17-allylamino-17-demethoxygeldanamycin (17-AAG) is a heat shock protein 90 ( HSP90) inhibitor. It is capable of target-inhibiting tumor-derived HSP90, leading to the depletion of on-cogenic client proteins which play key roles in several signal transduction pathways. Then cell growth and differetiation are inhibited. 17-AAG results in cytostasis and apoptosis. A lot of trials have indicated that 17-AAG is a selective target drug for cancer therapy. It can efficiently inhibit multiple signal transduction pathways involved in tumor cell proliferation and survival. Clinical phaseⅠand phaseⅡtrials have shown that 17-AAG has good pharmacokinetic-pharmacodynamic profile. Moreover, it can combine with radiation and the traditional chemotherapeutics and increase the therapeutic efficacy.

OBJECTIVETo investigate surgical outcomes of strip nail internal fixation with bone graft in treating tibial plateau fracture.

METHODSFrom May 2012 to May 2014,36 patients with tibial plateau fracture were retrospectively analyzed, including 25 males and 11 females with an average age of 43.5 (ranged from 17 to 65) years old. The time from injury to operation ranged from 3 to 10 days with an average of 5.8 days. All patients were treated with L-shaped and T-shaped strip nail internal fixation with bone graft. It was evaluated by the Knee Functional therapy assessment method of the Special Surgical Hospital of American at final following-up. Varus angle, caster angle and femorotibial angle were recorded and compared at 3 days and 1 year.

RESULTSOperative time was (2.2 ± 0.6) h on average, blood loss was (310.5 ± 36.2) ml on average, hospital stay was (14.8 ± 2.7) days on average. Thirty-six patients were followed up from 12 to 30 months with an average of 18.2 months. Fracture healing time ranged from 4 to 8 months with an average of 6.2 months. The difference is not significant among varus angle, caster angle and femorotibial angle at 3 days and 1 year. According to the knee functional therapy assessment method of the Specialized Surgical Hospital of American, 18 cases got excellent results, 13 good, 4 moderate and 1 poor.

CONCLUSIONStrip nail internal fixation with bone graft for the treatment of tibial plateau fracture could effectively prevent the joint surface from secondary collapse, and achieve anatomic reduction, stable fixation and earlier functional exercise in further to get satisfied clinical effects.

Adolescent ; Adult ; Aged ; Bone Nails ; Bone Transplantation ; Female ; Fracture Fixation, Internal ; methods ; Fracture Healing ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tibial Fractures ; physiopathology ; surgery

-2,and T)was detected on exon 11 in the mutational analysis of GABRG2.Our results indicate that genomic variations of GABRG2 are not likely to be substantially involved in the etiology of GEFS+in this family. Conclusion Our study fails to provide evidence supporting a causal relation between the SCN1A,SCN1B, GABRG2 mutation and the etiologic genes in this family,which indicates that GEFS+has with phenotypic and genotypic heterogeneity.

Objective To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene(HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results In the animal heating experiments, the temperature of tumor increased up to 39.6 ℃, 43.2 ℃, and 48.1 ℃ quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 ℃, 37.5 ℃ and 37.8 ℃ in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50 ±30.29) mg), D ((240.98 ±35.32)mg), E((231.87 ±27.41) mg) and F ((141.55 ±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P＜0. 01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05 ±24.02) mg) was higher than that in Group D (t =32. 805, P ＜0. 05). Semi-quantitative RT-PCR analysis showed that the expression of HSV-tk in Groups B and D (0.33 ±0. 13 and 0. 46 ±0.12) was significantly different from that in Groups E and F (0.66 ±0.13 and 0.74 ±0. 11)(F = 21. 573, P ＜ 0.05). Conclusion Combined use of hyperthermia, gene therapy and radionuclide brachytherapy could effectively depress the growth of MCF-7 breast carcinoma, thus possessing treatment potential for this tumor.

OBJECTIVETo investigate the influence of hepatitis C virus (HCV) serotype on the interferon (IFN) treatment of patients with chronic hepatitis C.

METHODSNinety-eight patients with chronic hepatitis C were divided into two groups: patients in group 1 (n=53) were treated with Pegasys, 180 ug injected subcutaneously once a week for 24 weeks, and those in group 2 (n=45) were injected with Roferon-A 3 MU three times a week for 24 weeks and then patients in both groups were followed up for another 24 weeks. The virological response at the end of follow up was the primary endpoint for evaluating the effects of IFN treatment. The HCV RNA levels of the chronic hepatitis C patients were determined with COBAS AMPLICOR MONITOR Test, version 2.0, and the HCV serotypes were examined by the means of ELISA using Murex HCV Serotyping 1-6 Assay.

RESULTSOf the 98 cases, HCV in 44 cases was serotype 1, in 23 was serotype 2, in 10 was serotype 3, in 1 was serotype 4, 1 was serotype 5 and in 2 was serotype 6; HCV serotypes in the remaining 17 patients could not determined. In Pegasys treatment group, the biochemical and virological response was not significantly different at the end of treatment between the patients with serotype 1 and non serotype 1 or serotype undetermined patients, but the sustained virological response rate of HCV serotype undetermined group (66.7 percent) was significantly higher than that of serotype 1 patients (27.3 percent) (p=0.035). In Roferon-A treatment group, the virological response rate at 24 weeks and sustained viral response rate at the end of follow-up was not significantly different between serotype 1 and non serotype 1 patients or serotype undetermined patients.

CONCLUSIONAfter the six months treatment course, the HCV serotype had some effects on the treatment response to Pegasys treatment for chronic hepatitic C.

Adult ; Antiviral Agents ; administration & dosage ; Drug Administration Schedule ; Female ; Hepacivirus ; drug effects ; immunology ; Hepatitis C Antibodies ; blood ; Hepatitis C, Chronic ; drug therapy ; immunology ; Humans ; Interferons ; administration & dosage ; Male ; Middle Aged ; Young Adult

Objective Background-study on genesis and development of tumor is mainly concentrated on gene mutation in nucleus. In recent years, however, the role of mitochondrial DNA (mtDNA) mutation in tumor genesis has been given more and more attention, which is the only extra-nucleus DNA in cells of higher animals. Carcinoma of the uterine cervix is a common tumor in gynecology, but there are few reports of mtDNA mutation in this area. The focus of this study was to investigate the mtDNA mutation in tumor tissues of cervical carcinomas and their relationship to tumorigenesis and tumor development. Methods The D-loop region of 24 cervical carcinomas together with the adjacent normal tissues were amplified by PCR and sequenced. Results Among the 24 cervical carcinomas, 30 mutations in 9 patients′ specimen were identified with the mutations rate of 37.5%(9/24). There were 8 microsatellite instabilities among the mutations and 13 new polymorphisms which were not reported previously in the Genbank. Conclusions The D-loop region of mitochondrial DNA is a highly polymorphoric and mutable region and the mutation rate is relatively high in patients with cervical carcinomas.

Objective Background-study on genesis and development of tumor is mainly concentrated on gene mutation in nucleus. In recent years, however, the role of mitochondrial DNA (mtDNA) mutation in tumor genesis has been given more and more attention, which is the only extra-nucleus DNA in cells of higher animals. Carcinoma of the uterine cervix is a common tumor in gynecology, but there are few reports of mtDNA mutation in this area. The focus of this study was to investigate the mtDNA mutation in tumor tissues of cervical carcinomas and their relationship to tumorigenesis and tumor development. Methods The D-loop region of 24 cervical carcinomas together with the adjacent normal tissues were amplified by PCR and sequenced. Results Among the 24 cervical carcinomas, 30 mutations in 9 patients′ specimen were identified with the mutations rate of 37.5%(9/24). There were 8 microsatellite instabilities among the mutations and 13 new polymorphisms which were not reported previously in the Genbank. Conclusions The D-loop region of mitochondrial DNA is a highly polymorphoric and mutable region and the mutation rate is relatively high in patients with cervical carcinomas.

Adult ; Aged ; Bacterial Infections ; diagnosis ; immunology ; Female ; Hepatitis B, Chronic ; diagnosis ; immunology ; microbiology ; Humans ; Male ; Middle Aged ; Prognosis ; T-Lymphocyte Subsets ; immunology ; Young Adult

Objective To explore the effect of silencing metastasis-associated in colon cancer 1 ( MACC1 ) gene on proliferation and invasion of cervical cancer Hela cells. Methods siRNA MACC1 and siRNA NC were transfected into cervical cancer Hela cells with liposomes. The expression of MACC1 protein and mRNA was detected by western blot and RT-PCR. Cell viability and invasion ability were measured by MTT and transwell assay, respectively. The expression of cyclin D1, cyclin E matrix metalloproteinase 2 (MMP2), MMP9 and the level of extracellular regulated protein kinases ( ERK) phosphorylation was detected by western blot. Results Compared with siRNA NC, the expression of MACC1 protein and mRNA was down-regulated, cell viability and invasion ability were reduced ( P < 0. 01 ) , cell cycle was arrested at G1 phase (P < 0. 01), the expression of cyclin D1, cyclin E, MMP2, MMP9 and p-ERK1/2 was down-regulated (P< 0. 01). Conclusions siRNA MACC1 can inhibit proliferation and invasion of cervical cancer Hela cells, which migiht be related to down-regulation of p-ERK.

OBJECTIVETo evaluate whether the rapid viral response (RVR) to combinational therapy with interferon and rabavirin can be used to predict the sustained viral response (SVR) in chronic hepatitis C patients.

METHODSAccording to their clinical characteristics, all patients in this study were given pegylated or conventional interferon injection and different dose of ribavirin according to their weight. Patients were injected Pegasys (pegierferon alpha-2a) 180 microg or 135 microg once a week, or pegyintron 50-80 microg once a week, or conventional interferon 3-5 MU every two days, in combination with a dose of 600-1500 mg/d ribavirin. The serum HCV RNA load was determined at 0, 4, 12 week, and then every 12 weeks. After the viral response obtained, the patients were treated for another 24-72 weeks and followed up 24 weeks. The main parameter to evaluate the efficacy was SVR rate. The influence factors associated with rapid viral response were investigated.

RESULTSRVR was obtained at week 4 in 84.2% of the 120 patients. The HCV RNA baseline of RVR group was (5.883+/-1.246) lg copies/ml, which was significantly lower than that of the group without RVR [(6.502+/-0.693) lg copies/ml, t=2.15, P=0.034]. 97 patients with RVR who finished treatment and follow-up, 90.7% of these patients obtained SVR, but the SVR rate in patients (82.4%) without RVR was lower than that in patients with RVR (x2=0.371, P=0.543). In this study, RVR rate was not associated with HCV genotype and the dose of interferon used. In the naive patients, the RVR to pegylated interferon was 87.8%, which was significantly higher than that in retreat patients (x2=4.651, P=0.031).

CONCLUSIONHigh RVR rate could be obtained in chronic hepatitis C patients treated combined with interferon and ribavirin. RVR rate is associated with the HCV RNA baseline load in both naive and retreat patients but not correlated to HCV genotype. RVR could predict the SVR.

Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Antiviral Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; blood ; drug therapy ; pathology ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Predictive Value of Tests ; RNA, Viral ; blood ; Recombinant Proteins ; Recurrence ; Ribavirin ; administration & dosage ; therapeutic use ; Time Factors ; Treatment Outcome ; Viral Load ; Young Adult