OBJECTIVES: To observe the reparative effects of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation on white matter injury (WMI) in neonatal rats and explore its mechanism through the nuclear factor-kappa B (NF-κB) signaling pathway mediated by microglial cells. METHODS: Sprague-Dawley rats, aged 2 days, were randomly divided into three groups: sham-operation,WMI, and hUC-MSC (n=18 each). Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in the white matter, and immunofluorescence staining was used to measure the expression level of ionized calcium-binding adapter molecule 1 (Iba1). Western blotting was used to measure the protein expression levels of inhibitory subunit of nuclear factor-kappa B alpha (IκBα), phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), myelin basic protein (MBP), and neuron-specific nuclear protein (NeuN). Quantitative real-time PCR was used to assess the mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), MBP, and NeuN. Immunohistochemistry was used to measure the protein expression levels of MBP and NeuN. On day 28, the Morris water maze test was used to evaluate spatial cognitive ability. RESULTS: Fourteen days after modeling, the sham-operation group exhibited intact white matter structure with normal cell morphology and orderly nerve fiber arrangement. In the WMI group, large-scale cell degeneration and necrosis were observed, and nerve fiber arrangement was disordered. The hUC-MSC group showed relatively normal cell morphology and more orderly nerve fibers. Compared with the sham-operation group, the WMI group had significantly higher proportions of Iba1-positive cells, increased protein levels of p-IκBα and p-NF-κB p65, and higher mRNA levels of TNF-α and IL-1β. The protein expression of IκBα and the positive expression of MBP and NeuN, as well as their protein and mRNA levels, were significantly reduced in the WMI group (P<0.05). Compared with the WMI group, the hUC-MSC group showed reduced proportions of Iba1-positive cells, decreased protein levels of p-IκBα and p-NF-κB p65, and lower mRNA levels of TNF-α and IL-1β. Furthermore, IκBα protein expression and MBP and NeuN expression (both at the protein and mRNA levels) were significantly increased in the hUC-MSC group (P<0.05). On day 28, the Morris water maze results showed that compared with the sham-operation group, the WMI group had significantly longer escape latency and fewer platform crossings (P<0.05). In contrast, the hUC-MSC group had significantly shorter escape latency and more platform crossings than the WMI group (P<0.05). CONCLUSIONS hUC-MSC transplantation can repair WMI in neonatal rats, promote the maturation of oligodendrocytes, and support neuronal survival, likely by inhibiting activation of the NF-κB signaling pathway mediated by microglial cells.
Animals ; Rats, Sprague-Dawley ; White Matter/metabolism* ; Rats ; Signal Transduction ; Mesenchymal Stem Cell Transplantation ; Humans ; NF-kappa B/metabolism* ; Animals, Newborn ; Umbilical Cord/cytology* ; Male ; NF-KappaB Inhibitor alpha/metabolism* ; I-kappa B Proteins/genetics* ; Microfilament Proteins/analysis* ; Calcium-Binding Proteins/metabolism* ; Female

OBJECTIVETo study the clinicopathologic features and differential diagnosis of adenoid cystic carcinoma in the esophagus.

METHODSTen cases of primary adenoid cystic carcinoma of the esophagus were retrieved from the archival file. The clinicopathologic and immunohistochemical features were studied. The differential diagnosis was analyzed.

RESULTSThe male-to-female ratio was 9: 1. The age of patients ranged from 59 to 76 years. There were 4 cases with tumor located in mid esophagus, 4 cases with tumor located in mid to lower esophagus and the remaining 2 cases in lower esophagus. Low-power histologic examination showed mainly expansive growth pattern, with cribriform, solid and focal tubular architectures identified. The tumor cells showed nuclear hyperchromasia. Both ductal and myoepithelial differentiation was demonstrated. The stroma showed myxoid degeneration in areas. Comedo-type necrosis was observed in 8 cases and moderate to severe squamous dysplasia was present in one case. Three cases showed focal areas of squamous cell carcinoma. Immunohistochemical study showed that the tumor cells were positive for p63 (10/10), CD117 (10/10) and S-100 protein (9/10). There was focal staining for calponin (2/10) and smooth muscle actin (2/10). The ductal structures expressed CK7 (10/10).

CONCLUSIONSAdenoid cystic carcinoma of the esophagus demonstrates unique morphologic features with expression of S-100 protein and consistent expression of CD117. The above characteristics help to distinguish this entity from basaloid squamous cell carcinoma, mucoepidermoid carcinoma and small cell carcinoma of the esophagus.

Aged ; Calcium-Binding Proteins ; analysis ; Carcinoma, Adenoid Cystic ; chemistry ; pathology ; Carcinoma, Small Cell ; chemistry ; pathology ; Carcinoma, Squamous Cell ; chemistry ; pathology ; Esophageal Neoplasms ; chemistry ; pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Microfilament Proteins ; analysis ; Middle Aged ; S100 Proteins ; analysis

No abstract available.
Child, Preschool ; DNA Mutational Analysis ; Diseases in Twins/*genetics/metabolism ; Ectopia Lentis/*genetics/metabolism ; Extracellular Matrix Proteins ; Humans ; Male ; Microfilament Proteins/*genetics/metabolism ; *Mutation ; *Twins, Monozygotic

BACKGROUNDChronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). Some HBV mutants and dysregulation of phosphatase and tensin homolog (PTEN) may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects.

METHODSQuantitative polymerase chain reaction was applied to genotype PTEN polymorphisms (rs1234220, rs2299939, rs1234213) in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic HBV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis.

RESULTSRs1234220 C allele was significantly associated with HCC risk compared to healthy controls (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.07-1.69) and HCC-free HBV-infected subjects (AOR = 1.27, 95% CI = 1.01-1.57). rs1234220 C allele was significantly associated with increased frequencies of HCC-risk A1652G, C1673T, and C1730G mutations in genotype B HBV-infected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients (AOR = 0.75, 95% CI = 0.62-0.92). The interaction of rs2299939 variant genotypes (GT+TT) with A3054T mutation significantly increased HCC risk (AOR = 2.41, 95% CI = 1.08-5.35); whereas its interaction with C3116T mutation significantly reduced HCC risk (AOR = 0.34, 95% CI = 0.18-0.66). These significant effects were only evident in males after stratification.

CONCLUSIONSPTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.

Carcinoma, Hepatocellular ; enzymology ; genetics ; DNA Mutational Analysis ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Liver Neoplasms ; enzymology ; genetics ; Microfilament Proteins ; genetics ; Mutation ; PTEN Phosphohydrolase ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Polymorphism, Genetic ; genetics ; Tensins

OBJECTIVETo investigate the effects of rapamycin (RAP) on pulmonary hypertension (PH) in rats, and to provide new insights into medication selection for the clinical treatment of PH.

METHODSFifty male Sprague-Dawley rats were randomly divided into blank control, PH model, solvent control, RAP 1, and RAP 2 groups. A rat model of PH was induced by left pneumonectomy (PE) and monocrotaline (MCT). At 5 days after PH model establishment, the solvent control group and the RAP 1 group received an intramuscular injection of solvent and RAP, respectively. At 35 days after PH model establishment, the RAP 2 group received an intramuscular injection of RAP. The mean pulmonary artery pressure (mPAP) and the right ventricle/left ventricle plus septum weight ratio (RV/LV+S) were measured in each group. Histopathological changes in the right lung were evaluated by hematoxylin-eosin (HE) staining. The relative expression of alpha-smooth muscle actin (α-SMA) and smooth muscle protein 22-alpha (SM22α) in each group was determined using real-time PCR.

RESULTSAt 35 days after surgery, the PH model and the solvent control groups had significantly higher mPAP and RV/LV+S than the blank control group, while the RAP 1 and the RAP 2 groups had significantly lower mPAP than the solvent control group (P<0.05). The RV/LV+S in the RAP 1 group was significantly lower than that in the solvent control group (P<0.05); however, there was no significant difference in RV/LV+S between the RAP 2 and the solvent control groups (P>0.05). HE staining in the right lung showed the substantially thickened pulmonary artery wall and narrowed arterial lumen in the PH model and the solvent control groups compared with the blank control group. Different degrees of reversal of the pulmonary artery wall thickening were observed after RAP administration. The results of real-time PCR revealed that the relative expression of α-SMA and SM22α in the PH model and the solvent control groups was significantly lower than in the blank control group, while the relative expression of α-SMA and SM22α in the RAP 1 and the RAP 2 groups was significantly higher than in the solvent control group (P<0.05).

CONCLUSIONSRAP can reverse the increase in pulmonary artery pressure and the right ventricular hypertrophy probably by regulation of the phenotypic conversion of vascular smooth muscle cells.

Actins ; genetics ; Animals ; Hemodynamics ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Hypertrophy, Right Ventricular ; etiology ; Male ; Microfilament Proteins ; genetics ; Muscle Proteins ; genetics ; Pulmonary Artery ; pathology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Sirolimus ; therapeutic use

OBJECTIVETo establish an animal model of gastric cancer by long-term infection of Helicobacter pylori (H.pylori) and to elucidate the pathogenesis by proteomics analysis.

METHODSFifty male Mongolian gerbils (4-5 week-old and weighted 60-100 g) were infected with H.pylori and the gastric tissues were obtained after the infection at 3, 6, 12 and 24 months. Histological changes were evaluated by H-E staining of the gastric tissue sections. Detection of H.pylori was performed by in-vitro culture of fresh gastric tissue samples, PCR amplification of H.pylori 16s rRNA and localization by silver staining. In addition, proteins extracted from gastric tissue samples were subjected to two-dimensional electrophoresis (2-DE) at various infection time points. Protein spots with increased quantity over the course of H.pylori infection were selected and analyzed by LC-MS/MS. Finally, differentially expressed proteins between human gastric cancer tissue samples and lymph nodes were analyzed by real-time RT-PCR.

RESULTSColonization of H.pylori was observed in gastric tissue of gerbils as early as 3 months after H.pylori infection, and persisted till 24 months. Pathological examination of infected animals showed various histological changes including acute gastritis, atrophic gastritis, intestinal metaplasia and gastric carcinoma. Seventy-eight differentially expressed proteins were identified by proteomics analysis, among which 36 proteins were up-regulated and 42 were down-regulated. Analyzed by LC-MS/MS, ten proteins were identified, including lactate dehydrogenase, ATP synthase, fatty acid-binding protein, COX5B, peroxiredoxin-4, peroxide reductase, transgelin, succinyl-CoA ligase, keratin and protein disulfide-isomerase A2, among which transgelin, ATP synthase and lactate dehydrogenase were highly expressed in human gastric carcinoma and lymph nodes.

CONCLUSIONSH.pylori infection induces the expression of transgelin, ATP synthase and lactate dehydrogenase, implying possible roles in the pathogenesis of gastric diseases including cancer.

Animals ; Disease Models, Animal ; Gastritis ; microbiology ; pathology ; Gerbillinae ; Helicobacter Infections ; complications ; metabolism ; Helicobacter pylori ; genetics ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Male ; Metaplasia ; Microfilament Proteins ; metabolism ; Muscle Proteins ; metabolism ; Proteomics ; Proton-Translocating ATPases ; metabolism ; RNA, Ribosomal, 16S ; analysis ; Stomach Neoplasms ; metabolism ; microbiology ; Tandem Mass Spectrometry

OBJECTIVETo screen for mutations of fibrillin-1 (FBN1) gene in 4 patients with Marfan syndrome in order to provide prenatal diagnosis and genetic counseling.

METHODSPotential mutations of the FBN1 gene in the probands were detected with PCR and DNA sequencing. Subsequently, genomic DNA was extracted from amniotic fluid sampled between 18 to 20 weeks gestation. The mutations were confirmed with denaturing high-performance liquid chromatography - robust microsatellite instability (DHPLC-MSI) analysis with maternal DNA as reference. The products were further analyzed by direct sequencing and BLAST search of NCBI database.

RESULTSAn IVS46+1G>A substitution was identified in patient A at +1 position of intron 46 of the FBN1 gene. Two novel missense mutations were respectively discovered at positions +4453 of intron 35 in patient B (Cys1485Gly) and position +2585 of intron 21 in patient C (Cys862Tyr). In patient D, a novel deletion (c.3536 delA) was found at position +3536 of intron 28. In all of the 4 cases, the same mutations have been identified in the fetuses.

CONCLUSIONFBN1 gene analysis can provide accurate diagnosis of Marfan syndrome, which can facilitate both prenatal diagnosis and genetic counseling.

Adult ; Base Sequence ; DNA Mutational Analysis ; Female ; Fibrillin-1 ; Fibrillins ; Humans ; Introns ; Male ; Marfan Syndrome ; diagnosis ; embryology ; genetics ; Microfilament Proteins ; genetics ; Molecular Sequence Data ; Mutation, Missense ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion

OBJECTIVESTo investigate the relationship between the expression of transgelin-2 and the clinicopathological factors of colorectal carcinoma and evaluate the value of transgelin-2 in prognostic assessment of the colorectal cancer patients.

METHODSUsing tissue microarray and immunohistochemical methods, we examined transgelin-2 of 120 colorectal cancer patients received surgical treatment from September 2002 to April 2004, including 74 male and 46 female, age from 26 to 89 years. Analyzed the relationship between transgelin-2 and both the clinicopathological features and prognosis of the colorectal cancer by using χ² test and Kaplan-Meier survival analysis. Cox proportion hazard regression analysis was used to study the independent prognostic factors.

RESULTSThe positive rate of transgelin-2 expression was 69.2% in colorectal carcinoma. The transgelin-2 expression correlated with differentiation degree (χ² = 5.420), lymph nodes metastasis (χ² = 45.577), distant metastasis (χ² = 12.009), and TNM staging (χ² = 47.577). The survival time was (39 ± 5) months in patients with positive expression of the transgelin-2, while (59 ± 3) months in patients with negative expression. The patient's survival time was statistically correlated with the transgelin-2 expression (P = 0.003). Distant metastasis (RR = 8.318, 95%CI: 4.119 - 16.790), lymph nodes metastasis (RR = 2.794, 95%CI: 1.246 - 6.263) and transgelin-2 expression (RR = 1.834, 95%CI: 1.118- 2.973) were independent prognostic factors in patients with colorectal cancer (P < 0.05).

CONCLUSIONSThe expression of transgelin-2 is correlated with clinicopathological features and prognosis in colorectal cancer, may be the potential marker of metastasis and the prognosis of colorectal cancer patients.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Microfilament Proteins ; metabolism ; Middle Aged ; Muscle Proteins ; metabolism ; Prognosis ; Regression Analysis

BACKGROUND: Alterations in the phosphatase and tensin homolog (PTEN) are correlated with tumor progression. Downregulation of PTEN is related to drug resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the prognostic significance of PTEN in patients with NSCLC and its correlation with EGFR. METHODS: Two hundred eighty eight surgically resected NSCLC samples, including 168 adenocarcinomas (ADCs), 99 squamous cell carcinomas (SCCs) and 21 other NSCLCs were analyzed for the PTEN. The results were correlated with other clinicopathological variables including EGFR amplification and mutation. RESULTS: Loss of PTEN was detected in 42.4% of NSCLCs, specifically 28.6% of ADCs, 66.7% of SCCs, and 38.1% of others. Loss of PTEN was significantly associated with SCC, smoking, male gender, and higher stage. In a multivariate analysis, loss of PTEN was significantly associated with short progression-free survival (p=0.037). No association between PTEN and EGFR was observed. CONCLUSIONS: These results suggest that loss of PTEN results in shorter progression-free survival in patients with NSCLC, and loss of PTEN is more associated with SCC, smoking, male gender, and higher T stage by the 7th tumor, node and metastasis staging system but not EGFR status.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Down-Regulation ; Drug Resistance ; Humans ; Immunohistochemistry ; Male ; Microfilament Proteins ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Smoke ; Smoking

BACKGROUND: Fascin is associated with motility in various transformed cells. Overexpression of fascin is known to aid in the progression of some cancers and is associated with a poor prognosis. E-cadherin is a major protein of epithelial cells and its expression is involved in the regulation of cell proliferation and differentiation. The aim of this study was to determine the expression pattern for fascin and E-cadherin and how it is related to the prognostic factors for renal cell carcinoma (RCC). METHODS: The expression of fascin and E-cadherin was evaluated in 208 RCCs including 175 clear cell, 20 papillary, and 9 chromophobe types using tissue array analysis. RESULTS: The expression of fascin increased as the tumor stage (p=0.00) and Fuhrman grade (p=0.00) increased. A high positive rate of expression for fascin was observed in cases with sarcomatoid changes (p=0.27). E-cadherin expression was seen in the distal tubules and collecting ducts of normal kidneys with a membranous pattern. The positive rate of expression for E-cadherin increased as the Fuhrman grade increased (1, 0%; 2, 23.2%; 3, 34.9%; and 4, 53.8%, p=0.00). An inverse correlation in RCCs was observed in the expression of fascin and E-cadherin (p=0.026, r=-0.158). CONCLUSIONS: In patients with RCC, the increased expression of fascin and E-cadherin was positively correlated to poor prognostic factors such as a higher Fuhrman nuclear grade and advanced pTNM stage.
Cadherins ; Carcinoma, Renal Cell ; Carrier Proteins ; Cell Proliferation ; Epithelial Cells ; Humans ; Kidney ; Microfilament Proteins ; Prognosis ; Tissue Array Analysis