Adolescent ; Body Height ; Body Weight ; Child ; Female ; Growth and Development ; Humans ; Male ; Papilloma ; surgery ; Thyroid Neoplasms ; surgery ; Thyroidectomy ; adverse effects

AIMBy genechip cDNA microarray, the genes expressions of Stearoyl-coenzyme A desaturase (Scd-2) and brain fatty acid-binding protein (B-FABP) were studied in the central nervous system (CNS) of the mice to discuss the mechanism of exercise-induced fatigue.

METHODSBuilding the model of fatigued animal and using the genechip cDNA microarray, the genes expressions were analyzed between the control group and fatigue group mice.

RESULTSThe genes expression of Scd-2 and B-FABP were obvious different in the brain of fatigued group mice than of control group.

CONCLUSIONExercise-induced nerve center fatigue is correlated with genes expressions of lipid metabolism.

Animals ; Base Sequence ; Brain ; metabolism ; Fatigue ; genetics ; metabolism ; Fatty Acid-Binding Protein 7 ; Fatty Acid-Binding Proteins ; genetics ; metabolism ; Gene Expression ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Nerve Tissue Proteins ; genetics ; metabolism ; Oligonucleotide Array Sequence Analysis ; Stearoyl-CoA Desaturase ; genetics ; metabolism

Human epidermal growth factor receptor 2 (HER2) belongs to the transmembrane glycoprotein receptor family. Overexpression of HER2 could directly lead to tumorigenesis and metastasis. This phenomenon could be observed in the breast cancer, ovarian cancer, gastric cancer, lung cancer and prostate cancer. Compared with the conventional chemotherapy, the targeted treatment of antibody is more specific and has lower side effects. This review describes the current status of monotherapy and combination therapies of anti-HER2 antibodies, trastuzumab and pertuzumab, with chemotherapeutic drugs. The development trends of new formats of anti-HER2 antibody drugs such as bispecific antibody, immunotoxin are also discussed.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Drug Delivery Systems ; Humans ; Immunoconjugates ; therapeutic use ; Immunotoxins ; therapeutic use ; Neoplasms ; metabolism ; therapy ; Receptor, ErbB-2 ; antagonists & inhibitors ; metabolism ; Trastuzumab

Monoclonal antibody-targeted therapy has been a hot spot in current clinical cancer treatment. As current antibody drugs have large molecule sizes leading to poor tissue penetration, and high dosage in clinical application leading to high cost, to overcome the problems, the development of new antibody drugs with miniaturization and high potency has become a new trend. In recent years, the conjugates of monoclonal antibodies and cytotoxins, called antibody-drug conjugates (ADCs), have entered the arsenal of anti-cancer drugs, becoming a new format of antibody drugs and attracting extensive attentions. The ADC molecule usually consists of antibody, linker and effector molecule. According to different effector molecules, ADCs can be divided into three categories as chemo-conjugates, immunotoxins and radio-conjugates. When ADC molecules are internalized into cancer cells, cytotoxins will be released by chemical, enzyme degradation or by action of lysosomal proteases, then kill targeted cells by inhibiting protein synthesis, depolymerizing microtubules or breaking double-strand DNA. Recently, two ADC drugs have been approved by the US FDA and more ADC drug candidates are in clinical phase II or III trials which show significantly clinical effects and attracting much attention and competition of pharmaceutical enterprises. In this review, antibody conjugates in the past and present will be summarized and the future development trends and challenges of this type of antibody drugs will be discussed.
Antigens, CD ; metabolism ; Hematologic Neoplasms ; metabolism ; therapy ; Humans ; Immunoconjugates ; chemistry ; therapeutic use ; Immunotherapy ; methods ; Immunotoxins ; chemistry ; therapeutic use ; Radioimmunotherapy ; methods

OBJECTIVETo study the digestive system manifestations in children infected with novel influenza A (H1N1) virus.

METHODSA prospective study of 153 children infected with novel influenza A (H1N1) virus in Shenzhen Children's Hospital from November 2009 to January 2010 was conducted. The clinical features and outcomes of 69 children with digestive system manifestations were analyzed.

RESULTSThe children presenting with digestive system manifestations accounted for 45% (69 cases) in the 153 hospitalized children with novel influenza A (H1N1) infection. Gastrointestinal manifestations were observed in 50 cases (33%) and liver function abnormality in 19 cases (12%). The incidence rate of coma, neurological complications, increase in creative kinase level, ICU admission, and death in the patients with digestive system manifestations were significantly higher than those without digestive system manifestations (P<0.05). In the 69 patients with digestive system manifestations, 5 died from severe complications and 64 recovered fully. Gastrointestinal manifestations disappeared through 1 to 3 days and abnormal liver function recovered through 4 to 7 days.

CONCLUSIONSDigestive system manifestations are common in children infected with novel influenza A (H1N1) virus. Neurological system involvements are more common in the patients with digestive system manifestations than those without.

Adolescent ; Child ; Child, Preschool ; Digestive System Diseases ; etiology ; therapy ; Female ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; complications ; Male ; Prospective Studies

OBJECTIVETo investigate the association of expression of c-kit (marker of interstitial cells of Cajal, ICC) in colon with slow transit constipation (STC) in rats.

METHODSSlow transit constipation (STC) rat model was induced by intragastric administration of compound diphenoxylate. Western blotting was used to measure the expression of c-kit in colon of STC rats (model group) and normal rats (control group). Gray scale ratio of c-kit to β-actin was used as the relative quantity of c-kit.

RESULTSFecal quantity per day of STC group was (1.3±0.7) g/100 g, significantly lower than that in normal rats [(1.6±0.9) g/100 g, t=10.798, P<0.05]. In model rats, the time of discharge of the first black fecal was (461.6±150.8) min, significantly longer than that in normal rats [(351.3±119.9) min, t=2.291, P<0.05]. Western blotting revealed that the average values of gray scale ratio of c-kit in proximal colon were 0.277±0.077 and 0.576±0.081 (t=10.719, P<0.05), in distal colon were 0.280±0.075 and 0.571±0.079 (t=10.700, P<0.05) in model group and control group respectively.

CONCLUSIONDown-regulation of c-kit expression in proximal colon and distal colon is associated to the pathogenesis of slow transit constipation in rats.

Animals ; Chronic Disease ; Colon ; metabolism ; pathology ; Constipation ; metabolism ; pathology ; Disease Models, Animal ; Female ; Interstitial Cells of Cajal ; pathology ; Male ; Proto-Oncogene Proteins c-kit ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDHuman urotensin II (UII) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UII is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UII mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UII.

METHODSIn primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UII were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UII was measured using Fura-2/AM.

RESULTSUII 10(-7) mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P < 0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P < 0.01). It promoted the cytosolic free calcium concentration increase of 18% (P < 0.01). CsA 10(-6) mol/L and H7 50 micromol/L inhibited UII-stimulated CaN activity by 45% (P < 0.01) and 21% (P < 0.05), respectively, while PD98059 50 micromol/L had no effect on CaN activity (P > 0.05). CsA 10(-6) mol/L inhibited UII-stimulated PKC activity by 14% (P < 0.05), while having no effect on MAPK activity (P > 0.05).

CONCLUSIONSUII increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.

Animals ; Calcineurin ; metabolism ; Cells, Cultured ; Enzyme Activation ; Mitogen-Activated Protein Kinases ; metabolism ; Mitogens ; pharmacology ; Myocytes, Smooth Muscle ; cytology ; Protein Kinase C ; metabolism ; Rats ; Signal Transduction ; physiology ; Trachea ; cytology ; Urotensins ; pharmacology

OBJECTIVETo study the significance of c-myc, p53 and p16 protein expression in fibrous dysplasia, to detect the GNAS1 gene mutation in fibrous dysplasia, and to explore the property of fibrous dysplasia.

METHODSThe expression of c-myc, p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy, 1 Mazabraud syndrome and 20 control cases (10 cases of bony callus, 10 cases of osteosarcoma). Genomic DNA extraction, PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia.

RESULTSC-myc protein immunoreactivity was detected in 91 percentage of FD (P = 0.001). Compared with the negative control group, the difference was significant. P16 positive was detected in 34 FD cases (P = 0.001). The difference was significant as compared with the positive control group. Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation. PCR amplification was successful in 12 of 35 FD cases. Two of the 12 FD cases were detected to have GNAS1 gene mutation, in which 1 case was FD of Mazabraud syndrome, 1 case was a monostotic lesion.

CONCLUSIONSC-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease. P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD. The abnormal expression of the gene p16 might play an important role in the formation of FD. The GNAS1 mutation exist in FD. All of the results indicate that FD could be a neoplasia disease, caused by multiple factors leading to a dysfunction of bone development.

Adolescent ; Adult ; Child ; Chromogranins ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Fibrous Dysplasia of Bone ; genetics ; metabolism ; pathology ; GTP-Binding Protein alpha Subunits, Gs ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Osteosarcoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Young Adult

OBJECTIVETo investigate the incidence and clinicopathologic significance of MSI and LOH on 3P in breast carcinoma and its precancerous lesions, intraductal papillary adenoma and ductal carcinoma in situ.

METHODS41 paired sporadic invasive breast carcinomas, 13 archival precancerous lesion specimens of the breast and 14 couples of benign hyperplasia were collected. Twelve microsatellites on chromosomes 2p, 3p, 5q, 6q, 16q, 17q, eleven markers on chromosome 3p were amplified for MSI and LOH, respectively, by polymerase chain reaction ( PCR ) with designed primers and detecting after polyacrylamide gel electrophoresis. In addition, the expression of protein of hMSH2, hMLHI, FHIT, ER, and PR were detected by immunohistochemistry.

RESULTSMSI was observed, at least two microsatellite markers, in 15 out of 41 (36. 6%) of the carcinomas, almost all belonging to poorly or intermediately differentiated carcinoma. Instability was shown in 9 of the 13 cases of precancerous lesions, but only 2 among them had more than 2 MSI sites. There was no MSI in benign hyperplasia. MSI was targeted predominately at D3S1766, D2S2739 in both carcinomas and precancerous lesions. Of the 11 loci examined, D3S1295, D3S1029 and D3S1038 were identified as the locus with most frequent LOH which were all correlated significantly with some clinicopathological parameters such as histological type, lymph node metastasis in breast cancer, while D3S1295 and D3S1029 were the most frequent markers in precancerous lesions. LOH of D3S1295 had significant correlation with negative expression of FHIT. Positive expression of hMLH1 and hMSH2 protein was detected in breast carcinomas in scattered distribution and their positive rate was 45% and 40% , respectively. In precancerous lesions, hMLH1 and hMSH2 protein showed diffuse expression and their positive rate was 61. 54% and 76. 92% , respectively, significantly lower than that in the control tissues.

CONCLUSIONDefective expression of MMR genes is closely associated with the development of breast cancer. Genomic instability might play a role in the early stage during multi-step mammary carcinogenesis. MSI indicates poor histological differentiation in breast carcinoma. D3S1766 and D2S2739 might be the sensitive sites to detect MSI in breast carcinoma and precancerous lesions. The smallest common LOH deletion regions seem likely to be situated between 3p14 and 3p25, indicating the existence of breast tumor related genes in those regions and some of them might affect tumor development.

Acid Anhydride Hydrolases ; metabolism ; Adaptor Proteins, Signal Transducing ; metabolism ; Adenoma ; genetics ; metabolism ; pathology ; Adult ; Aged ; Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Chromosome Deletion ; Chromosomes, Human, Pair 3 ; genetics ; DNA Mismatch Repair ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Loss of Heterozygosity ; Lymphatic Metastasis ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1 ; MutL Proteins ; Neoplasm Proteins ; metabolism ; Neoplasm Staging ; Nuclear Proteins ; metabolism ; Polymerase Chain Reaction ; Precancerous Conditions ; genetics ; metabolism ; pathology ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo study the effect of implant number and inclination on stress distribution in implant and its surrounding bone with three-dimensional finite element analysis.

METHODSA special denture was made for an edentulous mandible cast to collect three-dimensional finite element data. Three three-dimensional finite element models were established as follows. Model 1: 6 paralleled implants; model 2: 4 paralleled implants; model 3: 4 implants, the two anterior implants were parallel, the two distal implants were tilted 30° distally.

RESULTSAmong the three models, the maximum stress values found in anterior implants, posterior implants, and peri-implant bone were modle 3

CONCLUSIONSWithin the limitation of this study, when implants are placed parallel, the maximum stress of the distal implant can be reduced by increasing the number of implant.When the number of implant was decreased from six to four, the maximum stress around the implant can be reduced by tilting the distal implant. This design will provide a better prostheses effect than the design with six implants does.

Dental Implants ; Dental Prosthesis Design ; Dental Prosthesis, Implant-Supported ; Dental Stress Analysis ; Finite Element Analysis ; Mandible ; Prostheses and Implants ; Prosthesis Implantation