Objective · To investigate the histone methyltransferase capability of DOT1L-long form and its role in breast cancer metastasis.Methods · The existence of DOT1L-long form was confirmed by PCR, and the mRNA level of DOT1L was tested by real-time PCR. In HEK293T cells in which DOT1L canonical and DOT1L-long were overexpressed respectively, Western blotting was used to test the expression level of DOT1L and the histone methyltransferase capability. In the MCF10A cell line with inducible expression of DOT1L-long, real-time PCR was used to detect the mRNA level of epithelial-mesenchymal transition (EMT) marker, and transwell assay was used to detect the migration of breast cancer cells in which the expression level of DOT1L is low or high. Results · PCR demonstrated the existence of DOT1L-long form, and real-time PCR showed it widely exists in HCT116, T98G, MCF10A cells, etc. Western blotting showed the expression of DOT1L-long form and its H3K79 methyltransferase activity. In MCF10A cells in which overexpressed canonical DOT1L and DOT1L-long, mRNA levels of N-cadherin and fibronectine increased. Transwell showed canonical DOT1L and DOT1L-long both substantially increased the migration of breast cancer cells. Conclusion · The existence of DOT1L-long was confirmed and investigated, which is 202 amino acids longer than the canonical DOT1L, and is coded by a new exon, located between exon 27 and 28. Further, the DOT1L-long has H3K79 methyltransferase activity, and is able to promote breast cancer metastasis.

OBJECTIVETo study the combination of Mandibular distraction and orthognathic techniques for the reconstruction of adult hemifacial microsomia.

METHODSThe three-dimensional CT reconstruction data was used with Mimics for preoperation design. The osteotomy location, distraction vector, distraction distance were decided before operation with a surgical guider. At the first stage, internal distractor was implanted after ostetomy through an extra-oral approach. The distraction begun 5-7 days after operation with a frequency of 1 mm/day. After distraction, the distractor was maintained for 3-6 months. At the second stage, the distractor was removed. Le Fort I osteotomy was performed in order to correct the cross-bite and improve the facial contour. Usually, bone graft was inserted into the gap after Le Fort I osteotomy. The genioplasty was also performed if necessary.

RESULTS9 cases of adult hemifacial microsomia with severe mandibular deviation were treated. The facial asymmetry were improved greatly. 1 patient suffered an wound infection in the maxillary region after Le Fort I osteotomy and healed uneventfully with wound irrigation.

CONCLUSIONSMandibular distraction combined with orthognathic surgery is an effective procedure for adult hemifacial microsomia with complicated mandibular hypoplasia.

Adult ; Aged ; Bone Transplantation ; Facial Asymmetry ; surgery ; Goldenhar Syndrome ; surgery ; Humans ; Mandible ; surgery ; Osteogenesis, Distraction ; methods ; Osteotomy, Le Fort ; methods

0.05), but the level of albumin dropped significantly(P

Antibiotics, Antineoplastic ; pharmacology ; Breast Neoplasms ; enzymology ; pathology ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Female ; Glucosyltransferases ; biosynthesis ; genetics ; Humans ; Oligodeoxyribonucleotides, Antisense ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Transfection

Objective To study the effect of platelet-derived growth factor(PDGF)and lysosomes on lung injury in macaque with early-phase endotoxie shock.Method Eleven macaques were randomly divided into two groups,namely,control group(Co group,n=5)iand endotoxic group(En group,n=6).The macaque of the Co group injected with 1 ml/kg normal saline and the macque of the En group received a dose of 2.8 mg/kg Lipopolysaccharides(LPS)i.v.The blood gas was detected at 120 minutes after LPS challenging. Uhrastructure,cytochemistry of acid phosphatase(ACPase)detection by electronic microscopy and immunohistochemical assay of PDGF were completed in hmgs of all the macaque .Results Administration of LPS did not change the parameters of gas exchange,namely,PaO_2,PaO_2/Fi and PaCO_2.In the early phase,of endotoxic shock,ACPase activity products increased and lysosome destroyed in the alveolar cells.The pathologic changes of alveolus,such as degeneration of vessel endothelium,injury of alveolar epithelium and damage of basement membrane,and transudation of blood component were observed by electron microscopy in the En group. However,no pathological changes were found in the control group.By immunohistochemical staining,PDGF on alveolar wall in the En animals was observed,whereas no PDGF protein in the Co macaques was noticed. Conclusions Administration of LPS induced the expression of PDGF in the alveolar wall and lysosome injury in the alveolar cells,as a result of alveolar damage in early-phase endotoxin shock.In the meantime,the parameters of gas exchanges did not change.The PDGF may play an important role in the pathogenesis of lung during the early-phase of endotoxin shock.

AIMTo investigate protective effects of ginkgolide B (GB) in different administration modes on glutamate-induced neuronal damage.

METHODSEssential GB were obtained by supercritical CO2 fluid extraction. Glutamate excitotoxicity were examined in primary cultures from neonatal Wistar rat, by using of Trypan blue dye staining, testing the lactate dehydrogenase leakage from cultured neurons and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method. The protective effects of GB in different administration modes (pre-treatment and post-treatment) were adopted and compared with the NMDA receptor uncompetitive antagonist-MK-801 in acute-treatment.

RESULTSTreatment with GB in two administration modes both could increase ratio of surviving neuron, decrease LDH efflux and reduce ratio of neuron apoptosis in different degree, depended on dose in certain range. The protective effect of pre-treatment was superior to post-treatment, but inferior to MK-801.

CONCLUSIONGB can protect neurons against glutamate damage, and preventive using has more efficiency. The potential mechanism of its neural protection may be not only related to PAF receptor. If the predominant protection effect of GB in pretreatment is considered, precautionary intervention to high-risk population could have more value.

Animals ; Cells, Cultured ; Dizocilpine Maleate ; pharmacology ; Ginkgolides ; administration & dosage ; pharmacology ; Glutamic Acid ; adverse effects ; Hippocampus ; drug effects ; metabolism ; Lactones ; administration & dosage ; pharmacology ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Wistar

Objective To evaluate the multimodal treatment outcomes and patterns of treatment failure in esthesioneuroblastoma at a single institution. Methods One hundred and twelve patients who were newly diagnosed with esthesioneuroblastoma but no distant metastasis in our institution from 1979 to 2014 were retrospectively analyzed. The treatment modes, outcomes, and patterns of treatment failure in these patients were analyzed. According to the modified Kadish staging system, the numbers of patients with stage A, B, C, and D esthesioneuroblastoma were 1, 23, 60, and 28, respectively. Fifty?one patients received surgery and postoperative radiotherapy with or without chemotherapy;forty?six patients received radiotherapy with or without chemotherapy;eleven patients received preoperative radiotherapy and surgery with or without chemotherapy;three patients received surgery with or without chemotherapy; one patient received chemotherapy alone. The survival rates were calculated using the Kaplan?Meier method. Results In all patients, the 5?year sample size was 44, and the 5?year overall survival ( OS ) and disease?free survival ( DFS) rates were 66?4% and 54?7%, respectively. The 5?year OS and DFS rates were 91% and 82% in patients who received preoperative radiotherapy and surgery with or without chemotherapy, 80% and 66% in patients who received surgery and postoperative radiotherapy with or without chemotherapy, and 46% and 37% in patients who received radiotherapy with or without chemotherapy. Three patients treated with surgery alone had relapse of the disease;one patient treated with palliative chemotherapy survived 6 months. Treatment failed in 47 ( 42%) out of 112 patients. In patients with failed treatment, 53% had distant metastasis as the first pattern of treatment failure, 36% had locoregional relapse, and 11% had concurrent distant metastasis and locoregional relapse. Conclusions Surgery combined with radiotherapy is still the recommended multimodal treatment regimen for esthesioneuroblastoma. The multimodal treatment achieves satisfactory local?regional control rate and treatment outcomes in the treatment of esthesioneuroblastoma. The major pattern of treatment failure is distant metastasis.

Objective To explore the distribution of dendritic cells (DCs) and the expression of adhesion molecules in rat kidney with unilateral ureteral obstruction (UUO),as well as the regulatory effect of anti-P-selectin lectin-EGF domain monoelonal antibody (PsL-EGFmAb) on adhesion,maturation and function of human DCs cultured in vitro.Methods UUO rat models were established,which were divided into sham group (n=6),untreated group (n=18)and treated group with PsL-EGFmAb(n=18).DCs were analyzed with Axioplan 2 microscopy,while P-selectin being observed by immunohistochemistry.CD34~+ stem cells were isolated from cord blood and cultured in 20%IMDM medium with SCF,GM-CSF,TGF-?1,Flt-3L and TNF-?in vitro.During development, PsL-EGFmAb was added and IL-10 served as control.FACS was performed to detect the expression of HLA-DR,CD1a,CD11c,CD54,CD83,CD80,CD86,CD209 (DC-SIGN) and CD62-P,-E,-L (P-,E-,L-selectin) on DCs.RT-PCR was performed to detect the expression of NF-_KB P50, P65 mRNA.MLR was performed to detect the stimulatory effect of DCs on T cell proliferation and ELISA to determine IL-12p70 amount.Results Comparing with Sham group,the expression of P- selectin was up-regulated among tubulointerstitium mainly on renal tubular epithelial cell after unilateral ureteral obstruction on day 1,while CD1a~+CD80~+DCs being also found in renal interstitium. The expression of P-seleetin and CD1a~+CD80~+DCs was increased evidently on day 7,and correlated with the degree of renal tubulointerstitial fibrosis closely.However,these changes became less conspicuous in rat treated with PsL-EGFmAb.In vitro experiment showed on day 5 after cultured with the induction of TNF-?,immature DCs highly expressed C-type lectin DC-SIGN of pattern recognition receptors;the expression of co-stimulatory molecules such as CD11c,CD83,CD80 and CD86 on mature DCs was up-regulated in paralleling with the mRNA level of NF-_KB;the secretion of IL-12 was enhanced,as well as displaying the features of antigen-presenting cells with a higher ability to induce proliferation of T lymphocytes in vitro.In addition,L-selectin expressed highly on immature DCs,but lowly on mature DCs,neither of two DCs expressed P- and E-selectin.Compared with the IL-10 treated group,PsL-EGFmAb had an inhibitory effect on DC-SIGN of DCs with down- regulating the mRNA level of NF-_KB.PsL-EGFmAb could also inhibited CD11c,CD83,CD80, CD86 expression,reduced secretion of IL-12,and inhibited T cell proliferation stimulated by DCs in vitro.Conclusion DCs may play a critical role on initiating the inflammatory injury of renal tubulointerstitium,and the inhibitory effect of PsL-EGFmAb on DC maturation and function correlated with the inhibition of DC-SIGN,which is mainly mediated through NF-_KB signaling pathway.

Objective To evaluate the treatment effects of chemotherapy comparing with chemotherapy and radiotherapy in the limited-stage small cell lung cancer (SCLC). Methods 234 patients were cyto-pathologically diagnosed and staged as limited small cell lung cancer. The patients were treated with combined chemotherapy and radiotherapy,in which 22 cases were treated by alone chemotherapy (C),39 patients by chemotherapy plus radiotherapy(C+R),and 173 cases by combined chemotherapy and radiotherapy + chemotherapy (C+R+C). The chemotherapy regimen included CE (or PE),CAP or CAV for 4~6 cycles. Irradiation treatment covering the primary tumor,the ipsilateral hilar nodes and mediastinum was delivered once daily with 6 megavoltage X-ray beam to a median irradiation does of 56 Gy being given in 5~6 weeks. Results The 1-,2-,3-,and 5-year overall survival rates were 76.5%,38.2%,25.3%,15.6% respectively,and the median survival time (MST) was 19 months. There was a significantly difference on the survival rate between C+R+C group and C+R group or C group (P