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 clinicopathologic, radiological and immunohistochemical characteristics of osteochondroma with malignant transformation.

METHODSThe clinical data, radiological imagings and hematoxylineosin stained histologic sections were reviewed in 463 cases of osteochondroma diagnosed in Shanghai 6th Hospital from 1991 to 2008, including 11 cases with malignant transformation. Immunohistochemical two-step staining was used to detect CK, vimentin, S-100 protein, p53 and c-myc expression in seven cases of osteochondroma with malignant transformation and 10 cases without malignant transformation. The relevant literature was reviewed.

RESULTSAmong the 11 cases with malignant transformation, five were single osteochondroma (5/408, 1.2%), and six were multiple osteochondromas (6/55, 10.9%). The male to female ratio was 10:1. These 11 cases were derived from femur (4 cases), tibia (3 cases), ilium (3 cases), shoulder bone (1 case) and pubis (1 case). There was one case that showed malignant transformation in both the femur and ilium. The mean ages for the malignant and non-malignant cases were 39.8 years and 20.4 years respectively. All the malignant cases showed large sized lesions with prominent calcification in the thick cartilage caps. The malignant component was low grade, peripheral chondrosarcoma (grade I-II). In some areas the tumor cells infiltrated the peripheral soft tissue and bone marrow. Of the seven cases with malignant transformation that had immunohistochemical staining, all were positive for vimentin and S-100 protein; p53 protein was positive in 2 of 7 cases.

CONCLUSIONSMalignant transformation of osteochondroma was usually encountered in multiple lesions. Most patients were more than 30 years old with a long clinical history and with a male predominance. These tumors showed thick cartilage caps with prominent calcification. The lobulated nature of the tumors was evident and they infiltrated the surrounding soft tissue. The sarcomatoid component was peripheral type, well differentiated chondrosarcoma. p53 mutation may explain part of the molecular mechanism in the malignant transformation.

Adult ; Aged ; Bone Neoplasms ; diagnostic imaging ; metabolism ; pathology ; surgery ; Cell Transformation, Neoplastic ; pathology ; Chondrosarcoma ; diagnostic imaging ; metabolism ; pathology ; surgery ; Exostoses, Multiple Hereditary ; diagnostic imaging ; metabolism ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Osteochondroma ; diagnostic imaging ; metabolism ; pathology ; surgery ; Radiography ; S100 Proteins ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Vimentin ; metabolism ; Young Adult

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

To study the etiological factors and pathogenisis of venous thrombi and their relations with anticoagulation and fibrinolysis, In 47 patients with venous thrombi anticardiolipin antibody (ACA) was detected by ELISA. lupus anticoagulant (LA) and anti-activative protein C resistance (APCR) were examined by coagulation test; factor V Leiden was determined by PCR; activity of anticoagulation and fibrinolysis of antithrombin (AT), protein C (PC), plasminogen (Plg) were detected by chromophore substrate methods. The results showed that ACA and/or LA were positive in 34% of patients with VT, most of which consisted of ACA IgG and LA; Plg was negative in 9.5% of patients; tPAI elevated in 8.3% of patients (much more than control group, P < 0.005); ATIII, PC, tPA were negative in 4.5%, 4.5%, 2.8% of patients, respectively (no significant difference with control groups, P > 0.05); ATIII, PC and Plg were negative constantly in one patient; factor V Leiden was not detected by PCR. There were no significant differences in anticoagulation and fibrinolysis between antiphospholipoprotein antibody (APA) negative subjects and APA positive subjects, 4 patients of which were positive in APCR, 3 patients were positive in ACA and/or LA, two out of three patients didn't achieved APCR reversion after mixing their blood plasma with normal blood plasma. It is concluded that antiphospholipoprotein antibody and abnormal fibrinolysis were the common pathological factors in venous thrombi. LA and/or ACA disturbs the anticoagulation aspect to develop into acquired APCR which may be a possible cause leading to thrombophilia.
Adolescent ; Adult ; Aged ; Antibodies, Antiphospholipid ; blood ; Antithrombins ; metabolism ; Blood Coagulation ; Child ; Enzyme-Linked Immunosorbent Assay ; Factor V ; genetics ; Female ; Fibrinolysis ; Humans ; Male ; Middle Aged ; Plasminogen ; metabolism ; Polymerase Chain Reaction ; Protein C ; metabolism ; Venous Thrombosis ; blood ; genetics ; metabolism

OBJECTIVETo review the experience of diagnosis and treatment of primary cervical tracheal tumor.

METHODSMedical history records of 38 patients with primary cervical tracheal tumor who were treated at department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences between January 1981 and December 2002 were retrospectively analyzed. Twenty six patients underwent surgical resection, twelve patients received only radiotherapy. Eleven patients underwent sleeve tracheal resection, thirteen patients with partial tracheal wall resection and 6 of them with tracheal reconstruction immediately, two patients with total laryngectomy and resection of partial trachea and thyroid lobectomy.

RESULTSThirty four patients had malignant tumors, among which 19 cases were adenoid cystic carcinoma and 10 cases squamous cell carcinoma. The 3-year and 5-year survival rate were 79. 80% and 48. 36% respectively for the patients with adenoid cystic carcinoma, 80.00% and 20. 00% respectively for the patients with squamous cell carcinoma. The rate of complication was 18.4% (7/38), among which tracheal stenosis was 11.5% (3/26).

CONCLUSIONSMost of primary cervical tracheal tumors were malignant, adenoid cystic carcinoma and squamous cell carcinoma were the common malignant cervical tracheal tumors. Surgery is the first choice for cervical tracheal tumors, and the sleeve trachea resection is one of the optimal surgical modality.

Adult ; Aged ; Carcinoma, Adenoid Cystic ; diagnosis ; surgery ; Carcinoma, Squamous Cell ; diagnosis ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Tracheal Neoplasms ; diagnosis ; surgery ; Young Adult

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