12E7 Antigen ; Aged ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Diagnosis, Differential ; Giant Cell Tumors ; pathology ; Giant Cells ; pathology ; Humans ; Male ; Mesenchymoma ; pathology ; Mucin-1 ; metabolism ; Myositis Ossificans ; pathology ; Osteosarcoma ; metabolism ; pathology ; surgery ; Penile Neoplasms ; metabolism ; pathology ; surgery ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Vimentin ; metabolism

OBJECTIVETo investigate the prevalence of CHEK2 c.1100delC mutation among non-BRCA1/BRCA2 familial/early-onset breast cancer patients in Shanghai.

METHODSOne hundred and fourteen non-BRCA1/BRCA2 hereditary breast cancer patients were analyzed, among whom 76 cases had at least one first-degree relative affected with breast cancer and 38 cases were diagnosed as breast cancer below the age of 40 years without family history. The mutation genotyping of CHEK2 c.1100delC were carried out through long-range PCR amplifying of exons 10-14, and followed by amplification of exon 10 and then DNA direct sequencing.

RESULTSNo c.1100delC frame-shift mutation was identified in our studied population. One novel missense mutation 1111C>T (p.His371Tyr), located in kinase catalytic domain, was found in 3 familial breast cancer cases but no one in control group.

CONCLUSIONCHEK2 c.1100delC is rare variant for Chinese population and may not contribute to predisposition for hereditary breast cancer in Shanghai. Novel variant -1111C>T could be in association with genetic susceptibility to breast cancer. A further study is needed to confirm the results.

Adult ; Aged ; Apoptosis Regulatory Proteins ; Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; Checkpoint Kinase 2 ; China ; DNA Mutational Analysis ; Female ; Frameshift Mutation ; Genetic Predisposition to Disease ; genetics ; Humans ; Middle Aged ; Mutation, Missense ; Protein-Serine-Threonine Kinases ; genetics ; Sequence Deletion ; Young Adult

OBJECTIVEAromatase, encoded by CYP19A1, play an important role in estrogens biosynthesis from androgens. The present study is to investigate effect of R264C single nucleotide polymorphism in CYP19A1 gene on genetic susceptibility for hereditary breast cancer without BRCA1/2 mutant.

METHODSOne hundred and fourteen BRCA1/2 -negative hereditary breast cancer patients from independent families and 121 age-matched healthy control subjects were analyzed. Genotype analysis was performed through polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional Logistic regression model.

RESULTSThe frequency of R264C single nucleotide polymorphism CC, CT and TT genotype in case group and controls was 84(77.8%), 22(20.4%), 2(1.8%) and 87(77.7%), 24(21.4%), 1(0.9%), respectively. CT genotype (OR=1.16, 95%CI: 0.53-2.55) and TT genotype (OR=1.44, 95%CI: 0.12-17.15) did not confer a significantly increased risk for breast cancer. No significant association was found between T allele and susceptibility for breast cancer under analysis according to menopausal status and body mass index.

CONCLUSIONR264C polymorphism in CYP19A1 gene is not a candidate locus for low penetrance breast cancer susceptibility in Shanghai group of Chinese population and not recommended in clinical genetic test. Homozygous T allele of R264C is not common in Shanghai group of Chinese population.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Base Sequence ; Breast Neoplasms ; genetics ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Molecular Sequence Data ; Mutation ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Steroid 17-alpha-Hydroxylase ; genetics ; Young Adult

OBJECTIVETo investigate the prevalence of BRCA1 and BRCA2 gene mutations among breast cancer patients with affected relatives in Shanghai of China.

METHODSThirty-five breast cancer patients who had at least one first-degree relative affected were analyzed, among whom 13 patients suffered from breast cancer at age of less than 40 years. A comprehensive BRCA1 and BRCA2 mutation analysis was performed through denaturing high-performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing.

RESULTSFour mutations in BRCA1 gene, including 2 novel splice-site mutations (IVS17-1G>T, IVS21+1G>C) and 2 frameshift mutations (1100delAT; 5640delA) were identified. One frameshift mutation (5802delAATT) was detected in exon 11 of BRCA2. Additional 12 novel single nucleotide polymorphisms(SNPs) were detected, including a novel unclassified variant and 7 novel intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, with which all caused no alteration of amino acid coding. The mutation frequency of BRCA1 and BRCA2 in patients with family history was 11.4% and 2.9%, respectively.

CONCLUSIONTwo novel mutations in BRCA1 may be mutations characterized to familial breast cancer of Chinese Shanghai population. The BRCA2 may contribute to mutation less than BRCA1 in familial breast cancer. Our data contribute to information on mutation spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.

Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Breast Neoplasms ; genetics ; China ; DNA, Neoplasm ; analysis ; Family Health ; Female ; Humans ; Point Mutation ; Polymorphism, Single Nucleotide

OBJECTIVETo explore the prevalence of Val158Met polymorphism in Catechol-O-methyltransferase (COMT) gene and its effect on genetic susceptibility for breast cancer in Shanghai population.

METHODSA total of 114 patients with BRCA1/BRCA 2 negative hereditary breast cancer from independent families and 121 age-matched healthy controls were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression model.

RESULTSThe frequency of Val158Met polymorphism GG, GA and AA genotype in case group and control was 0.58 (65), 0.32 (36), 0.10 (11) and 0.60 (66), 0.35 (41), 0.03 (3), respectively. The frequency of allele-containing genotypes is significantly higher in early-onset breast cancer patients (0.57) than in familial ones (0.35). Compared with GG (Val/Val) genotype, AA (Met/Met) genotype confers a significantly increased risk for breast cancer (adjusted OR = 3.15; 95% CI, 0.70 - 14.19), especially among premenopausal women (adjusted OR = 9.98; 95% CI, 1.00 - 99.64). Borderline significantly association was found between AA genotype (adjusted OR = 7.57; 95% CI, 0.57 - 101.28) and susceptibility for breast cancer in BMI < or = 23 kg/m(2) group.

CONCLUSIONSVal158Met polymorphism in COMT gene could be a candidate for low penetrance breast cancer susceptibility in Shanghai population, especially among premenopausal women and early-onset breast cancer patients.

Adult ; Aged ; Breast Neoplasms ; enzymology ; genetics ; Case-Control Studies ; Catechol O-Methyltransferase ; genetics ; China ; Female ; Gene Frequency ; Genes, BRCA1 ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Middle Aged ; Mutation ; Polymorphism, Genetic

[Objective]Screening mutation sites of POGZ gene in 100 intellectual disability patients to explore their pathogenesis relationship.[Method]Genomic DNA was isolated from peripheral blood. All exons,exon-intron boundaries,5'UTR and 3'UTR of POGZ were amplified by PCR and PCR products were directly sequenced.[Results]A novel mutation was identified,and the mis?sense mutation disrupted the unique zing-finger like motif of POGZ,which is a critical element for binding Hp1. The mutated POGZ failed to bind with HP1 thus might lose its cell cycle regulation function.[Conclusion]Mutations of POGZ gene weighs more in intel?lectual disability etiology. Screening of POGZ in unexplained intellectual disability patients contributes to their pathogenesis analyze , screening of POGZ in pregnants with family history of intellectual disability can prevent intellectual disability from birthing.

OBJECTIVETo examine the distribution of fluorouracil in gastric cancer (CA), lymph node (LN), normal gastric mucosa (NG), peritoneum (PE), greater omentum (GO) and lesser omentum (LO) by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome (Co 5-Fu), and offer an experimental basis for clinic practice.

METHODSNinety-six gastric cancer patients were divided into four groups: Co 5-Fu i.v. injection group (Co 5-Fu i.v.), Co 5-Fu intraperitoneal perfusion group (Co 5-Fu i.p.), 5-Fu i.v. injection group (5-Fu i.v.) and intraperitoneal perfusion group (5-Fu i.p.) given on day-2, day-1 and 60 minutes before operation. Fluorouracil concentration in all tissues collected during operation were examined by high performance liquid chromatography (HPLC).

RESULTSThe fluorouracil concentration in the tissues in Co 5-Fu i.p. group was significantly higher than that in Co 5-Fu i.v. or 5-Fu i.p. group (P < 0.05 or P < 0.01), and that in 5-Fu i.p. group was greatly higher than that at 5-Fu i.v. group (P < 0.01). In Co 5-Fu i.p. group, the concentration of drug in LN, CA, PE, NG, GO and LO decreased gradually with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01), and adjacent lymph node was the highest. In Co 5-Fu i.v. group, the ranking was LN, CA, NG, PE, GO and LO with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01) and showing tumor tissues higher than the other tissues (P < 0.01). In 5-Fu i.p. group, the ranking was PE, LN, CA, NG, GO and LO with the former 2 tissues significantly higher than the latter tissues (P < 0.01).

CONCLUSIONCo 5-Fu possesses drug targeting, slow release and long effect in gastric cancer tissues and adjacent lymph nodes. Preoperative chemotherapy with Co 5-Fu i.p. is more advantageous than 5-Fu given i.v. or 5-Fu i.p.

Aged ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacokinetics ; Female ; Fluorouracil ; administration & dosage ; pharmacokinetics ; Gastric Mucosa ; metabolism ; Humans ; Infusions, Parenteral ; Injections, Intravenous ; Liposomes ; Lymph Nodes ; metabolism ; Male ; Middle Aged ; Omentum ; metabolism ; Panax ; chemistry ; Peritoneum ; metabolism ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacokinetics ; Preoperative Care ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology

OBJECTIVETo evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC).

METHODSFrom September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment.

RESULTSResponse in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths.

CONCLUSIONSThe combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Chemotherapy, Adjuvant ; Drug Administration Schedule ; Epirubicin ; administration & dosage ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives

This study was aimed to investigate the role of mitochondria pathway in signal transduction of chronic myeloid leukemia (CML). After bcr3/abl2 antisense oligodeoxynucleotide (ASO) was introduced into CML cell line K562 cells by liposomal transfection, the cell viability was detected by MTT assay, the cell apoptosis was determined by flow cytometry (FCM), the mitochondrial membrane potential (DeltaPsi) was labeled by Rhodamine 123 and examined by FCM, and the expression of mitochondrial apoptosis signal transduction pathway related proteins cytochrome C was analyzed by Western blot. The results showed that after K562 cells were exposed to 2 micromol/L of bcr3/abl2 ASO for 24 hours, bcr3/abl2 ASO significantly inhibited cell viability with inhibitory rate of 65.7%, induced the apoptosis of K562 cell line with apoptotic rate of 16.9%, and decreased mitochondrial Deltapsi of K562 cells with the reducing rate of 38.33%, enhanced the expression of cytochrome C with increase of optical density value from 2.33 +/- 0.3 to 4.78 +/- 0.1 by laser photometric scanning. It is concluded that mitochondria pathway plays an important role in signal transduction of chronic myeloid leukemia by directing apoptotic signal transduction.
Apoptosis ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; Membrane Potential, Mitochondrial ; Membrane Potentials ; Mitochondria ; metabolism ; Oligonucleotides, Antisense ; Signal Transduction

OBJECTIVETo study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice.

METHODSThe nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dose NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor cells were detected by flow cytometry. The endotumoral content of TNF-alpha was detected using a mouse TNF-alpha ELISA kit. The live virus was detected by hemagglutination (HA) test.

RESULTSThe moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-alpha. Live virus was not detected in important organs except in the tumor of nude mice by HA test.

CONCLUSIONIn the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.

Animals ; Apoptosis ; Cell Line, Tumor ; Colonic Neoplasms ; pathology ; therapy ; Humans ; Liver ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Newcastle disease virus ; physiology ; Random Allocation ; Tumor Burden ; Tumor Necrosis Factor-alpha ; metabolism ; Xenograft Model Antitumor Assays