Biomedical subjects

Caj Haglund

Publications and source records attributed to Caj Haglund.

At least 19 recordsLinked to original sources

PubMed2006

Pulmonary endostatin perinatally and in lung injury of the newborn infant.

OBJECTIVE: Endostatin is a potent angiogenesis inhibitor. Angiogenesis is central for the development of the human lung. The role of endostatin in the development of the human lung and its connection to chronic lung disease remain unclear. We set out to study the role of endostatin in the developing human lung and in acute and chronic lung injury in the preterm infant. METHODS: Nine fetuses, 14 control neonates without primary lung disease, 14 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia were included in the immunohistochemistry study. Tracheal aspirate-fluid samples of intubated very low birth weight infants during postnatal weeks 1 through 5 were analyzed with enzyme-linked immunosorbent assay. RESULTS: Endothelial cell staining was positive for endostatin in all 45 samples. Staining of epithelial cells (cuboidal, bronchiolar, and alveolar) was seen mostly in fetuses, as well as in infants with late respiratory distress syndrome and bronchopulmonary dysplasia. Staining in alveolar macrophages was most abundant in infants with late respiratory distress syndrome and bronchopulmonary dysplasia. Endostatin was expressed consistently in tracheal aspirate fluid, being highest during the first postnatal day. Higher endostatin concentrations correlated with parameters reflecting lower lung maturity. CONCLUSIONS: The pattern of pulmonary endostatin protein expression in immunohistochemistry and consistent endostatin protein appearance in tracheal aspirate fluid in human preterm infants indicate a role in the physiologic development of the lung. Preterm birth influences pulmonary endostatin protein expression, which may alter normal lung development and response to lung injury.

Angiogenesis Inhibitors↗

PubMed2006

Ki-67, p53, ER receptors, ploidy and S phase as long-term prognostic factors in T1 node-negative breast cancer.

BACKGROUND: The aim of the present study was to evaluate a series of biomarkers with regard to long-term prognostic value in patients with T1 (< or =2 cm) node-negative breast cancer. METHOD: The prognostic value of Ki-67, p53, oestrogen receptor (ER) immunohistochemical labelling, flow-cytometric S phase fraction and ploidy was evaluated in 212 patients with pT1N0M0 breast cancer. The median follow-up time was 15.9 years (range 0.2-27.2 years). RESULTS: In an analysis of breast cancer-specific survival up to 5 years, high Ki-67 (> or =10%; p = 0.002), high p53 (> or =20%; p = 0.01), negative ER (<30%; p = 0.01) as well as aneuploidy of the tumour (p = 0.02) were significant prognostic factors. When the follow-up was extended to 10 years, only Ki-67 (p = 0.03) was significantly associated with outcome and beyond 15 years none of the studied markers provided significant prognostic information when analyzed separately. There was a weak but significant difference in long-term survival when patients with a combination of high Ki-67 (> or =10%), high SPF (>3%) and high p53 (> or =20%) were compared to patients with other combinations (p = 0.03). CONCLUSION: According to the results of our series, it seems that several prognostic markers which are associated with short-term survival (< or =5 years) in pT1N0M0 breast cancer may not be significant predictors of long-term (>15 years) breast cancer-specific survival.

Adult↗

PubMed2006

Prognostic significance of cyclin A in gastric cancer.

High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in > or =5% of the tumor cells was considered the cut-off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the chi2-test, Fisher's exact test, Kaplan-Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279 of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR.

Aged↗

PubMed2006

Targeted gene-expression analysis by genome-controlled reverse transcription-PCR.

BACKGROUND: For gene-expression analysis, which is anticipated to play an important role in classification of tumors and premalignant conditions, PCR-based quantitative assays must have increased diagnostic quantitative accuracy and reproducibility and enable analysis of gene expression in formalin-fixed paraffin-embedded (FFPE) tissue samples. METHODS: We developed a reverse transcription-PCR-based quantitative assay that modifies the cDNA sequence to increase the melting temperature of short (56-64 bp) PCR amplicons, enabling their quantification in-tube by homogeneous melting-curve analysis. We used this method to analyze the expression of 8 genes, 7 potential colon cancer markers, and 1 control in samples obtained from 3 colon carcinoma cell lines, endoscopic biopsy from 8 patients undergoing gastroscopy for Barrett esophagus, and archival FFPE and frozen tissue from 20 patients who underwent surgery for colon carcinoma. RESULTS: The detection limit of the assay, when optimized for FFPE samples, was 100 copies of cDNA, and the dynamic range was 3 orders of magnitude. A prototype assay containing a panel of 8 genes displayed good reproducibility compared with the commercially available TaqMan assay (interassay CVs, 5%-20% vs 7%-43%, respectively). Gene-expression analysis was performed successfully in 26 (96%) of 27 endoscopic biopsy specimens, 30 (86%) of 35 archival FFPE samples, and 20 (100%) of 20 archival frozen samples. CONCLUSIONS: This new technology combines the reproducibility of competitive PCR with accurate quantitative detection by in-tube melting-curve analysis, enabling efficient analysis of mRNA profiles in samples with small numbers of cells or small amounts of tissue, as well as in archival FFPE tissues.

Barrett Esophagus↗

PubMed2006

Up-regulation of trypsin and mesenchymal MMP-8 during development of hyperoxic lung injury in the rat.

Acute lung injury is marked by damage to alveolar-capillary barrier. High pulmonary levels of matrix-degrading serine proteinase trypsin and matrix metalloproteinases (MMP)-2, -8, and -9 have been shown in preterm infants with respiratory distress syndrome (RDS). We studied expression of trypsin and MMP-2, -8, and -9 in rats exposed to >95% oxygen for 24, 48, or 60 h. As demonstrated by zymography and Western immunoblotting, levels of trypsin and MMP-2, -8, and -9 in bronchoalveolar lavage fluid (BALF) sharply increased after 48 h of hyperoxia relative to normoxia controls. This coincided with increase in alveolar-capillary permeability, as indicated by increased protein concentration in BALF. Both neutrophil-derived 80-kD and mesenchymal cell-derived 60-kD MMP-8 isoforms were detected in BALF. Of them, mesenchymal-type MMP-8 predominated. In immunohistochemistry, alveolar epithelium showed strong trypsin expression at 48 and 60 h of hyperoxia, whereas it was predominantly negative in controls. MMP-8 was mostly expressed in macrophages. Marked up-regulation of trypsin and MMP-8 early during hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury and may therefore be potential targets for therapy of lung injury.

Animals↗

PubMed2006

Pulmonary vascular endothelial growth factor-C in development and lung injury in preterm infants.

RATIONALE: In mice, vascular endothelial growth factor-C (VEGF-C) plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear. OBJECTIVES: We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants. METHODS: Included in the immunohistochemistry study were 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia. Tracheal aspirate fluid samples of intubated very-low-birth-weight infants during Postnatal Weeks 1-5 were analyzed with ELISA. RESULTS: Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen in most fetuses (8/10). In addition, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGF receptor-3 (VEGFR-3) staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first 2 postnatal days. Antenatal administration of glucocorticoids was associated with higher VEGF-C in tracheal aspirate fluid. CONCLUSIONS: The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiologic development of the lymphatic system of the lung.

Bronchi↗

PubMed2006

Frequent loss of heterozygosity at 6q in pheochromocytoma.

Multiple genetic alterations have been associated with pheochromocytoma (PCC). Most PCCs are sporadic, but they also occur in inherited tumor syndromes, including von Hippel-Lindau disease. Although the etiology of most inherited PCCs is well documented, little is known about the etiology of sporadic tumors. Mutations of those genes that harbor germ-line mutations in familial cases cover only 10% to 15% of somatic mutations in sporadic PCCs. A previous cytogenetic analysis indicated frequent loss of 6q in sporadic PCCs. We therefore investigated in detail 18 PCCs using 22 microsatellite markers spanning 6q to search for the presence of allele deletions and identify specific regions likely to contain tumor suppressor genes involved in PCC. Moreover, we sought to compare PCC with capillary hemangioblastoma, another von Hippel-Lindau disease-associated tumor that we previously found to harbor frequent loss of heterozygosity (LOH) at 6q. Our study revealed a high frequency (13/18; 72%) of overall 6q LOH in PCCs. Loss of heterozygosity at 6q was observed in 6 benign (6/9; 67%) and 7 borderline (7/9; 78%) tumors. We identified 2 regions where LOH or allelic imbalance was common (ie, 6q14 [9/18; 50%] and 6q23-24 [6/18; 33%]). We further focused the search using markers specific for the ZAC1 gene region located at 6q24-25. Altogether, for all 6q23-25 markers, including the ZAC1-specific ones, LOH or allelic imbalance was observed in 50% (9/18) of the PCCs. Similar to our findings for capillary hemangioblastomas, our data for the first time suggest that one or several tumor suppressor genes located at 6q, particularly at 6q23-24, may play a role in the tumorigenesis of PCCs.

Adult↗

PubMed2006

Tenascin-C expression in Merkel cell carcinoma lymph node metastasis.

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate.

Biomarkers, Tumor↗

PubMed2006

High concentrations of plasminogen activator inhibitor-1 in lungs of preterm infants with respiratory distress syndrome.

BACKGROUND: Among preterm infants, respiratory distress syndrome (RDS) is characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers inhibit surfactant function effectively. However, little is known about potential disturbances of intraalveolar fibrinolysis in RDS. We studied levels of major plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) in lungs of preterm infants with RDS. METHODS: The antigen levels of PAI-1, tPA, and uPA were measured in 262 samples of tracheal aspirate fluid collected from 37 intubated preterm infants during the first 2 postnatal weeks. To examine the expression of PAI-1, tPA, and uPA in lung tissue, immunohistochemical analyses were performed on autopsy specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary pathologic conditions. RESULTS: For infants with an immature surfactant profile, as indicated by lecithin/sphingomyelin ratios in tracheal aspirate fluid of < 10, PAI-1 levels and ratios of PAI-1 to uPA and tPA were significantly higher during postnatal days 1 to 2, compared with infants with lecithin/sphingomyelin ratios of > or = 10. Moreover, infants who subsequently developed bronchopulmonary dysplasia (BPD) (n = 15) had higher PAI-1 levels on days 3 to 4 and days 7 to 8 than did those who survived without BPD. For preterm infants with RDS, immunohistochemical analyses demonstrated increased expression of PAI-1, tPA, and uPA predominantly in alveolar epithelium. CONCLUSIONS: High concentrations of PAI-1 and an increased ratio of PAI-1 to uPA, with a concurrently less-increased ratio of PAI-1 to tPA, are associated with the severity of RDS among preterm infants during the first postnatal days. Pulmonary inhibition of fibrinolysis is a pathophysiologic feature of RDS and may play a role in the development of BPD.

Enzyme-Linked Immunosorbent Assay↗

PubMed2006

VEGF-C and COX-2 expression in papillary thyroid cancer.

In papillary thyroid cancer (PTC), age appears to be the most important single prognostic factor. Another characteristic feature is the lack of association between survival and lymph node metastases. Earlier, we found that expression of cyclooxygenase-2 (COX-2) is higher in older PTC patients, in agreement with the finding that older patients have a worse prognosis. Recent findings suggest that COX-2 can up-regulate vascular endothelial growth factor-C (VEGF-C) expression. Here, we investigated whether expression of VEGF-C differs between young and older PTC patients and whether expression of VEGF-C and COX-2 are correlated. Our retrospective study comprised 106 PTC patients selected by age: those under 35 or over 55 at diagnosis. Paraffin-embedded tissue samples were analysed by immunohistochemistry for VEGF-C protein expression. Furthermore, we investigated by quantitative RT-PCR and enzyme immunoassay the relationship between VEGF-C and COX-2 expression in papillary thyroid cancer cells (NPA cells). VEGF-C expression was significantly increased with age. In the tumours from older lymph node-positive (N1) patients, VEGF-C expression was significantly higher than in the tumours from young N1 patients. Moreover, all patients who died of cancer or who developed distant metastases were old, and most tumours from these patients (4 of 5) expressed VEGF-C and had had nodal metastases at the time of primary operation. Immunohistochemically, expression of COX-2 and VEGF-C correlated strongly. In cell culture, this correlation was not so clear, because the COX-2 selective inhibitor, NS-398, did not reduce VEGF-C expression. However, as both COX-2 and VEGF-C were induced by the tumour promoter phorbol 12-myristate 13-acetate (PMA), the same factors may control them both.

Adult↗

PubMed2006

Cyclooxygenase-2 expression in squamous cell carcinoma of the oral cavity and pharynx: association to p53 and clinical outcome.

Cyclooxygenase-2 (COX-2) expression is up-regulated in transformed cells and in malignant tissues, including tumours of the head and neck, and it has prognostic significance in many types of cancer. COX-2 expression is suppressed by the wild-type but not by the mutant tumour suppressor gene TP53. The purpose of this study was to investigate the association between the expression of COX-2 and the clinical outcome in patients with oral and pharyngeal squamous cell carcinoma (SCC), and to examine its relationship to p53. Immunohistochemistry showed an elevated COX-2 expression in 88% (n = 57; strong 38, weak 19) of the 65 tumour samples. The staining intensity was not associated with patient or tumour characteristics, nor with the immuhistochemical expression of p53. Kaplan-Meier analysis showed no significant correlation between COX-2 expression and recurrence-free or overall survival, but a strong p53 expression was associated with a poor recurrence-free (p = 0.001, log-rank) and overall survival (p = 0.003). We conclude that, unlike strong p53 expression, COX-2 expression does not have prognostic significance in advanced oral and pharyngeal SCCs.

Adult↗

PubMed2005

Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells.

Cyclooxygenase-2 (COX-2) expression is a marker of poor prognosis in gastric cancer patients, and its inhibition suppresses gastric tumorigenesis in experimental animal models. The mechanism that leads to COX-2 overexpression in this tumor type is unknown. We have now shown that inhibition of phosphatidylinositol 3-kinase by LY294002 suppresses both basal and phorbol myristate acetate-induced COX-2 expression in TMK-1 and MKN-28 gastric cancer cells. Furthermore, inhibition of glycogen synthase kinase-3beta (GSK-3beta) by SB415286 induced expression of COX-2 mRNA and protein as well as the enzyme activity in the gastric cancer cells. The effect of SB415286 was confirmed by the use of two additional GSK-3beta inhibitors, lithium chloride and SB216763. SB415286 had a modest 1.6-fold stimulatory effect on a 2-kb COX-2 promoter reporter construct, but more importantly, it was shown to block the decay of COX-2 mRNA. In contrast to modulation of phosphatidylinositol 3-kinase/Akt/GSK-3beta pathway, inhibitors of mitogen-activated protein kinases (MEK 1/2, p38, JNK) or the mammalian target of rapamycin did not alter COX-2 expression in gastric cancer cells. Our data show that inhibition of GSK-3beta stimulates COX-2 expression in gastric cancer cells, which seems to be primarily facilitated via an increase in mRNA stability and to a lesser extent through enhanced transcription.

Aminophenols↗

PubMed2005

Cyclooxygenase-2 is an independent prognostic factor in gastric cancer and its expression is regulated by the messenger RNA stability factor HuR.

PURPOSE: Cyclooxygenase-2 (COX-2) promotes carcinogenesis and its expression associates with clinicopathologic characteristics in gastric cancer. HuR is an mRNA binding protein that controls the stability of certain transcripts including COX-2. We evaluated the prognostic significance of COX-2 and HuR expressions in gastric cancer and whether there exists a link between HuR and COX-2 expressions. EXPERIMENTAL DESIGN: The study included 342 consecutive patients with histologically confirmed gastric adenocarcinoma, of whom 321 patients had tissue specimens available for COX-2 and 316 for HuR immunohistochemistry. Specimens were stained by COX-2- and HuR-specific monoclonal antibodies and scored by two independent observers. Correlation to clinical data and survival was assessed. TMK-1 gastric adenocarcinoma cells were treated with small interfering RNA against HuR and expressions of HuR and COX-2 were detected by immunofluorescence and Western blot analysis. RESULTS: Patients with low COX-2 expression had a cumulative 5-year survival of 53% and those with high COX-2 expression had 16% (P < 0.0001). In multivariate analysis, COX-2 was an independent prognostic factor (P = 0.003). Cytoplasmic HuR expression was associated with high COX-2 expression (P < 0.0001) and with reduced survival (P = 0.004) whereas nuclear positivity for HuR was not. When TMK-1 cells were treated with HuR small interfering RNA, expressions of HuR and COX-2 were reduced. CONCLUSIONS: High COX-2 is an independent prognostic factor in gastric cancer. Cytoplasmic expression of HuR associates with high COX-2 expression and with reduced survival, and tissue culture experiments show that HuR can regulate expression of COX-2 in gastric cancer cells.

Adenocarcinoma↗

PubMed2005

Prognostic role of cyclooxygenase-2 in neoadjuvant-treated patients with squamous cell carcinoma of the esophagus.

Based on our previous demonstration that elevated cyclooxygenase-2 (COX-2) expression is a prognostic factor for reduced survival in patients with adenocarcinoma of the esophagus, the aim of our study was to analyze the role of COX-2 expression in esophageal squamous cell carcinoma. We analyzed COX-2 protein expression from 117 consecutive patients by immunohistochemistry using a COX-2 specific monoclonal antibody. Eighty-one patients had not received any therapy before surgery whereas 36 patients received neoadjuvant chemotherapy as part of a randomized controlled trial. In the patients who received no chemotherapy, COX-2 expression was low in 75% and high in 25% of the specimens. In this patient group, high COX-2 expression associated with distal location of the tumor (p = 0.02), but did not correlate with any other clinicopathological parameter tested, including overall survival. In the patient group who received neoadjuvant chemotherapy, postoperative COX-2 expression was low in 69% and high in 31%. Interestingly, in this patient group low COX-2 expression correlated with development of distant metastases (p = 0.03) and to reduced overall survival (p = 0.02). Our results show that the prognostic significance of COX-2 depends on the histological type of esophageal carcinoma and preoperative treatment of the patient. In conclusion, COX-2 is not a prognostic marker in squamous cell carcinoma of the esophagus, but low COX-2 expression is associated with poor prognosis in the neoadjuvant-treated patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Syndecan-1 expression--a novel prognostic marker in pancreatic cancer.

OBJECTIVE: Syndecan-1 is a transmembrane receptor that participates in cell-cell and cell-matrix interactions, cell proliferation and cell migration. Expression of syndecan-1 is downregulated in many cancers, but in pancreatic ductal adenocarcinoma it is upregulated. METHOD: We studied the immunohistochemical expression of syndecan-1 in 144 pancreatic adenocarcinomas and evaluated the prognostic value of syndecan-1 expression. Formalin-fixed, paraffin-embedded specimens were stained with mouse monoclonal antibody B-B4 against human syndecan-1. The epithelial and stromal staining was separately evaluated and compared with patient survival, clinical stage and histological grade. RESULT: Epithelial immunoreactivity was observed in most of the pancreatic carcinoma samples: in 70 (49%) of the samples the epithelial staining was weak, in 48 (33%) moderate, in 18 (12%) strong and in only 8 (6%) of the samples the epithelial staining was negative. Stromal staining was weak in 24 (17%), moderate in 31 (22%), strong in 11 (8%) and negative in 78 (54%) of the pancreatic carcinoma samples. Lack of stromal expression predicted a better prognosis (p = 0.002; HR 1.7) and it was independent of stage (p = 0.01; HR = 1.5) and grade (p = 0.0004; HR 2.1) in multivariate analysis. Epithelial expression predicted better prognosis for patients that underwent surgery for cure (n = 94, p = 0.03). CONCLUSION: Stromal syndecan-1 expression is an independent prognostic marker in pancreatic cancer, whereas epithelial syndecan-1 expression predicts better prognosis only in resectable disease.

Acute Disease↗

PubMed2005

High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants.

Proteinase-activated receptor 2 (PAR(2)), a G-protein-coupled receptor activated by serine proteinases such as trypsin, has been suggested to play an important role in inflammatory and fibroproliferative processes. In preterm infants, the development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation and subsequent interstitial fibrosis. High pulmonary trypsin-2 has been shown to be associated with the development of BPD. We studied the expression and distribution of PAR(2) and trypsin-2 by immunohistochemistry in autopsy lung specimens of fetuses (n = 10), of preterm infants who died of acute or prolonged respiratory distress syndrome (RDS) (n = 8 and n = 7, respectively) or BPD (n = 6), and of newborn infants without lung disease (n = 5) who served as controls. In prolonged RDS and BPD, PAR(2) immunoreactivity was significantly higher in bronchial epithelium when compared with infants without pulmonary pathology (p < 0.05 and p < 0.005, respectively). In alveolar epithelium, expression of PAR(2) was elevated in prolonged RDS when compared with newborn infants without pulmonary pathology (p < 0.05). Moreover, strong expression of PAR(2) was detected in myofibroblasts of thickened and fibrotic alveolar walls in prolonged RDS or BPD. Trypsin-2 was co-localized with PAR(2) in bronchoalveolar epithelium. These findings suggest that PAR(2), possibly activated by trypsin-2, may participate in inflammation and fibroproliferation associated with progression of RDS toward BPD in preterm infants.

Acute Disease↗

PubMed2005

Prognostic factors in papillary thyroid cancer: an evaluation of 601 consecutive patients.

BACKGROUND: Although papillary thyroid cancer (PTC) is among the most curable cancer types, it can be a distressing disease for those patients suffering from frequent recurrences or even distant metastases leading to death. Age over 45 years is the most important indicator of poor prognosis. Our aim was to evaluate markers which might predict the outcome of an individual patient better than does TNM classification alone. MATERIALS AND METHODS: Of 601 consecutive patients who underwent surgery for PTC, retrospectively we selected 36 patient pairs in which one recovered completely after primary surgery, and the other suffered from aggressive disease. Formalin-fixed, paraffin-embedded tumor samples from these 72 patients were analyzed by immunohistochemistry for COX-2, MMP-2, VEGF-C, Bcl-2, Ki-67, and p21 expression. RESULTS AND CONCLUSIONS: None of the markers we studied showed a superiority over TNM classification in selecting patients likely to progress to aggressive disease. However, the expression of COX-2 and VEGF-C seemed to be increased in patients over 45, which could explain the more aggressive behavior of these tumors. Moreover, we found that age over 45, tumor size over 4 cm, extrathyroidal extension of tumor, nodal metastases, distant metastases, and stage IV had an unfavorable effect on survival.

Adult↗

PubMed2005

Mucosal expression of p21, p27, p53, Bcl-2, and bax after small bowel resection and autotransplantation in pigs.

Massive small bowel resection increases ileal villus height as part of normal adaptation. However, despite no gut loss, autotransplantation of the entire small intestine also increases ileal villus height. Our aim was to test whether similar modulation of enterocyte proliferation and apoptosis underpin these comparable increases in villus height. Fifteen pigs were randomly assigned for laparotomy (n=5), 75% proximal small bowel resection (n=5), or jejunoileal autotransplantation (n=5). Eight weeks postoperatively, full-thickness small bowel sections underwent routine immunohistochemistry for cell cycle inhibitors (p53, p21, and p27), antiapoptotic Bcl-2, and proapoptotic bax. The specimens were analyzed semiquantitatively, and the number of intensively positive epithelial cells for each group was compared from 20 digital images (0.32 mm(2)/image). Compared with laparotomy, small bowel resection decreased the number of p27-positive enterocytes in both jejunum and ileum, increased the number of bax-expressing cells in ileum, but decreased the number of bax-expressing cells in jejunum. In contrast, compared with laparotomy, jejunoileal autotransplantation altered neither mucosal bax nor p27 expression. In all groups, Bcl-2 expression was similarly confined to inflammatory cells of the lamina propria, while both p53 and p21 were negative. We conclude that long-term alterations in the enterocytic expression of certain cell cycle and apoptosis markers (p27 and bax) accompany small bowel resection. These changes differ between the jejunum and the ileum and are not seen after whole small bowel autotransplantation. Therefore, increased ileal villus height after autotransplantation, despite resembling postresectional intestinal adaptation, is underpinned by different regulation of enterocyte proliferation and apoptosis.

Animals↗