Objective The inhibitory effect of the PARP inhibitor olaparib on human acute myeloid leukemia HL-60 cells was studied.Methods The HL-60 cells in logarithmic growth phase were treated with different concentrations(1.25,2.5,5 and 10 μmol/L)of olaparib for different time.The CCK-8 assay was used to detect the inhibitory effect of olaparib on HL-60 cells.The apoptotic level of HL-60 cells was detected by Annexin-V/PI double staining method,and the expression of related signal proteins(PARP-1 and caspase-3)in HL-60 cells was detected by Western blot.Results HL-60 cells were inhibited by olaparib at different concentrations(1.25,2.5,5 and 10 μmol/L)for 48 h,and the inhibition rate gradually increased with the prolongation of the action time;at the same time,the apoptotic rate was increased in HL-60 cells after olaparib treatment for 48 h,showing a dose-dependent manner;the PARP activity was inhibited and caspase-3 was activated in HL-60 cells treated with olaparib.Conclusion The PARP inhibitor olaparib not only inhibits proliferation of HL-60 cells,but it also promotes apoptosis of HL-60 cells by inhibiting PARP activity and activating caspase-3.

Objective This study aimed to investigate the relationship between CLPTM1L gene and lung cancer 95-D cells sensitivity to gemcitabine,and to explore its potential mechanism of action.Methods Overexpression of lentivirus against CLPTM1L gene was constructed and infected with lung cancer 95-D cells;Cells were divided into the CLPTM1L overexpression group and control group;The proliferation of cells in the overexpressing and control groups after gemcitabine treatment was detected by CCK-8;The changes of CLPTM1L gene and protein were detected by real-time PCR,Western blot and immunochemiluminescence;The changes of caspase-3/7 and caspase-9 activities were detected by bioluminescence;Western blot was used to detect the changes of p-4E-BP1 protein.Results The expression of CLPTM1L gene(P=0.036)and its protein(P＜0.01)was significantly increased after CLPTM1L overexpressed lentivirus-infected 95-D cells;Compared with the control group,the proliferation of CLPTM1L overexpressing group after gemcitabine treatment was increased(P＜0.01);The activity of caspase activity showed that the activities of caspase-3/7 and caspase-9 in the CLPTM1L overexpression group were significantly lower than those in the control group(P＜0.01);The phosphorylated level of 4E-BP1 protein in the CLPTM1L overexpression group was significantly higher than that in the control group.Conclusion Overexpression of CLPTM1L can reduce the sensitivity of lung cancer cells to gemcitabine.Its mechanism may be to increase the phosphorylation level of 4E-BP1.

Objective The aim of this study was to observe the expression of human epidermal growth factor receptor(EGFR),epidermal growth factor receptor 2(HER2)and epidermal growth factor receptor 3(HER3)in cholangiocarcinoma(CCA),and to explore the relationship between the expression of EGFR,HER2,HER3 and the clinicopathological features,overall survival time and proliferation of CCA patients.Methods Fifty patients with CCA who underwent surgery in our hospital from January 2009 to October 2013 were enrolled,and their adjacent tissues were also collected as controls.Immunohistochemistry and qRT-PCR were used to detect the expression of EGFR,HER2 and HER3 in CCA and adjacent tissues.The clinicopathological parameters of patients were collected and the relationship between EGFR,HER2,and HER3 expression and clinicopathological parameters of CCA was analyzed.Kaplan-Meier survival curves were plotted,and the relationship between the expression of EGFR,HER2,and HER3 and total postoperative survival of 50 patients with CCA was analyzed using the Log-rank test and Cox proportional hazard model.The expression of EGFR,HER2 and HER3 in CCA QBC939 cell line was knocked down by RNA interference assay.The knockdown effect of EGFR,HER2 and HER3 was detected by Western blot.The effect of EGFR,HER2 and HER3 on proliferation of QBC939 cells was determined by MTT assay.Results The positive expression of EGFR,HER2 and HER3 was determined in CCA tissues.The relationship analysis of clinicopathological characteristics showed that the HER2 expression was associated with CCA lymph node metastasis(P＜0.05).EGFR and HER3 was associated with CCA lymph node metastasis and correlated with cancer differentiation(P＜0.05).The overall survival of patients with EGFR,HER2 and HER3 positive was significantly lower than that of negative patients(P＜0.05).After knocking EGFR,HER2 and HER3 expression,the proliferation was significantly decreased in QBC939 cells(P＜0.05).Conclusion The expression of EGFR,HER2 and HER3 in CCA tissues is closely related to the overall survival of patients,and the mechanism may be related to the promotion of proliferation of CCA cells.

Objective The aim of this study was to investigate the role and mechanism of ABL2 in lung cancer and its mechanism.Methods The expression of ABL2 in lung cancer and adjacent tissues was detected by Real-Time PCR.A lung adenocarcinoma A549 cell line stably expressing of ABL2 was established,and the changes of cell proliferation and migration ability were detected by MTT,cell migration and colony formation assays.Western blot was used to detect the expression of EMT,apoptosis and PI3K/AKT signaling pathway-related proteins.Results The expression of ABL2 in lung cancer tissues was significantly higher than that in adjacent tissues(P＜0.001).After silencing ABL2 in the A549 cells,compared with the control group,the migration ability of cells was weakened after 48 hours(P＜0.001),the growth rate of cells began to slow down from the third day(P＜0.05),and the average number of clones formed after 15 days also decreased(P＜0.01).The expression of E-cadherin(P＜0.001)was increased in the epithelial cell marker after silencing ABL2,and the expression of stromal cell markers N-cadherin(P＜0.001),Vimentin(P＜0.01)and Snail(P＜0.001)was decreased.The expression of apoptosis-related protein Bcl-XL(P＜0.01)was decreased and BAX(P＜0.001)expression was up-regulated.The expression of PI3K/AKT signaling pathway-associated proteins such as PI3K P110(P＜0.05),AKT(P＜0.01)and p-AKT(P＜0.05)was significantly decreased.Conclusion Silencing ABL2 gene can promote apoptosis,and inhibit proliferation and migration of lung cancer cells through a PI3K/AKT signaling pathway.

Objective The aim of this study was to investigate the effect and mechanism of pterostilbene on apoptosis and glycolysis of ovarian cancer SKOV3 cells.Methods SKOV3 cells were treated with 0,25,50,100 and 150 μmol/L of pterostilbene for 24,48 and 72 hours.The proliferation of SKOV3 cells was measured by CCK.The effect of pterostilbene on apoptosis of SKOV3 cells was determined by flow cytometry.The glucose consumption and lactate production were detected by glucose oxidase assay and chemical colorimetry.The expression of signal transducer and activator of transcription 3(STAT3),phosphorylated STAT3(p-STAT3)and hexokinase 2(HK2)proteins was detected by Western blot.The expression of glucose transporter 1(GLUT1)and M2 pyruvate kinase(PKM2)mRNA was detected by qRT-PCR.Results Pterostilbene inhibited the proliferation of SKOV3 cells in a time- and dose-dependent manner.According to CCK-8 results,100 μmol/L of pterostilbene was selected as the follow-up experimental group and 0 μmol/L as a control group.Pterostilbene could significantly promote the apoptosis of SKOV3 cells in a dose-dependent manner.The higher the concentration,the more obvious apoptosis effect,the difference was statistically significant(P＜0.05).In addition,the levels of glucose consumption and lactate production in the 100 μmol/L group were significantly lower than those in the 0 μmol/L group(P＜0.01).The expression of p-STAT3 and HK2 protein in the 100 μmol/L group was also significantly lower than those in the 0 μmol/L group(P＜0.001).The expression of GLUT1and PKM2 mRNA in the 100 μmol/L group was also significantly decreased than those in the 0 μmol/L group(P＜0.01).Conclusion Pterostilbene can inhibit the proliferation of SKOV3 cells and promote apoptosis,and may inhibit the glycolysis of ovarian cancer through a STAT3/HK2 pathway.

Objective The objective of this study was to investigate the clinical value of serum microRNA in predicting chemotherapy efficacy in patients with nasopharyngeal carcinoma.Methods A total of 187 patients with nasopharyngeal carcinoma who received cisplatin combined chemotherapy were enrolled in our hospital from January 2010 to December 2016,including 123 patients with chemotherapy sensitivity and 64 patients with chemotherapy resistance.The serum levels of miRNA before the initial chemotherapy were measured,the efficacy and predictive value of serum miRNA in nasopharyngeal carcinoma patients were evaluated using healthy subjects as controls.Results Serum level of miR-127 in nasopharyngeal carcinoma patients was significantly higher than that in healthy controls(4.3±1.6 vs. 1.4±0.5,P＜0.001).Serum level of miR-127 was significantly higher in chemotherapy-resistant patients than that in chemotherapy-sensitive patients(4.5±1.3 vs. 3.8±1.7,P＜0.001).The ROC curve showed that the predictive value of serum miR-127 for chemotherapy resistance in nasopharyngeal carcinoma patients was 0.702(P＜0.001),with the optimal cut-off value of 4.2,sensitivity of 82.3% and specificity of 76.3%.Compared with the chemotherapy-sensitive group,the proportion of patients with T_3-4,N3 and TNM Ⅲ~Ⅳ in the chemotherapy-resistant group was significantly increased(P＜0.01),and the proportion of miR-127≥4.2 was also increased(P＜0.001).Multivariate logistic regression analysis showed that TNM staging(OR=1.655,95% CI:1.142~2.584,P=0.016)and serum miR-127≥4.2(OR=2.231,95% CI:1.762~4.503,P=0.001)were independent risk factors affecting chemotherapy resistance in nasopharyngeal carcinoma patients.Conclusion The elevated serum level of miR-127 is an important risk factor for predicting chemotherapy resistance in patients with nasopharyngeal carcinoma.

Objective The objective of this study was to investigate the relationship between serum long-chain non-coding RNA MALAT1 and AFAP1-AS1 and clinicopathological features,and prognosis of nasopharyngeal carcinoma(NPC).Methods A total of 136 patients with nasopharyngeal carcinoma confirmed by pathology in our hospital were selected from April 2013 to June 2015.During the same time,54 outpatients for health examination in our hospital were selected as the control group and nasopharyngeal carcinoma group.Real-time fluorescence reverse transcription analysis was used to analyze the expression of lncRNA MALAT1 and AFP1-AS1.The relationship between the expression of lncRNA MALAT1 and AFP1-AS1,and clinicopathological characteristics was analyzed by χ² test.Log-rank assay was used to analyze serum long-chain non-coding RNA MALAT1 and prognostic differences in patients with different expression levels of AFAP1-AS1.Results Compared with the control group,the serum levels of RNA MALAT1 and RNA AFAP1-AS1 in the nasopharyngeal carcinoma group were significantly increased(P＜0.001);The expressions of lncRNA MALAT1 and AFAP1-AS1 was not related to age(P＞0.05);The maximum diameter of the tumor was ≥5 cm,the pathological stage was higher,the TNM stage was higher,the deeper in the infiltration depth,the infiltration of lymphatic vessels,the lymph node metastasis,and the recurrence and the higher in high expressive rates of lncRNA MALAT1 and AFAP1-AS1(P＜0.05).The 2-year survival rate and survival time of lncRNA MALAT1 and AFAP1-AS1 in the low expression group were significantly higher than those of the high expression group(P＜0.001);Multivariate Cox stepwise regression analysis showed that low expression of lncRNA MALAT1(HR=0.52,95% CI:0.37~0.81)and low expression of lncRNA AFAP1-AS1(HR=0.56,95% CI:0.51~0.83)were independent prognostic protective factors for NPC patients(P＜0.001).Conclusion The serum long-chain non-coding RNA MALAT1 and AFAP1-AS1 are elevated in patients with NPC,and are positively correlated with malignant progression of NPC.NPC patients with low expression of lncRNA MALAT1 and AFAP1-AS1 serum have a good prognosis;MALAT1 and AFAP1-AS1 can be used as new markers for the diagnosis of nasopharyngeal carcinoma.

Objective This article retrospectively analyzed the efficacy,toxicity,survival and related factors affecting prognosis of patients with small cell lung cancer(SCLC)who had recurrence or progression after first-course chemoradiotherapy.Methods A total of 86 patients with recurrence or progression recurrence after SCLC chemotherapy and radiotherapy from January 2007 to December 2015 in Harbin Medical University Cancer Hospital were enrolled.Patients were divided into the re-treatment group to receive secondary treatment with radiotherapy combined with chemotherapy and two control groups to receive secondary treatment with radiotherapy alone or chemotherapy alone.The factors affecting the prognosis of SCLC re-treatment were analyzed.The short-term and long-term efficacy,overall survival and toxicity of three groups were compared.Results The median progression-free survival time of the re-treatment group,radiotherapy group,and chemotherapy alone group was 4 months(1~20 months),2 months(1~7 months)and 3 months(1~6 months).There was no statistical difference(P＞0.05).The median overall survival time was 25 months(3~135 months)in the re-treatment group and 8 months in the radiotherapy group(1-59 months)and 12 months(1~108)in the chemotherapy alone group,the difference was statistically significant(P＜0.05).The 1-,2-,and 3-year survival rates were 73.70%,52.10% and 47.40% in the re-treatment group;32.90%、21.90% and 21.90% in the radiotherapy group,and 45.40%,19.90% and 19.90% in the chemotherapy alone group.The long-term effect of the re-treatment group was better than that of the radiotherapy group and the chemotherapy alone group(P＜0.05).Conclusion Re-treatment of patients with SCLC who failed after receiving radiotherapy and chemotherapy for the first time can prolong the survival time of patients and improve the life quality of patients.If the patient's physical condition permits,the treatment should be selective radiotherapy and chemotherapy as well as tolerable toxicity or side effects.Among them,patients with no distant metastasis and recurrent radiotherapy dose ≥5 000 cGy had greater survival benefit.However,the late toxic and side effects,and complications of patients after re-treatment are still to be further observed.

Objective The objective of this study was to investigate the expression of microtubule associated protein 1A(MAP1A)in bladder cancer and its correlation with clinicopathological features.Methods One hundred and thirty seven cases of bladder cancer and adjacent tissues were collected.qRT-PCR and immunohistochemistry were used to analyze the expression of MAP1A in bladder cancer and adjacent tissues.The relationship between the expression of MAP1A and clinicopathological parameters & prognosis of bladder cancer patients was studied.Results The results of qRT-PCR showed that the expression level of MAP1A in 20 cases of bladder cancer was significantly lower than that of the matched adjacent tissues(t=5.022,P＜0.001).The results of immunohistochemistry also showed that the positive expression rates of MAP1A in bladder cancer and adjacent tissues were 46.71%(46/37)and 79.56%(109/137),respectively,and the difference was statistically significant(χ²=23.52,P＜0.0001).The expression of MAP1A was closely related to clinical T stage,lymph node metastasis and TNM stage(χ²=9.982,P=0.0016;χ²=8.064,P=0.0045;χ²=7.199,P＜0.0073).Kaplan-Meier survival analysis showed that the overall survival(OS)and disease-free survival(DFS)of patients with low expression of MAP1A were significantly shorter than those with high expression of MAP1A(χ²=26.74,P＜0.0001;χ²=18.73,P＜0.0001).Cox multivariate regression analysis showed that TNM stage(HR=1.46,P=0.038)and MAP1A expression(HR=1.213,P=0.030)were independent risk factors for adverse prognosis of bladder cancer patients.Conclusion MAP1A is significantly down-regulated in bladder cancer tissues and is closely related to clinical TNM staging.The low expression of MAP1A may indicate the poor prognosis of bladder cancer patients.

Objective Dual-source CT(DSCT)energy imaging was used to analyze the difference of energy spectrum parameters and energy spectrum curves between mediastinal metastatic lymph nodes and non-metastatic lymph nodes in non-small cell lung cancer(NSCLC).The relationship between DSCT standardized iodine concentration and energy spectrum curve with mediastinal lymph node metastasis was discussed.Methods A total of 113 patients with NSCLC underwent DSCT energy imaging scans.Iodine images were obtained at the processing workstation.The normalized iodine concentrations of all mediastinal lymph nodes and energy spectrum curves at different energy levels were measured.According to the pathological results,the patients were divided into lymph node metastasis group and non-lymph node metastasis group.The normalized iodine concentration and energy spectrum curve slope of the two groups were analyzed by t-test.The best threshold of standardized working iodine concentration was calculated by receiver operating characteristic curve(ROC)to diagnose the mediastinal lymph node metastasis of NSCLC.Results There was a significant difference in the normalized iodine concentration between the two groups of mediastinal lymph nodes in NSCLC(P＜0.05);The ROC curve was used to calculate the standardized iodine concentration for the diagnosis of NSCLC.The optimal threshold for lymph node metastasis was 52.45%;The energy spectrum curve of mediastinal lymph nodes in NSCLC was gradually decreasing.There was a significant difference between the two groups in the range of 40~110 keV interval(P＜0.05).Conclusion The quantitative analysis of DSCT energy imaging parameters is of great significance in the diagnosis of mediastinal lymph node metastasis in NSCLC.It can be used as an important index for preoperative judgment of lymph node metastasis in NSCLC.

Objective The aim of this study was to investigate the dosimetric advantages of Gating in the treatment of primary hepatic cancer with large segmentation.Methods A retrospective analysis of 10 patients with primary liver cancer from August 2017 to November 2018 after interventional therapy was performed using three consecutive phases of end-tidal phase to achieve patient-controlled large-segment radiotherapy.Ten patients underwent 4DCT localization scan,and 10 respiratory phase sequences were reconstructed by respiratory wave-form,and the images were transmitted to the MIM6.7.6 workstation.In the MIM workstation,full-time phase maximum density projection(MIP-10),full-time phase average density projection(Mean-10),end-expiration 3 phase maximum density projection(MIP-3)and end-expiration 3 phase average density projection(Mean-3)were generated respectively,where MIP was used for target delineation and Mean for dose calculation.The radiotherapy doctor delineated IGTV-10 and IGTV-3 on the MIM workstation,and released CTV-10,CTV-3,PTV-10 and PTV-3 to compare the volume differences of the target area.After the target area was drawn,the image was transmitted from the MIM workstation to the Eclipse treatment planning system,and the full-time phase plan(Plan-10)with the same conditions and three consecutive phase-phase gating plans(Plan-3)were prepared.The prescriptive dosage was given at 50 Gy/10 f/2weeks.Comparing the HI and CI of the target area,the comparison of organs at risk included: the average dose of liver Dmean,the irradiation volume of liver less than 15Gy,the Dmax of small intestine,the Dmax of colon,the Dmax of stomach,the average dose of the kidney Dmean,the heart Dmax,and the spinal cord Dmax.Results The volume of the target area delineated at the end of expiratory phase was less than that of the target area outlined by the full-time phase in IGTV,CTV and PTV,and the difference was statistically significant(P＜0.05).In the two groups of seven field coplanar lage-segment radiotherapy plans,the 3-phase respiratory gating plan significantly reduced the dose of the organs at risk,and the difference was statistically significant(P＜0.05).At the same time,there was no statistically difference in the HI and CI between of the two groups(P＞0.05).Conclusion The gated target area delineation and planning design of the three consecutive phases of end-tidal phase reduce the volume of IGTV,CTV and PTV target regions compared with the selection of full-time phase,and have obvious advantages in the planned dosimetry.The irradiation dose that threatens the organs is worthy of being promoted and applied in the large-scale radiotherapy of liver cancer.

Natural killer T(NKT)cells are a special T lymphocytes subset,which is also natural immune lymphocytes in the liver.It can secrete a large number of cytokines involved in the immune regulation of liver cancer and play dual regulatory roles in the immune response such as the occurrence,development and metastasis of liver cancer.The dual regulation function of promoting tumor and anti-tumor is related to various factors.This paper summarizes the research progress of the two-way regulation mechanism of NKT cells on liver cancer immunity in recent years.

Osteosarcoma is a relatively common malignant tumor originating from bone tissue,which occurs in children and adolescents.In recent years,the role of microRNA in the development of bone tumors has become a hot topic.Numerous studies have shown that microRNA can affect the expression of target genes through MAPK/ERK,PI3K/AKT,Wnt/β-catenin and other signaling pathways,thereby regulating the biological functions such as proliferation,differentiation and invasion of tumor cells,and the development of osteosarcoma.MicroRNA is closely related to the development,clinical treatment and prognosis of osteosarcoma.

Circular RNAs(circRNAs)are a special type of circular non-coding RNA that is not easily degraded by RNase and plays an important role in the occurrence and development of many tumors.In this review,we mainly summarized the research progress in expression,action and mechanism of circRNA in ovarian cancer,in order to explore the developmental prospect of circRNAs in the diagnosis and treatment of ovarian cancer.

α-Hederin is a typical pentacyclic triterpenoid saponin obtained from high-pressure liquid phase mass spectrometry analysis of traditional Chinese medicine Changweiqing.It has a wide range of pharmacological effects,such as anti-tumor,anti-inflammatory and immune-modulation.The most striking of these pharmacological effects is the effect on anti-tumor.With the deepening of research,the molecular mechanism of α-hederin in effect on anti-tumor has made a certain breakthrough.This paper mainly summarizes the research progress of anti-tumor pharmacological action of α-hederin in recent years,and provides a basis for future research and development of α-hederin.

Ovarian cancer(OC)is an aggressive and fatal cancer.A growing number of studies have shown that the tumor microenvironment(TME)is involved in the promotion and development of ovarian cancer,immunosuppression and inflammatory response through various mechanisms.TME includes tumor blood vessels and lymphatic vessels,as well as cancer cells,mesenchymal cells,immune cells,and extracellular matrix(ECM).Based on recent literature reports,this paper reviews the commonly used three-dimensional(3D)cell culture model of ovarian tumor microenvironment,and summarizes many 3D models that do not contain primitive stromal cells,aiming to find new approaches for ovarian cancer treatment.

The incidence and death of lung cancer rank first among all malignant tumors,and drug resistance of lung cancer patients is becoming more and more severe,which has caused a great burden on the national economy and people′s health.MiR-26a is a small class of non-coding RNA that affects the biological effects on proliferation,migration and invasion of lung cancer cells by targeting related proteins and messenger RNAs(mRNAs).This article aims to elaborate the mechanism of miR-26a in lung cancer and provides the clinical biomarkers for the treatment and drug resistance of lung cancer.

Breast cancer is a common malignant tumor in women,and immunotherapy is one of the treatments with a good clinical prognosis.CA153 can activate immune response as a specific antigen in breast cancer immune response;participate in T cell activation;target binding peptide vaccine;enhance immune response;induce dendritic cell maturation,and eliminate cancer cells in vivo.Therefore,CA153 plays an important role in the immune response and treatment of breast cancer,and can be used as a new target for breast cancer immunotherapy.

Big data and artificial intelligence are fast developing in all walks of life,and deepening in the field of precision radiotherapy.In recent years,radiotherapy technology has developed rapidly and accumulated a large number of imaging and treatment data.In addition,big data analysis is urgently needed to help doctors make decision,improve the efficiency of doctors and physicists,and strengthen the quality control of radiotherapy.Therefore,artificial intelligence has emerged in the field of radiotherapy.This paper describes the application and development prospect of artificial intelligence in all aspects of radiation therapy.

Metastatic breast cancer(metastatic breast cancer,MBC)is a difficult-to-cure disease.However,its overall prognosis of patients has been improved significantly with the development and spread of systemic treatment.Whether the surgical resection of primary or metastatic foci of the first stage IV breast cancer(De novo stage IV breast cancer)can bring survival benefits on the basis of systemic treatment is currently controversial,and needs to be combined with the specific circumstances of the patient,individualized diagnosis and treatment.This paper reviews the hot issues in the field of surgical treatment for newly diagnosed stage IV breast cancer.