Objective The Objective of this study was to investigate the abnormal expression of Notch signaling pathway members in pancreatic cancer and its important effect on the development of pancreatic carcinoma.Methods Affymetrix gene expression microarray was used to screen the differentially expressed members of Notch signal pathway in 10 cases of pancreatic carcinoma and its adjacent tissues,and verified by real-time quantitative PCR and Western blotting.The lentivirus expression vector carrying the siRNA fragment of Jagged 2(JAG2)gene was transfected into the pancreatic cancer primary cells to construct the JAG2 gene repression-expressing pancreatic cancer cell line.MTT,flow cytometry and Transwell assays were used to analyze cell proliferation,changes of cell cycle and invasive transfer capabilities.Results A total of 512 differentially expressed genes were detected by Affymetrix gene expression microarray,including 419 up-regulated genes and 93 down-regulated genes.JAG2(up-regulated expression 8.20 times),NOTCH1(up-regulated expression 3.74 times),HES1(up-regulated expression 3.27 times),and NOTCH2(up-regulated expression 3.16 times)were differentially expressed in Notch signaling pathway.The results of PCR and Western blotting were consistent with those of gene chip.The growth curves of JAG2 gene repressed pancreatic cancer cells and pancreatic cancer primary cells were drawn by the standard OD490 value of d1-d5 by MTT assay.JAG2 gene repressor expression vector could significantly inhibit the proliferation of pancreatic cancer cells.The cell cycle analysis showed that the apoptosis and the arrested cell cycle at the S phase were significantly increased in pancreatic cancer cells with JAG2 gene repressor expression.The invasive ability was significantly reduced in JAG2 gene repressor expression pancreatic cancer cells(P＜0.05).Conclusion Some members of the Notch signaling pathway are significantly differentially expressed in pancreatic cancer tissues,and repression of this member can affect the growth,cell cycle,invasion and metastasis of pancreatic cancer cells.

Objective The aim of this study was to investigate the methylation status of fragile histidine triad(FHIT)gene,human mutl homolog 1(hMLH1)gene,p16 gene,retinoic acid receptor beta(RAR-beta)gene,Reprimo gene and tissue inhibitor of metalloproteinase 3(Timp3)gene in gastric cancer and corresponding paracancerous tissues.Methods The methylation levels of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in 42 clinically resected gastric cancer specimens and 42 corresponding paracancerous tissues were detected by sodium bisulfite sequencing.Results The average methylation rates of the genes in gastric cancer and corresponding paracancerous tissues were:FHIT(1.50%,1.36%),hMLH1(4.77%,0.48%),p16(9.63%,10.36%),RAR-beta(4.75%,4.17%),Reprimo(9.71%,3.76%)and TIMP3 genes(18.34%,14.06%).Compared with the paracancerous control group,the average methylation rate of Reprimo gene was only statistically different in gastric cancer patients(P=0.00787).The difference in methylation rate of Reprimo gene promoter in gastric cancer patients with the degree of tissue differentiation was statistically significant(P＜0.05).Conclusion There has methylation in the cytosine guanidine dinucleotide island of the Reprimo gene promoter region in gastric cancer.The high methylation rate of the Reprimo gene can be used as a potential biomarker for gastric cancer to detect the early stage of gastric cancer.

Objective The aims of this study were to investigate the expression of DKK2,a WNT signaling pathway regulator,in nephroblastoma cells and tissues of children,the effect on the proliferation of nephroblastoma SK-NEP-1 cells,and to explore its mechanism.Methods The relative expression of DKK2 in nephroblastoma cells and tissues was analyzed by qRT-PCR and immunoblotting assays.Overexpressing DKK2 SK-NEP-1 cells were set as the experimental group(DKK2 group);the blank control plasmid group was set as a control group(Vector group),transfected with pcDNA3.1(+)-Flag-DKK2 plasmid(Experimental group)and pcDNA3.1(+)-Flag-Vector plasmid(Control group).The over-expression of DKK2 was confirmed in SK-NEP-1 cells by RT-PCR and immunoblotting.CCK-8 and cell cloning assays were used to determine the effect of DKK2 on cell proliferation;flow cell cycle and apoptosis assays were used to confirm the effect on cell proliferation in overexpressed DKK2 cells.The xengraft formation assay in nude mice was to verify the effect of DKK2 on proliferation in overexpressed DKK2 cells;the mechanism of DKK2 in inhibitory proliferation was analyzed by qRT-PCR,Western blotting and immunohistochemistry.Results Compared with normal renal epithelial tissues,DKK2 mRNA was down-regulated in children with nephroblastoma,and the difference was statistically significant(P＜0.001).Compared with the control group,transfected DKK2 cell viability was significantly inhibited after treatment for 24,48 and 72h(P＜0.05),cell clone formation in the experimental group was significantly inhibited(31.11%±2.14%)(P＜0.05),the cell cycle in the experimental group was significantly arrested at the G1 phase(P＜0.001),and the apoptosis rate in the experimental group was significantly increased(P＜0.001).Compared with the control group,the tumor weight and volume in nude mice were significantly low in the experimental mice which were injected DKK2 overexpression cells(P＜0.001).Active-β-catenin and downstream genes were significantly inhibited in over-expressed DKK2 SK-NEP-1 cells.Conclusion DKK2 is down-regulated in human cutaneous nephroblastoma and participates in the mechanism of nephroblastoma by antagonizing Wnt/β-catenin signaling pathway.

Objective The aim of this study was to investigate the effect of miR-129 on the proliferative activity and apoptosis of osteosarcoma MG-63 cells.Methods Thirty cases of osteosarcoma and its adjacent paracancerous tissues were collected.RT-PCR was used to detect the expressions of miR-129 mRNA and SEPHS1 mRNA.Western blot was used to detect the protein level of SEPHS1.After MiR-129 was over-expressed and knocked down,the cell proliferation was detected in MG-63 cells by CCK-8,and apoptosis was detected in MG-63 cells by Westerm blot and hoechest staining.Results In this study,the expression of miR-129 in osteosarcoma tissues was significantly higher than that in para-cancerous tissues(P＜0.05).Through the established model in vitro of miR-129 overexpression or knockdown,it was determined that the miR-129 mimetic and inhibitor concentrations were optimal for overexpression and knockdown at 50nM and 200nM,respectively.The possibility of binding between miR-129 and SEPHS1 was predicted by software,and the luciferase reporter assay further confirmed the binding relationship between miR-129 and SEPHS1.Knockdown of miR-129 significantly inhibited the proliferation of MG-63 cells and accelerated the apoptosis of MG-63 cells.Conclusion miR-129 plays a key role in regulating the proliferation and apoptosis of osteosarcoma cells by binding to SEPHS1.

Objective The Objective of this study was to investigate the effect of depression on serum levels of C-reactive protein(CRP)and high-sensitivity C-reactive protein(hs-CRP),and prognosis in liver cancer patients.Methods A total of 251 patients with liver cancer undergoing hepatectomy were enrolled.The hospital anxiety and depression scale(HADS-D)and 9-item patients health questionnaire(PHQ9)were assessed for depression before 3 days for surgery.Patients were divided into depression group(n=95)and non-depression group(n=156)according to the scores.Preoperative serum levels of CRP,hs-CRP,ALT and AST were measured and compared between the depression and non-depression groups.Survival analysis Kaplan-Meier method was used to compare the disease-free survival(DFS)and total survival(OS)between the two groups.Results The serum levels of CRP,hs-CRP,ALT and AST in the depression group were significantly higher than those in the non-depression group(P＜0.05).The follow-up of 3.5-year showed that 164 patients(65 in depression group and 99 in non-depression group)had recurrence or metastasis and 47 patients(22 in depression group and 25 in non-depression group)died.The DFS and OS in the depression group were significantly lower than those in the non-depression group(P＜ 0.05).Cox multiple regression analysis showed that liver function grading,BCLC staging and depression were independent risk factors for the prognosis of liver cancer.Spearman correlation analysis showed that patients′ degree of depression was positively correlated with serum levels of CRP and hs-CRP(P＜0.05),DFS and OS were negatively correlated with serum levels of CRP and hs-CRP(P＜0.05).Conclusion Depression may mediate elevated serum levels of CRP and hs-CRP,maintain inflammatory response in patients,lead to increased liver function damage,elevate levels of ALT and AST,and thus adversely affect the prognosis of patients with liver cancer.

Objective The aim of this study was to compare the short-term and long-term prognostic significance of different systemic inflammatory scores in patients with gastric cancer:neutrophil lymphocyte ratio(NLR)and platelet lymphocyte ratio(PLR).Methods The clinical data of 240 patients with gastric cancer who underwent radical surgery were retrospectively analyzed.The relationship between NLR,PLR,glasgow prognostic score(GPS)and clinicopathological characteristics and perioperative complications were compared.Survival analysis was performed using Kaplan-Meier survival analysis.The Log-rank methods were used to test the difference significance,and the multivariate analysis was performed using the Cox regression risk model.Results Patients in the high NLR and PLR groups were older,had a high GPS,deep tumor infiltration,more lymph node metastasis,and a late TNM stage(P＜0.05).The rate of positive margin in the high NLR group was higher(P＜0.05).Patients in the high NLR and PLR groups required significantly higher transfusion rates than those in the low NLR and PLR groups(P＜0.05),and the high NLR group had more postoperative complications(P＜0.05).Univariate analysis showed that age,GPS,tumor location,tumor infiltration depth,lymph node metastasis status,TNM stage,vascular tumor thrombus,nerve infiltration,NLR and PLR were associated with postoperative survival of gastric cancer patients(P＜0.05).The overall survival(OS)in high NLR and high PLR groups was lower than that of low NLR and low PLR groups(P=0.018 and P＜0.001).Cox regression analysis showed GPS and lymph node metastasis were independent prognostic factors of OS(P＜0.001 and P=0.002).Conclusion Preoperative systemic inflammatory scores NLR and PLR are prognostic factors affecting the preoperative clinical outcomes of gastric cancer.It is recommended to be used in combination with other prognostic indicators for routine use in the prognosis of patients undergoing radical gastrectomy.

Objective The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma(ADC)remains controversial.The aim of present study was to investigate the prognostic value of PD-L1 combined with CD8⁺TILs expression in patients with resectable lung adenocarcinoma.Methods A total of 104 patients with lung adenocarcinoma who underwent radical resection were enrolled at the Affiliated Tumor Hospital of Harbin Medical University from January 2009 to December 2012.Immunohistochemistry was used to detect the expression of PD-L1 and CD8⁺TILs in primary tumor specimens.Its clinical pathological factors and its relationship with prognosis were statistical analysis.Results The positive expression rate of PD-L1 in tumor cells was 38.5%(40/104),and the positive rate of CD8⁺TILs was 44.2%(46/104).There was a significant correlation between the expression of CD8⁺TILs and TNM stages of patients with resectable ADC.The Kaplan-Meier survival analysis showed that low expression of PD-L1 and high expression of CD8⁺TILs were significantly associated with disease-free survival(DFS)and overall survival(OS),and could be used as an independent predictors for predicting prognosis of patients with resectable ADC.Conclusion The expression of PD-L1 and CD8⁺TILs in the postoperative specimens can help to judge the prognosis of patients.This study has certain significance for immunotherapy of PD-1/PD-L1 pathway in patients with surgically resected ADC.

Objective The of this study was to investigate the relationship between the molybdenum target imaging features and clinical signs of mammography,and the expression of HER-2 receptor in breast cancer patients with positive receptors of estrogen and progesterone.Methods One hundred and eleven patients with estrogen and progesterone receptor-positive breast cancer who were admitted to our hospital from July to September 2017 were examined with mammography before operation.Immunohistochemical analysis was performed on breast cancer tissues.Pathological features and features related to mammography were analyzed after operation.The relationship between clinicopathological features and mammography-related signs,and HER-2 expression was also analyzed statistically.Results Of the 111 patients,34 were HER-2 positive patients.There were significant difference between the observed indicators and the over-expression of HER-2(P＜0.05).These indicators included lymph node metastasis,calcification of the mass,margin of the mass,the shape of calcification,and the blood status of vessels.The mammography of patients with triple positive breast cancer is more likely to manifest as lymph node enlargement,mass with calcification or simple calcification,marginal burrs,granular calcification,and vascular thickening.Conclusion The expression of HER-2 in breast cancer patients with positive estrogen and progesterone receptors can be reflected to some extent by lymph node metastasis,tumor with calcification,tumor margin,calcification,calcification morphology and peripheral blood vessel thickening.In terms of clinical conditions,The biological behavior and characteristics of tumor can be inferred based on the clinicopathological features of the patient and the imaging findings of the mammography,providing a direction for the treatment and evaluation of prognosis in breast cancer patients.

Objective The aim of this study was to investigate the expression of COL5A2 in bladder cancer tissues,and its correlation with clinicopathological features and prognosis.Methods A total of 144 patients with bladder cancer were enrolled in this study.Real-time fluorescence reverse transcription and immunohistochemistry were used to detect the expression of COL5A2 at levels of mRNA and protein in bladder cancer tissues and normal bladder tissues.The relationship between COL5A2 expression and clinicopathological features and prognosis was analyzed.Results The expression of COL5A2 mRNA in the bladder cancer group was higher than that in the paracancerous group(P＜0.05).The positive rate of COL5A2 in the bladder cancer group was higher than that in the normal bladder tissues(P＜0.05).The expression of COL5A2 protein was not correlated with age(P＞0.05),positively associated with the TMN stage,pathological grade,tumor maximum diameter(≥5cm),depth of invasion,lymph node metastasis,lymphatic vascular infiltration,and recurrence;the difference was statistically significant(P＜0.05).The 3-year survival rate and survival time in the COL5A2 negative group were significantly higher than those in the COL5A2 positive group(P＜0.05).The higher TMN stage,the higher pathological stage,the maximum diameter of the tumor(≥5cm),the deeper infiltration depth,lymph node metastasis,lymphatic vascular infiltration,recurrence,the higher positive expression rate of COL5A2 protein.Conclusion COL5A2 is highly expressed in the bladder cancer tissues,which promotes the development of bladder cancer.Bladder cancer patients with low expression of COL5A2 can obtain a good prognosis.

Objective The aim of this study was to explore the effect of minimally invasive small incision surgery on early thoracic esophageal cancer patients and its impact on pain.Methods A total of 160 patients with early thoracic esophageal cancer who were treated in our hospital from March 2016 to March 2017 were randomly divided into the conventional surgery group and the minimally invasive small incision surgery group.Patients in the conventional surgery group were treated with routine operation,and patients in the minimally invasive small incision surgery group were treated with minimally invasive small incision surgery.Vital capacity(VC),forced expiratory volume 1(FEV1),visual analogue scale(VAS),hospitalization time,operation time and intraoperative bleeding volume were counted.Growth hormone(GH)was detected by ELISA.The levels of cortisol(Cor)and interleukin-8(IL-8)were measured by immunoassay and adverse reactions.Results The levels of VC and FEV1 in the minimally invasive small incision group were significantly higher than those in the conventional surgery group.The bleeding volume,operation time and hospitalization time were shorter than those in the conventional surgery group.The levels of GH and Cor,VAS score and incidence of adverse reaction rate were lower than those in the conventional surgery group,and the level of IL-8 was also higher in than that in the conventional surgery group.The difference was statistically significant(P＜0.05).Conclusion Minimally invasive small incision surgery is effective on the treatment of early thoracic esophageal cancer,relieving pain and reducing adverse reactions.

Objective The aim of this study was to describe the prevalence of malignant tumors in Harbin from 2015 to 2017 and provide the scientific evidence for cancer prevention and control.Methods The morbidity and mortality data of malignant tumors in Harbin were collected by Harbin Cancer Registry and Reporting System,and the incidence and death distribution of malignant tumors were described.Results In 2015-2017,there were 77,379 new cases of malignant tumors and 49,450 deaths in Harbin.The crude incidence of malignant tumors was 243.51/105,age-standardized incidence rates by Chinese standard population(ASIRC)was 171.76/105 in Harbin.The crude mortality of malignant tumors was 155.62/105,age-standardized mortality rates by Chinese standard population(ASMRC)was 106.79/105 in Harbin.The top 5 malignant tumors were lung cancer,colorectal cancer,thyroid cancer,breast cancer and liver cancer.The top 5 deaths were lung cancer,liver cancer,gastric cancer,colorectal cancer and pancreatic cancer.Conclusion The burden of malignant tumors is serious in Harbin.Lung cancer,liver cancer,gastric cancer,colorectal cancer,thyroid cancer and female breast cancer are the main malignant tumors that threaten residents.

In recent years,the overall incidence of cancer and mortality have been on an upward trend,cancer becomes a public health problem that seriously endangers human health in the world.Currently,except for radiotherapy and surgery to cancer treatment,chemotherapy plays an important role in greatly improving the survival rate of cancer patients.However,most of chemotherapies have drug-resistance and toxic effects on patients.In order to overcome these shortcomings,some natural phytochemicals have been used as chemosensitizers in chemotherapies.These natural phytochemicals not only increase the sensitivity of tumor cells to therapeutic drugs,but it also reduces their resistance and toxic effects on patients.Therefore,this review summarizes the sensitization of natural phytochemicals to target drug therapies and their possible mechanisms.

The Wnt/beta-catenin signaling pathway plays an important role in tumorigenesis and development,and is a key pathway mediating carcinogenesis.Therefore,further studies of Wnt/beta-catenin signaling pathway may provide powerful help for exploring the pathogenesis of tumors and seeking effective diagnosis and therapy.This article reviews the research progress of Wnt/beta-catenin signaling pathway and tumorigenesis.

Standard gastric cancer D2 radical surgery has become a global consensus.However,selective augmentation of lymph node dissection(D2+)surgery for a particular patient may increase their survival.D2 combined with No.8p,No.10,No.12b,No.13,No.14v,No.16a2/b1 lymph node dissection may lead to corresponding surgery-related complications.Therefore,we recommend that patients should be performed appropriate D2+ radical surgery at a medical treatment center with sufficient clinical experience.

Liposarcoma(LPS)is the most common type of soft-tissue sarcoma(STS).The current treatment methods are still based on complete surgical resection.Radiotherapy and chemotherapy as adjuvant treatment or distant metastasis,and the main treatment of unresectable liposarcoma have limited efficacy,have not widely recognized.With the extensive and in-depth of LPS molecular targeted therapy,the research achievements in this area are remarkable.Emerging targets for LPS include receptors such as tyrosine kinase receptor AXL,fibroblast growth factor receptor(FGFR),insulin-like growth factor-1 receptor(IGF-1R),nuclear export receptor XPO1(Exportin-1),and proteins/enzymes such as heat shock protein 90(Hsp90),bispecific tyrosine(Y)phosphorylation-regulated kinase 1B(DYRK1B)and signal pathways such as SRC/FAK/RHO/ROCK have shown good prospects for anti-LPS in preclinical studies.The research progress in the aspects is summarized as follows.

Radiotherapy is an important treatment for lung cancer.However,the radiation-induced lung injury(RILI)affects some patients and also affects the efficacy of treatment.Therefore,it is very important to identify high-risk patients who may have RILI and take action intervention or monitoring.Although the individual difference is often explained by clinical and dosimetric,genetic factors also influence the occurrence of RILI.Currently,there are reports on the relationship between single nucleotide polymorphism(SNP)and RILI.The SNP of these specific genes may become an important predictor of RILI,and thus reduce the incidence of radiation-induced lung injury.

Local and/or regional recurrence is a common cause of the failure of primary radical radiotherapy for nasopharyngeal carcinoma,and it is also a clinically existing treatment problem.Re-radiation therapy is one of main effective means of treatment for recurrent nasopharyngeal carcinoma.The article summarizes the recent domestic and abroad literatures on radiotherapy in vitro(including conventional two-dimensional,three-dimensional conformal,intensity-modulated radiotherapy),stereotactic radiotherapy,brachytherapy,proton beam and heavy ion therapy for recurrent nasopharyngeal carcinoma,and summarized the advantages and disadvantages of different radiotherapies as well as their efficacies.