Objective： A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma. Methods： The patients with locoregionally advanced nasopharyngeal carcinoma were treated with either radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (20 mg/m2 on Day 1 to Day 5), bleomycin (7 mg/m2 on Day 1 and Day 5), and 5-FU (500 mg/m2 on Day 1 to Day 5) followed by radiotherapy was given to CT/RT group. All patients were treated in a uniform definitive-intent radiation therapy in two groups. Results： From 1992 to 1993, 457 patients were enrolled and 440 patients (221 in RT group, 219 in CT/RT group) were assessable. The 5-year overall survival (OS) rates were 62％ for CT/RT group and 55％ for RT group (P=0.1335)； The 5-year relapse free survival rate was 48％ versus 58％ , respectively (P=0.0539). The 5-year free local recurrence (FLR) rate was 82％ for CT/RT group, 74％ for RT group (P=0.0412). There was no significant difference in free distant metastasis (FDM) between two treatment groups (CT/RT group, 79％ ; RT group, 75％ ; P=0.4177). Subgroup analyses showed that neoadjuvant chemotherapy improved local control in patients with T3-4 disease, and had no effect in preventing distant metastases in patients with N2-3 disease. Conclusion： Despite improving FLR and RFS, neoadjuvant chemotherapy and radiatherapy failed to gain other survival benefit or reduce distant metastases in patients with locoregionally advanced nasopharyngeal carcinoma. The indication for neoadjuvant chemotherapy is proposed.

BACKGROUND AND OBJECTIVEWe previously reported that C-KIT overexpression and mutation exist in biopsy samples of nasopharyngeal carcinoma (NPC). Yet whether Imatinib had an inhibitory effect on the proliferation of NPC in vitro was still unknown. So, this study examined whether sensitivities to Imatinib of other cell lines are different and whether C-KIT expression and mutations exist, to analyze the correlations between them.

METHODSThe expression of C-KIT in NPC cell lines, including CNE-1, CNE-2, Hone-1, C-666, SUNE-1, 5-8F, and nasopharyngeal epithelial (NPE) cell line NP-69, were detected by Western blot. Direct sequencing of polymerase chain reaction (PCR) products was performed to analyze the sequences of C-KIT from the above-mentioned cell lines. Inhibitory effects on proliferation by Imatinib on these cell lines were determined by CCK-8 assay. Pearson product moment correlation and t test were used to analyze the correlation betweeen C-KIT overexpression, C-KIT gene mutation, and the inhibitory effect of Imatinib.

RESULTSCompared with NPE cell line NP-69, NPC cell lines CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F had significantly higher levels of C-KIT expression. Heterozygous IVS17+78T>C were found in CNE-1, CNE-2, Hone-1, and NP-69 cell lines, homozygous IVS17+78T>C was found in C-666, and no mutation was found in SUNE-1 or 5-8F. Imatinib had a dose-dependent inhibitory effect on proliferation for CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F. No significant correlation between the inhibitory effects of Imatinib, C-KIT overexpression, or C-KIT mutation was found.

CONCLUSIONC-KIT overexpression and intron mutation were found in NPC cell lines and Imatinib had a dose-dependent inhibitory effect on proliferation for NPC cell lines, yet no significant correlation between C-KIT overexpression, C-KIT mutation, or the inhibitory effect of Imatinib was found.

Antineoplastic Agents ; pharmacology ; Benzamides ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; virology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Epithelial Cells ; cytology ; metabolism ; Herpesvirus 4, Human ; isolation & purification ; Heterozygote ; Homozygote ; Humans ; Imatinib Mesylate ; Introns ; Mutation ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; virology ; Nasopharynx ; cytology ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Pyrimidines ; pharmacology

OBJECTIVETo clone human bone morphogenetic protein-2 (hBMP2) gene and construct its eukaryotic expression vector pcDNA3.1 -hBMP2.

METHODSHuman BMP2 gene was amplified by RT-PCR method from human osteosarcoma cells and constructed into eukaryotic expression vector pcDNA3.1-hBMP2. The gene in the vector pcDNA3.1-hBMP2 was identified by PCR amplification, enzyme digestion and DNA sequencing.

RESULTSThe cloned DNA was confirmed to be hBMP-2 gene.

CONCLUSIONIn this study, hBMP2 gene is successfully cloned and its eukaryotic expression vector pcDNA3.1-hBMP2 is constructed, which provides the foundation of using BMP2 gene therapy to accelerate new bone formation in distraction osteogenesis.

Bone Morphogenetic Protein 2 ; Cloning, Organism ; Genetic Therapy ; Genetic Vectors ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Transfection

Objective： The current study was designed to investigate the diagnosis and the treatment of osteoradionecrosis of the skull base (ORN) in the patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods： All patients (n=12) diagnosed as nasopharyneal carcinoma and osteoradionecrosis of the skull base were studied retrospectively with their clinical manifestations, diagnoses, therapies and prognoses. Results： ORN was found with characteristic CT and endoscopic findings, they were never seen in the patients with NPC relapse. The latent periods of ORN in the patients after primary radiotherapy were 3 - 15 years, while the periods were 7 months - 2 years in the patients after reirradiation. Six patients with local ORN were operated, 1 patients was died of exhaustion; Six patients with extensive ORN were treated using conservative methods, 3 patients were died of severe nasopharyngeal bleeding, while one were died of exhaustion. Conclusion： The ORN of the skull base after radiotherapy could be diagnosed by CT and endoscopic findings. The patients with extensive ORN or radiation induced cranial neuropathy were associated with poor prognosis. The most common causes of death were severe nasopharyngeal bleeding and exhaustion.

Objective：The fifth edition of the International Union Against Cancer (UICC) staging manual defines new rules for classifying nasopharyngeal carcinoma (NPC). The study was conducted to assess the effectiveness of the manual to predict the prognosis for Chinese patient populations. Methods：From August 1992 to December 1993, a total of 621 consecutively admitted patients with nondisseminated NPC were treated with definitive-intent radiation therapy alone. A computer database containing all information for staging was formed on presentation. The extent of disease of each patient was restaged according to the 1997 UICC system. Results：The 1997 UICC system creates subgroups (Stages Ⅰ -Ⅳ ) that are assigned to 38 (6.1％ ), 270 (43.5％ ), 156 (25.1％ ), and 157 (25.3％ ) patients, respectively. The incidence of parapharyngeal extension was 74.1％ (460/621). Of these patients (460) with parapharyngeal extension, 310 (67.4％ ) patients were classified as T2 disease, The 5-year Overall survival(OS) rates were 89％ , 70％ , 53％ , and 37％ for Stages Ⅰ -Ⅳ , respectively. The 1997 UICC system showed highly significant differences between the overall stages for both OS and relapse-free survival(RFS). The 1997 UICC T-classifications showed significant correlation with local failure, and N classification was accurate in predicting freedom from distant metastasis(FDM). Conclusion：The 1997 UICC staging system for NPC is prognostically useful for Chinese patient populations. However, an uneven patient number distribution was noted. Subdivision of parapharyngeal extension should be included in future revisions of the staging system.

Background Infantile hemangioma (IH) is the most common benign tumor in children with prevalence in the face and neck.Various treatment options including oral propranolol have been described for IH,but the mechanism of drugs remains enigmatic.The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration.Methods Stem cells from the proliferating hemangiomas (HemSCs) were isolated by CD133-tagged immunomagnetic beads.Their phenotype and angiogenic property were investigated by flow cytometry,culturing on Matrigel,real-time polymerase chain reaction (PCR),immunofluorescent staining and injection into BALB/c-nu mice.Results HemSCs had robust ability of proliferating and cloning.The time of cells doubling in proliferative phase was 16 hours.Flow cytometry showed that HemSCs expressed mesenchymal markers CD29,CD44,but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45.The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell (MSC).Real-time PCR showed that the mRNA levels of vascular endothelial growth factor (VEGF),basic fibroblast growth factor (bFGF) and matrix metalloproteinase-1 (MMP-1) of HemSCs were higher than that of neonatal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs).After HemSCs were cultured on Matrigel in vitro,they formed tube-like structure in a short time (16 hours) and differentiated into endothelial cells in 7 days.After 1-2 weeks of implantation into immunodeficient mice,HemSCs generated glucose transporter 1 positive blood vessels.When co-injected with HUVECs,the vascularization of HemSCs was greatly enhanced.However,the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice (P ＜0.05).Conclusions HemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability,which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.

OBJECTIVETo investigate the effect of bilateral mandibular distraction osteogenesis in the condyles.

METHODS16 adult hybrid dogs were randomly divided into normal control group and experiment group. Experimental dogs underwent bilateral mandibular osteodistraction at a rate of 1 min/day. 4 dogs were killed respectively in distraction period, 2 and 8 weeks after completion of 10 days distraction. The bilateral condyles specimens were harvested and examined with histological and immunohistochemical methods.

RESULTSCompared with normal control group, various degrees of irregularities and erosion were found in fibrocartilage of condyle in experiment group, including damage in fibrous layer, hyperplasia layer and proliferative layer and osteogenic activity in cartilage layer. A significant increase of TGF-beta1 expression was also found in experiment groups. TGF-beta1 positive staining was noted in hypertrophic cell, matrix and chondroblast, osteoblast and matrix in osteogenic activity areas. These changes were the most obvious in 2 weeks after completion of distraction.

CONCLUSIONGradual bilateral mandibular distraction at a rate of 1 mm/day brought degenerative changes of condyle, but the changes are reversible.

Animals ; Dogs ; Mandible ; Osteoblasts ; Osteogenesis, Distraction ; Temporomandibular Joint ; Transforming Growth Factor beta1

BACKGROUNDInfantile hemangioma (IH) is the most common benign tumor in children with prevalence in the face and neck. Various treatment options including oral propranolol have been described for IH, but the mechanism of drugs remains enigmatic. The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration.

METHODSStem cells from the proliferating hemangiomas (HemSCs) were isolated by CD133-tagged immunomagnetic beads. Their phenotype and angiogenic property were investigated by flow cytometry, culturing on Matrigel, real-time polymerase chain reaction (PCR), immunofluorescent staining and injection into BALB/c-nu mice.

RESULTSHemSCs had robust ability of proliferating and cloning. The time of cells doubling in proliferative phase was 16 hours. Flow cytometry showed that HemSCs expressed mesenchymal markers CD29, CD44, but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45. The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell (MSC). Real-time PCR showed that the mRNA levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-1 (MMP-1) of HemSCs were higher than that of neonatal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). After HemSCs were cultured on Matrigel in vitro, they formed tube-like structure in a short time (16 hours) and differentiated into endothelial cells in 7 days. After 1 - 2 weeks of implantation into immunodeficient mice, HemSCs generated glucose transporter 1 positive blood vessels. When co-injected with HUVECs, the vascularization of HemSCs was greatly enhanced. However, the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice (P < 0.05).

CONCLUSIONSHemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability, which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.

AC133 Antigen ; Animals ; Antigens, CD ; analysis ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Collagen ; Disease Models, Animal ; Drug Combinations ; Glycoproteins ; analysis ; Hemangioma ; pathology ; Humans ; Laminin ; Male ; Mice ; Mice, Inbred BALB C ; Neoplastic Stem Cells ; chemistry ; pathology ; Peptides ; analysis ; Proteoglycans ; Vascular Endothelial Growth Factor A ; physiology

OBJECTIVETo find out the vector ability and function of Nosopsyllus wualis leizhouensis in the transmitting plague.

METHODSIn T: 19 degrees C +/- 1 degrees C, RH: 85% +/- 5%, data regarding the vector ability as cluster spreading, single flea spreading, single flea transmitting plague to single animal, formative bacterial embolus and infection fleas life-span through experiments was gathered.

RESULTSThe rate of infection on fleas was 94.64%, with 100% transmission rate of colony to spread, and 30% from single flea spreading to single animal. In the experiment of single flea transmission, all of the 388 rattus loseas were bitten by the fleas with bacterial, but only 9 animals were characteristically infected with the transmission potential, vector efficiency, survival potential of embolus, vector index as 0.360, 0.257, 0.868 and 0.223 respectively. The mean survive days of infected flea feed with blood were 17.58 (1 - 58), and the mean survive days of hunger infected flea were 7.25 (1 - 16). Formative bacterial embolus days were 8.80 (2 - 16) and the rate of embolus flea was 78.12%.

CONCLUSIONNosopsyllus wualis leizhouensis could serve as vector and important in the mode of plague transmittion.

Animals ; Female ; Insect Vectors ; microbiology ; Male ; Plague ; transmission ; Rats ; Siphonaptera ; microbiology

OBJECTIVETo evaluate the reliability and validity of parent proxy-report scales of Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales, the Chinese Version.

METHODS3493 school students aged 6-18 years were recruited using multistage cluster sampling method. Health-related quality of life was assessed using the above-mentioned PedsQL 4.0 scales. The internal consistency was assessed, using Cronbach's a coefficient, while its validity was tested through correlation analysis, t-test and exploratory factor analysis.

RESULTSThe internal consistency reliability for Total Scale Score (Cronbach's alpha = 0.90), Physical Health Summary Score (alpha= 0.81), and Psychosocial Health Summary Score (alpha= 0.89) were excellent. Six major factors were extracted by factor analysis which basically matched the designed structure of the original version accounting for nearly 66% of the variance. The total Scale Score significantly decreased by 3.5 to 13.3 (P < 0.05) in children and adolescents who had diseases including cold, skin hypersensitiveness, food allergy, courbature or arthralgia, breathlessness with a frequency of 6 times or more per year or had asthma as compared to those with lower frequency (< or = 5 times/y) of the diseases or without asthma. We found moderate to high correlations between items and the subscales. Correlation coefficients ranged between 0.45 to 0.84 (P < 0.01).

CONCLUSIONThe reliability and validity of the parent proxy-report scales of PedsQL 4.0 Generic Core Scales of the Chinese Version were as good as the original version. Our findings suggested that the scales could be applied to evaluate the health-related quality of life in childhood children in similar Chinese regions to Guangzhou.

Adolescent ; Child ; Child Welfare ; psychology ; statistics & numerical data ; China ; Humans ; Psychometrics ; methods ; Quality of Life ; Students ; Surveys and Questionnaires