Objective To study the role of expressions of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) on the lymphangio-genesis and prognosis in gastric cancer. Methods The tissue microarray technology was used to detect the expressions of VEGF-C, VEGFR-3 and LYVE-1 in 125 gastric cancer specimens, 96 adjacent normal tissues and 20 benign gastric lesion samples. The lymphatic vessel density (LVD) marked by Podoplanin was detected as well. Results The positive rates of VEGF-C, VEGFR-3 and LYVE-1 in gastric cancer tissues were 62.4%, 56.0%and 58.4%, which were significantly higher than those in adjacent normal tissues (10.4%,12.5%and 9.4%) and benign gastric lesion tissues (20%, 30%and 25%, P<0.05). The LVD score was significantly higher in gastric intra-tumoral and peri-tumoral samples (2.98±0.81 and 4.22±1.09) than that in adjacent normal tissues or benign gastric lesion samples (1.82±0.63 or 0.89±0.45, P<0.01). The LVD score was significantly higher in peri-tumoral samples than that of intra-tumoral samples (P<0.01). There was a positive relationship between expression levels of VEGF-C,VEGFR-3 and LYVE-1 with LVD (P<0.05). The positive expressions of the three indexes were the risk factors of lymph node metastasis and distant metastasis (P<0.05). There was a significantly longer 5-year survival rate in patients with negative expression of the three indexes (P<0.05). Conclusion VEGF-C, VEGFR-3 and LYVE-1 proteins were positively highly expressed in gastric cancer tissues, which were risk factors affecting the progno-sis of gastric cancer. The expression levels of the three indexes can be used to predict the prognosis and lymphangiogenesis of gastric cancer.

Objective To evaluate the availability and sensitivity of MR whole body diffusion weighted imaging (DWI) in searching primary tumors in patients with metastases.Methods Thirty-four patients with symptoms of metastases and unknown primary leasions were scanned by whole body DWI.All the metastases cases were diagnosed by CT,single photon emission computed tomography(SPECT) or MRL For the cases of suspected primary tumors,apparent diffusion coefficient (ADC) values of the primary and metastatic lesions were measured respectively.For the cases with primary lung cancers and metastases proved by pathology of biopsy or surgical specimens,statistics analysis of ADC values of primary and metastatic lesions was performed with paired samples t-test.The detection rate and sensitivity of this technique for screening primary tumors were evaluated.Results By whole body DWI,24 cases were found with suspected primary lesions,in which 23 cases were proved primary tumors,and 1 case was proved benign lesion.Ten cases were not identified with primary lesions on whole body DWI,but in which 2 cases were proved primary malignant tumor by biopsy later,and the other 8 cases remained unknown within follow-up of half a year to one year.For the 14 definite cases of lung cancers,the average ADC values of primary and metastatic lesions was (1.24±0.18)×10-3 and(1.16±0.27)×10-3mm2/s,respectively (t=1.28,P>0.05).The detection rate and sensitivity of whole body DWI for searching primary tumors was 67.6% (23/34) and 92.0% (23/25),respectively.Conclusion The sensitivity of whole body DWI for searching primary tumors is relatively high,and it can be used to search primary tumors in patients with metastases.

Objective To detect gene polymorphisms of ABCB1/MDR1 in breast cancer and to analyze the association between ABCB1 gene polymorphisms and curative effect of paclitaxel-based chemotherapy in breast cancer.Methods Genotyping of ABCB1exon12 (1236),exon21 (2677)and exon26 (3435)was determined by polymerase chain reaction (PCR)-high resolution melting (HRM)method in 146 cases of female stage IV breast cancer to explore the relationship between the efficacy of chemotherapy in breast cancer patients with paclitaxel chemotherapy.Results In 146 patients with stage IV breast cancer,C1236T CC genotype accounted for 15.86%, CT genotype 44.83%,TT genotype 44.83%,G2677T/A GG genotype 16.67%,GT genotype 45.83%,GA genotype 6.25%,TT genotype 28.47%,AT genotype 2.78%,C3435 CC genotype 22.22%,CT genotype 56.25%,and TT genotype 21.53%.ABCB1 gene polymorphisms did not significantly differ between patients of Hui and Han Nationalities (P>0 .0 5 ).Hardy-Weinberg genetic equilibrium testing showed that polymorphisms of C1236T,G2677T/A and C3435T had group representation (P>0.05).In 146 stage IV breast cancer patients who had received paclitaxel-based chemotherapy,CT/TT genotype of C3435T site had a better response rate (74.11%) (χ2 =12.556,P<0.05),better curative effect than CC genotype (OR=4.183,95% CI 1.838 -9.521,P<0.05),T allele carriers more efficient than C allele carriers with paclitaxel-based chemotherapy (χ2 =8 .5 0 7 ,P<0 .0 5 ). Conclusion Detection of ABCB1 C3435T gene polymorphisms has a significantly clinical value in predicting the efficacy of taxanes chemotherapy in breast cancer patients.

Objective To examine the effects of genetic polymorphisms in GSTM1, GSTT1 and GSTP1 (rs1695) genes on hematologic toxicities of breast cancer patients receiving Anthracycline/Paclitaxel- based chemotherapy. Methods Multiply PCR technique and High Resolution Melting method were used to examine these 3 genes polymorphsim in female breast cancers (n=252). Results The GSTP1(rs1695) AG/GG genotype was a risk factor forⅢ-Ⅳdegree of neu-trophil toxicity when patients received Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy (OR=6.111, 95%CI 1.526-24.469, P<0.05 and OR=9.257, 95%CI 2.903-29.522, P<0.01). There were no statistic differ-ence onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-) patients after they receiced Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy( P>0.05);There was no statistic difference onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-), GSTP1AA and GSTP1AG/GG patients after they receiced Anthracycline-based chemotherapy (P>0.05). Conclusion The genetic polymorphisms in GSTP1(rs1695) can be used as a gene marker for forecasting the chemotherapy, inducing neutrope-nia toxicities in breast cancer patients receiving Paclitaxel-based chemotherapy.

AIM:To establish the quality standard of Biling Weitong Granules (Rhizoma Corydalis, Radix et Rhizoma Rhei, Rhizoma Coptidis, etc.). METHODS: Rhizoma Corydalis, Radix et Rhizoma Rhei, Rhizoma Coptidis, Fructus Evodiae, Fructus Litseae were identified by TLC. The content of berberine hydrochloride was determined by RP-HPLC C_ 18 column(ODS, 250 mm?4.6 mm, 5 ?m) was used as chromatographic column. The acetonitrile-0.02 mol/L potassium dihydrogen phosphate (Adjust with phosphoric acid to a pH of 3.0) (25∶75) was used as mobile phase. The detection wavelength was at 347 nm. The flow rate was kept to 1.0 mL/min. RESULTS: The TLC sports developed were fairly clear, and the blank test showed no interference. The linearity of berberine hydrochloride was good in the range of 0.041 32-0.619 8 ?g(r= 0.999 9 ). The average recovery of berberine hydrochloride was 101.93%, RSD=0.60%(n=6). CONCLUSION: The method is simple, reliable, accurate and can be applied as the quantity control method of Biling Weitong Granules.

Objective:To investigate the protective effects and possible mechanisms of cortex phellodendri water extract and etha -nol extract on the myocardial injury induced by pituitrin and isoproterenol hydrochloride in rats .Methods:SD rats as the experimental animals were randomly divided into the normal control group , model group , compound Danshen tablets group , phellodendron water ex-tract group and phellodendron ethanol extract group .Pituitrin and isopropyl adrenaline hydrochloride were used to establish the myocar-dial injury model in rats.The serum CK, LDH activity, myocardial tissue SOD activity and MDA content were detected and compared . Results:Compared with those in the normal control group , the serum LDH activity , CK activity and MDA content were significantly in-creased , and the SOD activity in cardiac muscle and myocardial tissue was significantly decreased in the pituitrin -established myocardi-al injury model group (P<0.01).In the isopropyl adrenaline hydrochloride-established myocardial injury model group , the MDA con-tent in myocardial tissue was obviously increased , and the SOD activity in myocardial tissue was decreased obviously (P<0.01).The serum LDH activity, CK activity and MDA content were significantly decreased , and the SOD activity in cardiac muscle and myocardial tissue was increased significantly in all drug-taken groups when compared with those in the pituitrin-established myocardial injury model group, and the differences were statistically significant (P<0.05 or P<0.01).The MDA content in myocardial tissue was significant-ly reduced , and the SOD activity was increased significantly in all drug-taken groups when compared with those in the isopropyl adrena-line hydrochloride-established myocardial injury model group , and the differences were statistically significant (P<0.05 or P<0.01). Conclusion:Cortex phellodendri extract has certain protective effect on myocardial injury induced by pituitrin and isopropyl adrenaline hydrochloride in rats .

ABSTRACT:Objective To observe the influence of saikosaponin-d (SSd)on the proliferation and the function of autophagy of human hepatocellular carcinoma (HCC)cell line SMMC-7721 to explore the possible mechanisms. Methods SMMC-7721 was cultured invitro and then treated with SSd of various concentrations (5.0,7.5,10.0, 12.5,15.0 and 17.5 mg/L)for 24,48 and 72 h.We used MTT to detect cell proliferation,selected the optimal concentration and time,and detected the expressions of BECN1 at mRNA and protein levels by PCR and Western blot.Results The inhibition rate of the proliferation of SMMC-7721 cell line increased with the increase of the concentration of SSd,and the highest inhibition rate (60%)appeared when the concentration reached 12.5 mg/L. The expression of BECN1 in the group with SSd was obviously higher than that in the control group (P<0.05). 3-MA decreased not only the expressions of BECN1 at mRNA and protein levels but also the expression of BECN1 when used in conjunction with SSd.Conclusion The inhibiting function of SSd on SMMC-7721 presents a dependency between drug concentration and function time,basically in line with the drug dose-effect relationship. SSd induces the occurrence of autophagic cell death through up-regulating the expression of BECN1 ,thus inhibiting the proliferation of SMMC-7 7 2 1 .

Objective To investigate the expression of DNA methyltransferase 3b (DNMT3B) in hepatocellular carcinoma (HCC) and its effect and mechanism on the proliferation,invasion and migration of HCC cells.Methods The expression of DNMT3B gene was detected by qRT-PCR in 46 cases of HCC tissues and corresponding adjacent tissues;the results and clinical pathological parameters were analyzed.SiRNA targeting DNMT3B was transfected into MHCC97-H cells by RNA interference (RNAi) technique.The mRNA and protein expression levels of related genes were detected by qRT-PCR and Western blot.The cell proliferation was measured by MTT assay,and the invasion and migration abilities were measured by Transwell assay.Results In 46 HCC patients,the expression of DNMT3B (73.91％) was significantly higher in HCC than in adjacent normal tissue.The high expression of DNMT3B gene was associated with histological type and tumor size of HCC (all P＜0.05).Inhibition of DNMT3B gene expression decreased proliferation,invasion and migration of MHCC97-H cells.Interference with DNMT3B gene increased the expressions of tumor suppressor genes RASSFA1,APC and MTSS1 at mRNA and protein levels.Conclusion DNMT3B is associated with the progression of HCC.It may inhibit the proliferation,invasion and migration of HCC cells by regulating the methylation of downstream tumor suppressor gene.

Objective:To explore the expression of polypyrimidine tract-binding protein 1 (PTBP1) in gastric cancer (GC) tissues and GC cell lines, and the role of PTBP1 in the proliferation and metastasis of GC cells.Methods:From January to June in 2019 at The First Affiliated Hospital of Xi′an Jiaotong University, the cancer tissues and corresponding para-cancer tissues of GC patients underwent surgical resection were collected. The Kaplan-Meier Plotter database was used to analyze the survival of GC patients. The expression of PTBP1 was down-regulated by transfecting small interfering RNA (siRNA) in human GC cell lines SGC7901 and AGS with relatively high expression of PTBP1. The cells were divided into blank control group, negative control group, and PTBP1 knockdown group. The expression of PTBP1 at mRNA and protein level were detected by real-time fluorescence quantification polymerase chain reaction (RT-qPCR) and Western blotting. At 24, 48, 72 and 96-hour after transfection, the effect of PTBP1 on the proliferation of GC cells was observed by 3-(4, 5 dimethylthiazol)-2, 5 diphenyltetrazolium bromide (MTT) experiment. The changes of invasion and migration of GC cells after down-regulation of PTBP1 were detected by transwell assay. The expression changes of epithelial-mesenchymal transition (EMT) markers E-cadherin, N-cadherin and vimentin after down-regulation of PTBP1 in GC cells were determined by Western blotting. Indenpendent samples t test, analysis of variance and rank sum test were used for statistical analysis. Results:The Kaplan-Meier Plotter prognostic analysis showed that the overall survival of GC patients with high PTBP1 expression was shorter than that of GC patients with low PTBP1 expression (9.2 months, 6.2 months to 17.2 months vs. 19.0 months, 14.5 months to 28.4 months), and the difference was statistically significant ( Z=5.31, P<0.05). The results of RT-qPCR showed that in GC cell lines SGC7901 and AGS, the expression of PTBP1 at mRNA level of PTBP1 knockdown group was lower than that of blank control group and negative control group (SGC7901: 0.78±0.11 vs.3.10±0.19 and 2.99±0.23; AGS: 0.80±0.09 vs. 3.55±0.24 and 3.50±0.18), and the differences were statistically significant ( tSGC7901=10.57 and 8.08, tAGS=10.91 and 13.42; all P<0.01). The results of Western blotting indicated that in GC cell lines SGC7901 and AGS, the expression of PTBP1 at protein level of PTBP1 knockdown group was lower than those of blank control group and negative control group (SGC7901: 0.38±0.04 vs. 1.42±0.05 and 1.35±0.09; AGS: 0.17±0.02 vs. 1.52±0.08 and 1.38±0.45), and the differences were statistically significant ( tSGC7901=15.94 and 10.57, tAGS=16.60 and 20.80; all P<0.01). The results of MTT showed that at 48, 72 and 96-hour after transfection the absorbance values of PTBP1 knockdown group decreased by 0.25±0.01, 0.38±0.02, and 0.84±0.04 as compared with those of negative control group, and the decrease was the most significant at 96-hour after transfection, and the differences were statistically significant ( t=10.21、14.32, both P<0.01). The results of transwell experiment demonstrated that the number of invasion and migration cells of PTBP1 knockdown group were both less than that of the blank control group and the negative control group (SGC7901: 42.00±5.91 vs. 116.40±10.23 and 114.40±10.43; 39.60±6.77 vs. 125.80±11.51 and 122.40±5.90; AGS: 40.20±7.25 vs. 115.60±14.63 and 117.40±9.12; 36.00±5.20 vs. 122.40±12.10 and 125.40±12.74), and the differences were statistically significant ( tSGC7901=14.07, 13.50, 14.43 and 20.62; tAGS=10.27, 14.75, 14.68 and 16.76; all P<0.01). The results of Western blotting showed that the expression of E-cadherin of PTBP1 knockdown group was higher than that of the blank control group and the negative control group (SGC7901: 1.42±0.05 vs. 0.53±0.05 and 0.57±0.03; AGS: 1.34±0.04 vs. 0.54±0.03 and 0.61±0.01), however the expression levels of N-cadherin and vimentin were both lower than those of the blank control group and the negative control group (SGC7901: 0.50±0.03 vs. 1.64±0.05 and 1.46±0.07; 0.32±0.07 vs. 1.42±0.07 and 1.33±0.07; AGS: 0.37±0.06 vs. 1.47±0.04 and 1.36±0.04; 0.41±0.04 vs. 1.53±0.06 and 1.37±0.04), and the differences were statistically significant ( tSGC7901=11.63, 13.19, 18.83, 11.68, 11.43 and 10.43; tAGS= 15.02, 16.23, 14.67, 12.97, 14.45 and 17.18; all P<0.01). Conclusions:The expression levels of PTBP1 increase in GC tissues and cells, which may be involved in regulating the proliferation, metastasis and EMT of GC cells.

OBJECTIVETo study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze their relationship with the occurrence, recurrence, metastasis, angiogenesis and prognosis of colorectal cancer.

METHODSImmunohistochemistry with SP method was used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens.

RESULTSThe positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates of two or three coexpression were significantly higher than that of a single expression in the cancer tissues (61.02% vs 15.25%). The microvascular density (MVD) of colorectal cancer tissues was 31.43∓10.50, significantly higher than that of the adjacent normal tissues (10.61∓3.76) and benign colorectal lesions (16.89∓3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences between cases with tumor recurrence/metastasis and those without 5 years after radical mastectomy, and were all positively correlated with the 5-year survival rates (P<0.05).

CONCLUSIONAng-2, Tie-2 and VEGFR-2 are involved in the development, invasion, metastasis, and prognosis of colorectal cancer, and play important roles in the angiogenesis of the tumors.

Adolescent ; Adult ; Aged ; Angiopoietin-2 ; metabolism ; Colorectal Neoplasms ; blood supply ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; Prognosis ; Receptor, TIE-2 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Young Adult