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U H Stenman

Publications and source records attributed to U H Stenman.

At least 19 recordsLinked to original sources
PubMed2002

Elevated levels of trypsinogen-2 and trypsin-2-alpha1-antitrypsin in sera of infants and children after cardiac surgery.

Acute pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass but amylase is not a reliable marker in infants. We evaluated whether the serum concentrations of trypsinogen-2 and trypsin-2-alpha1-antitrypsin (AAT) can be used to study disturbances in pancreatic function in children and infants undergoing cardiac surgery. The study comprised 21 infants < 1 year and 25 children aged 1-16 years undergoing cardiopulmonary bypass at the Children's Hospital, Helsinki University Central Hospital. Consecutive serum samples were taken before surgery, at 12 h, 1, 2 and 3 days after surgery, and before discharge from the hospital. A moderate increase in trypsinogen-2 and trypsin-2-AAT in serum was found in more than two-thirds of the patients. On day 3, there was a 4.3-fold mean increase (CI 95% 2.8-6.5) in trypsinogen-2 and a 2.4-fold mean increase (CI 95% 1.8-3.1) in trypsin-2-AAT. In 4 patients trypsinogen-2 was elevated by more than 20-fold. One patient had clinical pancreatitis, but there were no clinical signs of pancreatitis in the other three patients. The changes in trypsinogen-2 and trypsin-2-AAT were similar in infants and children. The moderate increase in the serum concentrations of trypsinogen-2 and trypsin-2-AAT after cardiac surgery in the absence of signs of pancreatitis may be due to a subclinical pancreatic disturbance, but it could also be caused by an inflammatory response and expression of extrapancreatic trypsin. Contrary to amylase, trypsinogen-2 is expressed in the pancreas of infants.

Acute Disease↗
PubMed2001

Preoperative serum concentration of hCGbeta as a prognostic factor in ovarian cancer.

In spite of a gradual improvement, survival in epithelial ovarian cancer is disappointingly low. New therapeutic regimens are emerging, and it would be important to be able to predict the prognosis and to stratify patients for clinical trials before therapy. We have evaluated the prognostic value of the pretreatment serum concentrations of 3 tumor markers. The free beta subunit of human chorionic gonadotropin (hCGbeta), CA125 and tumor-associated trypsin inhibitor (TATI) were measured in pretreatment serum samples from 146 patients treated for ovarian cancer between 1990-1995. The patients were followed up until 1998. Elevated concentrations of hCGbeta, CA125 and TATI were observed in 29%, 79% and 33%, respectively. When tested as single variables in Cox's proportional hazards model, stage, grade, size of residual tumor and hCGbeta (all p < 0.001) and CA125 (p = 0.004) correlated with prognosis. However, when fitted as multiple variables together with stage, grade and age in the same model, hCGbeta (RR = 3.42) stage (RR = 2.77) and grade (RR = 3.80) were the only significant variables. When serum hCGbeta was normal, 5-year survival was 80%, but it was only 22% when hCGbeta was elevated. In patients with stage III or IV and minimal residual disease, 5-year survival was 75% if hCGbeta was normal compared with 0% if hCGbeta was elevated. hCGbeta in serum is a strong independent prognostic factor in epithelial ovarian cancer, and its prognostic value is similar to that of grade and stage. The availability of this marker before surgery could facilitate selection of treatment modalities.

Adult↗
PubMed2001

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation.

Proteolysis mediated by matrix metalloproteinases (MMPs) and serine proteinases is associated with cancer invasion and metastasis. Activation of latent proMMPs, and especially the proforms of the type IV collagen degrading gelatinases A and B (proMMP-2 and proMMP-9), is thought to be a critical step in this process. We have recently found that human tumour-associated trypsin-2 is a potent activator of proMMP-9 and it also activates proMMP-2 in vitro. Trypsinogen, MMP-2, and MMP-9 are expressed in ovarian cancer. To elucidate the function of trypsin in vivo, we studied whether high concentrations of trypsinogen-1, trypsinogen-2, their alpha(1)-proteinase inhibitor (API) complexes, and tumour-associated trypsin inhibitor (TATI) are associated with proMMP-2 and proMMP-9 activation in ovarian tumour cyst fluids. Zymography and immunofluorometric analysis of 61 cyst fluids showed a significant association between high trypsin concentrations and the activation of MMP-9 (P = 0.003-0.05). In contrast, the trypsin concentrations were inversely associated with the activation of MMP-2 (P = 0.01-0.02). Immunohistochemical analysis of ovarian tumour tissue demonstrated expression of trypsinogen-2 and TATI in the secretory epithelium. MMP-2 was detected both in stromal and epithelial cells whereas MMP-9 was detected in neutrophils and macrophage-like cells in stromal and epithelial areas. These results suggest that trypsin may play a role in the regulation of the MMP-dependent proteolysis associated with invasion and metastasis of ovarian cancer.

Adolescent↗
PubMed2001

Plasma prolactin and prostate cancer risk: A prospective study.

Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate growth in experimental models. In humans, prolactin receptors are present in the prostate and are particularly abundant in pre-cancerous lesions. This suggests that prolactin could also be involved in the development of prostate cancer. In this study, we tested the hypothesis that elevated levels of circulating prolactin are associated with an increase in prostate cancer risk. We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort using plasma samples collected from 29,560 men at a health survey. We measured prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a median follow-up time of 4 years after health survey and from 289 controls matched for age and date of recruitment. Risk was not associated with plasma prolactin levels in univariate regression analysis. Odds ratios of prostate cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65), 0.82 (0.45-1.51) and 0.85 (0.49-1.47). Relative risk estimates remained unchanged after adjustments for height and weight or for plasma levels of testosterone, sex hormone-binding globulin, IGF-I and IGF-binding protein-3. Elevated circulating levels of prolactin were not related to an increase in prostate cancer risk, indicating that high circulating prolactin is not associated with development of prostate cancer.

Adult↗
PubMed2001

Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression.

Production of the glycoprotein hormone human chorionic gonadotropin beta (hCGbeta) has been associated with more aggressive behavior in non-trophoblastic tumors. In this study, the prognostic value of immunohistochemical hCGbeta expression was evaluated in 239 patients with colorectal cancer. Paraffin-embedded, formalin-fixed specimens were stained with hCGbeta-specific monoclonal antibody, and the results were compared with serum levels determined with an assay based on the same antibody. hCGbeta immunoreactivity was seen in 52 of 239 tumors (22%). The difference in survival time between patients with histologically hCGbeta-negative (median survival 94 months) and -positive (median survival 27 months) tumors was statistically significant (p = 0.014). The risk ratio during follow-up for patients with positive hCGbeta tissue expression was 1.65 (95% CI 1.11-2.46). In a Cox multivariate analysis, Dukes' stage, hCGbeta and age remained independent prognostic factors. There was moderate agreement between immunohistochemical and serum expression levels of hCGbeta (kappa = 0.30). Using a combination of histological and serum levels of hCGbeta, the difference between survival rates was highly significant (p < 0.001). The accuracy when predicting 5-year survival status with the combined results of serum and tissue expression was 1.3% higher compared to hCGbeta tissue expression alone. Our results show that hCGbeta expression in both tumor tissue and serum has prognostic significance independent of other clinicopathological variables. Positive tumor staining does not always occur together with elevated serum levels, and the prognostic accuracy can slightly be increased by combining the results.

Adult↗
PubMed2001

Validity of the prostate specific antigen test for prostate cancer screening: followup study with a bank of 21,000 sera in Finland.

PURPOSE: We investigate the validity of prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: A registry of serum samples drawn from 1968 to 1976 from 21,387 men was linked to the Finnish Cancer Registry. During followup from 1968 to 1991, 104 prostate cancers were identified. A matched case control design with incidence density sampling and nested in the serum sample bank was applied, and PSA was assessed. RESULTS: The estimated sensitivity of the test was 44% and specificity 94% at a cutoff of 4.0 microg./l. in the total material. The sensitivity had improved to 86% in patients diagnosed in 5 years after the sample drawing. The test had a better sensitivity (93%) and specificity (96%) in men younger than 65 years at the time of the sample drawing compared to those older. The sensitivity further improved to 100% with a cutoff of 2.5 microg./l. CONCLUSIONS: PSA is a valid screening test for prostate cancer, which compares favorably with mammography for breast cancer. However, until an effect on mortality has been shown, routine screening cannot be recommended.

Adolescent↗
PubMed2001

Specific staining of human chorionic gonadotropin beta in benign and malignant gastrointestinal tissues with monoclonal antibodies.

AIMS: Human chorionic gonadotropin (hCG) beta in serum is a promising tumour marker for gastrointestinal malignancies. Our aim was to investigate the expression of hCGbeta by immunohistochemistry in various gastrointestinal cancers and benign tissues. METHODS AND RESULTS: A monoclonal antibody (MAb) specific for free hCGbeta was used to stain 107 tissue samples from various gastrointestinal malignancies and 36 benign or normal tissue samples. The specificity of the staining was verified and the results compared with those obtained with a widely used commercial polyclonal antibody (PAb) which reacts with both free hCGbeta and intact hCG, as well as with luteinizing hormone beta. With the MAb, we observed positive immunohistochemical staining in 24% of the malignant gastrointestinal tumours. Gastric (60%) and pancreatic (56%) carcinomas, as well as extrahepatic cholangiocarcinomas (36%), were positive most frequently. We also discovered immunoreactivity in half of the non-malignant samples from pancreatic and biliary tissues. With the PAb, hCG immunoreactivity was evident more frequently in some cancers, but the staining was diffuse and occasionally polymorphonuclear leucocytes were strongly stained. CONCLUSIONS: This study shows that our MAbs specific for hCGbeta are well suited for immunohistochemistry. Our results confirm previous findings on gastrointestinal cancers and, furthermore, we demonstrate hCGbeta tissue expression in pancreatic adenocarcinoma. The results support reports on hCGbeta as a serum tumour marker for digestive tract diseases.

Adenocarcinoma↗
PubMed2001

Trypsinogen-1, -2 and tumour-associated trypsin-inhibitor in bile and biliary tract tissues from patients with biliary tract diseases and pancreatic carcinomas.

The bile concentrations of trypsinogen-1, -2 and tumour-associated trypsin-inhibitor (TATI) were determined in 23 patients with benign biliary tract disease, two with biliary tract cancer, and in 15 with pancreatic cancer. We also examined the trypsinogen and TATI expression by immunohistochemistry in tissue specimens from biliary tract cancer and non-neoplastic extrahepatic biliary tract. High levels of trypsinogen-1, trypsinogen-2, and TATI occur in bile of most patients. In contrast to the trypsinogens, the levels of TATI were significantly higher in patients with malignant disease than in those with benign diseases (p=0.04). There was no significant correlation between trypsinogen-2 and amylase (r=0.13, p=0.40), indicating that the occurrence of trypsinogen in bile is not a result of reflux of pancreatic fluid into the bile duct. Immunohistochemically, trypsinogen-2 was detected in five and TATI in 12 out of 15 non-neoplastic biliary tract specimens, and in four and seven out of 11 cholangiocarcinomas, respectively. High concentrations of trypsinogen-1, trypsinogen-2 and TATI occur in the bile of patients with non-neoplastic and malignant biliary tract disease and in patients with pancreatic cancer. At least part of the trypsinogen-2 and TATI found in bile appears to be derived from the biliary epithelium itself.

Bile↗
PubMed2001

Serum tumour markers CA 15-3, TPA, TPS, hCGbeta and TATI in the monitoring of chemotherapy response in metastatic breast cancer.

The clinical utility of CA 15-3, polypeptide specific antigen (TPS), tissue polypeptide antigen (TPA), human chorionic gonadotropin (hCGbeta) and tumour-associated trypsin inhibitor (TATI) as indicators of chemotherapy response was assessed in advanced breast cancer. Serum was prospectively collected in one center before treatment (after the first course of chemotherapy) and at response evaluation from 57 patients taking part in a multicentre randomized trial comparing docetaxel with sequential methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. The pretreatment levels of the serum markers were not predictors of the later response to treatment. Changes in the TPS level showed the strongest association with clinical response after the first course of chemotherapy and CA 15-3 at the best response evaluation. However, distinct mismatches occurred with every marker. The most problematic error was an increase in marker levels in patients with clinical responses, which might have caused interruption of therapy. This occurred in 8% and 17% of patients after the first course of chemotherapy and in 4% and 17% of patients at the best response evaluation with CA 15-3 and TPS, respectively. Moreover, after the first course of chemotherapy only 39% and 33% of the patients with progressive disease could be identified on the basis of increasing levels of CA 15-3 and TPS. respectively. Later, at clinical disease progression, TPA and TPS were found to be better indicators of disease progression than CA 15-3. In conclusion, changes in CA 15-3 or TPS levels usually correlate with clinical response, but owing to distinct discordances, they should not be used as sole indicators of response to chemotherapy in advanced breast cancer.

Adult↗
PubMed2001

A comparison of serum trypsinogen-2 and trypsin-2-alpha1-antitrypsin complex with lipase and amylase in the diagnosis and assessment of severity in the early phase of acute pancreatitis.

OBJECTIVE: The aim of the study was to compare the recently introduced laboratory markers trypsinogen-2 and trypsin-2-alpha1 antitrypsin complex (trypsin-2-AAT) in serum with lipase and amylase in the diagnostic and prognostic evaluation of patients with acute pancreatitis (AP). METHODS: The analytes were measured on admission in 64 consecutive patients with AP and in 30 controls with acute abdominal disease of extrapancreatic origin. Twenty-one patients had severe and 43 mild AP. As reference methods we used serum amylase and C-reactive protein. RESULTS: In subjects with AP, elevated trypsinogen-2 values (> or = 90 microg/L) were observed in 63 patients (98%), trypsin-2-AAT values (> or = 12 microg/L) in 64 patients (100%), lipase values (> or = 200 U/L) in 64 patients (100%), and amylase values (> or = 300 IU/L) in 62 patients (97%). The diagnostic accuracy of the markers was evaluated by receiver operating characteristic (ROC) analysis. On admission, trypsinogen-2, trypsin-2-AAT, lipase, and amylase differentiated patients with AP from controls with high accuracy and ROC analyses showed similar areas under the ROC curves (AUC) for trypsinogen-2 (AUC 0.960), trypsin-2-AAT (0.948), lipase (AUC 0.947), and amylase (AUC 0.930). For differentiation between severe and mild AP, trypsin-2-AAT (AUC 0.805) was slightly better than trypsinogen-2 (AUC 0.792), and they were both clearly better than lipase (AUC 0.583), C-reactive protein (AUC 0.519), or amylase (AUC 0.632) (p < 0.05). CONCLUSIONS: All the markers studied showed high accuracy for differentiating between AP and extrapancreatic diseases. However, trypsinogen-2 and trypsin-2-AAT displayed the best accuracy for predicting a severe AP already at admission, which makes these markers superior for clinical purposes.

Acute Disease↗
PubMed2001

Expression and regulation of MMP-20 in human tongue carcinoma cells.

Human matrix metalloproteinase-20 (MMP-20, enamelysin) fragments the enamel-specific protein amelogenin and has been shown to be synthesized exclusively by odontoblasts and ameloblasts and in certain odontogenic tumors. Here we demonstrate, for the first time, the expression of MMP-20 mRNA and protein in two carcinoma cell lines originating from the tongue. Treatment of the SCC-25 and HSC-3 cells with phorbol 12-myristate 13-acetate (10 nmol/L) up-regulated MMP-20 mRNA and protein expression by up to 1.6-fold, but transforming growth factor beta (10 ng/mL) had no effect. The latent proform of recombinant (r) human MMP-20 was converted by tumor-related trypsin-2. Activated rMMP-20 did not degrade type I or type II collagen, but efficiently hydrolyzed fibronectin, type IV collagen, laminin-1 and -5, tenascin-C, and beta-casein. This implies that MMP-20 not only participates in dental matrix remodeling but is also present in tongue carcinoma cells.

Amelogenin↗
PubMed2001

Ratios of IGF-I, IGF binding protein-3, and prostate-specific antigen in prostate cancer detection.

Recent studies have suggested that IGF-I and IGF-binding protein (IGFBP)-3, in combination with prostate-specific antigen (PSA), may enhance prostate cancer detection. In this study, we sought to determine the effect on the prediction of future prostate cancer occurrence by incorporating ratios of total and free PSA, IGF-I, IGFBP-3 into PSA testing. Within a population-based prospective cohort study, we investigated the validity (sensitivity and specificity) of plasma concentrations of total and free PSA, IGF-I, and IGFBP-3 and combinations thereof, in 114 cases and 97 controls, in the range of 1.75-13.5 microg/l for PSA, as used by Khosravi et al. (See Ref. 7 ). Validity estimated by the area under the curve in receiver operator characteristics analysis (with 95% confidence interval) for total PSA was 0.78 (range, 0.71-0.84); total/free PSA, 0.69 (range, 0.62-0.76); total PSA/IGF-I, 0.72 (range, 0.65-0.79); free PSA/IGF-I, 0.55 (range, 0.48-0.63); total PSA/IGFBP-3, 0.74 (range, 0.68-0.81); and free PSA/IGFBP-3, 0.57 (range, 0.49-0.64). Analysis of ratios of IGF-I, IGFBP-3, and free and total PSA did not improve validity of PSA testing in the prediction of future occurrence of prostate cancer. It is unlikely that these combinations will improve prostate cancer detection.

Biomarkers, Tumor↗
PubMed2001

Leptin is associated with increased prostate cancer risk: a nested case-referent study.

A Western lifestyle has been implicated in the pathogenesis of prostate cancer. However, no clear association between obesity and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin are present in the prostate. Leptin may, thus, be associated with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in Northern Sweden. Blood pressure, body mass index, and use of tobacco were recorded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and sex hormone-binding globulin were analyzed in stored samples. Their influences on prostate cancer were estimated by conditional logistic regression analysis. Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables, testosterone, and IGF-I and its binding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium. Moderately elevated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic intraepithelial neoplasia lesions, or to indirect actions through other mechanisms. A critical fat mass related to an interior milieu favorable for prostate cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.

Adult↗