Adult ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar ; genetics ; Male ; Middle Aged ; Pedigree

OBJECTIVETo analyze potential mutation in keration 9 (KRT9) gene in a large Chinese family with epidermolytic palmoplantar keratoderma (EPPK) and to perform prenatal diagnosis on the fetus at 10th gestational week.

METHODSPeripheral venous blood samples were obtained from 5 affected and 8 unaffected individuals of the family. Fifty unrelated healthy individuals were also recruited as controls. PCR was used to amplify exons 1 and 6 of KRT9 gene, and the products were sequenced directly. After the mutation was confirmed, prenatal diagnosis was performed on the fetus during the first trimester of pregnancy.

RESULTSA heterozygous missense mutation c.482A to G in the KRT9 gene, which has led to substitution of Asparaginate by Serine at codon 161 (p.N161S), was detected in all patients but not in other individuals of the family and the 50 healthy controls. The fetus was found to have carried the p.N161S mutation too. Following selected abortion, analysis of fetal tissue was consistent with prenatal diagnosis.

CONCLUSIONThe missense mutation c.482A to G (p.N161S), which has been shown previously to cause EPPK, is found in the KRT9 gene of patients in this family. Gene mutation analysis for prenatal diagnosis is efficient to facilitate detection of affected fetus in time.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; methods ; Humans ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; diagnosis ; genetics ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Prenatal Diagnosis ; methods

OBJECTIVE: To investigate the differential expression of the sensitive and resistant relative proteins in human breast cancer tissue. METHODS: A drug sensitive group and a drug resistant group for chemotherapy in patients with breast cancer were selected through neoadjuvant. The differential protein expression in 2 groups was detected by proteomics techniques, and parts of differential proteins were identified by Western blot. RESULTS: There were 13 differential proteins in the 2 groups, in which the expression of 3 proteins was up-regulated and 10 down-regulated. Seven proteins were identified by Western blot. The expression of keratin type I cytoskeletal 19 (KIC19), thymidine phosphorylase (TYPH) was upregulated, and the expression of heat shock protein 27 (HSP27), keratin type I cytoskeletal 9 (KIC9), collagen alpha-2(VI) (CO6A2), vimentin (VIME), and actin cytoplasmic 1 (ACTB) was down-regulated in the drug resistant group. There was significant difference between the 2 groups (P<0.01). CONCLUSION The expression of KIC19 and TYPH may be correlated with drug resistance in patients with breast cancer, and HSP27, KIC9, CO6A2, VIME, and ACTB may be correlated with drug sensitivity.
Adult ; Aged ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; Carcinoma, Ductal, Breast ; drug therapy ; genetics ; metabolism ; Drug Resistance, Neoplasm ; genetics ; Female ; Gene Expression Profiling ; HSP27 Heat-Shock Proteins ; metabolism ; Humans ; Keratin-19 ; metabolism ; Keratin-9 ; metabolism ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Proteins ; metabolism ; Proteome ; metabolism ; Proteomics ; Thymidine Phosphorylase ; metabolism

OBJECTIVETo analyze potential mutation of keration 9 gene (KRT9) in a Chinese family affected with epidermolytic palmoplantar keratoderma (EPPK) and to correlate genotype with the phenotype.

METHODSGenomic DNA was extracted from peripheral blood samples of 12 patients and 13 healthy individuals from the family and 100 unrelated individuals. Polymerase chain reaction (PCR) was used to amplify exons 1 and 6 of KRT9 gene. PCR products were sequenced bidirectionally in order to identify potential mutations.

RESULTSA heterozygous transversional mutation, 488G→A, was identified in exon 1 of KRT9 gene in all patients, which has resulted in substitution of a glutamine residue for arginine acid at position 163 (R163Q) of the KRT9 protein. The same mutation was not found in the 13 healthy members from the family and 100 unrelated individuals.

CONCLUSIONThe 488G→A mutation of KRT9 gene is probably the cause of EPPK in this Chinese family.

Adult ; Base Sequence ; DNA Mutational Analysis ; methods ; Female ; Humans ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; genetics ; Male ; Molecular Sequence Data ; Mutation

Adenocarcinoma ; metabolism ; pathology ; Adenoma ; pathology ; Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Intrahepatic ; CA-19-9 Antigen ; metabolism ; Cadherins ; metabolism ; Caroli Disease ; pathology ; Cholangiocarcinoma ; pathology ; Cystadenocarcinoma ; metabolism ; pathology ; Cystadenoma ; metabolism ; pathology ; Cysts ; pathology ; Diagnosis, Differential ; Hamartoma ; pathology ; Humans ; Keratin-19 ; metabolism ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Liver Diseases ; pathology

OBJECTIVETo assess the diagnostic value of tumor markers in the cerebrospinal fluid (CSF) for meningeal carcinomatosis (MC).

METHODSTwenty-one MC patients (including 13 adenocarcinoma and 8 non-adenocarcinoma patients), 72 patients with tuberculous meningitis (TBM) and 23 with primary intracerebral tumors (PIT) were enrolled in this study. Blood and CSF tumor markers including CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP and NSE were measured by Roche E170 electrochemiluminescence analyzer and sandwich assay.

RESULTSCSF tumor markers CEA, CA125, CA199 and CYFRA21-1 and the serum tumor markers CEA, CA125, CA153, CA199 and AFP were significantly higher in MC group than in the other two groups. CSF CEA and CA15-3 were significantly higher in adenocarcinoma MC than in non-adenocarcinoma MC patients, but no significant differences were found in the serum tumor markers between the two groups (P>0.05). CSF tumor markers including CEA, CA125, CA15-3, CA72-4 and CYFRA21-1 were positively correlated to the serum tumor markers (P<0.05). CA199 was positively correlated to the disease course (P<0.05), and age was not correlated to any of the indexes (P>0.05).

CONCLUSIONDetection of the tumor markers in the CSF, especially CEA, CA125, CA19-9 and CYFRA21-1, may help in the early diagnosis of MC. CEA and CA15-3 can serve as indicators for differential diagnosis of adenocarcinoma and non-adenocarcinoma.

Adenocarcinoma ; cerebrospinal fluid ; diagnosis ; Adult ; Aged ; Antigens, Neoplasm ; cerebrospinal fluid ; Biomarkers, Tumor ; cerebrospinal fluid ; CA-125 Antigen ; cerebrospinal fluid ; CA-19-9 Antigen ; cerebrospinal fluid ; Carcinoembryonic Antigen ; cerebrospinal fluid ; Female ; Humans ; Keratin-19 ; cerebrospinal fluid ; Male ; Membrane Proteins ; cerebrospinal fluid ; Meningeal Neoplasms ; cerebrospinal fluid ; diagnosis ; Middle Aged ; Young Adult

OBJECTIVETo map and identify the disease gene for the epidermolytic palmoplantar keratoderma (EPPK) in a Uighur family of China.

METHODSBlood samples were collected and genomic DNA was extracted from 48 members of the Xinjiang Uighur family. Six microsatellite repeat sequences on chromosome region 17q12-q21 and 12q13 were selected based on the two known candidate genes KRT9 and KRT1. Two-point linkage analysis and haplotype analysis were performed. Exons and their flanking intronic sequence of the KRT9 gene were amplified by polymerase chain reaction (PCR) and sequenced.

RESULTSData from the marker D17S1787 suggested linkage and yielded a Lod score of 8.65 at theta=0 by using MLINK software. Genotypes and haplotypes were acquired. The disease gene of the EPPK family is located between markers 17/TG/36620115 and D17S846. Chromosome 12q13 region was excluded with the negative Lod score obtained in marker D12S96 (Lod=-infinity at theta=0). No pathogenic mutation was detected in the KRT9 gene.

CONCLUSIONThe disease gene of the EPPK family is located on chromosome region 17q21.2. The keratin 9 gene might not be the disease gene.

China ; Chromosomes, Human, Pair 17 ; genetics ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; ethnology ; genetics ; Male ; Microsatellite Repeats ; Mutation ; Pedigree

OBJECTIVETo screen the serum proteins associated with the metastasis of hepatocellular carcinoma (HCC) using a comparative proteomic approach.

METHODSThe serum samples of HCC patients with the same disease background were divided into metastatic (n=20) and non-metastatic (n=20) groups. The proteins extracted from the patients and 20 normal subjects, after depletion of the highly abundant proteins, underwent two-dimensional gel electrophoresis (2-DE). Comparative analyses of the 2-DE protein patterns between the 3 groups were conducted using a computerized image analysis system. The proteins with statistically significant differential expression between the metastatic and non-metastatic patients were identified by mass spectrometry. Western blotting was performed to examine the differential expression of the candidate proteins.

RESULTSFour protein spots were identified by mass spectrometry among the 12 differentially expressed protein spots in the serum samples of HCC patients with intrahepatic metastasis, and confirmed by searching in MASCOT database. Of the 4 proteins, cytokeratin 9 (CK9) was up-regulated by 2 folds, and inter-alpha (globulin) inhibitor H4, complement factor H-related protein 1 precursor (FHR-1), and apolipoprotein E were down-regulated by 2 folds. CK9 was found to be specifically over-expressed in the metastatic group in comparison with the non-metastatic group, as confirmed by Western blotting.

CONCLUSIONThe metastasis of HCC might be correlated to the specific variation of protein expression profiles. The overexpression of CK9 may play a crucial role in HCC metastasis, and can be used as a potential serum marker for predicting HCC metastasis.

Adult ; Blood Proteins ; genetics ; Carcinoma, Hepatocellular ; blood ; pathology ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Glycoproteins ; blood ; genetics ; Humans ; Keratin-9 ; blood ; genetics ; Liver Neoplasms ; blood ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; genetics ; Proteinase Inhibitory Proteins, Secretory ; blood ; genetics ; Proteomics ; Up-Regulation

OBJECTIVETo investigate the clinical value of pleural effusion lung ProGRP, neuron specific enolase (NSE), cytokeratin fragment 19 (CYFRA21-1), carcino-embryonic antigen (CEA), carbohydrate antigen 153 (CA153), carbohydrate antigen 19 - 9 (CA19-9) in differential diagnosis and histological typing of malignant pleural effusion caused by lung cancer.

METHODSAll the 171 patients with malignant hydrothorax caused by lung cancer were from coal-mine area of Kailuan. They were divided into the small cell lung cancer (SCLC) group (n = 39), the adenocarcinoma group (n = 99) and the squamous cell carcinoma group (n = 37). The patients with benign pleural effusion served as the controls (n = 30). The diagnostic value of pleural effusion ProGRP, NSE, CYFRA21-1, CEA, CA153 and CA19-9 was compared for each group.

RESULTSYouden index and the accurate rate of pleural effusion ProGRP + NSE (sequence test) were the highest in the diagnosis of malignant hydrothorax caused by SCLC. CEA + CA153 + CA19-9 (sequence test) was the highest in the diagnosis of malignant hydrothorax caused by adenocarcinoma. CYFRA21-1 + CEA + CA153 (on parallel test) were the highest in the diagnosis of malignant hydrothorax caused by squamous cell carcinoma. The Yonden index and the accurate rate were the highest by the single detection of CYFRA21 (0.5514 and 0.6878), and by the combined detection of ProGRP + CYFRA21-1 + CEA (on parallel test) (0.7029 and 0.8878).

CONCLUSIONThe first pleural effusion tumor markers of malignant hydrothorax caused by the SCLC, adenocarcinoma of lung, and lung squamous cell carcinoma are ProGRP, CEA and CYFRA21-1, respectively. The best combinations of pleural effusion tumor marker in diagnosis of malignant hydrothorax caused by the SCLC, adenocarcinoma of lung, lung squamous cell carcinoma and lung cancer are the combined detection of ProGRP + NSE (sequence test), combined detection of CEA + CA153 + CA19-9 (sequence test), the combined detection of CYFRA21-1 + CEA + CA153 (on parallel test) and ProGRP + CYFRA21-1 + CEA (on parallel test), respectively.

Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; analysis ; Biomarkers, Tumor ; analysis ; CA-19-9 Antigen ; analysis ; Diagnosis, Differential ; Female ; Humans ; Keratin-19 ; analysis ; Lung Neoplasms ; complications ; diagnosis ; Male ; Middle Aged ; Peptide Fragments ; analysis ; Pleural Effusion, Malignant ; diagnosis ; etiology ; Recombinant Proteins ; analysis

OBJECTIVETo analyze the mutation of the keratin 9 gene (KRT9) in a pedigree with epidermolytic plamoplantar keratoderma (EPPK).

METHODSBlood samples were obtained from 4 affected and 3 normal individuals in this family. Mutation screening was carried out by polymerase chain reaction (PCR) and direct DNA sequencing.

RESULTSA heterozygous nucleotide C to T transition at position 484 in exon 1 of the KRT9 gene was detected in the 3 affected in this family, but was not found in normal individuals in the family and 100 unrelated individuals.

CONCLUSIONA missense mutation (484 C to T) in the KRT9 gene has been detected in this EPPK family, which is probably one of the molecular bases of the pathogenesis of the disease.

Adult ; Child, Preschool ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Humans ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar ; genetics ; Male ; Molecular Diagnostic Techniques ; Mutation ; Mutation, Missense ; Pedigree