Objective The objective of this study was to investigate the effect and mechanism of novel multi-target kinase inhibitor ON123300 on the proliferation,cycle and apoptosis of ER-positive and HER2-negative human breast cancer MCF-7 cells.Methods MCF-7 cells in logarithmic growth phase were treated with ON123300 or palbocilib for 48 h.DMSO was used as the control.The cellular morphology of MCF-7 cells was observed by optical microscope and the cell proliferation was measured by CCK8 assay.Flow cytometry(FCM)was used to detect cell cycle and apoptosis.Western blot was used to examine the expression of cyclinD1,CDK4,pRb1,survivin and PI3K protein in MCF-7 cells.Results No cell morphological changes of MCF-7 cells were observed in the control group.In the palbocilib group,MCF-7 cells showed slight inhibition of cell proliferation and a small amount of cell shedding.In the ON123300 group,cell proliferation was significantly inhibited and cell morphology changes,showing a shedding phenomenon.The inhibitory rate increased with increasing drug concentration,showing a dose-dependent manner.The cells in the ON123300 treated group were significantly arrested at the G1/S phase of cell cyde and were associated with increased apoptosis,with a statistically significant difference(P＜0.05).The protein expression of cyclinD1,CDK4,pRb1,survivin and PI3K in the ON123300-treated group were obviously reduced than those in the control group(P＜0.05).Conclusion ON123300 can significantly inhibit proliferation,promote cell cycle arrest and apoptosis of MCF-7 cells.The mechanism may be related to the inhibition of survivin/cyclinD1/CDK4/Rb1/PI3K signaling pathways.

Objective The aim of this study was to investigate the synergistic anti-tumor effect of cryptotanshinone and cisplatin in non-small cell lung cancer NCI-H1975 cells and its possible molecular mechanism.Methods NCI-H1975 cells were treated with control,cryptotanshinone,cisplatin or combination of cryptotanshinone and cisplatin groups(referred to as the combination group).The inhibitory rate of cell proliferation was determined in NCI-H1975 cells by CCK-8 assay;Flow cytometry was used to determine the rates of survival and cell apoptosis;The expression of apoptotic protein,anti-apoptotic protein,JAK2/STAT3 protein and its phosphorylation levels were detected in NCI-H1975 cells by Western blot.The localization and transcription activity of STAT3 cells were determined by laser confocal microscopy/luciferase assays.Results 1.The survival rates in cryptotanshinone,cisplatin and combination groups at each time-point were lower in NCI-H1975 cells than that in the control group(P＜0.05);The proliferation of NCI-H1975 cells in the combination group were inhibited when compared to the control,cryptotanshinone,or cisplatin groups(P＜0.05);2.After treatments for 24 h,the expression levels of Bcl-2 and Survivin protein were decreased(P＜0.01),the activity of Caspase3 and Caspase9 protein was increased(P＜0.01),and the expression levels of p-STAT3 and p-JAK2 protein were decreased in NCI-H1975 cells(P＜0.01);3.After NCI-H1975 cells treated with the combination of cryptotanshinone and cisplatin,the STAT3 in the nucleus was decreased,and STAT3 activity was also decreased in the nucleus.Conclusion Cryptotanshinone combined with cisplatin can exert a synergistic antitumor effect on non-small cell lung cancer NCI-H1975 cells,and its mechanism is related to the inhibition of JAK2 and STAT3 phosphorylation signal pathways.

Objective The objective of this study was to investigate the effect of salinomycin on proliferation and autophagic flux of human melanoma M21 cells.Methods The cell survival rate was determined by MTS assay and IC₅₀ values(half inhibitory concentration)were calculated.The morphological changes of cells after salinomycin administration were observed under optical microscope.Flow cytometry was used to examine the apoptosis rate of M21 cells.Western blot was used to detect the expression of autophagic-related protein LC3B and p62 in M21 cells.The presence of autophagosomes in M21 cells after salinomycin administration was observed under transmission electron microscope.Western blot and immunofluorescence were used to detect the level of p62 protein and localizing changes in M21 cells.Results Salinomycin significantly inhibited proliferation of M21 cells,and the IC₅₀ values were(1.38±0.18)μM.After salinomycin administration,the proliferation rate of M21 cells was slowed down,and obvious vacuoles appeared in the cells.Salinomycin could not only induce cell apoptosis,but it also increased the ratio of LC3B-Ⅱ/LC3B-Ⅰ in M21 cells.The increase and accumulation of autophagosomes were directly observed under transmission electron microscope.The level of p62 protein was slightly elevated after salinomycin treatment and gradually aggregated into the cytoplasm,indicating that autophagic flux was inhibited.Conclusion Salinomycin can inhibit the proliferation of human malignant melanoma M21 cells,and its mechanism may be related to the accumulation autophagosomes granules and inhibition of autophagic flux.

Objective The aim of this study was to investigate the expression of microRNA-150(miR-150)in human epithelial ovarian cancer cells and its effect on proliferation,apoptosis,invasion and metastasis of human epithelial ovarian cancer cells.Methods The expression level of miR-150 in cells from each treatment group was detected by Real-Time PCR(qRT-PCR);effects of proliferation,apoptosis,invasion and metastasis of epithelial ovarian cancer cells was investigated by MTT,flow cytometry,and transwell assays.Results Compared with normal ovarian epithelial cells(T29),the expression of miR-150 was significantly decreased in epithelial ovarian cancer cells(A2780 and OVCAR3)(P＜0.01); After transfection miR-150 mimic,the expression of miR-150 in A2780 and OVCAR3 cells was significantly increased(P＜0.01);After 3 d of transfection,the OD values of the miR-150 mimic group(A2780:1.12±0.03;OVCAR3:1.91±0.03)were lower than that in the blank group(A2780:2.35±0.09;OVCAR3:2.63±0.07)and the miR-150 NC group(A2780:2.18±0.07;OVCAR3:2.43±0.11)(P＜0.01);The apoptotic rate in the miR-150 mimic group(A2780:16.10±0.58%;OVCAR3:15.16±1.30%) were significantly increased when compared to the blank group(A2780:10.07±0.66%;OVCAR3:3.81±0.24%) and the miR-150 NC group(A2780:10.36±1.08%;OVCAR3:4.89±0.07%)(P＜0.01);The number of transmembrane cells in the miR-150 mimic group(A2780:38.67±2.03;OVCAR3:28.67±2.03)was higher than that in the blank group(A2780:76.30±7.45;OVCAR3:55.67±3.18)and the miR-150 NC group(A2780:74.33±5.78;OVCAR3:56.33±3.84)(P＜0.01).Conclusion The decreased expression of miR-150 in epithelial cancer cells may be one of the mechanisms of proliferation,invasion and metastasis of epithelial ovarian cancer.Up-regulation of miR-150 may inhibit the proliferation of epithelial ovarian cancer cells and promote apoptosis to reduce the abilities of invasion and metastasis in epithelial ovarian cancer cells.

Objective The aims of this study were to analyze the clinical characteristics and laboratory test results of stage Ⅳ lung cancer patients with Pulmonary thromboembolism(PTE),and to find out the risk factors for pulmonary thromboembolism.Methods A total of 70 patients with stage IV lung cancer were selected from the First Affiliated Hospital of Nan Chang University from January 2011 to October 2017.Blood routine,blood biochemistry,coagulation function,tumor markers(CEA,CA199,CA125,NSE,Cyfra211)and multi-slice spiral CT pulmonary angiography(CTPA)were collected in these patients.Univariate analysis was applied to compare the clinical features and laboratory tests between PTE and non-PTE groups.Multivariate logistic regression analysis was applied to explore significant risk factors of PTE.Results Univariate analysis showed that serum albumin,blood leukocyte,neutrophil percentage,increased Cyfra211 and abnormal tumor markers were risk factors for PTE in patients with stage IV lung cancer.Multivariate logistic regression analysis showed that the number of abnormal tumor markers ≥ 4(OR=7.016,95% CI:1.916 ~ 25.686)was an independent risk factor for PTE in stage IV lung cancer.Conclusion The number of abnormal tumor markers is an independent risk factor for pulmonary thromboembolism in stage Ⅳ lung cancer.When the number of abnormal tumor markers is ≥4,it is necessary to highly alert the possibility of stage IV lung cancer with pulmonary thromboembolism.

Objective The aim of this study was to illuminate effects of LncRNA MEG3 on the viability and apoptosis of human glioma cells as well as the mechanisms involved.Methods The expressions of MEG3 and microRNA-21(miR-21) in normal human astrocytes cell line(NHAs)and human glioma cell line(U87)was detected by Real-Time quantitative polymerase chain reaction(RT-qPCR).U87 cells was transfected with MEG3 plasmid alone or transfected with both MEG3 plasmid and miR-21 mimic,cell viability was detected by CCK-8 assay,cell apoptosis was detected by TUNNEL,and the expression of Bcl-2/Bax and Cleaved caspase-3 in cells was detected by Western blot.Results Compared with NHAs,the expression of MEG3 in U87 was significantly decreased and the expression of miR-21 was significantly increased.Overexpression of MEG3 significantly decreased the expression of miR-21 in U87 cells,inhibited the viability of U87 cells,decreased the level of Bcl-2/Bax,increased the content of Cleaved-caspase-3 to promote apoptosis;Co-overexpression of MEG3 and miR-21 significantly increased the viability of U87 cells,elevated Bcl-2/Bax levels,and decreased the expression of Cleaved caspase-3 to inhibit apoptosis.Conclusion Overexpression of MEG3 reduces the viability and promotes apoptosis of glioma cells by inhibiting miR-21.

Objective The objective of this study was to investigate effects of stellate ganglion blocking on the hemodynamics and cardiac function in patients with coronary heart disease(CHD).Methods A total of 54 colon cancer patients with CHD undergoing laparoscopic surgery underwent elective general anesthesia in our hospital from June 2014 to March 2017 were randomly divided into three groups(18 cases per group).They were the control,left stellate ganglion block(L-SGB),and right stellate ganglion block(R-SGB)groups.The patients′ mean arterial pressure(MAP),heart rate(HR),cardiac output(CO),cardiac index(CI),stroke output(SV),stroke,quantitative change thin(SVV)and heart rate and systolic blood pressure product(RPP),and other changes in hemodynamic parameters were compared in each group,after home invasion(T₀),induction of general anesthesia(T₁),the endotracheal tube into the glottis immediately(T₂),and 5 min after intubation(T₃).The changes of patients in superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO)and cardiac troponin I(cTnI),creatine kinase isoenzyme(CK-MB)were also compared to T₀,6 h(T₄)and 24 h after anesthesia(T₅)in each group.Results Compared with T₀,the MAP,HR,CO,CI,SV and RPP of patients in each group were all decreased at T₁,but no statistical significance was found in these groups(P＞0.05).Compared with T₀,the MAP,HR,CO,CI,SV and RPP of patients in each group were significantly increased at T₂;there showed a statistical significance(P＜0.05).Compared with T₀,the MAP,HR,CO,CI,SV and RPP of patients in each group were decreased at T₃,but the decreased changes in the R-SGB group were more great than those in the L-SGB group(P＜0.05).Compared with L-SGB and R-SGB groups,the MAP,HR,CO,CI,SV,SVV and RPP were significantly increased at T₂ of patients in the control group(P＜0.05).Compared with T₀,the MDA,NO,cTnI and CK-MB in each group were significantly increased and significantly decreased in the SOD at T₄ of patients(P＜ 0.05).Compared with the control group,there had small changes in each index of patients in R-SGB and L-SGB groups at T₄,but there was a significant difference(P＜ 0.05).Compared with T₄,the levels of MDA,NO,cTnI and CK-MB were significantly decreased and the level of SOD were significantly increased at T₅ of patients in each group(P＜0.05),but all indexes in the control group compared with T₀ had statistical significance(P＜0.05).Although there had changes of R-SGB and L-SGB groups,they did not statistical significance(P＞0.05).Conclusion In patients with CHD during general anesthesia with colorectal cancer surgery,stellate ganglion blocking can increase hemodynamic stability,improve cardiac function,and reduce myocardial oxygen consumption,thereby reducing surgical stress damage to the cardiomyocytes.The right side of the stellate ganglion blocking has better effect than that in the left side block.

Objective The objectives of this study were to use Nutrition Risk Screening 2002(NRS2002)to conduct nutritional assessment research on patients with advanced cancer in our hospital,and to assess the patients′ nutritional deficiencies,nutritional risk and nutritional support,and to discuss the nutritional status and clinical indicators of patients with different tumor types in order to provide a scientific evidence for individualized nutritional support.Methods Patients with advanced tumors met the requirements were enrolled from January 2016 to February 2017.Nutritional questionnaires and anthropometry were conducted and recorded the information of measurements and relevant laboratory tests.NRS2002 was used to screen nutritional risk of patients.Results The nutritional insufficiency rate was 19.54% in 517 patients with advanced cancer and 49.52% in nutrition risk.The proportion of nutrition-free patients receiving nutritional support was 14.56%,and the nutritional support patients with nutritional support were 63.67%.The average length of hospital stay was(14.43±11.82)days for patients with nutritional risk,and(8.29±6.93)days for patients without nutritional risk.The incidence of nutritional risk in patients with digestive tract cancer was higher than other tumor types.Conclusion As an effective nutritional screening tool,NRS2002 can help clinicians to screen the potential nutritional risk of patients in oncology and provide the basis for patients to develop rational nutrition support.

Objective The aim of this study was to investigate the predictive value of p53 protein expression in postmenopausal hormone receptor(HR)positive and HER-2 positive postoperative breast cancer patients with adjuvant endocrine drugs.Methods A total of 172 cases of postoperative breast cancer patients were collected in Harbin Medical University Cancer Hospital from January 2005 to December 2011.All patients were postmenopausal,including 84 patients received aromatase inhibitors(AI)treatment and 88 patients received tamoxifen(TAM)treatment.The median follow-up time was 68 months(4~131 months).χ² test was used to analyze the relationship between p53 protein expression and the clinicopathological features of breast cancer.Kaplan-Meire analysis,Log-rank test and Cox regression model were used for survival analysis.Results The expression of p53 protein was not correlated with tumor size,lymph node status,histological grade,ER and PR expression.Cox univariate analysis showed that p53 protein was related to lymph node status(χ²=46.602;P＜0.001)and radiation therapy(χ²=9.617;P=0.002).But p53 expression was not associated with DFS in breast cancer patients(χ²=0.002,P=0.968).Cox multivariate analysis showed that DFS was only associated with lymph node metastasis in breast cancer patients(HR=2.121,95%CI:1.630~2.760,P＜0.001).Subgroup analysis showed that DFS in patients with p53-positive was superior to patients with p53-negative in oral TAM(χ²=4.695,P=0.030).In patients with oral AI,DFS in with p53-negative patients was superior to p53-positive patients(χ²= 5.995,P=0.014).Conclusion The positive expression of p53 protein is a predictor of effective treatment of TAM,while the negative expression of p53 protein is a predictor of effective treatment of AI.

Photodynamic therapy(PDT)utilizes a photodynamic reaction,that is,a photosensitizer(PSs)activated by light of a specific wavelength in the presence of molecular oxygen to produce a reactive oxygen species including singlet oxygen to kill tumor cells.PDT has the advantages of less trauma,high selectivity,low toxicity,and good applicability.However,the lack of an ideal PS,lack of light source tissue penetration depth,and hypoxia of tumor tissue have been severely restricted in clinical practice.Nanomaterials can solve the above problems encountered in photodynamic therapy,and have recently been widely used in PDT of tumor.Thus,this review will summarize the application progress of nanoparticles in PDT.

The JMJD family is an important group of histone demethylase.JMJD2B belongs to one of its family members,and is a JMJD containing a JmjC domain.It mainly regulates chromatin structure,transcription and cell appearance.Recent studies from domestic and foreign have demonstrated that JMJD2B protein is high expressed in human malignant tumors,such as liver cancer,gastric cancer,breast cancer,kidney cancer,and skin cancer.Moreover,it also shows that JMJD2B is involved in the occurrence,development,migration,infiltration,and proliferation of malignant tumors.

Osteosarcoma(OS)is a primary malignant bone tumor,characterized by a high degree of malignancy,prone to early metastasis,and poor prognosis.The survival rate of traditional surgical treatment is less than 20%.After the continuous improvement of the OS chemotherapy regimen,the 5-year survival rate of neoadjuvant chemotherapy combined with surgery-based treatment program is increased to 60%~70%.However,the current chemotherapy regimen does not increase the survival rate of patients with OS,and the prognosis is extremely poor if patients have developed chemotherapy resistance.In order to solve the“bottleneck”problem of chemotherapy,in recent years,a comprehensive treatment plan combining immunotherapy,gene therapy,targeted therapy and chemotherapy has been advocated.In this review,the progress of OS in the immunotherapy,gene therapy and targeted therapy is discussed in recent years,and summarized the treatment of OS.

Oral squamous cell carcinoma is a common malignancy in the oral cavity.It has biological features such as invasive growth,local or distant lymph node metastasis and poor prognosis.In recent years,more and more studies have found that Long non-coding RNAs(LncRNAs)are abnormally expressed in oral squamous cell carcinoma and regulated its biological behavior.This article reviews the research progress of LncRNA in oral squamous cell carcinoma.

QKI protein is a kind of STAR protein family and mainly contains three subtypes of QKI-5,QKI-6 and QKI-7.Early studies showed that QKI protein is closely related to the development of nerve myelin and embryo.With the development of molecular biology and the extensive application of gene technology,the effect of QKI protein on malignant tumors has received increasing attention.The studies of QKI protein from lung,gastric and prostate cancers have shown that it has the ability to inhibit tumor invasion,and may become a new target for the diagnosis and treatment of malignant tumors.Although significant progress has been made in the extensive research of QKI protein in malignant tumors,there are still many doubtful points that need to be answered.Thus,further research and exploration of QKI are needed in malignant tumor.

Metformin as the first-line medication for diabetes treatment can not only reduce blood sugar,but it also induces apoptosis in breast cancer cells.The effect and mechanism of metformin on various types of breast cancer are confirmed by in vitro and in vivo,and metformin can also co-treat breast cancer in neoadjuvant chemotherapy and radiotherapy.This article will review the progress of metformin in the treatment of breast cancer.

Helicobacter is a class of genus associated with many human diseases.The existing studies have found that helicobacter infection is closely related to the occurrence and development of primary liver cancer.Not only can it promote the formation of liver cancer through inflammatory stimuli and regulation of cell cycle,but it can also enhance the invasive ability of liver cancer cells through TLR4 / MyD88 signaling pathway.This article summarizes the relationship between helicobacter infection and the occurrence and development of primary liver cancer.

Cancer-associated fibroblasts(CAFs)are one of the most important cellular components in the external microenvironment of tumors.CAFs can interact with tumor cells and secrete a variety of soluble factors such as growth factors,chemokines,and so on.CAFs are also involved in the proliferation,invasion,migration,metastasis and drug resistance of colorectal cancer through regulating multiple signaling pathways that play a key role in the progression of colorectal cancer.Recent studies have found that CAFs related markers and genes can be used as reference indicators for the predicting prognosis of colorectal cancer.Therefore,targeting CAFs may be a key target for early diagnosis,treatment and prognosis of colorectal cancer.This article summarizes the characteristics of CAFs,recruitment and activation process,and its role in the development of colorectal cancer in order to provide a new scientific direction for the mechanism of action and clinical application of CAFs in colorectal cancer.

At present,most chemotherapy schemes for malignant tumors use the standard chemotherapy regimen recommended by the National Comprehensive Cancer Network(NCCN)clinical practice guidelines,because they ignore the inherent heterogeneity of the tumor,resulting in low efficiency,high toxic and side effects,and high costs issues.Therefore,the realization of “individualized and accurate medical care” for cancer is a general trend.The sensitivity screening of chemotherapy drugs for cancer patients to achieve individualized precise drug delivery is one of the main contents of “individualized precision medicine”.The three-dimensional histoculture drug response assay(HDRA)is a method for detecting drug sensitivity after in vitro cultivation of active tumor tissue blocks obtained by surgical resection or biopsy.It not only has a short experimental cycle,but it also maintains the tumor tissue structure,heterogeneity and micro-environment,which have high clinical practice consistency,and it is a relatively promising technique for detecting drug susceptibility.Therefore,this article reviews the development history,clinical application and the future development trend of HDRA.

Immune suppression caused by cancer can accelerate the spread and metastasis of cancer cells,resulting in further deterioration of perioperative cancer patients.Surgery is an important method of cancer treatment,which is widely used in clinical practice.However,surgery-induced over-stress response can also cause immunosuppression.Anesthetics can inhibit excessive stress response caused by surgical trauma and pain in the perioperative period,but at the same time it directly or indirectly affects the body′s immune function.This article reviews the relationship between different anesthetic drugs and immune function in patients with perioperative cancer,providing basic information for clinical treatment.