Adult ; Aged ; CpG Islands ; genetics ; DNA Methylation ; Endometrial Neoplasms ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Humans ; Middle Aged ; Neoplasm Staging ; Receptor, Endothelin B ; genetics

OBJECTIVEThe FHIT (fragile histidine triad) is a candidate tumor suppressor gene (TSG) located on chromosome 3p14.2. Hypermethylation and loss of heterozygosity (LOH) are major mechanisms in the inactivation of tumor suppressor genes. In this study, the methylation status of FHIT and LOH of 3p14 in 61 cases of human sporadic ovary carcinomas were investigated.

METHODSSixty-one primary ovary carcinomas and 10 borderline ovarian tumors were analyzed with methylation specific PCR (MSP) to detect the CpG island methylation status in the FHIT promoter region. In addition, 45 cases of ovary carcinomas and their corresponding non-tumor ovary tissues were investigated with D3S1287 microsatellite polymorphic marker for LOH.

RESULTSHypermethylation of FHIT gene was observed in 39.3% (24/61) of ovarian carcinomas. The frequencies of hypermethylation in serous ovarian carcinoma, mucinous ovarian carcinoma, endometrioid ovarian carcinoma and ovary borderline tumor were 45.2% (19/42), 14.3% (1/7), 33.3% (4/12) and 60.0% (6/10), respectively. Ten of twenty-three (43.5%) informative tumors showed LOH and 6 of 18 (33.3%) informative cases showed homozygous deletions. The status of FHIT methylation was not associated with clinical stage and differentiation grade, there was no significant difference between the malignant and borderline tumors.

CONCLUSIONHypermethylation and allelic deletion of FHIT are frequent events in ovarian carcinomas and are important mechanisms for the loss of expression of this gene.

Acid Anhydride Hydrolases ; genetics ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Chromosomes, Human, Pair 3 ; CpG Islands ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; DNA Methylation ; DNA, Neoplasm ; genetics ; Female ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Middle Aged ; Neoplasm Proteins ; genetics ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism

OBJECTIVESTo evaluate and compare thoracic vertebrae morphology between patients with idiopathic and normal adolescents through MRI.

METHODSTwo-dimensional sagittal MRI of the spine was performed in 10 normal adolescent, 10 patients with mild idiopathic thoracic scoliosis (Cobb angle 15 degrees - 39 degrees ) and 10 patients with moderate thoracic scoliosis (Cobb angle 40 degrees - 75 degrees ), all of them were female and between 13 - 14 years old. Sagittal imaging was reconstructed on image working station (Easy Vision, Philips Medical Systems, Best, Netherlands). Anterior height, posterior height and width of vertebral body as well as length between spinous process were measured on each thoracic spine.

RESULTSAnterior height, posterior height and width of vertebral body increased from T(1) to T(12) with the values from scoliotic groups larger than normal group. The anterior height/width ratio and anterior/posterior column ratio were also larger in scoliotic group especially at apical area.

CONCLUSIONThe thoracic vertebrae are higher and slimmer in scoliotic patient than in normal age-matched girls which implied that there is abnormal endochondral ossification on spine during adolescent growth spurt.

Adolescent ; Case-Control Studies ; Female ; Humans ; Magnetic Resonance Imaging ; Scoliosis ; pathology ; Thoracic Vertebrae ; pathology

This study was aimed to retrospectively analyze and compare the clinical curative efficacy of patients with hematologic malignancies after G-CSF-mobilized sibling HLA-matched (sm) peripheral blood hematopoietic stem cell transplantation (sm-allo-PBHSCT) and sm-allo-PBHSCT combined with bone marrow transplantation (BMT). 100 patients received sm-allo-HSCT in a single center from October 2001 to October to 2010, included 38 patients received sm-allo-PBHSCT and 62 patients received sm-allo-PBHSCT combined with BMT. The myeloablative or reduced intensity conditioning regimens were chosen according to the condition of patients. All patients received standard cyclosporine (CsA) and mycophenolate mofetil (MMF) as prophylaxis for GVHD. The results showed that the rapid hematopoietic reconstitution was observed in all patients. The median time of ANC ≥ 0.5 × 10(9)/L in both groups were 12 days, the median time of platelet count ≥ 20 × 10(9)/L was 15 days in sm-allo-PBHSCT group and 16 days in sm-allo-PBHSCT + BMT group. The incidence of acute GVHD, acute GVHD of III-IV grade and chronic GVHD in sm-allo-PBHSCT and sm-allo-PBHSCT + BMT groups were 37.1% and 34.2%, 7.89% and 8.06%, 36.11% and 41.38% respectively, there were no statistical differences. The relapse rates were similar in two groups (sm-allo-PBHSCT 13.16% vs sm-allo-PBHSCT + BMT 12.9%). The 3-year disease-free survivals in sm-allo-PBHSC and sm-allo-PBHSCT + BMT groups were 57.1 ± 8.7% and 61.3 ± 6.4% respectively (p = 0.852). The 2-year overall survival of high-risk patients was 41.4 ± 12.8% in sm-allo-PBHSCT group, while 60.9 ± 9.6% in sm-allo-PBHSCT + BMT group (p = 0.071). It is concluded that the rhG-CSF mobilized sibling matched allo-PBHSCT + BMT is superior to the rhG-CSF mobilized sibling matched allo-PBHSCT in increasing the overall survival of high-risk hematologic malignancies.
Adolescent ; Adult ; Aged ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; HLA Antigens ; immunology ; Hematologic Diseases ; immunology ; therapy ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies ; Siblings ; Tissue Donors ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of oxymatrine in the treatment of chronic hepatitis B.

METHODSA multicenter randomized double-blind placebo-controlled trial was conducted. A total of 144 patients with chronic hepatitis B entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a placebo. Before and after the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reactions were observed.

RESULTSIn 144 patients, 14 were dropped and excluded due to inconsistencies in the included standard. Therefore, the efficacy and safety of 130 patients were analyzed. After being treated for 52 weeks, 70.77% of the patients in the study group had a normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33% had their HBV DNA and HBeAg become negative. The rates of complete response and partial response in the oxymatrine group were 23.08% and 58.46%, and in the placebo group they were 3.08% and 44.62%. They were significantly higher in the oxymatrine group than in the placebo group. In the oxymatrine treated patients, 12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33% had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of complete response and partial response in the oxymatrine group were 21.54% and 47.69%, and in the placebo group they were 0 and 41.54%. They were significantly higher in the study group than in the placebo group. The adverse reaction rates of oxymatrine in the study and the placebo group were 7.69% and 6.15%, respectively, but there was no statistical significant difference between them.

CONCLUSIONOxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

Adolescent ; Adult ; Aged ; Alkaloids ; adverse effects ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Quinolizines

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.