Objective The aim of this study was to construct the stable cell line of colorectal cancer HT29 cells with high expression of DAB2IP and its effect on invasion and migration of HT29 cells.Methods The pcDNA3.1 plasmid carrying the DAB2IP gene sequences was transfected into HT29 cells.After 24 hours,10μg/mL of G418 was added the cells to screen the cells with high expression of DAB2IP.Two weeks later,DAB2IP at levels of mRNA and protein in screened cells was detected to verify high expression of DAB2IP by real-time quantitative PCR(RT-qPCR)and Western blot.Further,the effects of DAB2IP on the invasion and migration of HT29 cells were detected by Trans well and scratch assays.Finally,the expression of E-cadherin and vimentin proteins was detected to explore the mechanism of DAB2IP affecting the invasion and migration ability of HT29 cells by Western blot.Results After screening with G418,the mRNA and protein levels of DAB2IP were significantly higher than those of the control cells.Over-expression of DAB2IP could significantly inhibit the invasion and migration of HT29 cells;the difference was statistically significant(P＜0.001).Over-expression of DAB2IP could promote the expression of E-cadherin protein and inhibit the expression of vimentin protein in TH29 cells.Conclusion The HT29 stable cell line with high expression of DAB2IP was successfully screened.Over-expression of DAB2IP can inhibit the invasion and migration in HT29 cells by inhibiting the process of cell epithelial-mesenchymal transition(EMT).

Objective The aim of this study was to explore effects of FOXD3 on proliferation and migration of lung cancer A549 cells.Methods The expression of FOXD3 in various tumors was analyzed in the TCGA database.The online database GEPIA was used to assess the prognostic impact of FOXD3 mRNA expression.FOXD3 overexpressing lung cancer cell line was constructed and functional assay was performed to detect the role of FOXD3 in lung cancer cells.The STRING database was used to predict the regulatory network in which FOXD3 is involved.Results By comparing the expression profiles of tumors,among them,FOXD3 is up-regulated in tumors with skin cutaneous melanoma(SKCM),and FOXD3 is down-regulated in tumors:colon adenocarcinoma(COAD),rectal adnocarcinoma(READ)and testicular germ cell tumor(TGCT).Through the using of the GEPIA database to study the survival of cancer patients,FOXD3 was found to have an impact on the overall survival of patients with lung squamous cell carcinoma(LUSC),SKCM,adrenocortical carcinoma(ACC),and lower grade glioma(LGC).FOXD3 could inhibit the proliferation and migration of lung cancer cells.FOXD3 could be involved in the regulation of expression of various genes by using the STRING database.Conclusion FOXD3 overexpression inhibits proliferation and migration of lung cancer cells is closely associated with the prognosis of patient.Therefore,FOXD3 can be a good indicator for indicating good prognosis of lung cancer and provide new ideas for cancer treatment.

Objective The aim of this study was to explore the expression of pregnancy-upregulated nonubiquitous calmodulin kinase(PNCK)in nasopharyngeal carcinoma(NPC)and its effect on proliferation and apoptosis of NPC cells.Methods Immunohistochemistry was used to detect the expression of PNCK in NPC and normal tissues.The lentiviral vector was constructed to interfere with the expression of PNCK gene,confirming by real-time PCR and Western blot assays.The MTT assay,Annexin V staining with flow cytometry(FCM)analysis and caspase 3/7 activity assays were used to detect proliferation and apoptosis of CNE-2Z cells knocked-down PNCK.Results PNCK protein was highly expressed in NPC tissues.RT-qPCR and Western blot results confirmed that lentivirus successfully interfered with PNCK expression in nasopharyngeal carcinoma CNE-2Z cells.MTT assay result confirmed that the knock-down of PNCK significantly inhibited proliferation and induced apoptosis of CNE-2Z cells.Conclusion Interfering with PNCK gene expression inhibits proliferation of nasopharyngeal carcinoma cells and induces cell apoptosis,which can be potential targets for cancer treatment of nasopharyngeal carcinoma.

Objective The aim of this study was to investigate the inhibitory effects of palmitic acid(PA)on proliferation,migration,invasion and apoptosis of human cervical carcinoma Hela cells and its mechanism.Methods Hela cells cultured in vitro were divided into the control group(without PA)and PA treatment group(25,50,100μg/mL of PA).CCK-8 assay was used to detect the ability of proliferation in Hela cells in each group.The abilities of migration and invasion were detected in Hela cells by the Transwell assay.After treatment with different concentrations of PA,RT-qPCR was used to detect the expression of apoptosis-related genes including bcl-2,bax and cleaved-caspase-3.Flow cytometry were used to detect apoptosis of Hela cells double-labeled with annexin V/propidium iodide.Results Compared with the control group,the inhibitory proliferative rates of Hela cells treated with PA increased gradually(P＜0.05).After PA treatment,the abilities of migration and invasion in Hala cells significantly decreased(P＜0.05).At the same time,after treatment with PA,the expression of bcl-2 gene was decreased gradually,and the expression of bax and cleaved-caspase-3 genes were gradually increased.The apoptosis rates of Hela cells treated with PA increased in a dose-dependent manner(P＜0.05).Conclusion PA can inhibit proliferation,reduce migration and invasion,and induce apoptosis of Hela cells,which may be related to the regulation of bcl-2 family in HeLa cells.

Objective The objective of this study was to explore the effect and mechanism of astragaline(ATG)on inhibition of HIF-1α,proliferation and invasion of ovarian cancer cells.Methods OVCAR-8 and SK-OV-3 cells were cultured in hypoxic conditions and treated with ATG(ATG group)or ATG combined with PHD2 inhibitor IOX2(ATG+IOX2 group)for 24h.The cells were just cultured in hypoxic condition for 24 h as a blank control.Western blot and real-time fluorescent quantitative PCR were used to detect the expression of HIF-1α,PHD2,PCNA,MMP-2 and MMP-9 at levels of mRNA and protein in each group.The cells cultured under normal conditions were used as a negative control,and the changes of hypoxic status in cells were detected after ATG treatment by hypoxia kit.Transwell assay was used to detect the invasive ability of cells in each group;CCK-8 kit was used to determine the activity of cell proliferation in each group.OVCAR-8 and SK-OV-3 cells were treated with gradient concentrations of ATG combined with gradient concentrations of carboplatin or cisplatin for 72h,the cell proliferation activity was detected by CCK-8 kit,and combined effect analysis was also performed.Results Under hypoxic conditions,compared with the blank control group,the expression of PHD2 at levels of protein and mRNA in the ATG group were increased,cell proliferation and invasion ability were decreased,and the expression of HIF-1α protein was decreased in OVCAR-8 and SK-OV-3 cells;the expression of PCNA,MMP-2 and MMP-9 at levels of protein and mRNA were decreased;but the expression of HIF-1α mRNA and cell hypoxia status did not change.When compared with the ATG group,the abilities of proliferation and invasion in the ATG+IOX2 group were increased in OVCAR-8 and SK-OV-3 cells;the expression of PCNA,MMP-2 and MMP-9 at levels of protein and mRNA as well as the expression of HIF-1α protein were increased,but the mRNA level of HIF-1α did not change.In addition,ATG could significantly enhance the sensitivity of OVCAR-8 and SK-OV-3 cells to cisplatin and carboplatin,and both combinations showed a good synergistic effect.Conclusion ATG can promote the degradation of HIF-1α by hypoxia via up-regulating PHD2 expression,resulting in inhibiting proliferation and invasion of ovarian cancer cells.

Objective The aim of this study was to investigate the expression of PTPN9 in colorectal cancer and its relationship with various clinical indicators.Methods A retrospective study of 146 patients with colorectal cancer who had a clear pathology and complete clinical data from December 2007 to December 2008 at Harbin Medical University Cancer Hospital was performed.Tumor tissues from 132 patients and non-cancerous tissues from 14 patients were randomly selected for determination of PTPN9 protein by immunohistochemistry,and double-blind scores were performed by two senior pathologists.According to the staining score,the clinical indicators such as age,gender,gross morphology,degree of differentiation and prognosis were compared.Survival analysis was performed by Kaplan-Meier curve using Cox proportional hazard model for multivariate analysis.Results The expression of PTPN9 in tumor tissues was statistically different from non-tumor tissues(P=0.009).There was a relationship between PTPN9 expression and N stage(P=0.021),M stage(P=0.022),pathological stage(P=0.008),clinical indicators such as diabetes(P=0.022)and survival(P=0.001).High expression of PTPN9 would result in a decrease overall survival in patients with colorectal cancer(P＜0.001).Multivariate Cox regression analysis showed that the expression of PTPN9 was one of the independent risk factors affecting the prognosis of patients with colorectal cancer(HR=1.202,P＜0.05).Conclusion The expression of PTPN9 is significantly different between cancer tissues and non-cancerous tissues,and the expression of PTPN9 is higher in cancer tissues.As the expression of PTPN9 was increased,the pathological stage of tumors was also increased.The high expression of PTPN9 is a correlation with the onset of diabetes and also leads to a decrease in overall survival of patients with colorectal cancer.

Objective The objective of this study was to investigate the relationship between the methylation and clinical features of deubiquitinating enzyme USP1 in peripheral blood and the prognosis risk of colorectal cancer.Methods A total of 286 patients with colorectal cancer were enrolled in the cohort study.The level of DNA methylation status of USP1 was detected using high resolution melting curve analysis(HRM).The Cox regression model was used to assess the association between USP1 methylation and clinical features and prognosis risk of colorectal cancer.Results In male colorectal cancer cases,USP1 methylation could incerease the risk of colorectal cancer with poor pregnosis(HR=2.091,95% CI:1.195~3.661,P=0.010).Among the clinicopathological features,UICC tumor stage 4(HR=2.464,95% CI:1.205~5.039,P=0.014),tumor size over 50 mm(HR=1.610,95% CI:1.016~2.550,P=0.043)and histological non-adenotype(HR=5.117,95% CI:1.142~22.930,P=0.033)were contributing factors to the increased risk of colorectal cancer with poor pregnosis.Conclusion UICC tumor stage 4,tumor size over 50 mm and histological non-adenotype will increase the risk of colorectal cancer with poor pregnosis.The methylation of promoter region of USP1 gene in peripheral blood is associated with an increased risk of poor pregnosis in male colorectal cancer.

Objective The objective of this study was to investigate the correlation between D-dimer levels and the occurrence of catheter related thrombosis(CRT)in tumor patients.Methods A prospective study was performed on 100 cancer patients with deep venous catheterization.The plasma D-dimer and intravenous Doppler ultrasonography were used to observe the incidence,time and thrombus type of CRT.Results The incidence of CRT was 12.6%,and asymptomatic thrombosis accounted for 83.3%.58.3% of the thrombosis occurred within 2 weeks after catheterization,and 91.7% occurred within 4 weeks after catheterization.After 2 weeks of catheterization,the level of D-dimer in the thrombosis group was significantly higher than that in the non-thrombosis group(P=0.013).Conclusion Most of the CRT in tumor patients is formed within 4 weeks after deep venous catheterization.The proportion of asymptomatic thrombus is high,and dynamic monitoring of D-dimer may be helpful for early diagnosis.

Objective The aim of this study was to investigate the effect of delayed radiotherapy on the prognosis of breast cancer patients with different molecular subtypes.Methods A total of 341 patients with radical mastectomy were enrolled in our hospital from January 2007 to December 2012.There were 149 patients with Luminal A type,83 patients in the control group,and 66 patients in the delayed radiotherapy group.There were 105 cases with Luminal B type,63 cases of control group and 42 cases of delayed radiotherapy.There were 43 cases of HER2+,28 cases of control group and 15 cases of delayed radiotherapy.There were 44 patients with triple-negative,27 cases in the control group,and 17 patients in the delayed radiotherapy group.Analyzed the difference in progposis betueen the delayed radiotherapy group and the contrel group.Results The local recurrence rate of Luminal A,Luminal B,HER2+ and triple negative type in the control group and the delayed radiotherapy group were(4.8% vs. 9.1%,P=0.301),(4.7% vs. 19.0%,P=0.019),(7.1% vs. 33.3%,P=0.027),(11.1% vs. 35.3%,P=0.053),respectively;distant metastasis rate:(9.6% vs. 10.6%,P=0.8 45),(11.1% vs. 14.2%,P=0.234),(32.1% vs. 40.0%,P=0.937),(37.0% vs. 41.2%,P=0.784),respectively;tumor-free survival rate:(85.5% vs. 80.3%,P=0.395),(84.1% vs. 66.7%,P=0.037),(60.7% vs. 33.3%,P=0.087),(55.5% vs. 23.5%,P=0.037),respectively;overall survival rate:(94.0% vs. 90.9%,P=0.539),(84.1% vs. 80.9%,P=0.672),(67.9% vs. 60.0%,P=0.606),(59.2% vs. 41.2%,P=0.242),respectively.Cox regression analysis showed that tumor size(HR=3.156,P=0.043),lymph node metastasis(HR=1.074,P=0.001),TNM(HR=8.591,P=0.009)and molecular subtype(HR=2.092,P＜0.001)were independent factors influencing prognosis of breast cancer patients.Conclusion The local recurrence rate of Luminal B type and HER2+ is significantly increased due to delayed radiotherapy.The disease-free survival rates of Luminal B type and triple negative type are significantly increased reduced due to delayed radiotherapy.Tumor size,lymph node metastasis,TNM staging and molecular subtypes are independent risk factors for patient survival.

Objective The study aimed to investigate the clinicopathological features of patients with bone metastasis from gastric cancer and to screen the independent prognostic factors.Methods The clinical data of 157 patients with bone metastasis from gastric cancer in Zhongnan Hospital of Wuhan University from April 2007 to December 2013 was retrospectively analyzed.Results The median time from diagnosis of gastric cancer to bone metastasis was 280.5 days in 157 patients with gastric cancer.There were 124 cases of multiple bone metastases and 22 cases of single bone metastasis.The most common sites of bone metastasis were the spine(88.5%),the pelvis(51.6%)and the ribs(51.0%).Many patients were accompanied by extra-organic metastasis(78.3%).The pathological differentiation of gastric cancer patients with bone metastasis was mostly poor,with poorly differentiated adenocarcinoma(69.3%)and signet ring cell or mucinous adenocarcinoma(33.1%).The median survival time after gastric metastasis in gastric patients was 109 days.Univariate analysis showed that the levels of CEA and LDH,hemoglobin concentration,albumin concentration,extra-osseous metastasis,systemic chemotherapy and bisphosphonate treatment were associated with prognosis of patients with bone metastasis from gastric cancer(P＜0.05).Multivariate analysis showed that the CEA level with extra-osseous metastasis,systemic chemotherapy and bisphosphonate treatment were independent prognostic factors.Conclusion Elevated CEA and extra-osseous metastasis are independent prognostic factors.Chemotherapy and bisphosphonate therapy may improve the prognosis of patients.

Objective The objective of this study was to investigate the expression of serum ferritin in patients with head and neck squamous cell carcinoma(HNSCC),and to verify whether it could be used as a biomarker for predicting HNSCC metastasis.Methods The different levels of serum ferritin among tumor patients,precancerous lesions,inflammatory patients and normal controls were compared,and ROC curves were used to verify the efficacy of ferritin and Doppler ultrasound in the differentiation between HNSCC patients with lymph node metastasis and without lymph node metastasis.Results The serum level of ferritin in tumor patients was significantly higher than that in non-tumor patients,but there was some overlap compared with precancerous lesions.Compared with non-metastatic HNSCC,the serum level of ferritin was significantly elevated in HNSCC patients with lymph node metastasis.Compared to Doppler ultrasound,ferritin had a larger area under the curve and a higher sensitivity and likelihood ratio for the prediction of cervical lymph node metastasis.Conclusion Ferritin may have some shortcomings in the early diagnosis of HNSCC,but it is a good biomarker for predicting cervical lymph node metastasis in patients with HNSCC.

Objective The aim of this study was to investigate the distribution of metastatic lymph nodes and other common lymph node in the neck anatomy of high frequency ultrasound.Methods A retrospective analysis of 547 cases of neck lymph nodes from September 2016 to September 2017 was performed.According to the pathological results,it was divided into non-specific lymphadenitis,lymph node tuberculosis,lymphoma and metastatic lymph nodes.The routine ultrasound parameters of lymph nodes and its distribution in the anatomical section of the neck lymph nodes were recorded.Results The distribution of different neck lymph node diseases in the anatomical section of the neck lymph nodes was different.The neck lymph node metastasis of head and neck tumors was mostly distributed in Ⅱ(62.00%),Ⅲ(54.00%)and Ⅳ areas(53.00%).The neck lymph node metastasis of primary subclavian tumors was mainly distributed in Ⅴ(72.56%)and Ⅳ areas(34.15%).For specific tumors,there were also high risk area of lymph node metastasis.Conclusion Ultrasound can show the distribution of lymph nodes disease in the anatomical section of the neck.Preoperatively clear the distribution of lymph node disease in the anatomical zone can provide a more accurate basis for clinical diagnosis,surgical operation and cleaning range.

Acute T lymphoblastic leukemia(T-ALL)is a highly invasive and heterogeneous hematological malignancy derived from thymic T cell progenitor cells.T-ALL accounts for approximately 15% of childhood acute lymphoblastic leukemia(ALL)and approximately 25% of adult ALL.The use of intensive chemotherapy regimens has significantly improved the prognosis of children with T-ALL,but the prognosis of adult and relapsed T-ALL patients remains poor.The development of novel targeted drugs specifically blocking T-ALL cell survival and drug-related abnormal activation signaling pathways has been considered as a new strategy for the treatment of adult and relapsed refractory T-ALL patients in recent years.The phosphatidylinositol 3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)pathway is a representative of the abnormal activation signaling pathways in T-ALL cells.A variety of small molecule inhibitors targeting this pathway has been successfully developed and has achieved good results in the treatment of T-ALL.PI3K/AKT/mTOR pathway-related inhibitors have higher specificity and lower toxicity than traditional chemotherapeutic drugs,and many studies have shown that they can exert synergistic effects with low-dose chemotherapeutic drugs or other targeted drugs in the treatment of T-ALL.This review will summarize recent research results in the field of PI3K/AKT/mTOR pathway and T-ALL,and elaborate the research progress of T-ALL based on targeting this pathway.

The RNA binding protein Lin28 is expressed in a variety of malignant tumor tissues.The certain transcription factors and RNA binding proteins can up-regulate the expression of Lin28 at both transcription and post-transcription levels.The high level of Lin28 can induce malignant transformation of normal cells by affecting the expression of miRNA or regulating the transcription,splicing,stability and translation of target mRNA,and can promote the proliferation and metastasis of tumor cells.The high expression of Lin28 has an important role in inducing tumorigenesis and progression,and is also an important biomarker for assessing the prognosis of malignant tumors.This review summarizes the existing literature about the role of Lin28 in malignant tumors,the molecular mechanisms of upregulation,and the downstream regulatory mechanisms at the time of action,which is of great significance for fully understanding the Lin28 molecule.

Angiogenesis is one of key conditions for tumorigenesis.Anti-angiogenic drugs block angiogenesis and are considered to be an important breakthrough in the treatment of various types of cancer,especially advanced cancer.Anti-angiogenic drugs have shown good efficacy in combination chemotherapy in patients with advanced gastric cancer,colorectal cancer,prostate cancer and advanced liver cancer.However,many studies have shown contradictory results in breast cancer,causing controversy about the value of this drug.In this article,we review the evidence for anti-angiogenic therapy options for breast cancer,discuss possible factors limiting the effectiveness of anti-angiogenic drugs,and suggest future research on these therapies for the treatment of breast cancer.

Steroid hormones,especially estrogens and progestins,play an important role in the pathogenesis,progression and treatment of breast cancer.At the same time,a large number of studies have confirmed that cancer stem cells also play a key role in the occurrence,progression and metastasis of breast cancer.In preclinical models of breast cancer,although tumor cells have been significantly inhibited by conventional anti-endocrine therapy,only a small number of breast cancer stem cells(BCSCs)are needed to maintain tumor re-growth.In the past,a large number of studies have focused on the relationship between hormones in the development of normal breast and breast cancer.Recently,many studies have examined effects of hormones on the activity of breast cancer stem cell,which has opened up a new research direction for breast cancer treatment and CSCs.This paper comprehensively discusses the role of steroid hormones(estrogen and progesterone)in breast cancer and their regulation of breast BCSCs.

LncRNA is easy to detect in tumor tissues and body fluids of cancer patients.When lncRNA is used as a biomarker,it can help the diagnosis and treatment of a variety of cancers.Detection of lncRNA by molecular tools such as real-time PCR can diagnose cancer,and SNPs in lncRNA can also predict cancer risk in patients.Some lncRNAs have been used as therapeutic targets to treat cancer.Therefore,lncRNA plays an important role in the diagnosis,treatment and prognosis of cancer patients.

Many studies indicate that the CDK-RB-E2F pathway and the PI3K-AKT-mTOR pathway play key roles in the mechanism of drug resistance in breast cancer.Through studies of two pathways,the combination of CDK4/6 inhibitors and endocrine drugs can improve the survival rate of patients with hormone receptor-positive breast cancer,and mTOR inhibitors also show the anti-tumor strength.Recent studies have shown that the combination of mTOR inhibitors and CDK4/6 inhibitors can further inhibit the activation of the CDK-RB-E2F pathway and synergistically controls tumor cell proliferation.It was also found that the CDK-RB-E2F pathway in CDK4/6 inhibitor-resistant patients was reactivated and sensitive to mTOR inhibitor.Other studies have also shown that CDK4/6 inhibitors and mTOR inhibitors can synergistically control tumorigenesis through autophagy.This article reviews several mechanisms of combination of two drugs.