最新刊期
卷 27 ， 期 11 ， 2017
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- 摘要：Background and purpose: Redifferentiation therapy with MAPK inhibitor is a novel strategy for radioiodine-refractory differentiated thyroid cancer, but its efficacy is relatively low. Histone deacetylase inhibitor (HDACI) is another kind of redifferetiation drug, given histone deacetylation at the sodium/iodide symporter (NIS) promoter by histone deacetylase (HDAC) as a mechanism, combined therapy using HDACI and BRAF/MEK inhibitor may produce better effect. In the present study, we assessed whether combining HDACI with BRAF/MEK inhibitor suppressing both BRAF/MEK and HDAC could more effectively induce thyroid gene expression and radioiodine uptake in thyroid cancer cells. Methods: We tested iodine and glucose handling gene expression and radioiodine uptake in BCPAP, K1, BHP 2-7 cells treated with dabrafenib/selumetinib and panobinostat alone or in combination using (real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR), Western blot, immunofluorescence, flow cytometry, radionuclide uptake/efflux assay and in vitro clonogenic assay. Results: Dabrafenib/selumetinib induced modest expression of thyroid genes and radioiodine uptake and suppressed GLUT1 expression in BCPAP and K1 cells, panobinostat showed redifferetiation effect in all the cells. Dabrafenib/selumetinib and panobinostat showed synergistic effect on redifferentiation in BCPAP and K1 cells. Conclusion: Simultaneously suppressing BRAF/MEK and HDAC induced more robust expression of thyroid genes and radioiodine uptake in thyroid cancer cells harboring BRAFV600E compared with suppressing BRAF/MEK or HDAC alone, which warrants further investigation in animal and clinical trials.关键词：Thyroid cancer;Redifferentiation therapy;MAPK inhibitor;Histone deacetylase inhibitor;Sodium-iodide symporter2|1966|0更新时间：2025-12-31
- 摘要：Background and purpose: LASP1 is a novel actin-binding protein and involved in the process of cytoskeleton reorganization and cell migration. Expression of LASP1 is significantly up-regulated in several malignant tumors and is closely related to the tumor proliferation, invasion and metastasis. However, the specific mechanism of LASP1 is not clear in gastric carcinogenesis. This study aimed to detect the effect and mechanism of LASP1 in the proliferation and invasion of gastric cancer cells. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were employed to determine the expression of LASP1 in gastric cancer cell lines, as well as human normal gastric epithelial cell line GES-1. RNA interference (RNAi) was used to silence the expression of LASP1 in gastric cancer cell BGC823. RTFQ-PCR and Western blot were used to analyze the expression of LASP1 after siRNA transfection. In vitro proliferation, migration and invasion assay were performed to detect the effect of LASP1 on BGC823 cells. F-actin polymerization assay was used to detect F-actin recognition ability in cells. Western blot was used to analyze phosphorylation of Akt. Results: Overexpression of LASP1 was detected in human gastric cancer BGC823 cells. Down-regulated expression of LASP1 at both mRNA and protein level was detected after siRNA transfection. Cell proliferation assay showed that the growth rate was significantly reduced in RNAi group (P<0.05). In transwell assay, the cell migration and invasion were significantly decreased (P<0.05). F-actin content was reduced compared with the control group (P<0.05). The phosphorylation of Akt was significantly reduced after siRNA transfection. Conclusion: LASP1 was highly expressed in gastric cancer cells. Down-regulation of LASP1 suppressed the capacities of proliferation, migration and invasion of human gastric cancer BGC823 cells in vitro. LASP1 can induce migration and invasion of gastric cancer through regulation of F-actin polymerization and Akt phosphorylation.关键词：LASP1;Human gastric cancer BGC823 cells;Proliferation;Migration and invasion2|2328|0更新时间：2025-12-31
- 摘要：Background and purpose: In colorectal cancer tissues, little thymidine phosphorylase (TP) expression was detected. In this study, the inhibitory effects of 5’-deoxy-5-fluorouridine (5’-DFUR) and 5-fluorouracil (5-FU) combined with interferon-α2a (INF-α2a) on nude mice transplanted with colorectal cancer cell line LS174T carrying TP cDNA were investigated. Methods: TP cDNA was transfected into human colorectal cancer cell line LS174T with lentiviral vector, and the LS174T cell line with high TP expression was obtained. Then 96 BALB/c nude mice were randomly divided into two groups. Wild LS174T and TP-transfected LS174T (LS174T-TP) cells were inoculated hypodermically into the nude mice back respectively to obtain the colorectal cancer graft models. Two days later, each group was randomly divided into 6 groups again, and different drug interventions were performed continuously for 5 days with normal saline, INF-α2a, 5-FU, 5-FU+INF-α2a, 5’-DFUR and 5’-DFUR+INF-α2a, respectively. All the nude mice were executed after 2 weeks, and tumor tissues were dissected and weighed. The tumor tissue specimens were immunohistochemically stained using the mouse anti-human CD34, VEGF and PDECGF monoclonal antibodies. And then the positive cells and microvessels were quantified respectively. Results: In all of the nude mice transplanted with wild LS174T, the tumor weights of those nude mice injected with antitumor drugs (group 3-6) were significantly lower compared with the control (normal saline), and their tumor inhibition rates were 48%, 27%, 48% and 57% (P<0.05), respectively. Also the inhibition rates of those mice injected with 5’-DFUR, 5’-DFUR+INF-α2a were 48% and 57%, respectively (P<0.05). The inhibition rates of the mice injected with 5-FU+INF-α2a and 5'-DFUR+INF-α2a were 27% and 57%, respectively (P<0.05). In LS174T-TP-transplanted nude mice, the tumor inhibition rates of the mice injected with 5’-DFUR, 5’-DFUR+INF-α2a were 27% and 48%, respectively (P<0.05). However, there was no efficacious antitumor effect on the mice injected with 5-FU and 5-FU+INF-α2a. Immunohistochemical staining showed that in tumor tissues of the mice transplanted with wild LS174T, TP expression was negative and the number of microvessels was significantly less than that in TPtransfected tissues (P<0.05), in which the TP expression was also significantly positive. Conclusion: After colorectal cancer cell line LS174T was transfected with TP cDNA, the TP expression in tumor graft tissues of nude mice was significantly higher than in tumor tissues of those transplanted with wild LS174T. The antitumor effect of 5’-DFUR was significantly enhanced on the nude mice transplanted with LS174T carrying TP cDNA, and it could be futher powered by combination with INF-α2a. However, the antitumor effect of 5-FU, even combined with INF-α2a, was not increased on these nude mouse models.关键词：Colorectal cancer;LS174T;Thymidine phosphorylasegene;5’-deoxy-5-fluorouridine;Interferon-α2a2|1612|0更新时间：2025-12-31
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BRD4 induces proliferation, invasion and migration of thyroid cancer cells via SHH signaling pathway
摘要：Background and purpose: Thyroid cancer is the endocrine malignant tumor with the highest incidence. Although comprehensive treatment has gotten considerable effect, some patients have low iodine uptake and poor 131I therapeutic effect in the subsequent treatment which causes recurrence and distant metastasis. Recent studies have found that double bromodomain-containing protein 4 (BRD4) plays a key role in promoting the progression of some malignant tumors. Therefore, we aimed to investigate the effect of BRD4 in papillary thyroid cancer (PTC), and search for the specific target of thyroid cancer. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to examine the BRD4 expression in PTC tissue and para-cancerous tissue. PTC cell line TPC-1 was transfected with the siBRD4. And then the silence efficiency was examined by Western blot. The effects of BRD4 on cell viability, proliferation, migration and invasion were examined by MTT assay, colony formation assay and transwell assay. Besides, Western blot and RTFQ-PCR were used to examine the expression of sodium iodide symporter (NIS) and the downstream gene SHH and GLI1 of SHH signaling pathway. Results: BRD4 was overexpressed in PTC tissue (P<0.05). In vitro experiment showed that the viability, proliferation, invasion and migration of BRD4-silencing cells were decreased. Besides, the mRNA and protein expression levels of NIS were up-regulated while the downstream gene of SHH signaling pathway SHH and GLI1 were down-regulated (P<0.05). Conclusion: BRD4 would promote the invasion and migration of papillary thyroid cancer cells via up-regulating the genes of SHH signaling pathway. Silencing BRD4 can promote the expression of NIS. BRD4 may be a new target for the treatment of thyroid cancer.关键词：Thyroid cancer;Double bromodomain-containing protein 4;SHH signaling pathway;Sodium iodide symporter gene2|2355|0更新时间：2025-12-31 - 摘要：Background and purpose: Aspirin (one of the nonsteroidal anti-inflammatory drugs) is effective in the prevention and treatment of colon cancer. And recently, it has been indicated that regulating colon cancer stem cells might be the underlying mechanism. When colon cancer stem cells become mature, colon cancer will not progress, and even subside. Therefore, this study aimed to explore the effects of aspirin on differentiation in human colon cancer cell line HT-29. Methods: The inhibitory effects of different concentrations of aspirin on HT-29 cells were detected by living cell counting kit CCK-8, and the IC50 was calculated. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the mRNA expressions of intestinal differentiation markers [mucin 2 (MUC2), trefoil factor 3 (TFF3) lysozyme and sucrase-isomaltase] after aspirin IC50 intervention for 24, 48 and 72 h. Immunocytochemistry was used to detect the MUC2 protein expression. And Western blot was used to detect the protein expressions of lysozyme and sucrase-isomaltase. Results: Aspirin inhibited the proliferation of HT-29 cells significantly in a time- and dose-dependent manner. RTFQ-PCR and Western blot showed that the mRNA expressions of goblet cell markers (MUC2 and TFF3) were increased (P<0.05), and the mRNA and protein expressions of Paneth cell marker (lysozyme) and absorptive cell marker (sucrase-isomaltase) were decreased (P<0.05), compared with the control group, after aspirin intervention for 48 and 72 h. Immunocytochemistry showed that the MUC2 protein expression was increased (P<0.05) compared with the control group after aspirin intervention for 48 h. Conclusion: Nonsteroidal anti-inflammatory drug aspirin can affect the expressions of intestinal differentiation markers in human colon cancer HT-29 cells, and may lead to their differentiation into the phenotype of goblet cell.关键词：Aspirin;Colon cancer;Mucin 2;Trefoil factor 3;Sucrase-isomaltase;Lysozyme2|3221|0更新时间：2025-12-31
- 摘要：Background and purpose: It has been demonstrated that decoy receptor 3 (DcR3) is overexpressed in pancreatic cancer, and DcR3 correlates with the expression of FasL, which may contribute to chemotherapy resistance in pancreatic cancer. The purpose of this study was to investigate the effect of RNA interference silencing DcR3 gene on chemosensitivity of human pancreatic cancer cells and its possible mechanism. Methods: A stable expression plasmid with DcR3-siRNA sequence was constructed and transfected into human pancreatic cancer cell line AsPC-1 by LipofectamineTM2000. The DcR3-expressing pancreatic cancer cells with stable and low expression were selected. The protein expression of DcR3 in AsPC-1 cells was detected by ELISA and Western blot. MTT assay was used to detect the sensitivity of each group of AsPC-1 cells to gemcitabine. Flow cytometry was used to detect the apoptosis of AsPC-1 cells after treatment with gemcitabine. The expressions of FasL, Caspase-8, Caspase-3 and mRNA in AsPC-1 cells were detected by Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). Results: The expression of DcR3 protein in AsPC-1 cells was significantly lower than those in the other control groups. The sensitivity of AsPC-1 cells to gemcitabine was significantly increased after transfection with DcR3- siRNA compared with control and mock cell lines. Transfection of DcR3-siRNA significantly increased the apoptosis of AsPC-1 cells induced by chemotherapeutic drugs. The expression of FasL, Caspase-8 and Caspase-3 protein and mRNA were up-regulated after transfection with DcR3-siRNA. Conclusion: RNA interference silencing DcR3 gene can activate FasL/Caspase apoptosis pathway, promote tumor cell apoptosis and increase the sensitivity of human pancreatic cancer AsPC-1 cells to gemcitabine.关键词：Decoy receptor 3;RNA interference;Pancreatic cancer;Apoptosis;Chemosensitivity2|1879|0更新时间：2025-12-31
- 摘要：Background and purpose: Glutathione S-transferase P1 (GSTP1) protects cells from DNA damage and cancer cell formation. Inhibition of GSTP1 activity could increase susceptibility to DNA damage and increase the risk of cancer occurrence, which was associated with cancer. This study aimed investigate the relationship between GSTPl gene methylation and clinical pathological features of prostate cancer. Methods: Forty-six patients with prostate cancer who were hospitalized in Hainan Provincial Hospital of Traditional Chinese Medicine and Haikou People’s Hospital from Apr. 2015 to Dec. 2016 were enrolled in this study. The expression level of GSTPl mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The methylation level of CpG island in GSTP1 gene promoter region was detected by methylation-specific polymerase chain reaction (MSP), then its associations with the gender, age, tumor TNM staging and other clinical data were analyzed. Results: The expression of GSTP1 mRNA in prostate cancer tissues was lower than that in para-cancerous tissues (P<0.01), and the decrease of GSTP1 mRNA was negatively correlated with GSTPl methylation (P<0.05). The positive rates of methylation in prostate cancer and para-cancerous tissues were 66.0% and 23.5%, respectively, and the difference was statistically significant (P<0.05). The promoter methylation frequency of GSTP1 gene was significantly correlated with different tumor staging (r=073, P<0.05). However, compared with other clinical trials, there was no significant difference (P>0.05). Conclusion: GSTP1 gene promoter methylation may cause low expression of GSTP1 gene, which is closely related to the pathogenesis of prostate cancer. Monitoring GSTP1 gene promoter methylation is expected to be a new method for the detection and diagnosis of prostate cancer.关键词：Prostate cancer;Glutathione S-transferase P1;Methylation;Correlation2|2299|0更新时间：2025-12-31
- 摘要：Background and purpose: Breast cancer is one of the most serious malignant tumors that threaten women’s life. The incidence of breast cancer and the difference of HER-2 gene expression among Chinese Han and other ethnic minorities have become the focus of scholars’ attention. This study aimed to analyze the ethnic differences of HER-2 gene expression in breast cancer in Guizhou province, to evaluate the clinical efficacy of trastuzumab molecular-targeted therapy and to explore the influence of various clinical factors on the prognosis of patients with breast cancer in Guizhou province. Methods: In the study, we retrospectively analyzed the clinical data of 720 patients with breast cancer who were treated in the Cancer Hospital of Guizhou Medical University from Jan. 2007 to Dec. 2013. The Kaplan-Meier method in SPSS 17.0 was used to study the survival analysis including disease-free survival (DFS) and overall survival (OS). Then the log-rank test was used to compare groups. Cox regression model was used to analyze the independent prognostic factors of breast cancer. Results: There were 520 cases (72.2%) with HER-2 negative expression and 200 cases (27.8%) with positive expression in the group of 720 patients. Among 200 HER-2-positive breast cancer patients, 177 patients (177/645, 27.4%) were the Han ethnicity and 23 patients (23/75, 30.7%) are the ethnic minorities. Then 37 patients were treated by anti-HER-2 therapy (18.5%) and 163 were not treated (81.5%) of the 200 HER-2-positive breast cancer patients who were divided into treatment group and control group. According to statistical analysis, the differences in DFS and OS between the treatment group and the control group were significant (P=0.041, P=0.022). Cox regression model showed that estrogen receptor (ER) and Ki-67 were independent prognostic factors in patients with breast cancer (P=0.03, P=0.016), but progesterone receptor (PR) and HER-2 were not independent prognostic factors (P>0.05). Among them, ER and Ki-67 were independent prognostic factors in the Han ethnicity (P=0.018, P=0.031), while PR and HER-2 were not (P>0.05). In the ethnic minorities, ER, PR, HER-2 and Ki-67 were not independent prognostic factors (P>0.05). Conclusion: HER-2 gene positive expression does not have ethnic difference. Treatment with trastuzumab as anti-HER-2 therapy improves prognosis and prolongs DFS and OS in HER-2-positive patients. However, there are less than 20% patients receiving anti-HER-2 treatment in Guizhou Province currently. In this study, we can see that ER or Ki-67 as a prognostic factor for breast cancer has a trend of ethnic difference.关键词：Breast cancer;HER-2 expression;Targeted molecular therapy;Prognostic factors2|1861|0更新时间：2025-12-31
- 摘要：Background and Purpose: This study aimed to evaluate the efficacy and toxicity of chemotherapy using the modified EOF (oxaliplatin, epirubicin, calcium folinate, 5-fluorouracil) regimen in patients with locally advanced gastric cancer. Methods: Thirty patients diagnosed with locally advanced gastric cancer were included into this clinical trial. All these patients received the chemotherapy of modified EOF regimen. This regimen consisted of oxaliplatin at 130 mg/m2 intravenously (2 h) on day 1, epirubicin at 50 mg/m2 intravenously (2 h) on day 1, 5-fluorouracil at 2 400 mg/m2 intravenously (48 h). All patients received two to four cycles of chemotherapy. After completing the two cycles of chemotherapy, the clinical efficacy and toxicity of chemotherapy would be evaluated. Results: Thirty patients completed the planned treatment. The clinical efficacy rate was 30.0% (9/30) with 3.3% (1/30) complete response (CR) and 26.7% (8/30) partial response (PR) according to the RECIST criteria. The rates of stable disease (SD) and progressive disease (PD) were 46.7% (14/30) and 23.3% (7/30), respectively. In the trial, 66.7% (20/30) patients underwent surgery, 46.7% (14/30) patients had curative gastrectomy, and 20.0% (6/30) patients received palliative gastrectomy. The most common toxicities were leukopenia 53.3% (16/30), neutropenia 53.3% (16/30), and anorexia 43.3% (13/30). Conclusion: The EOF regimen is one of the effective and well-tolerated conversional chemotherapy regimens in locally advanced gastric cancer.关键词：Gastric cancer;Conversional chemotherapy;Oxaliplatin;Epirubicin;5-fluorouracil2|2439|0更新时间：2025-12-31
- 摘要：Background and purpose: Transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma is characterized by a low rate of necrosis, while 125I seed implantation, as a new radiotherapy technique, has strong targeting advantages. In this study, we aimed to explore the clinical efficacy of 125I seed implantation combined with TACE therapy (combined with lobaplatin as a chemotherapy drug) and 3-year survival of patients with advanced unresectable primary hepatocellular carcinoma, and to provide reference for the clinical treatment. Methods: In the prospective study, 102 patients with advanced unresectable primary hepatocellular carcinoma at the Affiliated Tumor Hospital of Zhengzhou University from January 2010 to January 2013 were selected and randomly divided into control group and observation group with 51 cases in each group. Patients in control group were treated with TACE, and the patients in observation group were treated with TACE combined with 125I particles implantation. The changes of alpha-fetoprotein (AFP), liver function, cell immune indexes and tumor metastasis and curative effect were observed before and after 6 months of treatment. The clinical effect, 3-year survival rate and adverse reactions of the two groups were recorded and compared. Results: There was no statistically significant difference between the two groups of patients in general information and clinical related indicators before the treatment (P>0.05). After different treatment procedures, the effective rate of observation group (86.3%) was significantly higher than that of the control group (68.6%); Six months after the treatment, the serum level of AFP was significantly lower in both groups, and the serum AFP content of the observation group was significantly lower than that of the control group (P<0.05). There was no statistically significant difference in liver function indexes and cellular immune function indexes before the treatment and after the treatment for 6 months (P>0.05). The incidence of distant metastasis in the observation group was 7.8%, significantly lower than that of the control group (23.5%), survival rates of 1, 2 and 3 year were 68.6%, 43.1% and 31.4%, which were significantly higher than those of the control group (41.2%, 29.4% and 13.7%, P<0.05). Both groups had no serious complications during the follow-up period. Conclusion: The 125I seed implantation combined with TACE therapy (combined with lobaplatin as a chemotherapy drug) is more effective in controlling tumor metastasis and improving the survival rate, which is worthy of clinical application.关键词：Lobaplatin;Transcatheter arterial chemoembolization;125I seed implantation;Advanced unresectable primary hepatocellular carcinoma;Prospective study2|2632|0更新时间：2025-12-31
- 摘要：Background and purpose: Postoperative anastomotic fistula of rectal cancer is one of the serious complications, and the incidence of anastomotic fistula is a clinical problem. This study aimed to explore the rate and risk factors of anastomotic leakage in sphincter-preserving surgery of rectal (Dixon surgery) with dual stapler technique. Methods: A retrospective study was conducted on 150 patients with rectal cancer. All patients underwent anterior resection with dual stapler technique. Patients’ clinical characteristics, including gender, age, body mass index (BMI), tumor grade, anastomotic location, TNM stage, comorbidity and preoperative treatment, were included in univariate and multivariate analyses. Results: A total of 7 cases (4.7%) had anastomotic leakage, among which 3 cases were cured by ileostomy and the other 4 cases were cured by conservative therapy. Univariate and multivariate analyses found that the location of anastomosis and preoperative chemoradiotherapy were independent risk factors for anastomotic leakage. Conclusion: Dual stapler technique was a safe technique to achieve low anastomotic leakage rate. The location of anastomosis and preoperative treatment were independent risk factors for anastomotic leakage.关键词：Dual stapler technique;Rectal cancers;Anastomotic fistula2|2601|0更新时间：2025-12-31
- 摘要：High risk human papillomavirus (HPV) has been considered as the most pathogenic factor in cervical cancer patients. Since the HPV vaccine was launched on the market, the detection of HPV and its clinical significance have become hot topics. We analysed the difficulties in peripheral blood detection of HPV and clinical practice, and demonstrated the significance including the latest research progress on prognosis and treatment. It has been verified that the persistent detection of HPV in peripheral blood is in accordance with poor prognosis. On this basis, the targeted therapy and immunotherapy for HPV appear more important in treatment. Focusing on the problem we want to solve, this review presented the current state of blood detection. In the end, we gave our perspective on the precise examination means and clinical application.关键词：Cervical cancer;Human papillomavirus detection;Clinical significance2|5486|0更新时间：2025-12-31
- 摘要：Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeted therapy has great advantages compared to conventional chemotherapies and has become the first-line treatment of EGFR sensitive mutations in patients with advanced non-small cell lung cancer. However, the development of acquired drug resistance is inevitable. EGFR T790M mutation is the main mechanism of the first and second generation EGFR-TKIs. The thirdgeneration EGFR-TKIs including AZD9291 and CO-1686 showed favorable treatment effect in clinical trials. However, resistance problems appeared soon. This review summarized the resistance mechanisms of the third-generation EGFRTKIs and the potential coping strategy.关键词：Epidermal growth factor receptor;Non-small cell lung cancer;The third-generation epidermal growth factor receptor tyrosine kinase inhibitors;Resistance mechanism2|3906|0更新时间：2025-12-31
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