ABSTRACT
Objective To investigate the role and significance of neuropilin-2(NRP2)for regulating the angiogenesis of pancreatic neuroendocrine tumors(PNETs).Methods The NRP2 expression in pancreatic neuroendocrine tumer BON-1 cell line was intevened.The BON-1 cells cultural supernatants in the control group and interference group were used to treat human umbilical vein endothelial cells(HUVEC).CCK-8 was used to detect the cell proliferation,Transwell was used to detected the cell migration and the tubule formation test was used detect the pro-angiogenesis.Results The CCK-8 detection showed that there was no statistically significant difference in the supernatant treated HUVEC proliferations between the interference group and control group medium(P>0.05):the absorbancy in the control group was 0.35±0.04,while which in the interference group was 0.32±0.04.The Transwell test showed that the invasion ability of HUVEC treated with cultural supernatants in the interference group was weakened compared with the control group,the control group was(203±13)/hole,while the interference group was(100±10)/hole(P<0.01);the tubule formation test showed that HUVEC tubular formation treated by cultural supernatant in the interference group was decreased,the control group was 40±5,while the interference group was 24±3(P<0.01).Conclusion Interfering NRP2 expression of BON-1 cells can inhibit the vessel formation ability of co-cultured HUVEC,suggesting that NRP2 may have the pro-angiogenesis effect of PNETs,and may be a potential new target for the treatment of PNETs.
ABSTRACT
Standardized rotary residency training is an important part of clinical medical education. Traditional clinical teaching can't meet the rapid development of oncology medicine. In the rotary residency training in oncology department, we put forward the problems encountered in clinical practice, stimulate the interest and initiative of residence, the PBL teaching model is combined with the evidence-based medicine in the teaching process through the relevant training, literature review and discussion. By standardizing the treatment concept the residence's understanding of the basic theory and frontier knowledge of oncology was improved, the thinking innovation and clinical practice ability of the residency doctors were enhanced.
ABSTRACT
Objective To evaluatethe effect of mTORC1 inhibitor on the proliferation in human pancreatic neuroendocrine tumors(pNET)cell line BON,to explore the function of glutamine metabolism in it.Methods In vitro cultured human pancreatic neuroendocrine tumors(pNET)cell line BON,BON cells were treated with different concentrations of rapamycin(1,5,10,25,50, 100 nM)for 12,24 h.Then CCK-8 assay are used to calculate the growth inhibitory rate.Rapamycin treated with BON 12 h,test the glutamine uptake level compared with control.Then deprive of glucose and/or glutamine,CCK-8 assay were used in observation of cell proliferation,cell cycle distribution was analyzed by flow cytomety.Results Rapamycin significantly inhibited the growth of BON cells in a time-and dose-dependent manner(P <0.05).Meanwhile,rapamycin can reduce the glutamine uptake level compared with control.BON obviously depends on glutamine for growth,without glucose and glutamine group have obvious difference in growth rate(P <0.05).Conclusion mTORC1 inhibitor can inhibit BON cells proliferation and influence the glutamine uptake lev-el.suggesting that mTORC1 inhibitor might inhibit BON cells proliferation by influenced the glutamine metabolic pathway.
ABSTRACT
Objective To study the expression of splice variant of progesterone-induced blocking factor (PIBF) of healthy adult and hepatocellular carcinoma (HCC) patients. Methods Western blot was used to find out the expression in 3 normal livers and tumor and para-tumor tissue of 8 HCC patients. Use T Test to compare the difference. Immunohistochemistry was used to detect the expression in tumor and para-tumor tissue of 48 HCC patients. The splice variant of PIBF serum concentrations of 103 healthy adult, pre-operation and part of 5 days post-operation of 109 HCC patients was tested with ELISA. Result The expression of HCC tissue is lower than para-tumor tissue. The serum concentrations of healthy adult and HCC patients is 73.04 ± 6.29 ng/mL and 49.10 ± 4.07 ng/mL, and the difference was statistically significant (P=0.010). The analysis of blood concentrations of pre-operation and part of 5 days post-operation of 15 HCC patients indicate that the expression of pre-operation is lower than post-operation, and the difference was statistically significant (P = 0.008). Conclusion The splice variant of PIBF is low expressed in HCC tissue and serum. PIBF is a potential protein plays important role in cancer.
ABSTRACT
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are exceedingly rare tumor,with an increasing incidence in recent years.According to the NANETS consensus guidelines for the diagnosis of neuroendocrine tumor,the algorithm for diagnosis of GEP-NENs includes clinical syndrome suggestive of NENs,biochemical testing,genetic testing,tumor localization by imaging and tissue diagnosis.GEP-NENs could be divided into functional versus non-functional based on the clinical manifestations.Radical surgery is the standard firstline therapy for limited-stage tumors.However,two-thirds of GEP-NENs patients are inoperable for tumor metastasis at initial diagnosis.For these advance staged patients,multidisciplinary treatment is the best choice,which includes surgery,chemotherapy,biotherapy,molecular targeted therapy,somatostatin receptor-targeted radionuclide therapy.Molecular targeted therapy may turn into a standard first-line therapy for its good curative effect in recent studies.
ABSTRACT
Objective: To examine the expression of glucocorticoid receptor in human colon cancinoma tis-sues and call lines and to explore the survival of colon cancer cell lines treated with dexamethasone alone or in combination with 5-Fu and L-OHP in a way of dexamethasone pretreatment or co-administration in vitro.Methods: The expression of glucocorticoid receptor was detected in 61 cases of colon cancer tissue samples and 4 types of colon cancer cell lines by immunohistochemistry. Apoptosis was detected by Hoechst33342 staining and flow cytometry. MTT assay was employed to detect the chemosensitivity of colon carcinoma cells to L-OHP and 5-Fu with dexamethasone pretreatment for 24 hours or co-administretion. Results: Positive GR expression was found in 57.3% colon cancer tissue samples and in Lovo and HCT-116 cell lines, not in HT-29 and SW-480. Apoptosis was detected in GR-expressed Lovo and HCT-116 cells at 72 hours after 1×10~(-4)mol/L Dex treatment, and the rates of apoptosis were higher than those in the control groups without Dex (P<0.01),GR-negative cells, HT-29 and SW-480 even treated with 1 × 10~(-4)mol/L Dex for 72 hours. Pretreatment and co-administration for Lovo cells with 1×10~(-4)mol/L Dex could decrease the IC50 of L-OHP from 13.7±1:1.3μg/mL to 5.9±0.6μg/mL and 4.8±0.7μg/mL, respectively. IC50 of 5-Fu was decreased from 72.2±8.1 μg/mL to 21.1±4.1μg/mL and 18.6±4.0μg/mL, respectively. Conclusion: There is expression of glucocorticoid receptor in part of colon carcinoma tissue samples and cell lines. Apoptosis does occur in GR-expressed Lovo and HCT-116 cells induced by dexamethasone in vitro. Pretreatment for 24h and co-administration with Dex can increase the chemosensitivity of Lovo cells to L-OHP and 5-Fu.
ABSTRACT
Objective To observe the inhibitory effect of Gefitinib,a selective oral epidermal growth factor receptor tyrosine kinase inhibitor,on the growth of human colon cancer cells,and investigate the relationship between the sensitivity of colon cancer cells to Gefitinib and PIEN expressions.Methods The inhibitory effects of Gefitinib on 6 kinds of colon cancer cells(Lovo,HCT116,HT29,Lsl74T,SW480 and SW620),the levels of PTEN mRNA in different colon cancer cells.and PTEN protein expressions in colon cancer cells were detected by MTT assay,RT-PCR and Westem blot,respectively.Results The inhibitory effects of Gefitinib on the 6 colon cancer cells in vitro varied a lot.When the concentration of Gefitinib was 1 μmol/L,LoVO cells had the most sensitivity to Gefitinib with an IC50<10μmol/L;HT29 and SW480 had moderate sensitivity,and the IC50 ranged from 10 μnol/L to 100 μmol/L;HCT116,LS174T and SW620 were insensitive to Gefitinib,and their IC50>100 μmol/L.All the colon cancer cell lines exhibited PTEN mRNA and protein expressions.Conclusions PTEN mRNA andprotein expressions might not be associated with the inhibitory effects of Gefitinib on the growth of colon cancer cells.The expression of PTEN can not be taken as the indication of the sensitivity of colon cancer cells to Gefitinib.
ABSTRACT
Medical education on oncology is urgently enhanced in China.We analyse a host of questions in medical education on oncology in our country at present,and study didactical methods,goal and task on oncology education.
ABSTRACT
<p><b>BACKGROUND</b>No chemotherapeutic regimen and agent are effective for most patients with advanced non-small cell lung cancer (NSCLC). This study is designed to evaluate the efficacy and toxicity of the combination of gemcitabine and cisplatin in the treatment of NSCLC..</p><p><b>METHODS</b>Sixty cases of NSCLC in stage III and IV were treated with gemcitabine 1200mg/m² by intravenous infusion on 1st and 8th days, and cisplatin 100mg/m² by intravenous infusion on 1st day or 30mg/m² by intravenous infusion on 1st and 8th days in a 28-day cycle. Each patient was treated at least for 2 cycles.</p><p><b>RESULTS</b>An objective response was obtained in 46.67% of patients (3 complete and 25 partial responses), whereas 22 patients had no change and 10 patients were progressive. The response rate was 57.14% in patients without prior chemotherapy and 22.22% in patients with prior treatment. Significant difference existed between the two groups (P < 0.05). The main toxicities were leukopenia and thrombocytopenia, but didn't influence the chemotherapy.</p><p><b>CONCLUSIONS</b>The combination of gemcitabine and cisplatin is a feasible, well-tolerated and effective scheme in the treatment of advanced NSCLC.</p>
ABSTRACT
<p><b>BACKGROUND</b>Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.</p><p><b>METHODS</b>Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .</p><p><b>RESULTS</b>Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .</p><p><b>CONCLUSIONS</b>The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .</p>
ABSTRACT
0.05).CONCLUSION:The domestic tropisetron hydrochloride is equivalent to the imported one in terms of the efficacy and safety in the treatment of cisplatin-induced nausea and vomiting.
ABSTRACT
Objective To evaluate the efficacy and toxicity of the combination of gemcitabine and cisplatin in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 30 cases of non-small cell lung cancer (stages Ⅲ and Ⅳ) were treated with gemcitabine (1 200 mg/m 2, iv infusion, at 1 and 8 d) and cisplatin (100 mg/m 2, iv infusion, at 1 d or cisplatin at 30 mg/m 2, iv infusion, at 1 and 8 d). The administration course was 28 d. Results An objective response was obtained in 46.67% of patients (2 complete and 12 partial responses), whereas 11 patients had no change and 5 patients were progressive. The response rate was 52.38% in patients with no prior chemotherapy and the response rate of 33.33% was achieved in patients who had been given prior treatment. There was significant difference between the two groups (P
ABSTRACT
Objective To investigate of the expression of vascular endothelial growth factor receptor 3 (VEGFR-3) and its relationship with the prognosis of esophageal carcinoma. Methods VEGFR-3 in 156 cases of esophageal carcinoma tissues was detected by immunohistochemistry. The follow-up data for 3 years in 47 cases were analyzed. Results The VEGFR-3 expression in esophageal carcinoma tissues with lymph node metastasis was higher than that in those without lymph node metastasis. VEGFR-3 expression was associated with the clinicopathological stages. Analysis of the follow-up data also showed that there was a statistically positive correlation between VEGFR-3 expression and lymph node metastasis in primary tumors (P
ABSTRACT
Objective To investigate the relationship of apoptosis, proliferation and its related factors (p53, Fas ) with clinical pathological characteristics in hepatocellular carcinoma (HCC). Methods Apoptosis, nuclear antigen of proliferating cells (PCNA), p53, and Fas proteins were detected by labelling technique of in situ terminal deoxynucleotide transferase and immunohistochemical method on 35 HCC samples. Statistical analysis was employed to evaluate the correlations between the experimental data and clinical pathological characteristics. Results There was no significant difference between the apoptotic index (AI), PCNA index (LI), expressions of p53 and Fas and the age, sexual distinction of patient, and tumor size. Expressions of p53, Fas, and AI were not associated with the histological types of tumor at all. However, the index of PCNA was much higher in poorly differenciatiated type than that in trabecular type and pseudo glandular type of HCC. Importantly, following the advanced Edmondson stages and the TNM stages, p53 expression and LI increased in HCC, but AI showed a lower level at same time. Conclusion The malignancy of HCC is negatively correlated with AI but positively with PCNA. The apoptosis in HCC occurs in a p53-dependent manner. The higher mutant of p53 and the lower regulation of Fas expression may contribute to the genesis and progression of HCC.
ABSTRACT
Objective To study the mechanism of multicellular drug resistance of pulmonary adenocarcinoma cell line A549 mediated by cell-cell adhesion. Methods We compared the sensitivity of monolayer cells (MCs) to adriamycin (ADM) with that of multicellular spheroids (MCSs) which was employed as a three dimensional cell culture model. Transmission electron microscopy was applied to observe the cellular ultrastructure. Bcl-2, Bcl-xL, and Bax expression levels were detected by flow cytometry and indirect immunofluorescent staining. Results Compared with MCs, MCSs had more than two layers of cells, more extensive and compact cell adhesion, and inlay junctions were found within them. MCSs were more resistant to ADM. At the same time, Bcl-2 and Bcl-xL expressions in MCSs were much higher. After treatment with ADM, expressions Bcl-2 and Bcl-xL increased markedly in MCSs. Conclusion MCSs could simulate the solid tumors in vivo and has multicellular drug resistance mediated by cell-cell adhesion. The possible mechanisms may be associated with the upregulation of Bcl-2 and Bcl-xL.
ABSTRACT
Objective Taking CNE-2Z multicellular spheroids (MCSs) as the simulation of solid tumors, to investigate the role of SAPK/JNK signaling pathway in multicellular resistance to radiotherapy for human nasopharyngeal carcinoma (NPC). Methods Human NPC cell line CNE-2Z were cultured into multicellular spheroids by using liquid overlay technique, then divided into control MCSs, irradiated MCSs (average dose in one minute: 2 Gy), sp-600125(a specific inhibitor for SAPK/JNK signaling pathway)+irradiated MCSs, sp-600125+MCSs. Western blotting was employed to analyze the activity of SAPK/JNK signaling pathway in MCSs, and the expression of Caspase-3 protein before and after sp-600125 treatment; X-ray induced cell apoptotisis in MCSs before and after sp-600125 treatment was detected by TUNEL. Results The level of SAPK/JNK phosphorylation in MCSs was a dynamic course after radiation, and the phosphorylation peaked at 2 h after irradiation; The apoptotic rate of MCSs (P
ABSTRACT
Objective To construct Neuropilins-2 eukaryotic expression vector for RNA interference.Methods Recombinant targeting on gene NRP2 was designed and established with plasmid pGenSil-1 based on NRP2 cDNA equences of Genomes.Two pairs of oligonucleotides were synthesized according to the Tuschl and inserted into plasmid pGenSil-l to generate siRNA eukaryotic expression vector,DH5? strains were transformed,plasmid were extracted,and recombinant vectors were identified by the restriction map and the sequence analysis.The recombinant plasmid(pGenSil-NRP2) was transfected into the cultured LOVO cells.At 48 h after transfection,the whole cell protein was extracted,and the protein level was detected by Western blotting with mouse-anti-human NRP2 monoclonal antibody.Results Recombinant plasmids were completely coincided with the designs by the restriction map and the sequence analysis.pGenSil-NRP2 expression vector into LOVO cells down-regulated the protein level of NRP2 at 48 h after transfection.The recombinant eukaryotic expression vector were constructed successfully.Conclusion siRNA recombinant can be constructed successfully by RNAi technique for inhibiting NRP2 expression.
ABSTRACT
Objective To explore an optimal model of three dimensional in vitro cell culture for simulating solid tumors in vivo . Methods The model of three dimensional cell culture was constructed under the conditions of inhibiting the cell wall attachment and stirring the medium. Multicellular spheroids (MCS) were cultured using microcarriers (CutiSpher). Drug sensitivity of monolayer cells (MC) and MCS was tested by MTT staining and cytometry, respectively. Ultrastructures of the MC and MCS were observed by transmission electron microscopy. Results Cells in three dimensional cell culture model without microcarriers were compacted into mass at 4 d while cells in MCS were found to attach to the microcarriers at 0.5 h. MCS had more than two layers of cells growing within it at 5 d. Compared with MC, MCS was more resistant to the anticancer drug, and had more plenty of organell and microvilli with more extensive and compact cell adhesion. Conclusion MCS has strong developmental properties and can simulate the cell cell interactions in vivo , especially cell adhesion, which may contribute to the drug resistance of MCS.
ABSTRACT
Objective To understand the roles of JAK STAT pathway in the process of differentiation of human cord blood CD34 + hematopoietic stem cells into dendritic cells (DCs) by detecting the expressions and activation of JAK2 and STAT5. Methods CD34 + hematopoietic stem cells isolated from human umbilical cord blood and cultured for two weeks were induced to differentiate into DCs in vitro . Total cellular JAK2 and STAT5 and tyrosine phosphorylated protein stimulated by granulocyte/macrophage colony stimulating factor (GM CSF) at different time points (0, 7, and 14) during DC differentiation were detected by Western blotting. Results The amount of JAK2 protein was similar at 0, 7, and 14 d without GM CSF stimulation. With the differentiation of cells into DCs, the amount of tyrosine phospho JAK2 induced by GM CSF increased markedly. Both total cellular and tyrosine phospho STAT5 expression increased markedly during DC differentiation. Maximal tyrosine phospho STAT5 expression was later than JAK2. Conclusion JAK STAT pathway may take part in the signal mechanism of DCs differentiation from CD34 + hematopoietic stem cells stimulated by GM CSF.
ABSTRACT
Objective To investigate the relationship between the expression of vascular endothelial growth factor receptor 3 (VEGFR 3) and lymphangiogenesis in esophageal carcinoma. Methods VEGFR 3 expression in the esophageal carcinoma tissues from 73 cases was detected by RT PCR and immunobistochemical method. and the relationship between VEGFR 3 and lymphangiogenesis was analyzed. Results There was a statistically positive correlation between VEGFR 3 mRNA expression and lymph node metastasis in primary tumors ( P