Hemangioma ; genetics ; Humans ; Infant

Adult ; Consanguinity ; Female ; Hemangioma ; genetics ; Humans ; Male ; Middle Aged ; Pedigree ; Young Adult

OBJECTIVETo set up the animal model of hemangioma by microinjecting the PyMT transgenic DNA.

METHODSConstructing the transgenic PyMT gene, and microinjecting it into fertilized embryos which were transferred to pseudopregnant recipients then. Observing the phenotype of the newborn-mice, detecting the integration of transgenic DNA by PCR, and analyzing the histological morphon of the neoplasm of the mice.

RESULTSThe transgenic DNA was proved to be right and has been microinjected into 579 fertilized embryos, 62 mice were born. Within the 62 mice, one mouse was found being the phenotype of hemangioma. PyMT gene was expressed in the total DNA of the transgenic mouse by PCR.

CONCLUSIONIt could be a good way to build animal model of hemangioma with transgenic PyMT DNA.

Animals ; Antigens, Polyomavirus Transforming ; genetics ; physiology ; Female ; Hemangioma ; etiology ; Male ; Mice ; Mice, Transgenic ; Microinjections

OBJECTIVETo investigate the differentially expressed genes of proliferating and involuting hemangiomas by cDNA microarray analysis of gene-expression profiles in an effort to identify the key disease-related genes.

METHODSSamples were processed from total RNA and purified to mRNA, which was reverse-transcripted and hybridized onto Biodoor Genechip expression microarrays. Analyses were performed to determine the consensus pattern of gene expression in the proliferating and involuting stages of the same hemangioma and the changes in the expression level.

RESULTSIn proliferating hemangioma, 79 genes were overexpressed, and 115 genes were underexpressed in comparison with the involuting hemangioma. Some cytokines and growth factors such as neurotensin, Nov, CYR6, keratinocyte growth factor, interleukin-10 were overexpressed in proliferative hemangioma. In involuting hemangioma, apoptotic factors such as bcl-2 binding component, cytochrome C were overexpressed. The overexpression of Nov, CYR6, c-myc implied that angiogenesis and oncogenes might participate in the pathogenesis of hemangiomas. Mitochondria activated apoptotic passage (cytokines, bcl-2, cytochrome C) and Wnt/beta-catenin passage(Frizzled, beta-catenin, c-myc) were involved.

CONCLUSIONThe development of hemangiomas may be the results of imbalance of cell proliferation and apoptosis.

Apoptosis ; Cell Division ; Female ; Gene Expression Profiling ; Hemangioma ; genetics ; pathology ; Humans ; Male ; Oligonucleotide Array Sequence Analysis

OBJECTIVETo study the effect of CCM1 gene mutations in Chinese patients with intracranial cavernous angiomas(ICCA).

METHODSTwenty-one ICCA patients confirmed by pathology after operations in hospital from June 2002 to Feb.2003 and 15 healthy individuals as contrast were recruited. The peripheral venous blood samples of all the individuals were collected, and then DNA was extracted from the blood samples followed by amplification of exon 12 and some of its intron sequence using PCR. After purification, the PCR products were directly sequenced by ABI PRISM377 sequencing instrument.

RESULTSThree mutations of CCM1 gene were found in 5 patients and reported firstly. There existed a missense mutation of 1172C-->T in exon 12 in 5 patients, which led the No.391 amino acid of KRIT1 protein, serine, to phenyalanine. There existed a missense mutation of 1160A-->C in one patient, which led the No.387 amino acid, glutamine, to proline. Another mutation was an intronic mutation of IVS12-4C-->T in 4 patients. In contrast no mutations were found.

CONCLUSIONThe authors firstly report that mutations of CCM1 gene in exon 12 also exist in Chinese ICCA patients and those mutations are related with the occurring of ICCA.

Adolescent ; Adult ; Brain Neoplasms ; genetics ; Exons ; Female ; Hemangioma, Cavernous ; genetics ; Humans ; KRIT1 Protein ; Male ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Middle Aged ; Mutation ; Proto-Oncogene Proteins ; biosynthesis ; genetics

This study examined the roles of HLA-G in the pathogenesis, development and immune tolerance of hemangioma. From 2000 to 2007, 52 paraffin-embedded specimens (26 from males and 26 from females) of skin capillary hemangioma and 7 samples of adjacent normal skin tissues were collected. Four fresh specimens of hemangioma were also harvested. All samples were HE-stained and proliferative cell nuclear antigen (PCNA) was immunohistochemically detected by using SP method. The samples were classified into proliferative group and degenerative group according to the Mulliken criteria and the expression pattern of PCNA. SP method and quantum dots double staining were applied to detect the expression of HLA-G and PCNA in hemangioma and normal tissue samples. The expression of HLA-G was detected by RT-PCR. The results showed that among the 52 samples of hemangioma, 29 were of proliferative type and 23 degenerative type, and of the four fresh samples of hemangioma, 2 were of proliferative type and 2 degenerative type. SP method results showed that HLA-G was expressed in both proliferative and degenerative hemangioma, but not in normal tissues. The quantum dots double staining exhibited that HLA-G expression was significantly higher in proliferative group than in degenerative (P<0.05) and normal groups (P<0.05), but there was no statistically significant difference between the latter two groups (P>0.05). RT-PCR revealed that HLA-G was transcribed in both the proliferative and degenerative hemangioma tissues, but not in normal tissues. We are led to conclude that the elevated expression of HLA-G in proliferative hemangioma cells may lead to immune tolerance, which allows cells to escape immune surveillance and proliferate. On the other hand, the lower expression of HLA-G in degenerative hemangioma may result in immune cells-induced degeneration of hemangioma.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; HLA-G Antigens ; genetics ; Hemangioma, Capillary ; genetics ; Humans ; Infant ; Male ; Middle Aged ; Skin Neoplasms ; genetics ; Young Adult

OBJECTIVETo detect the expression of TRAIL protein and mRNA in hemangiomas and vascular malformations.

METHODSSections of 33 proliferative hemangiomas,28 involuting hemangiomas and 29 vascular malformations were immunostained for TRAIL protein, TRAIL mRNA was examined by in situ hybridization in these tissue.

RESULTSThe TRAIL protein positive rates in proliferative hemangiomas, involuting hemangiomas, vascular malformations and normal skins were respectively 45.45% (15/33), 78.57% (22/28), 0% and 0%. There were significant differences among the four pathologies (P < 0.01). The difference between proliferative hemangiomas and involuting hemangiomas was also significant (P < 0.01). The TRAIL mRNA positive rates were 66.67% (11/33), 89.29 (25/28), 0% and 0% respectively. There were also significant differences among the four pathologies (P < 0.01). The difference between proliferative hemangiomas and involuting hemangiomas was also significant (P < 0.01).

CONCLUSIONSTRAIL could induce endothelial apoptosis and cause regression of hemangiomas.

Apoptosis ; Female ; Hemangioma ; metabolism ; pathology ; Humans ; In Situ Hybridization ; Infant, Newborn ; Male ; Microcirculation ; RNA, Messenger ; genetics ; TNF-Related Apoptosis-Inducing Ligand ; genetics ; metabolism ; Vascular Malformations ; metabolism ; pathology

OBJECTIVETo study the expressions of β-catenin in hepatocellular carcinoma (HCC) tissue, adjacent cirrhotic liver tissue and hemangioma-surrounding liver tissue to understand whether their difference in expression will influence on the prognosis and to study the relationship between Wnt/β-catenin signaling pathway and HNF-1α expression.

METHODS50 specimens of HCC, 50 specimens of adjacent cirrhotic liver tissue and 7 specimens of hemangioma-surrounding liver tissue were used to detect the differences in the expression of β-catenin and HNF-1α in them by immunohistochemistry.

RESULTSThe expression rate of β-catenin was 74.0% (37/50) in the HCC tissue, 18.0% (9/50) in cirrhotic liver tissue, and 14.3% (1/7) in hemangioma-surrounding liver tissue. The expression rate of β-catenin in HCC tissue was significantly higher than that in the hemangioma-surrounding liver tissue (P = 0.002) and cirrhotic liver tissue (P < 0.001). The patients with abnormal expression had worse prognosis. Among the 50 HCC cases, the expression of HNF-1α was negative in 20.0% (10/50), weak positive in 40.0% (20/50), moderately positive in 26.0% (13/50), and strong positive in 14.0% (7/50). Among the 50 adjacent cirrhotic liver tissues, the expression of HNF-1α was negative in 12.0% (6/50), weak positive in 20.0% (10/50), moderately positive in 52.0% (26/50) and strong positive in 16.0% (8/50). In the 7 cases of hemangioma-surrounding liver tissue, the expression of HNF-1α was negative in 0(0/7), weak positive in 14.3% (1/7), moderately positive in 28.6% (2/7) and strong positive in 57.1% (4/7). The positive expression rate of HNF-1α in the HCC tissue was significantly lower than that in the hemangioma-surrounding liver tissues (P = 0.029) and adjacent cirrhotic liver tissues (P = 0.008). The patients with positive HNF-1α expression had a better prognosis. The abnormal expression of β-catenin was negatively correlated with positive HNF-1α expression (r = -0.673, P < 0.001).

CONCLUSIONSThe occurrence and development of HCC is related to the abnormal β-catenin expression. There is a negative correlation between Wnt/β-catenin signaling pathway and HNF-1α expression.

Carcinoma, Hepatocellular ; diagnosis ; metabolism ; Hemangioma ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; diagnosis ; metabolism ; Prognosis ; beta Catenin ; genetics ; metabolism

OBJECTIVETo study the clonality of polygonal cells and surface cuboidal cells in the so-called pulmonary sclerosing hemangioma (PSH).

METHODS17 female surgically resected PSH were found. The polygonal cells and surface cuboidal cells of the 17 PSH cases were microdissected from routine hematoxylin and eosin-stained sections. Genomic DNA was extracted, pretreated through incubation with methylation-sensitive restrictive endonuclease HhaI or HpaII, and amplified by nested polymerase chain reaction for X chromosome-linked androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism of AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining. The PGK gene products were treated with Bst XI and resolved on agarose gel.

RESULTSAmongst the 17 female cases of PSH, 15 samples were successfully amplified for AR and PGK genes. The rates of polymorphism were 53% (8/15) and 27% (4/15) for AR and PGK genes respectively. Polygonal cells and surface cuboidal cells of 10 cases which were suitable for clonality study, showed the same loss of alleles (clonality ratio = 0) or unbalanced methylation pattern (clonality ratio < 0.25).

CONCLUSIONSThe polygonal cells and surface cuboidal cells in PSH demonstrate patterns of monoclonal proliferation, indicating that both represent true neoplastic cells.

Chromosomes, Human, X ; genetics ; DNA, Neoplasm ; genetics ; Female ; Humans ; Male ; Phosphoglycerate Kinase ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Pulmonary Sclerosing Hemangioma ; genetics ; pathology ; Receptors, Androgen ; genetics ; X Chromosome Inactivation

OBJECTIVE: To explore the effect of HNF1A-AS1 on the proliferation, migration and invasion of IL-6-induced hemangioendothelial cells (HemEC) and possible mechanism. METHODS: RT-qPCR was used to detect the expression level of HNF1A-AS1 and miR-363-3p in the tumor tissue and adjacent normal skin tissue from 35 patients with hemangioma. Pearson correlation was used to analyze the correlation between the expression of HNF1A-AS1 and miR-363-3p in tumor tissues. HemEC were isolated and cultured in vitro.Dual luciferase reporter gene experiment was used to study the regulatory effect between HNF1A-AS1 and miR-363-3p. IL-6 was added to HemEC transfected with si-NC, si-HNF1A-AS1, si-HNF1A-AS1 and anti-miR-NC, or si-HNF1A-AS1 and anti-miR-363-3p, respectively. CCK-8 method and clone formation experiment were used to detect cell proliferation in each group. Transwell method was used to detect cell migration and invasion in each group. Western blotting was used to detect the expression of Ki67, MMP-2 and MMP-9 proteins in each group. RESULTS: Compared with normal skin tissues, the expression of IL-6 mRNA in hemangioma tissues was increased (P<0.05), and the expression of IL-6 mRNA in the proliferative phase was lower than that in the degenerative phase (P<0.05). Expression of HNF1A-AS1 in hemangioma tissue was increased (P<0.05), while that of miR-363-3p was decreased (P<0.05), and the two were negatively correlated (r=-0.758, P<0.05). HNF1A-AS1 down-regulated the expression of miR-363-3p in HemEC.IL-6 promoted the expression of HNF1A-AS1, OD value, number of colonies, number of migration and invasion of HemEC cells, and the expression of Ki67, MMP-2 and MMP-9proteins (P<0.05), while reduced the expression of miR-363-3p (P<0.05). Down-regulating si-HNF1A-AS1 reduced the IL-6-induced HemEC cell OD value, colony numbers, migration and invasion and the expression of Ki67, MMP-2 and MMP-9 proteins (P<0.05). Down-regulating miR-363-3p attenuated the inhibitory effect of down-regulating si-HNF1A-AS1 on the proliferation, migration and invasion of HemEC cells induced by IL-6 (P<0.05). CONCLUSION Expression of HNF1A-AS1 is increased in hemangioma tissues. Down-regulating HNF1A-AS1 may inhibit proliferation, migration and invasion of IL-6-induced hemangioma endothelial cells by targeted up-regulation of miR-363-3p.
Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Endothelial Cells ; Gene Expression Regulation, Neoplastic ; Hemangioma/genetics* ; Hepatocyte Nuclear Factor 1-alpha/genetics* ; Humans ; Interleukin-6/genetics* ; MicroRNAs/genetics* ; RNA, Long Noncoding