BACKGROUND: Metastasis is one of the most important characteristics of cancer in terms of its impact on patient survival. Unfortunately, identification of altered genes during tumor metastasis is limited. METHODS: Using high-throughput microarrays containing 19K spotted human oligonucleotides, gene expression of primary and matched metastatic colon cancer were compared in previous study. Although DNA microarray analysis did not demonstrate complete classification of primary and metastatic carcinoma, 80 differentially expressed genes were identified. Among these, expression of osteopontin, matrix metalloproteinase-1 (MMP-1) and serpin A1 was assessed using immunohistochemistry in a validation set containing 43 pairs from tissue microarrays. RESULTS: The expression of osteopontin was significantly higher in metastatic carcinoma than in primary carcinoma, as indicated by mRNA expression. The expression of MMP-1 was significantly lower in metastatic carcinoma. Expression of serpin A1 was not correlated with the microarray results. CONCLUSIONS: Osteopontin and MMP-1 expression successfully classified primary and metastatic colorectal carcinomas and further studies on their clinical application is encouraged.
alpha 1-Antitrypsin ; Colonic Neoplasms ; Colorectal Neoplasms ; Gene Expression ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 1 ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides ; Osteopontin ; RNA, Messenger

OBJECTIVETo study the value of the determination of serum and urine haptoglobin (HP) and alpha 1-antitrypsin (AAT) in predicting the response to glucocorticoid therapy in children with primary nephrotic syndrome (PNS).

METHODSA total of 84 children with PNS were classified to steroid-sensitive nephrotic syndrome (SSNS) (n=58) and steroid-resistant nephrotic syndrome (SRNS) groups (n=26). Forty healthy children were randomly selected for the control group. HP and AAT levels in blood and urinary samples were determined using ELISA. The efficiency of HP and AAT in predicting the response to glucocorticoid treatment of PNS was evaluated by the receiver operating characteristic (ROC) curve.

RESULTSCompared with the control group, both the SSNS and SRNS groups had significantly higher serum HP concentrations and urine AAT/Cr ratio before treatment (P<0.05); compared with the SSNS group, the SRNS group had significantly higher serum HP concentrations and urine AAT/Cr ratio before treatment and after one week and four weeks of treatment (P<0.05). Serum HP had the highest efficiency in predicting the response to glucocorticoid treatment of PNS at the concentration of 37.935 mg/mL, with the sensitivity and specificity being 92.3% and 86.2% respectively. Urine AAT/Cr ratio had the highest prediction efficiency at 0.0696, with the sensitivity and specificity being 100% and 79.3% respectively. ROC curve analysis of serum HP combined with urine AAT/Cr ratio showed a better prediction efficiency, with the sensitivity and specificity being 92.3% and 96.6% respectively.

CONCLUSIONSThe increase in serum HP level or urine AAT/Cr ratio may indicate glucocorticoid resistance in the early stage of PNS. A combination of the two can achieve better efficiency in the prediction of SRNS.

Child ; Child, Preschool ; Creatinine ; urine ; Female ; Glucocorticoids ; therapeutic use ; Haptoglobins ; analysis ; urine ; Humans ; Male ; Nephrotic Syndrome ; blood ; drug therapy ; urine ; alpha 1-Antitrypsin ; analysis ; blood ; urine

OBJECTIVETo study the effect of imbalance between lysosomal enzymes and their inhibitors in blood on disturbance of the local and whole body after trauma.

METHODSThe dynamic changes of lysosomal enzymes and proteinase inhibitors were studied in 12 pigs with femoral comminuted fractures in both hind limbs caused by high velocity missiles. Four normal pigs served as controls.

RESULTSAfter injury, the activity of Cathepsin D in arterial plasma increased gradually and reached the highest level at 8 hours, acid phosphatase in serum began to increase at 12 hours and the value of serum elastase did not change significantly. The level of alpha1-antitrypsin, a proteinase inhibitor in plasma, decreased significantly in the early stage after injury [73.5%+/-6.4% and 81.0%+/-5.1% of the baseline value (1.67 micromol x ml(-1) x min(-1)+/- 0.29 micromol x ml(-1) x min(-1)) at l and 2 hours after injury, respectively, P<0.05], then increased gradually and was higher than the baseline value at 12 hours after injury.

CONCLUSIONSImbalance between lysosomal enzymes and proteinase inhibitors occurs soon after injury, which might result in continuous tissue damage and play an important role in the disturbance of general reaction after injury.

Acid Phosphatase ; blood ; Animals ; Cathepsin D ; blood ; Endopeptidases ; blood ; Female ; Lysosomes ; enzymology ; Male ; Pancreatic Elastase ; blood ; Swine ; Wounds, Gunshot ; blood ; alpha 1-Antitrypsin ; analysis

No abstract available.
Actins/analysis ; Adult ; Female ; Human ; Immunohistochemistry ; Lactoferrin/analysis ; Muramidase/analysis ; Phosphopyruvate Hydratase/metabolism ; Pregnancy ; S100 Proteins/analysis ; Salivary Gland Neoplasms/chemistry/*pathology ; Salivary Glands/chemistry/*embryology ; Submandibular Gland/embryology ; alpha 1-Antitrypsin/analysis

BACKGROUND: Effective treatment and monitoring of tuberculosis (TB) requires biomarkers that can be easily evaluated in blood samples. The aim of this study was to analyze the serum proteome of patients with TB and to identify protein biomarkers for TB. METHODS: Serum samples from 26 TB patients and 31 controls were analyzed by using nano-flow ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in data-independent mode, and protein and peptide amounts were calculated by using a label-free quantitative approach. The generated data were analyzed by using principal component analysis and partial least squares discriminant analysis, a multivariate statistical method. RESULTS: Of more than 500 proteins identified, alpha-1-antitrypsin was the most discriminative, which was 4.4 times higher in TB patients than in controls. Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis. CONCLUSIONS: Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants. Alpha-1-antitrypsin levels may aid in the diagnosis of TB.
Adult ; Aged ; Antithrombin III/analysis ; Biological Markers/blood ; Chromatography, High Pressure Liquid ; Discriminant Analysis ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proteome/*analysis ; *Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tuberculosis/*blood/genetics/metabolism ; alpha 1-Antitrypsin/analysis

Alpha 1-antitrypsin (AAT) deficiency is a genetic disorder that primarily affects the lungs and liver. While AAT deficiency is one of the most common genetic disorders in the Caucasian population, it is extremely rare in Asians. Here, we report the case of a 36-year-old Korean woman with AAT deficiency who visited the emergency department of our hospital for the treatment of progressive dyspnea that had begun 10 years ago. She had never smoked. Chest computed tomography revealed panlobular emphysema in both lungs, which suggested AAT deficiency. The serum AAT level was 33 mg/dL (reference interval: 90-200 mg/dL). Four exons of the SERPINA1 gene, which is responsible for AAT deficiency, and their flanking regions were analyzed by PCR-direct sequencing. The patient was found to have 1 missense mutation (c.230C>T, p.Ser77Phe; Siiyama) and 1 frameshift mutation (c.1158dupC, p.Glu387ArgfsX14; QOclayton). This is the first Korean case of AAT deficiency confirmed by genetic analysis and the second case of a compound heterozygote of Siiyama and QOclayton, the first case of which was reported from Japan.
Adult ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Exons ; Female ; Frameshift Mutation ; Heterozygote ; Humans ; Mutation, Missense ; Pedigree ; Pulmonary Emphysema/diagnosis/radiography ; Republic of Korea ; Sequence Analysis, DNA ; Tomography, X-Ray Computed ; alpha 1-Antitrypsin/genetics ; alpha 1-Antitrypsin Deficiency/diagnosis/*genetics/radiography

BACKGROUND/AIMS: Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B. METHODS: The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared. RESULTS: Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B. CONCLUSIONS: Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.
Adolescent ; Adult ; Aged ; Area Under Curve ; Biological Markers/blood ; Female ; Hepatitis B, Chronic/complications/*diagnosis/pathology ; Humans ; Liver Cirrhosis/complications/*diagnosis ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Retrospective Studies ; Transferrins/*blood ; Young Adult ; alpha 1-Antitrypsin/blood

Protein-losing enteropathy (PLE) is a syndrome characterized by excessive gastrointestinal protein loss, resulting in hypoproteinemia and edema. A variety of benign and malignant conditions can be associated with PLE and acute leukemia is a very rare cause of PLE. We report a case of PLE associated with acute lymphoblastic leukemia. A 27-year-old man was admitted due to watery diarrhea, epigastric pain and bilateral leg edema. Laboratory findings showed hypoproteinemia and polycythemia. The diagnosis of PLE and acute lymphoblastic leukemia were confirmed on the measurement of fecal alpha1-antitrypsin clearance and bone marrow examination. After systemic chemotherapy and autologous stem cell transplantation, his clinical symptoms and abnormal laboratory findings were gradually improved.
Adult ; Bone Marrow Cells/pathology ; Endoscopy, Gastrointestinal ; Humans ; Magnetic Resonance Imaging ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/*diagnosis/genetics ; Protein-Losing Enteropathies/complications/*diagnosis ; Thoracic Vertebrae/radiography ; Tomography, X-Ray Computed ; Translocation, Genetic ; alpha 1-Antitrypsin/analysis

Serum levels of alpha-1-Antitrypsin(AAT) were determined in 42 patients with hepatocellular carcinoma(HCC), 5 patients with metastatic liver cancer from stomach adenocarcinoma, 10 patients with liver cirrhosis, 10 patients with chronic hepatitis, and 66 controls by rocket immunoelectrophoresis using rabbit antiserum. The mean level of serum AAT was 225.5 +/- 73.0 mg/dl in 66 controls. The serum AAT in patients with HCC was 428.7 +/- 123.3 mg/dl, which was significantly higher than those in the controls and in patients with liver cirrhosis or chronic hepatitis(p less than 0.02). The level of AAT in metastatic liver cancer was similar to that in HCC. The positive cut-off value for elevation of serum AAT in this study was determined as above 445 mg/dl, the mean plus 3 standard deviations in the controls. Elevations of serum AAT were observed in 54.8%, 60.0%, and 10.0% of patients with HCC, metastatic liver cancer, and liver cirrhosis, respectively, while none of the patients with chronic hepatitis or the controls was positive. The serum AAT levels in 42 patients with HCC were analyzed with regard to sex, age, serum albumin, HBsAg, alpha-fetoprotein(AFP), and diameter of HCC, with no significant differences being observed between these factors and the serum AAT levels except for the diameter of the HCC. The positive rate in the HCC with a diameter of 10 cm or more was 74.1%, which was a significantly higher rate compared with 20.0% in the HCC with diameters less than 10cm. The positive rate of AFP for HCC was 61.9%, when 500 ng/ml of AFP was used as the cut-off value.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Carcinoma, Hepatocellular/blood/*diagnosis ; False Negative Reactions ; False Positive Reactions ; Female ; Humans ; Liver Neoplasms/blood/*diagnosis ; Male ; Middle Aged ; Tumor Markers, Biological/*blood ; alpha 1-Antitrypsin/*analysis

Renal cell carcinoma (RCC) is one of the most malignant tumors in urology, and due to its insidious onset patients frequently have advanced disease at the time of clinical presentation. Thus, early detection is crucial in management of RCC. To identify tumor specific proteins of RCC, we employed proteomic analysis. We prepared proteins from conventional RCC and the corresponding normal kidney tissues from seven patients with conventional RCC. The expression of proteins was determined by silver stain after two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The overall protein expression patterns in the RCC and the normal kidney tissues were quite similar except some areas. Of 66 differentially expressed protein spots (p<0.05 by Student t-test), 8 different proteins from 11 spots were identified by MALDI-TOF-MS. The expression of the following proteins was repressed (p<0.05); aminoacylase-1, enoyl-CoA hydratase, aldehyde reductase, tropomyosin alpha-4 chain, agmatinase and ketohexokinase. Two proteins, vimentin and alpha-1 antitrypsin precursor, were dominantly expressed in RCC (p<0.05).
Aged ; Aldehyde Reductase/analysis ; Amidohydrolases/analysis ; Carcinoma, Renal Cell/*metabolism/pathology ; Comparative Study ; Electrophoresis, Gel, Two-Dimensional ; Enoyl-CoA Hydratase/analysis ; Female ; Fructokinases/analysis ; Humans ; Kidney Neoplasms/*metabolism/pathology ; Male ; Middle Aged ; Proteome/*analysis ; Proteomics/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tropomyosin/analysis ; Ureohydrolases/analysis ; Vimentin/analysis ; alpha 1-Antitrypsin/analysis