealed a significantly higher percentage of locally advanced tumors in the older age group (stage II: 28.0% vs. 34.4%). In contrast, no increase in metastasizing tumors was found in the older age group (stage IV: 17.4% vs. 14.1%). Logistic regression showed that, in concert with a number of other parameters, age is a significant influencing factor on postoperative morbidity and mortality. The increase in postoperative morbidity and mortality rates associated with aging is a result of the increase in general postoperative complications, in particular, pneumonia and cardiovascular complications. Age as such does not represent a contraindication for surgical treatment. The short-term outcome and quality of life are of overriding importance for the geriatric patient.

Age Factors↗

PubMed2005

Comparison of the ovine and porcine animal models for biocompatibility testing of vascular prostheses.

OBJECTIVE: Evaluation of the pig and sheep models for biocompatibility investigations of vascular prostheses (VP). DESIGN: Comparative analysis of animal experimental investigations involving two different animal models. MATERIALS AND METHODS: Commercially available polyester vascular prostheses (PET-VP) were implanted into two different animal models (infrarenal porcine aorta and ovine carotid artery). The costs, surgical handling, patency rate, and healing on the basis of macroscopic, microscopic, and immunohistochemical criteria were analyzed over a period of 3 months. RESULTS: Handling and operating times (63 +/- 10 versus 76 +/- 16 min; P = 0.125) did not differ significantly. The cost of the two animal models was comparable. Integration of the VP was complete in the sheep model, but varied in the pig model (two complete, four incomplete). Complete endothelialization of all VPs was observed in the pig, which contrasted with the sheep with complete (circular) endothelialization only in the region of the anastomosis. The thickness of neointima in the region of the anastomosis differed insignificantly; immunohistochemically, only periprosthetic Ki67 was significantly reduced (28.7 +/- 9.9 versus 6 +/- 0.9%; P = 0.002) in the sheep. CONCLUSIONS: In the porcine model, extremely good endothelialization of the VP was observed, with formation of a rapid neointimal hyperplasia. The ovine model was characterized by the fact that postoperative follow-up investigations were easy to perform. Complete endothelialization was not observed.

Animals↗

PubMed2005

Endoscopic treatment of thoracic esophageal anastomotic leaks by using silicone-covered, self-expanding polyester stents.

BACKGROUND: Surgery, as well as conservative treatment, in patients with clinically apparent intrathoracic esophageal anastomotic leaks often is associated with poor results and carries a high morbidity and mortality. The successful treatment of esophageal anastomotic insufficiencies and perforations when using covered, self-expanding metallic stents is described. METHODS: The feasibility and the outcome of endoscopic treatment of intrathoracic anastomotic leakages when using silicone-covered self-expanding polyester stents were investigated. Twelve consecutive patients presented with clinically apparent intrathoracic esophageal anastomotic leak caused by resection of an epiphrenic diverticulum (n = 1), esophagectomy for esophageal cancer (n = 9), or gastrectomy for gastric cancer (n = 2), were endoscopically treated in our department. The extent of the dehiscences ranged from about 20% to 70% of the anastomotic circumference. After endoscopic lavage and debridement of the leakage at 2-day intervals (mean duration, 8.6 days), a large-diameter polyester stent (Polyflex; proximal/distal diameters 25/21 mm) was placed to seal the leakage. Simultaneously, the periesophageal mediastinum was drained by chest drains. OBSERVATIONS: All 12 patients were successfully treated endoscopically without the need for reoperation. A complete closure of the leakage was obtained in 11 of 12 patients after stent removal (median time to stent retrieval, 4 weeks, range 2-8 weeks). In one patient, a persistent leak was sealed endoscopically after stent removal by using 3 clips. Distal stent migration was obtained in two patients. CONCLUSIONS: The placement of silicone-covered self-expanding polyester stents seems to be a successful minimally invasive treatment option for clinically apparent intrathoracic esophageal anastomotic leaks.

Aged↗

PubMed2005

Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach.

Although the incidence of Barrett's carcinomas (BC) and proximal gastric adenocarcinomas (PGC) is increasing, little is known about different epigenetic changes in these etiopathogenetically distinct entities. Therefore, 29 adenocarcinomas [10 BC, 7 PGC and 12 tumors of the esophagogastric junction (JC)] and corresponding non-tumor controls (NT) were examined using methylation-specific PCR. The most striking result was a significantly higher promoter methylation frequency of O6-methylguanine methyl transferase (MGMT) in BC compared with JC and PGC (0.7 vs. 0.08 vs. 0.29, respectively; p = 0.011; methylation exclusively in tumors), confirmed immunohistochemically by a significant loss of MGMT protein in BC (p = 0.006). Therefore, MGMT might become a prognosticator and key for chemotherapy with alkylating agents in BC. Frequencies of p16INK4a promoter methylation were 0.5 (BC), 0.42 (JC) and 0.29 (PGC; n.s.), but methylation was almost absent in NT controls. As immunonegative tumors slightly outnumber methylation-positive cases, other mechanisms of gene inactivation must be discussed. Methylation of E-cadherin was rarely observed (1/10 BC, 0/12 JC and 2/7 PGC). This is the first report on promoter methylation of death-associated protein kinase (DAPK) and fragile histidine triad gene (FHIT) in BC; both DAPK (BC 0.7, JC 0.92 and PGC 0.86) and FHIT (BC 0.88, JC 1.0 and PGC 1.0) were found to be highly methylated, suggesting that epigenetic silencing of these tumor suppressors is a common event in adenocarcinomas of the upper gastrointestinal tract, including BC. DAPK (0.54 on average) and FHIT methylation (0.77 on average) were also observed in NT samples. This might constitute an early epigenetic precursor lesion in the normally-appearing tissue surrounding the tumor.

Acid Anhydride Hydrolases↗

PubMed2004

A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa.

TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the surface integrity of mucous epithelia, and is typically secreted by intestinal goblet cells together with the mucin MUC2. Reports of the expression of TFF3 within the normal human stomach are contradictory and the precise localisation of TFF3 is unknown. We have mapped the human gastric mucosa by reverse transcription/polymerase chain reaction and Western blot analysis and by immunohistochemistry. Small amounts of TFF3 were detectable in the oxyntic mucosa of the corpus, whereas TFF3 synthesis increased sharply distal to the corpus-antrum transitional zone. TFF3 secretion was demonstrated in the antrum, the pyloric region and the proximal duodenum. High TFF1 levels were present in all regions of the gastric mucosa including the corpus, whereas the proximal duodenum was nearly devoid of TFF1. Immunohistochemistry localised TFF3 to antral and pyloric surface mucous cells. In the antrum, an increasing concentration gradient was found towards cells deeper in the isthmus. TFF1 was confined to superficial pit cells in the antrum. TFF3 was also present in specific layers of the laminated mucous gel of the antral and pyloric regions and variable concentrations of TFF3 (2-62 nmol/l) were measured in gastric juice. Here, a probably N-terminally shortened variant is present that forms disulphide-linked dimers. Thus, TFF3 is a typical secretory peptide of the normal human antral and pyloric gastric mucosa and has a gastric expression pattern different from that of TFF1 and TFF2. TFF3 might therefore have important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa.

Gastric Juice↗