The epidermal growth factor receptor (EGFR) provides a rational target for cancer therapy as it is commonly overexpressed in a variety of solid tumors, and its deregulation is correlated with resistance to chemotherapy and radiotherapy and a poor prognosis. Cetuximab (C255), a specific monoclonal antibody directed against EGFR, is synergistic with chemotherapy and radiotherapy and has been licensed for the treatment of irinotecan refractory colorectal cancer (CRC) and squamous cell cancer of the head and neck (SCCHN), which express EGFR. In addition, the clinical trials about cetuximab for the treatment of non-small cell lung cancer (NSCLC), breast and pancreas carcinoma are ongoing, and cetuximab has been proven to a novel strategy for the treatment of cancer with the overexpression of EGFR.

Multidrug resistance(MDR)of tumor cells has become the main impediment that influence the curative effect of cancer chemotherapy. Although there are many mechanisms can generate the multidrug resistance, the overexpression of P-glycoprotein encoded by the multidrug resistance-1(mdr1) gene is the main cause in the formation of MDR. Seaching for innocuous and effective reversal of MDR is not only a method of improving the efficiency of cancer chemotherapy but also the problem desiderated to be resolved in chemotherapy domain.

Through the system of medicine centralized bidding and purchasing, it intends to solve the problems of high medicine price and drug rebate; however, it failed which was against the willing. It requires exploding regardless hospital regulation system and the current drug production and circulation system to finally stop the high medicine price and drug debate.

The purpose of this paper is to clarify the structure-activity relationship of anti-tumor activity of diosgenin derivatives in vitro. Study has found that diosgenin can inhibit the reproduction of tumor cells by inducing apoptosis and the main target spot of this effect is Bcl-2. Based on the characteristics of pharmacophoric points' of the three-dimensional pharmacophore for Bcl-2 inhibitors, we have docked lots of diosgenin derivatives with Bcl-2, then synthesized 31 compounds of them, finally assessed the anti-tumor activity of the diosgenin derivatives in vitro against A375, A549, HepG-2 and K562. Preliminary studies of SAR have indicated that the aliphatic esters, and aromatic esters of diosgenin without F ring have no anti-tumor activity in vitro. The triazole bromides of diosgenin all achieve fairly good anti-tumor activity in vitro, and those with larger hydrophobic group have the better activity. The stronger is the hydrogen bonding interaction and dipole-dipole interaction of the heterocyclic of diosgenin and diosgenin without F ring and the acid ester of diosgenin without F ring, the better is the activity of derivatives.

Objective To investigate the efficacy of zoledronic acid in the treatment of senile unstable femoral intertrochanteric fractures with anatomical locking plate. Methods 67 patients were randomly divided into two groups. Five days after the operation, group A received one intravenous injection of 5 mg zoledronic acid, while patients in group B did not receive the injection. The two groups were compared in terms of hospitalization time, complications, limb weight-bearing time, fracture healing time, hip function score after operation, preoperative and postoperative serum calcium and serum ALP, bone mineral density of proximal femur before operation and 1 year after operation. Results There were no statistically significant differences between the two groups in age, type of fracture, hospital stay, partial weight-bearing time, fracture healing time, hip function at 1 month and 1 year after operation, preoperative bone mineral density and blood calcium. But the differences were statistically different in hip function at 3 months after operation , averaged bone mineral density of proximal femur and serum ALP 1 year after operation. Moreover, 5 patients in group A developed muscle pain or fever after intravenous injection of zoledronic acid. Conclusion The locking plate combined with zoledronic acid injection in treatment of elderly patients with unstable femoral intertrochanteric fracture could inhibit bone loss, increase bone mineral density, and accelerate limb function recovery after operation. On the other hand, Zoledronic acid has a high incidence of adverse reaction.

AIM: To investigate in vitro effects of cholecystokinin octapeptide(CCK-8) on the expressions of B7.1 and B7.2 and the costimulatory activity of T lymphocytes in unstimulated macrophages.METHODS: Mouse peritoneal macrophages were isolated and incubated with CCK-8(10-12-10-6 mol/L) for indicated time.The B7.1 and B7.2 expressions of murine peritoneal macrophages were analyzed by flow cytometry.CD4+T cells were isolated from mouse spleen using immunomagnetic beads,and cultured with 1/4 numbers of macrophages which were pretreated with CCK-8 and/or anti-B7.1 antibody,anti-B7.2 antibody,CCK1R antagonist CR1409,CCK2R antagonist CR2945 for 24 h.ConA was added into the culture medium to stimulate CD4+T cell proliferation.The proliferation was determined by measuring -TdR incorporation in a ?-scintillation counter.RESULTS: B7.1 and B7.2 expressions and costimulatory activity of peritoneal macrophages were enhanced by CCK-8 in a dose-dependent manner,and the maximal effects occurred at the concentrations of 10-9 mol/L to 10-7 mol/L.Anti-B7.2 antibody,but not anti-B7.1 antibody,reduced the modulatory role of CCK-8 on costimulatory activity.Both CR1409 and CR2945 reversed the effect of CCK-8 on costimulation,and the role of CR1409 was more significant.CONCLUSION: CCK-8 enhances macrophage costimulatory activity by upregulating B7.2 expression,which is mediated by CCK1R and CCK2R.CCK1R might be the major receptor responsible for the modulation of CCK-8 on costimulation.

OBJECTIVETo investigate the effects of Osterix (Osx) overexpression on the osteogenic differentiation of human periodontal ligament cells in response to mechanical force.

METHODSHuman periodontal ligament cells were isolated and cultured in vitro with explant method. Cells were transfected with either an Osx expression vector pcDNA3.1 flag-Osx or the mock control vector pcDNA3.1 flag. Then, cells were centrifuged for 6 h. After transfection and centrification, the expression of Osx mRNA and protein in untransfected cells, mock-transfected cells and Osx-transfected cells were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. Furthermore, the changes of mRNA expressions of core-binding factor cal (Cbfal), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OC), bone sialoprotein(BSP) and collagen protein al (Col I ) genes were measured to assess the differentiation of human periodontal ligament cells.

RESULTSAt 24 h after transfection, Osx mRNA and protein level increased significantly in Osx-transfected cells (P < 0.01), while there were no significant difference in Osx mRNA and protein levels between mock-transfected cells and untransfected cells(P > 0.05). Simultaneously, the upregulated mRNA expressions of all the five osteogenic genes were observed (P < 0.05, P < 0.01). After 6 h of mechanical stimulation, a significant increase in Osx expression was shown in all three groups. However, compared to mock-transfected and untransfected cells, Osx-transfected cells further showed the highest Osx mRNA and protein expression level. Furthermore, the mRNA expressions of all five osteogenic markers in Osx-transfected cells also exhibited the greater increase and showed the highest levels.

CONCLUSIONThe overexpression of Osx promotes the mechanical stress-induced osteogenic differentiation of human periodontal ligament cells. Osx may be essential for mechanical stress-induced differentiation of human periodontal ligament cells to osteoblas tic-like cells and be involved in orthodontic osteogenic remodeling.

Alkaline Phosphatase ; Cell Differentiation ; Cells, Cultured ; Humans ; Integrin-Binding Sialoprotein ; Osteocalcin ; Osteogenesis ; Osteopontin ; Periodontal Ligament ; RNA, Messenger ; Stress, Mechanical ; Transfection

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
Animals ; Apoptosis ; Cause of Death ; Cell Proliferation ; Colon ; Colorectal Neoplasms* ; Fluorouracil ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Repression, Psychology ; RNA, Small Interfering

Objective To explore the influence of Methylphenidate Hydrochloride prolonged-release tablets on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods Thirty ADHD children and 30 healthy controls were enrolled in this study,and the ADHD subjects were treated with Methylphenidate Hydrochloride prolonged-release tablets for (28 ± 3) days.Pre-test and post-test by the Das-Naglieri:Cognitive Assessment System(DN:CAS) were done to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group with healthy control group were compared.The difference between before and after treatment of ADHD was also compared.Results Compared with healthy control group,there were lower of planning score [(21.86 ± 4.61) scores vs.(29.33 ± 5.06) scores],attention score [(25.00 ± 4.57) scores vs.(29.83 ± 3.79) scores],and the total scores [(111.93 ± 13.95) scores vs.(127.26 ±15.53) scores] in ADHD group,and there were significant differences (t =-5.976,-4.455,-4.023,all P ＜0.05).The matching number,planned codes,planned connections,expressive attention,number detection and receptive attention scores were also lower in ADHD group,and there were significant differences (t =-4.787,-3.703,-4.991,-2.216,-2.488,-3.219,all P ＜ 0.05).Compared with healthy control group,there were lower of planning score with significant difference [(25.53 ± 4.98) scores vs.(29.33 ± 5.06) scores,t =-2.931,P ＜ 0.05] in ADHD group after treatment,matching number and planned codes were lower with significant difference (t =-2.654,-2.044,all P ＜ 0.05) in ADHD group after treatment.In ADHD group,the scores of planning [(25.53 ± 4.98)scores vs.(21.86 ± 4.61) scores],simultaneous processing [(36.10 ± 7.10) scores vs.(34.13 ± 6.04) scores],attention [(27.90 ± 5.69) scores vs.(25.00 ± 4.57) scores] and the total score [(121.50 ± 16.55) scores vs.(111.93 ± 13.95) scores] were significantly higher after treatment than that before treatment and there were significant differences (t =-5.679,-2.949,-3.869,-5.963,all P ＜ 0.05);matching number,planned codes,planned connections,nonverbal matrices,number detection,receptive attention and word series were significantly higher after treatment than that before treatment,and there were significant differences (t =-2.528,-3.209,-3.890,-2.276,-4.489,-2.208,-2.373,all P ＜ 0.05).Conclusion The Methylphenidate Hydrochloride prolonged-release tablets can improve the function of cognitive processing in children with ADHD,especially in attention.