Objective: To investigate the function and mechanism of phospholipase Cγ1 (PLCγ1) in cell-matrix adhesion in colorectal cancer. Methods: Highly metastatic colorectal cancer cell line LoVo and lowly metastatic colorectal cancer cell line SW480 were subjected to cell-matrix adhesion assay. U73122 (a specific inhibitor of PLC) and pyrrolidine dithiocarbamate (PDTC) (an inhibitor of NF-κB) were used to study the effect of PLCγ1 and NF-κB on cell-matrix adhesion. Furthermore, Western blot and gel electrophoresis mobility shift assay (EMSA) were performed to detect the mechanism of PLCγ1 in colorectal cancer cell adhesion to matrix. Results: Inhibition of PLCγ1 or NF-κB resulted in reduction of cell-matrix adhesion in a dose-dependent manner in LoVo cells(P<0.05), but had no marked effect on SW480 cells. Western blot analysis showed that epidermal growth factor (EGF) stimulated the phosphorylation of PLCγ1 in LoVo. The results of EMSA indicated that inhibition of PLCγ1 signaling pathway also down-regulated the activity of NF-κB while EGF reversed the function. Conclusion:These data suggest that PLCγ1 plays a pivotal role in the EGF-induced cell-matrix adhesion of highly metastatic colorectal cancer cells and that NF-κB is also functional in this signaling pathway.

Child, Preschool ; Humans ; Male ; Nevus, Blue ; pathology ; Skin Neoplasms ; pathology

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".
Antineoplastic Agents ; chemistry ; Drug Carriers ; chemistry ; Liposomes ; chemistry ; Polyethylene Glycols ; chemistry

Animals ; Cells, Cultured ; Electrophysiology ; Mice ; Mice, Inbred Strains ; Neurons ; physiology ; Potassium Channels ; physiology ; Spiral Ganglion ; physiology

Objective: To discuss the conversion coefficient of morphine injection with continuous intravenous pump delivery or subcutaneous injection for the patients with advanced cancer pain demanding high dose of opioids.Methods: Using a retrospective survey, the patients with advanced cancer pain demanding high dose of opioids with poor efficacy were divided into 3∶1 group and 2.5∶1 group, and the conversion coefficient of 3∶1 or 2.5∶1 was used for the opioids equivalently conversed to intravenous or subcutaneous injection of morphine.After the conversion, the degree of pain relief, the analgesic efficiency in the conversion process, titration time, daily oral morphine equivalent amount at stable pain, morphine related adverse reactions and the other indicators were studied to evaluate the analgesic effect of morphine injection with different conversion coefficient.Results: There was no statistical significant difference between the two groups in the degree of pain relief, the effective rate of analgesia and the daily oral akministration amount of morphine at sable pain(P>0.05).The adjustment times for morphine in the two groups was (1.57±0.93) and (1.0±0.00), respectively, and the difference was statistically significant (P<0.05).The daily oral administration amount of morphine at stable pain in the two groups respectively was (226.67±69.74) mg and (258.67±101.34) mg;the morphine related adverse reactions were mainly constipation, and there was no significant difference in the incidence (P>0.05).Conclusion: Giving morphine injection to the patients with terminal cancer pain demanding high dose of opioids with poor effect, the use of PCA pump through intravenous or subcutaneous injection can effectively relieve pain.Using the conversion coefficient of 2.5:1 can quickly complete the titration process, and safely achieve the effective analgesia.

Objective: To investigate the effect of silver nanoparticles (AgNPs) on hemichannel activity in human skin keratinocytes (HaCaT) and to explore the role of hemichannel in AgNP-induced anti-proliferative effect on HaCaT cells.Methods: HaCaT cells were exposed to 0, 0.1, 0.2, 1.0, 5.0, 10.0, 15.0 and 20.0 μg/cm2 of AgNPs for 24 h and cell viability was assessed by propidium iodide (PI) staining with flow cytometry.Hemichannel activity was examined by ethidium bromide (EB) uptake experiments in cells exposed to AgNPs with and without hemichannel inhibitor carbenoxolone (CBX).Afterward, HaCaT cells were seeded at a low density of 1×104cell /cm2 or a normal density of 4×104cell /cm2 and cultured for 24 h.Cell proliferation was measured by cell counting kit-8 (cck-8) in low-or normal-density cultured cells exposed to AgNPs for 24 h with and without 100 μmol/L CBX.Results: Cell viability showed no significant differences between the control and AgNP-exposed groups with the concentration less than 10 μg/cm2.Exposure to AgNPs increased EB uptake in a time-and dose-dependent manner in HaCaT cells and EB fluoresce density was increased to 116.67%, 124.85% and 139.53% of the control after exposure to 10 μg/cm2 AgNPs for 2 h, 12 h and 24 h.After being treated with 25, 50 and 100 μmol/L CBX, 10 μg/cm2 AgNP-induced increase in EB uptake was significantly reduced in HaCaT cells (P<0.01).The cellular proliferation rate was increased inlow-and normal-density cultured cells after AgNPs exposure with 100 μmol/L CBX.After being treated with 100 μmol/L CBX, 10 μg/cm2 AgNP-induced anti-proliferation in low-density cultured cells was significantly restrained (P<0.01).Conclusion: AgNPs could enhance hemichannel activity of HaCaT cells.Hemichannel activation was involved in AgNP-induced anti-proliferative effect.

Objective To explore the possibility of rapamycin to up-regulate radiosensitivity of nasopharyngeal carcinoma (NPC) and its molecular mechanism.Methods In vitro,with untreated cells as the control,NPC cells were treated with rapamycin,irradiation (IR),or both rapamycin and IR.Phosphorylation of S6 and GSK3β,expression of Cyclin D1,clonogenic survival,number of residual γH2AX foci,and cell cycle status between study groups were compared.In vivo,athymic mice bearing CNE1 tumor were similarly treated.Tumor weight,Cyclin D1 and phosphorylated S6 in the xenograft model were compared between study groups.Results The results showed that rapamycin alone decreased the phosphorylation of S6 and glycogen synthase kinase 3 β (GSK3β),and the expression of Cyclin D1 in NPC cells.Thus,rapamycin-treated NPC cells had lower cell viability,higher DNA damage and more G1 arrest than the control,which was reflected by the in vivo study that rapamycin significantly attenuated tumor growth and decreased the levels of Cyclin D1 and phosphorylated S6.Moreover,the combination of rapamycin and IR caused the highest cell death,DNA damage,G1 arrest and tumor regression compared to those treated either alone.Conclusions Rapamycin up-regulate NPC radiosensitivity by inhibiting signal transduction of Akt/mammalian target of rapamycin (mTOR)/S6 pathway and Akt/GSK3β pathway,and by downregulating Cyclin D1 expression.

Objective: To investigate the function and mechanism of phospholipase C?1 (PLC?1) in cell-matrix adhesion in colorectal cancer. Methods: Highly metastatic colorectal cancer cell line LoVo and lowly metastatic colorectal cancer cell line SW480 were subjected to cell-matrix adhesion assay. U73122 (a specific inhibitor of PLC) and pyrrolidine dithiocarbamate (PDTC) (an inhibitor of NF-?B) were used to study the effect of PLC?1 and NF-?B on cell-matrix adhesion. Furthermore, Western blot and gel electrophoresis mobility shift assay (EMSA) were performed to detect the mechanism of PLC?1 in colorectal cancer cell adhesion to matrix. Results: Inhibition of PLC?1 or NF-?B resulted in reduction of cell-matrix adhesion in a dose-dependent manner in LoVo cells(P

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".

Objective To investigate the characteristics of children′s recurrent abdominal pain(RAP) with gastroscopy and analyze the etiology.Methods Three hundred and thirteen children were investigated with gastroscopy.Gastric antrum mucosa was taken for histo-pathology and the determination of helicobacter pylori(Hp) antibody.Results Ninty-nine point six eight percent of the cases had lesions under the gastroscope.The former 4 cases had chronic superficial gastritis(CSG),CGS and bile reflux,CGS and duodenitis,CGS and bulb ulcer,and Hp infection rate was 31.36%,25%,38.64%,60.61%.Hp infection rates of active gastritis and inactive gastritis were 92% and 23.19%,which showed significant differences in 2 groups(P