Objective The mechanism of apoptosis induced by polyphenyl propenoid-polysaccharide complex(PPC)in human breast cancer MCF-7 cells was studied.Methods MCF-7 cells were cultured with different concentrations of PPC for different time.The effects of PPC on proliferation and apoptosis were detected in MCF-7 cells by MTT assay,fluorescent staining,apoptosis detection kit,DNA gel electrophoresis and Western blot.Results PPC induced apoptosis in MCF-7 cells.When apoptosis occurred,the enzyme activities of caspase-3 and-9 were increased,and the expression of pro-caspase-3 protein was decreased.Caspase-3 inhibitor(z-DEVE-fmk)could partially inhibit PPC-induced apoptosis and inhibit activation of caspase-3 precursor enzyme.Conclusion PPC induces apoptosis of MCF-7 cells by activating caspase family.

Objective The aim of this study was to investigate the effect of Ca²⁺/calmodulin-dependent kinase II(CaMKII)γ RNA interference on the expression of nuclear factor of activated T-cells cytoplasmic 1(NFATc1),tyrosine kinase(c-Src)and tartrate resistant acid phosphatase(TRAP)genes,and its role and molecular mechanism in osteoclast differentiation.Methods The CaMKII γ RNA interference vector was constructed by lentivirus and transfected into RAW264.7 cells.The experiment was divided into three groups:A,B and C,which were the control group,negative vector group and interference vector group.After transfection for 12 hours,osteoclasts induced by 50 ng/mL RANKL and the cells were harvested after induction for 5 days.Real-time quantitative PCR,Western blot and immunofluorescence were used to detect the expression of NFATc1,TRAP and c-Src genes in three groups.Results The mRNA levels of NFATc1,TRAP and c-Src in the group C decreased by 49.86%,43.65% and 53.57%,respectively(P＜0.001),and the protein levels decreased by 54.22%,46.75% and 45.86%,respectively(P＜0.001).There was no significant difference between the A and the B groups(P＞0.05).The fluorescence intensity of the above genes in the group C was significantly weaker than that in the A and B groups,and the formation of osteoclasts was significantly less than that in the A and B groups.Conclusion CaMKIIγ RNA interference significantly inhibited the expression of NFATc1,TRAP and c-Src genes,suggesting that CaMKIIγ plays a key regulatory role in osteoclast differentiation.

Objective The Objective of this study was to investigate the effect of microRNA-409-3p(miRNA-409-3p)expression on proliferation of cervical cancer Hela cells and chemotherapy sensitivity of cisplatin.Methods HeLa cells were divided into normal control,miRNA-409-3p mimic and RNA control groups.The mRNA expression of miRNA-409-3p was detected by RT-qPCR.The cell viability was detected by CCK-8 assay,and the expression of Fip200,LC3 and Caspase-3 was detected by Western blot.Results The relative expression level of microRNA-409-3p mRNA in cervical cancer tissues was significantly lower than that in normal cervical tissues and adjacent tissues(P＜0.05).After transfection of microRNA-409-3p mimic,the relative expression level of microRNA-409-3p mRNA in the microNA-409-3p mimic group was significantly up-regulated compared with the normal control group(P＜0.05).The relative expression level of miRNA-409-3p mRNA in the RNA control group was not different from that in the normal control group(P＞0.05).The proliferative rate of HeLa cells int the microRNA-409 mimic group was significantly lower than that in normal control and RNA control groups(P＜0.05).After cisplatin treatment,the proliferation of Hela cells was significantly inhibited in the miRNA-409-3p mimic group(P＜0.05);the expression of Fip200 protein and LC3II/LC3I ratio in the microRNA-409-3p mimic group were significantly lower than those in the normal control and RNA control groups(P＜0.05).Conclusion The low expression of microRNA-409-3p in cervical cancer tissue may be related to the occurrence and development of cervical cancer.Upregulation of microRNA-409-3p level can inhibit the proliferation of HeLa cells and increase the sensitivity of HeLa cells to cisplatin.

Objective The aim of this study was to investigate the mechanism of sanguinarine(SANG)on the inhibitory proliferation in ovarian cancer SKOV3 cells.Methods CCK-8 assay was used to detect proliferation of SKOV3 cells.Flow cytometry was used to detect the effect of SANG on apoptosis in SKOV3 cells.The spectrophotometer was used to detect the production of reactive oxygen species(ROS)by SANG.The mouse ovarian cancer xenograft model was used to detect the inhibitory effect of SANG on tumor growth.Results SANG promoted apoptosis in SKOV3 cells in a dose-and time-dependent manner.The SANG-induced apoptosis was associated with the production of ROS,Activated the c-Jun-N-terminal kinase(JNK)and nuclear factor-κB(NF-κB)signaling pathways.In mouse model of ovarian cancer xenografts,after intravenous injection of mice with SANG,SANG was significantly inhibited the growth of ovarian cancer xenografts when compared to the control group.SANG also significantly induced apoptosis in ovarian cancer xenografts.Conclusion SANG can significantly inhibit the proliferation of ovarian cancer SKOV3 cells,induce apoptosis,increase the production of ROS,and inhibit the growth of ovarian cancer.

Objective To investigate the mechanism of Mi-362 targeting Six1 inhibiting proliferation and migration of cervical cancer cells.Methods The expression levels of microRNA-362 in cervical cancer tissues and adjacent tissues were measured in 142 patients with cervical cancer in our hospital.At the same time,Hela cancer cell group,microRNA-362 mimics group and microRNA-362 inhibitor group were set up to determine the viability of cancer cells,the number of monoclonal formation of cancer cells,the apoptotic rate of cancer cells,cell cycle,the number of perforations,and the levels of microRNA-362 and Six1 in cervical cancer fluid of Hela.Results The expression level of miR-362 in cervical cancer tissue was lower than that in adjacent tissue(P＜0.05).The higher the infiltration of lymphatic vessel space,pathological stage,TNM stage,lymph node metastasis and depth of infiltration,the lower the expression rate of miR-362(P＜0.05).The OD value and survival rate in the miR-362 mimics group were lower than those in the Hela cancer cells group(P＜0.05),while the OD value and survival rate in the mir-362 inhibitor group were higher than those in the Hela cancer cells group and the miR-362 mimics group(P＜0.05).The number of clones formed in the miR-362 mimics group was lower than that in the Hela cancer cell group(P＜0.05),and the number of clones formed in the miR-362 inhibitor group was higher than that in the Hela cancer cell group and the miR-362 mimimics group(P＜0.05).The apoptotic rate of miR-362 mimics group was higher than that of Hela cancer cell group(P＜0.05),and that of miR-362 inhibitor group was lower than that of Hela cancer cell group and miR-362 mimics group(P＜0.05).The G1 phase in the miR-362 mimics group was higher than that in the Hela cancer cell group(P＜0.05),and the G1 phase in the miR-362 inhibitor group was lower than that in the Hela cancer cell group and the miR-362 mimimics group(P＜0.05).The number of cell membrane penetration in the miR-362 mimics group was lower than that in the Hela cancer group(P ＜ 0.05),and that in the miR-362 inhibitor group was higher than that in the Hela cancer group and the miR-362 mimimics group(P＜0.05).The expression level of miR-362 in the miR-362 mimics group was higher than that in the Hela cancer cell group(P＜0.05),and the expression level of miR-362 in the miR-362 inhibitor group was lower than that in the Hela cancer cell group and the miR-362 mimics group(P＜0.05).The expression level of Six1 in the miR-362 mimics group was lower than that in the Hela cancer cell group(P＜0.05),and that in the miR-362 inhibitor group was higher than that in the Hela cancer cell group and the miR-362 mimics group(P＜0.05).Conclusion miR-362 plays an important inhibition in the occurrence and development of cervical cancer,and its mechanism is related to the inhibition of proliferation,migration and invasion of cancer cells by microRNA-362 through negative regulation of Six1.

Objective The Objective of this study was to investigate the expression and function of TMEM45A(transmembrane protein 45A)in clear cell renal cell carcinoma(ccRCC).Methods The data of TMEM45A in Oncomine database were extracted by R language.The relationship between the expression level of TMEM45A and the stage or survival time of ccRCC was analyzed by GEPIA database.qRT-PCR and Western blot were used to detect the expression of TMEM45A in ccRCC tissues and renal cell carcinoma cell lines.After transfection of TMEM45A siRNA,the low expression ofTMEM45A in Caki-1 cells was confirmed by qRT-PCR and Western blot.Cell proliferation after knockdown TMEM45A was analyzed in Caki-1 cells by CCK8.The mechanism of action in the low expression of TMEM45A inhibited cell proliferation was analyzed in Caki-1 cells by qRT-PCR and Western blot.Results A total of 384 TMEM45A-related studies were collected in the Oncomine database,with 35 statistically significant differences,25 of them elevated and 10 decreased.Four studies were associated with ccRCC with a total of 115 samples.The expression of TMEM45A was significantly increased in ccRCC(P＜0.05).It was also found that the high expression of TMEM45A was closely associated with high ccRCC stage and poor prognosis(P＜0.05).When compared with the normal kidney tissues,TMEM45A mRNA was significantly increased in ccRCC tissues(P＜0.05).The expression of TMEM45A at levels of mRNA and protein in Caki-1 and 786-0 cells was higher than that in normal renal tubular epithelial HK-2 cells.After transfection with TMEM45A siRNA for 48h and 72h,the proliferation of Caki-1 cells was significantly decreased(P＜0.001).At the same time,it was found that the expression of PCNA and cyclin D1 at levels of mRNA and protein was significantly decreased(P＜0.05).Conclusion The expression of TMEM45A is elevated in ccRCC and is associated with ccRCC staging and prognosis.It may be involved in the proliferation of renal carcinoma cells by regulating PCNA and Cyclin D1.

Objective The aim of this study was to investigate the expressions of and clinical significance of F-box/WD-40 domain protein 10(FBXW10)as well as the expression of cell cycle protein cyclin E(cyclin E)in renal clear cell carcinoma.Methods Immunohistochemistry SP method was used to detect the expressions of FBXW10 and cyclin E protein in 60 cases of renal clear cell carcinoma and 20 cases of adjacent normal tissues.The relationship between the expressions of FBXW10 and cyclin E,and the clinical pathological characteristics was analyzed.Results The expression rates of FBXW10 and cyclin E protein in renal clear cell carcinoma were 40.0%,70.0%,respectively and adjacent normal tissues were 55.0% and 25.0%(P＜0.05).The expression of FBXW10 was correlated with the histologic grade of renal clear cell carcinoma(P=0.041),histologic grade(P=0.030);the expression of cyclin E was correlated with the pathological tumor stage of clear cell renal cell carcinoma(P=0.005),degree of differentiation(P=0.035),and distant metastasis(P=0.011).There was a significant correlation between the expressions of FBXW10 and cyclin E in renal clear cell carcinoma(r=0.533,P＜0.001).Conclusion FBXW10 and cyclin E may play important roles in the development of renal clear cell carcinoma.

Objective The aim of this study was to explore the expression of constitutive photomorphogenesis factor 9 signaling complex subunit 6(CSN6)in hepatocellular carcinoma(HCC),and its clinicopathological factors and prognosis.Methods The expression of CSN6 at levels of protein and mRNA in hepatocellular carcinoma and normal hepatic tissues was analyzed using public human protein Atlas database and StarBase database.The TCGA database was used to analyze the differential expression of CSN6 in patients with different tumor stages and graded of hepatocellular carcinoma.Immunohistochemistry was used to detect the expression of CSN6 protein in 106 patients with HCC and analyzed its relationship with multiple clinicopathological factors and overall survival.Results The expression of CSN6 was elevated in hepatocellular carcinoma tissues when compared to normal hepatic tissues.CSN6 was more highly expressed in patients with high pathological grades(G3 and G4)and high stages (Ⅱ and Ⅲ);patients with hepatocellular carcinoma with high expression of CSN6 had a shorter overall survival.The expression of CSN6 in hepatocellular carcinoma was associated with tumor differentiation and hepatitis B virus infection,and was an independent predictor of overall survival.Conclusion The expression of CSN6 is significantly increased in hepatocellular carcinoma.The increased expression of CSN6 in HCC tissues suggests a poor prognosis.The increased expression is associated with the malignant progression of hepatocellular carcinomaand has a potential new prognostic marker and therapeutic target.

Objective The aim of this study was to investigate the expression of MAGEA4 and EB1 proteins in lung cancer tissues and their correlation with clinicopathological features and prognosis.Methods A total of 136 patients with lung cancer in our hospital were enrolled.The expression levels of MAGEA4 and EB1 at levels of mRNA and protein were measured by real-time fluorescence reverse transcription and immunohistochemistry.The correlation between MAGEA4 and EB1 expression and clinical pathological features,and prognosis were analyzed by χ² test and Cox regression analysis.Results The expression of MAGEA4 and EB1 mRNA in lung cancer tissues was higher than those in adjacent tissues(P＜0.05).The positive rates of MAGEA4 and EB1 in lung cancer tissues were higher than those in adjacent tissues(P＜0.05).The expression of MAGEA4 and EB1 proteins in lung cancer tissues was higher than those in adjacent tissues(P＜0.05).The positive rates of MAGEA4 and EB1 proteins were not significantly correlated with age(P＞0.05),but they were related to the maximum diameter,pathological grade,TNM stage,infiltration depth,lymphatic vascular infiltration,lymph node metastasis and recurrence(P＜0.05).The 3-year survival rate and total survival time of MAGEA4 and EB1 negative group were significantly higher than those of MAGEA4 and EB1 positive group(P＜0.05).Lymphatic vascular infiltration,lymph node metastasis,MAGEA4 positive and EB positive were independent risk factors for prognosis of patients with lung cancer(P＜0.05).Conclusion The positive expression rates of MAGEA4 and EB1 proteins in lung cancer tissues are increased,and their high expression may be related to the occurrence and development of lung cancer.Lung cancer patients with negative expression of MAGEA4 and EB1 proteins can obtain better prognosis.

Objective The aim of current study was to evaluate the effect of growth differentiation factor 15(GDF-15)on predicting and monitoring the cardiotoxicity of epirubicin/cyclophosphamide-docetaxel-trastuzumab(EC-D-T)in the treatment of HER-2 positive breast cancer patients.Methods Seventy-three patients with HER-2 positive breast cancer who received EC-D-T adjuvant therapy were enrolled.Serum levels of GDF-15,cardiac troponin I(cTnl)and amino terminal brain natriuretic peptide precursor(NT-proBNP)were measured before adjuvant therapy(M0)and after adjuvant therapy at 3 months(M₃),6 months(M₆),9 months(M₉),12 months(M₁₂)and 15 months(M₁₅).At the same time,patients underwent echocardiography at various time points to assess the left ventricular ejection fraction(LVEF).The cardiotoxicity of this study was defined as:(1)LVEF level decreased by ≥10% after treatment and the absolute value of LVEF was below 53%(normal);(2)heart failure,acute coronary syndrome or severe life-threatening heart rate abnormal.Results After initiation of EC-D-T treatment,the level of LVEF gradually decreased.During the whole study,a total of 21(28.8%)patients developed cardiotoxicity.At the same time,patients with cardiotoxicity had significantly higher levels of GDF-15 at M0 and cTn1 at various time points than those without cardiotoxicity.The level of ProBNP was comparable to those without cardiotoxicity.In addition,Univariate logistic regression analysis showed that baseline GDF-15 might affect the risk of cardiotoxicity. Multivariate logistic regression analysis showed that only cTnl level was an independent predictor for the risk of cardiotoxicity, while NT-proBNP level did not predict the risk of cardiotoxicity.Conclusion The incidence of cardiotoxicity in patients with HER-2 positive breast cancer after receiving EC-D-T is high,and GDF-15 can predict and monitor the risk of cardiotoxicity.

Objective The aim of this study was to investigate the relationship between STAT1,STAT3 gene promoter CpG island methylation status and prognosis of patients with colorectal cancer(CRC)and the prognostic factors of CRC patients.Methods The cohort study was conducted to biosamples and follow up 239 patients with primary colorectal cancer pathologically diagnosed in Cancer Hospital of Harbin Medical University(Tumor Hospital).The methylation status of STAT1,STAT3 gene promoter CpG island was analyzed by methylation specific high-resolution melting curve(MS-HRM).Results The survival rates of 239 patients with colorectal cancer at 1 year,3 years and 5 years were 94.90%,86.00% and 67.20%,respectively.The methylation status of STAT1 and STAT3 genes was not associated with postoperative survival in colorectal cancer patients(STAT1:HR=0.85,95% CI:0.55~1.30,P=0.44;STAT3:HR=0.75,95% CI:0.36~1.58,P=0.45).Dukes stage(HR=1.31,95% CI:1.14~1.51,P＜0.01)and intraoperative intestinal stapler use(HR=1.98,95% CI:1.25~3.14,P＜0.01)were important factors affecting the prognosis of colorectal cancer patients.The risk of death in patients with stage D and Dukes was significantly higher than that in stages A and B(HR=1.31,95% CI:1.14~1.51,P＜0.01).Intestinal anastomosis was used during operation.The patient′s prognosis was better than that of patients without an intestinal stapler.However,gender,age,tumor location,gross tumor type,histological classification and postoperative chemotherapy were not associated with the prognosis of colorectal cancer.Conclusion Dukes stage is an independent factor affecting the prognosis of colorectal cancer.The prognosis of patients with intestinal stapler is better than that of non-users.The methylation status of STAT1 and STAT3 in peripheral blood is not a biomarkers for the prognosis of patients with colorectal cancer.

Objective The aim of this study was to evaluate the clinical efficacy and hematologic toxicity of docetaxel in the treatment of metastatic breast cancer patients in different age groups.Methods The clinical data of three groups of single-agent docetaxel in the treatment of metastatic breast cancer patients were retrospectively analyzed.The clinical efficacy of docetaxel was analyzed statistically.Results The Objective response rate(ORR)and clinical beneficial rate(CBR)in the group of age＜=45 year group were 30.6% and 38.7%,and the ORR and CBR in the 46~59 age were 27.5% and 35.7%,while ORR and CBR in the ≥60 age group were 20.0% and 27.5%.The median progress free survival(PFS)in three groups was 6.0(2.9~9.1)months,5.0(2.9~7.1)months and 4.0(3.3~4.7)months,respectively.There was no statistical difference in three different age groups(P=0.477,0.492 and 0.460,respectively).Cox regression analysis showed that the docetaxel rescue treatment of PFS had not associated with clinical stage,pathological type,ipsilateral axillary lymph node metastasis,disease free survival,unit dose of body surface area dose,number of rescue treatment lines,number of recurrence and metastasis,etc.in three different age groups of patients with metastatic breast cancer.Hematological toxicity was mainly manifested by a decrease in white blood cells and neutrophils,and docetaxel has less effect on hemoglobin and platelets.Conclusion The clinical efficacy and hematologic toxicity of docetaxel have a certain degree of correlation with ages.With the increase of age,the clinical curative effect is reduced and the blood toxicity is aggravated.

N6-methyladenine(m⁶A),a major RNA methylation modification,affects the development and progression of human cancer through a variety of mechanisms.The m⁶A modification also affects multiple aspects of RNA metabolism,ranging from RNA processing,nuclear export,RNA translation to decay.In this review,the basic concepts of m⁶A methylation,regulation of m⁶A methyltransferase complex and m⁶A demethylases in several cancers and some m⁶A performed the biological function of the modification as m⁶A-binding proteins are introduced.In addition,the dual role of m⁶A methylation and its potential in clinical application are summarized in this review.

There is a high risk of myelosuppression in pelvic malignant tumors during concurrent chemoradiotherapy.The dose-volume relationship of pelvic exposed bone marrow(bone)is related to acute hematological toxicity during radiotherapy and chemotherapy,but lacks recognized parameters in this respect.The hematopoietic capacity of the bone marrow(bone)in different parts of the pelvic cavity is heterogeneous,and the pelvic bone marrow near the central axis has the strongest hematopoietic capacity,namely functional bone marrow.The relationship between dose-volume parameters of pelvic functional bone marrow and acute hematologic toxicity during chemoradiotherapy of pelvic malignant tumors may be the future direction.

Long non-coding RNAs(lncRNAs)is a functional RNA molecule with a sequence length greater than 200 nucleotides that is not translated into a protein.LncRNA is of great value in the clinical application of malignant tumors and is closely related to the diagnosis,prevention,treatment and prognosis of tumors.CCAT1(human colon cancer associated transcript-1)can play a carcinogenic role by promoting cell proliferation,invasion and migration.CCAT1 can be used as a biomarker for tumor prognosis.In this review,the research progress on the relationship between CCAT1 and digestive system malignant tumors is reviewed in recent years,the current status and prospects of malignant tumor treatment by CCAT1 are discussed.

The treatment of gastric cancer is limited and the prognosis is poor.Tumor immunotherapy has been an effective new treatment for cancer in addition to surgery,chemotherapy,radiotherapy and targeted therapy because of its remarkable survival benefit.As one of the methods of tumor immunotherapy,immunological checkpoint inhibitors have been approved for the treatment of various tumors,suggesting that the era of gastric cancer immunotherapy has arrived.This article describes the mechanism of action and related research progress of immunological checkpoint inhibitors in immunotherapy.

Aberrant crypt foci(ACF)is highly similar to colorectal cancer(CRC)in phenotypic and molecular changes,and is positively correlated with the risk of CRC.It is considered as precancerous lesion of CRC.Many compounds have therapeutic effects on ACF,inhibiting their occurrence and malignant transformation,which can be regarded as a preventive effect on CRC.In this paper,we will review the treatment of ACF by various compounds in different ways in recent years.

About 15% to 20% of patients with small cell lung cancer(SCLC)have brain metastases at the time of initial diagnosis,and more than 80% of patients eventually develop brain metastases.Whole brain radiotherapy(WBRT)is the standard treatment for brain metastases in lung cancer.Whole brain prophylactic irradiation(PCI)is an effective treatment for preventing brain metastases in SCLC.With the improvement of treatment technology and the standard of treatment,the survival of SCLC patients is prolonged.The use of spiral tomography(TOMO)technology for hippocampal-protected WBRT in PCI or brain metastasis can reduce neurocognitive impairment and improve the life quality of patient.