Extraskeletal Ewing's sarcoma (EES) is a branch of neuroectodermal tumor (PNET), which is very rare soft tissue sarcoma. We report a case of EES/PNET arising is the lung of a 67-yr-old man. Computed tomography, bone scintigraphy, and positron emission tomography confirmed the mass to have a primary pulmonary origin. The mass showed positive reactivity in the Periodic Acid Schiff (PAS) stain and MIC-2 immunoreactivity in immunohistochemical stain. Fluorescence in situ hybridization (FISH) was performed, which revealed an EWSR1 (Ewing sarcoma breakpoint region 1) 22q12 rearrangement. The diagnosis was confirmed both pathologically and genetically. The mass lesion was resected, and the patient is currently undergoing chemotherapy.
Aged ; Calmodulin-Binding Proteins/genetics ; Chromosome Breakage ; Chromosomes, Human, Pair 22/genetics ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*diagnosis/genetics/metabolism/pathology ; Male ; Neuroectodermal Tumors, Primitive, ; RNA-Binding Proteins/genetics ; Sarcoma, Ewing's/*diagnosis/genetics/metabolism/pathology

OBJECTIVETo investigate the relationship between the polymorphism of alpha-adducin (ADD1) gene and the two phenotypes of constitution in patients with essential hypertension, the Yang-hyperactive (YH) type and phlegm-dampness (PD) type, classified by traditional Chinese medicine (TCM) approach.

METHODSTwo hundred and seven patients differentiated by TCM approach as YH type (113 cases) or PD type (94 cases) were observed, with the systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting blood glucose (FBG), serum creatinine (Cr), uric acid (UA), total cholesterol (TC) and triglycerides (TG) as the criteria of observation. Gly460Trp polymorphism of the ADD1 gene was detected by MALDI-TOF mass spectrometry. Results The levels of BMI, DBP, FBG and UA, etc. in the PD group were significantly higher than those in the YH group respectively. The rate of GG, GT and TT type of ADD1 gene was 29.2%, 41.6% and 29.2% in the YH group, 28.7%, 48.9% and 22.3% in the PD group, showing no significant difference in ADD1 genotype distribution between the two groups, while there was also no difference in the hypertension phenotype distribution among different genotypes (both P > 0.05). For the patients with TT genotype, there were significant differences between the YH group and the PD group in BMI (24.11 +/- 3.04 kg/m2 vs 26.20 +/- 2.30 kg/m2), DBP (96.79 +/- 4.05 mmHg vs 99.56 +/- 3.90 mmHg), FBG (5.01 +/- 0.53 mmol/L vs 5.51 +/- 1.07 mmol/L) and UA level (302.22 +/- 71.95 micromol/L vs 358.25 +/- 88.75 micromol/L, all P < 0.05).

CONCLUSIONThere was no relation between ADD1 gene polymorphism and the TCM genotype of constitution in patients with essential hypertension. However, it is likely that for hypertension patients with TT genotype, those of PD type are more susceptible to cardiovascular disease and have worse prognosis than those of YH type.

Adult ; Aged ; Calmodulin-Binding Proteins ; genetics ; Diagnosis, Differential ; Female ; Humans ; Hypertension ; diagnosis ; genetics ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phenotype ; Polymorphism, Genetic

OBJECTIVETo investigate the association between the alpha-adducin gene G460T, angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphisms and salt-sensitive hypertension and early renal injury in Chinese people.

METHODSThe case-control study was performed in 200 essential hypertension (EH) and 200 normal control subjects in China. The 200 EH patients were divided into salt-sensitive(SS= 109) and non-salt-sensitive(NSS= 91) groups according to modified Sullivan's method. The genotypes of alpha-adducin gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The ACE genotypes were determined by PCR. The urine microalbum (Alb) in 200 EH subjects was measured by radioactive immunoassay.

RESULTS(1) A higher frequency of alpha-adducin gene G460T TT in EH patients was observed (P< 0.05). No significant difference of the ACE gene I/D polymorphism was found between the EH patients and normal control (P> 0.05). There were significant differences in the alpha-adducin gene TT genotype and combined genotype of TT+ II between SS and NSS subjects (P< 0.05). (2) The levels of urine Alb/Cr in SS patients were significantly higher than that in NSS patients (P< 0.05); in SS group, the levels of urine Alb/Cr in ACE II and alpha-adducin gene TT genotypes were higher than that in ACE ID, DD genotype and alpha-adducin gene GT and GG genotypes. The levels of urine Alb/Cr in the group of alpha-adducin gene TT+ ACE II combined genotype were higher than that in other combined genotypes (P< 0.05).

CONCLUSIONThe alpha-adducin gene TT genotype or combined with ACE II are significantly associated with SS hypertension. The alpha-adducin gene TT and ACE II genotypes might be genetic susceptibility factors to hypertension accompanying renal injury.

Adult ; Albuminuria ; genetics ; metabolism ; Calmodulin-Binding Proteins ; genetics ; Female ; Genotype ; Humans ; Hypertension ; genetics ; metabolism ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; genetics ; Radioimmunoassay

BACKGROUNDBrain acid soluble protein 1 (BASP1) is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated.

METHODSBASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed. pcDNA-BASP1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines (BHT-101 and KMH-2). The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenograft tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay.

RESULTSBASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues (P = 0.000). pcDNA-BASP1 restored the expression of BASP1 and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice (P = 0.000). pcDNA-BASP1 induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration.

CONCLUSIONSDownregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASP1 expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASP1 gene might act as a potential therapeutic agent for the treatment of thyroid cancer.

Aged ; Animals ; Apoptosis ; genetics ; physiology ; Calmodulin-Binding Proteins ; genetics ; metabolism ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; genetics ; physiology ; Cytoskeletal Proteins ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; genetics ; physiology ; Humans ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Nude ; Middle Aged ; Nerve Tissue Proteins ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; Xenograft Model Antitumor Assays

This study was designed to evaluate the role of bcl-2 transcriptional regulation induced by calmodulin I (CaM I) in pressure overload rat hypertrophic hearts. The model of hypertensive Sprague-Dawley rat was established by abdominal aortic constriction. The hearts were collected four weeks after abdominal aortic constriction. Velocity and isopyknic gradient centrifugation was employed to fractionate rat myocardial nuclei. Western blot analysis revealed a marked increase in phosphorylated cAMP response-element binding protein (pCREB) of cardiac hypertrophy group compared with that in control group (P<0.05), while the protein level of cAMP response-element binding protein (CREB) was constant (P>0.05). Immunohistochemistry results showed a significant increase of CaM I protein in cardiac hypertrophy group relative to the control group (P<0.05). Nuclear run off transcription assay displayed a significant increase in bcl-2 mRNA treated with trifluoperazne compared with non-drug treatment (P<0.05). The results obtained suggest that the transcription of bcl-2 is possibly regulated by CaM I hypertrophic rat hearts, and CREB phosphorylation seems to be a minor factor in bcl-2 transcriptional regulation.
Animals ; Aorta, Abdominal ; pathology ; Calmodulin ; physiology ; Cardiomegaly ; metabolism ; physiopathology ; Constriction ; Cyclic AMP Response Element-Binding Protein ; genetics ; metabolism ; Male ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVEThis study investigated the association between a missense SNP in the codon of ADD1 phosphorylation site and the susceptibility of non-cardia gastric cancer in a Chinese population.

METHODSPhosphoSitePlus and dbSNP database were combined to discover missense SNPs in the codon of phosphorylation site. Then, we genotyped the missense SNP in 1, 998 cases with non-cardia gastric cancer and 2, 008 cancer-free controls of Chinese descent. Analysis was conducted by using Logistic model adjusted by gender and age.

RESULTSThe rs4963 in the codon of ADD1 phosphorylation site was found. The frequencies of the 3 rs4963 genotypes, CC, CG, GG, among controls were 25.2%, 50.4%, and 24.4%, respectively, among patients were 20.1%, 50.6%, and 29.3%, respectively. Compared with CC genotype, the rs4963 CG genotype and GG genotype significantly increased the risk of non-cardia gastric cancer with the odds ratios being 1.24 (95%CI: 1.06 ∼ 1.46, P = 0.008) and 1.49 (95%CI: 1.25 ∼ 1.78, P < 0.001), respectively.

CONCLUSIONSFnnctional polymorphism in the phosphorylation site of ADD1 (rs4963) may influence the susceptibility of non-cardia gastric cancer.

Aged ; Asian Continental Ancestry Group ; genetics ; Calmodulin-Binding Proteins ; genetics ; Codon ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Mutation, Missense ; Odds Ratio ; Phosphorylation ; Polymorphism, Single Nucleotide ; Stomach Neoplasms ; ethnology ; genetics

OBJECTIVETo investigate the association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in Chinese.

METHODSWe randomly selected 6 villages from JingNing County, ZheJiang Province. We invited nuclear families to take part in our study. We measured each participant's blood pressure at the non-dominant arm by means of a standard mercury sphygmomanometer at subjects' homes. Five consecutive readings were averaged for analysis. Central blood pressures were obtained by use of SphigmoCor pulse wave analysis system. The observers administered a standardized questionnaire to collect information on smoking habits, alcohol consumption and use of antihypertensive drugs. Venous blood was sampled and the adducin genotype was determined by restrictive fragment length polymorphism (RFLP).

RESULTSFour hundred and forty-two subjects included 230 (52.0%) women, and 116 (26.2%) hypertensive patients, of whom 49 (11.1%) took antihypertensive drugs. The frequencies of alpha -adducin GlyGly, GlyTrp and TrpTrp genotypes were 21.3%, 54.5% and 24.2%, respectively. There was no association between the alpha-adducin Gly460Trp polymorphism and peripheral systolic and diastolic blood pressure and pulse pressure. However, both before and after adjustment for sex, age, age(2), body-mass index, current smoking, alcohol intake, and antihypertensive treatment, the alpha-adducin polymorphism was significantly (P < 0.02) associated with central systolic blood pressure and central pulse pressure. After adjustment, central systolic blood pressure (+/- SE) averaged 122.5 +/- 3.5, 114.1 +/- 1.5 and 109.1 +/- 1.8 mm Hg (P = 0.01) in the GlyGly, GlyTrp and TrpTrp subjects, respectively. The corresponding values for central pulse pressure were 39.4 +/- 1.3, 36.4 +/- 1.0 and 32.9 +/- 0.9 mm Hg (P = 0.002), respectively.

CONCLUSIONSIn the JingNing population, the adducin 460Trp allele was associated with lower levels of central systolic pressure and pulse pressure.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; Calmodulin-Binding Proteins ; genetics ; Child ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; physiopathology ; Male ; Middle Aged ; Pedigree ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVETo investigate the association of the polymorphisms of rs4961 in alpha-adducin (ADD1) and rs28933400 in Na+/K+ -ATPase a2 (ATP1A2) genes, the products of which are important for sodium transport, with essential hypertension.

METHODSMutagenically separated PCR (MS-PCR) was used to detect the genotypes of the two loci. The subjects were recruited randomly including 196 patients of essential hypertension and 192 healthy controls.

RESULTSThe frequencies of genotypes and alleles of in the ADD1 gene were significantly different between the patients and controls respectively (P=0.03, P=0.04). There was significant relationship between the genotypes of rs4961 and systolic blood pressure and blood sodium concentration. However, there was no significant relationship between the rs4961 genotypes and diastolic blood pressure, body mass index, blood kalium and chlorine concentrations. There was no polymorphism at the rs28933400 locus in the subjects analyzed.

CONCLUSIONThe rs4961 polymorphism of the ADD1 gene is associated with essential hypertension, but the rs28933400 locus in the ATP1A2 gene may have no association with essential hypertension in the studied population.

Calmodulin-Binding Proteins ; genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; genetics ; pathology ; physiopathology ; Ion Transport ; Male ; Middle Aged ; Polymorphism, Genetic ; Sodium ; metabolism ; Sodium-Potassium-Exchanging ATPase ; genetics

OBJECTIVETo study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of solid variant of angiomatoid fibrous histocytoma.

METHODSThe clinicopathologic features of 3 cases of solid variant of angiomatoid fibrous histocytoma were analyzed and the literature was reviewed.

RESULTSThere were a total of 2 males and 1 female. The age of patients ranged from 9 to 12 years. The patients presented with a painless mass located in left forearm, left knee or back. The lesions were treated by complete surgical resection. On gross examination, the tumors varied from 1.6 cm to 4.5 cm in greatest dimension. They were well-circumscribed and had pale yellow to grayish-red solid cut surface. Histologically, the tumor was composed of histocytoid cells arranged in sheet-like pattern. A fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. Immunohistochemical study showed that the tumor cells in all cases were positive for vimentin and CD68. They were negative for S100 protein, cytokeratin, CD34, CD31, smooth muscle actin, CD35, CD21 and CD30. Two cases also expressed CD99 and one of them was positive for desmin and epithelial membrane antigen. Fluorescence in-situ hybridization was positive for EWSR1 gene.

CONCLUSIONSSolid type represents a variant of angiomatoid fibrous histocytoma and is considered as tumor of borderline malignant potential. Definitive diagnosis requires thorough histologic examination and clinical correlation. Immunohistochemistry and EWSR1 gene study are helpful in further delineation and differential diagnosis. Complete resection or wide local excision with post-operative follow up is the main modality of treatment.

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Back ; Calmodulin-Binding Proteins ; genetics ; Child ; Dendritic Cell Sarcoma, Follicular ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Forearm ; Histiocytoma, Malignant Fibrous ; genetics ; metabolism ; pathology ; surgery ; Humans ; Knee ; Male ; Neoplasms, Muscle Tissue ; pathology ; Neurilemmoma ; metabolism ; pathology ; RNA-Binding Protein EWS ; RNA-Binding Proteins ; genetics ; Soft Tissue Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

OBJECTIVETo explore the association between G614T single nuclear polymorphism (SNP) of the alpha-adducin gene and the antihypertensive effect of hydrochlorothiazide (HCTZ) in essential hypertensive (EH) patients.

METHODSEight hundred twenty nine EH patients were given 12.5 mg HCTZ/d for six weeks. Alpha-adducin gene G614T SNP in the tenth exon was determined by PCR-RFLP in 754 patients with complete records. All the patients were grouped according to TT, GT and GG genotypes.

RESULTSAfter 6 weeks of HCTZ treatment, the decreases in DBP and MAP of patients carrying 614T allele of alpha-adducin were significantly greater than that of those carrying GG homozygotes (P < 0.05). The decreases in SBP and MAP were significantly greater in patients with the TT genotype as compared with GT or GG genotype (P < 0.05). The effective rate of BP fall by HCTZ was higher in patients with TT genotype than those with GT or GG genotype (P < 0.05). Multivariate stepwise regression analysis showed that the TT genotype and the baseline SBP were the two major predictors affecting the decrease in SBP.

CONCLUSIONThe present study suggests that the alpha-adducin G614T polymorphism is associated with the antihypertensive effect of HCTZ, which is more effective in patients with TT genotype.

Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; Calmodulin-Binding Proteins ; genetics ; Female ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Single-Blind Method ; Treatment Outcome