Journal of International Oncology

Expressions and clinical significances of aldehyde dehydrogenase 1 and transforming growth factor-β2 in triple negative breast cancer

Guo Chongyong, Li Yongmei, Li Bocheng, Zhou Ling, Zhang Jian, Jia Zongshi

2017, 44 (11): 801-805. doi: 10.3760/cma.j.issn.1673-422X.2017.11.001

Abstract ( 477 )

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Objective To investigate the expressions and clinical significances of breast cancer stem cell markers such as aldehyde dehydrogenase 1 (ALDH1) and transforming growth factorβ2 (TGFβ2) in patients with triple negative breast cancer. MethodsSamples of 60 triple negative breast cancer tissues were investigated for the expressions of ALDH1 and TGFβ2 proteins by immunohistochemical staining. The correlation analysis, diseasefree survival analysis and overall survival analysis were performed. ResultsThe positive expressions of ALDH1 protein and TGFβ2 protein in the 60 breast cancer primary lesions were 23 cases (38.33%) and 38 cases (63.33%) respectively. The expression of ALDH1 protein was not correlated with tumor size (χ2=0.307, P=0.580), histological grade (χ2=4.244, P=0.120), clinical stage (χ2=0.982, P=0.612) or lymph node metastasis (χ2=1.111, P=0.292). The expression of TGFβ2 protein was not correlated with histological grade (χ2=4.651, P=0.098), lymph node metastasis (χ2=3.513, P=0.061), clinical stage (χ2=1.310, P=0.519) or tumor size (χ2=0.629, P=0.428). The diseasefree survival time ［(38.43±3.86) months vs. (53.38±2.58) months］ and the overall survival time ［(42.00±3.11) months vs. (53.84±2.19) months］ of ALDH1positive patients were significantly shorter than those of ALDH1negative patients, and the differences were statistically significant (χ2=8.490, P=0.004; χ2=11.270, P=0.001). The diseasefree survival time ［(42.81±3.32) months vs. (54.72±2.50) months］ and the overall survival time ［(44.74±2.68) months vs. (57.18±1.55) months］ of TGFβ2 positive patients were significantly shorter than those of TGFβ2negative patients, and the differences were statistically significant (χ2=4.300, P=0.038; χ2=8.900, P=0.003). The expression of ALDH1 protein was positively correlated with the expression of TGFβ2 protein (r=0.360, P=0.005). ConclusionThe ALDH1 phenotype is an independent predictor of poor prognosis. The activation of TGFβ2 signaling pathway may be involved in the regulation of triplenegative breast cancer stem cells.

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Primary study of the effects of ursolic acid on colorectal tumor and tumor microenvironment in mice

乐红红，郝文斌，相芬芬，倪振华，许军，吴蓉，康向东

2017, 44 (11): 806-811. doi: 10.3760/cma.j.issn.1673422X.2017.11.002

Abstract ( 487 )

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ObjectiveTo investigate the effect of ursolic acid (UA) on the colorectal tumor and microenvironment in mice, and to provide a theoretical basis for the clinical application of UA. MethodsThe models of subcutaneous transplanted tumor of mouse CT26 cells was established. The models were divided into four groups: control group, tumor bearing group, tumor bearing dimethyl sulfoxide (DMSO) group and tumor bearing UA group. The serum levels of interleukin6 (IL6) were detected by enzyme linked immunosorbent assay (ELISA). The number and percentage of myeloidderived suppressor cell (MDSC) in the spleen of mice were analyzed by flow cytometry. The mRNA levels of IL6 and signal transducer and activator of transcription 3 (STAT3) in tumor were examined by realtime quantitative polymerase chain reaction (RTPCR). The protein levels of STAT3 and pSTAT3 in tumor were detected by Western blotting. ResultsThe results showed that UA could significantly decrease the number of spleen MDSC. The accounts of spleen MDSC of tumor bearing UA group (249.60±17.12) was lower than that of tumor bearing DMSO group (366.40±34.08), and the difference was statistically significant (P=0.021). The serum level of IL6 in tumor bearing UA group ［(46.40±17.05) pg/ml］ was decreased than that in tumor bearing DMSO group ［(94.27±21.51) pg/ml］, and the difference was statistically significant (P=0.012). The expression levels of IL6 and STAT3 mRNA in tumor tissues of tumor bearing UA group (0.12±0.01, 0.21±0.08) were lower than those of tumor bearing DMSO group (0.69±0.14, 0.79±0.06), and the differences were statistically significant (P=0.008; P=0.003). The protein expression levels of STAT3 and pSTAT3 in tumor tissues of tumor bearing UA group (0.81±0.02, 0.28±0.04) were lower than those of tumor bearing DMSO group (0.98±0.02, 0.91±0.22), and the differences were statistically significant (P=0.027; P=0.029) . ConclusionUA may inhibit the activation of STAT3 signaling pathway and the amplification of MDSC in microenvironment by reducing IL6, thus to enhance the function of immunekilling tumor cells to regulate tumor immune microenvironment and inhibit the immune escape of mouse colorectal cancer cells.

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miR-92a promotes colorectal cancer cell proliferation by regulation of KLF4 gene expression

黄虞，杜冀晖，龚慧，王秀，王磊，李一凡

2017, 44 (11): 812-818. doi: 10.3760/cma.j.issn.1673-422X.2017.11.003

Abstract ( 538 )

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ObjectiveTo evaluate the effect of microRNA92a (miR92a) on regulating cell proliferation by targeting Krüppellike factor 4 (KLF4) in colon cancer. MethodsThe miR92a expressions in 21 colon cancer tissues and matched normal tumoradjacent tissues and 4 colon cancer cells (HT29, SW480, SW620, HCT116) were detected using quantitative realtime polymerase chain reaction (qRTPCR). Models of overexpression and suppression of miR92a were established by transient transfection of miR92a3p mimic to HCT116 and transient transfection of miR92a3p inhibitor to SW620, respectively. Cell proliferation activity was detected by the CCK8 colorimetry method, cell cycles were detected by flow cytometry, KLF4 protein expression was detected by Western blotting, and cell luciferase activity was detected by the dual luciferase reporter gene experiment. ResultsThe expression level of miR92a in colon cancer tissues was (0.648±0.489) fmol/μg total RNA, significantly higher than that in matched normal tumoradjacent tissues ［(0.064±0.062) fmol/μg total RNA］, with statistically significant difference (t=-5.420, P＜0.001). In 4 colon cancer cell lines, the miR92a expression level in HCT116 cells was the lowest, and highest in SW620 cell. When the expression of miR92a was upregulated, the cell proliferation activity of 72 h in HCT116 cells was higher than that in the negative control group (0.919±0.014 vs. 0.765±0.025), with statistically significant difference (t=-9.309, P=0.001), the proportion of S phase cells was also significantly increased ［(41.670±0.461)% vs. (38.703±0.554)%, t=-7.127, P=0.002), and KLF4 protein expression was decreased (0.460±0.048 vs. 0.758±0.109, t=22.865, P=0.028). When the expression of miR92a was downregulated, the cell proliferation activity of 72 h in SW620 cells was lower than that in the negative control group (0.608±0.011 vs. 0.713±0.005), with statistically significant difference (t=15.920, P＜0.001), while the proportion of S phase cells was decreased ［(31.935±0.365)% vs. (34.955±0.465)%, t=8.849, P=0.001］, and KLF4 protein expression was increased (0.694±0.121 vs. 0.479±0.044, t=-5.246, P=0.034). KLF4 3′UTR wildtype dual luciferase report plasmids were cotransfected with miR92a3p mimic to HCT116 cell, and dual luciferase assay showed that miR92a slightly repressed firefly luciferase actively, but the difference was not statistically significant (t=0.878, P=0.429). There was a negative correlation between the expression of miR92a and the expression of KLF4 protein in colon cancer tissues, but with no statistical significance (r=-0.163, P=0.699). ConclusionmiR92a is highly expressed in colon cancer tissues. It can promote colon cancer cells proliferation via enhancement of the cell cycle transition of G0G1 phase to S phase. Upexpression of miR92a may play a role in downregulating the expression of KLF4 protein in colon cancer cells. However, KLF4 is not a direct target gene of miR92a.

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miR-320 inhibits glycometabolism in colorectal cancer by targeting E2F1 gene

刘延锋，王铎，张华洲，张允东

2017, 44 (11): 819-823. doi: 10.3760/cma.j.issn.1673-422X.2017.11.004

Abstract ( 454 )

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ObjectiveTo study the effect of microRNA320 （miR320） targeting E2F1 gene on tumor glycometabolism in colorectal cancer. MethodsThe miR320 expression level in colorectal cancer cell lines and cancer tissues was detected using quantitative realtime polymerase chain reaction (qRTPCR). The binding sites of miR320 and E2F1 were predicted by bioinformatics. Luciferase assay was used to detect the targeting regulation of miR320 on E2F1. The relationship between E2F1 and miR320 was verified in mRNA level and protein level. When the miR320 in SW480 and LOVO cells was upregulated and the E2F1 was downregulated, the changes of glycometabolism in tumor cells were analyzed using glucose/glucose oxidase kit and lactate test kit. ResultsThe qRTPCR results showed low expressions of miR320 in colorectal cancer cell lines and cancer tissues (F=42.327, P＜0.001; t=4.345, P=0.023). Luciferase assay showed that miR320 could negatively regulate the expression of E2F1 (t=4.716, P=0.042). The expression levels of E2F1 protein and mRNA (t=4.780, P=0.041; t=5.506, P=0.031) confirmed that miR320 could interact with E2F1 in LOVO and SW480 cells. Overexpression of miR320 could reduce the contents of glucose (t=5.262, P=0.034; t=21.079, P=0.002) and lactic acid (t=9.609, P=0.011; t=18.582, P=0.003) in the cellular supernatant in SW480 and LOVO cells. Downregulating the expression of E2F1 at the same time could enhance the inhibitory effect of miR320 on glucose (t=5.128, P=0.036; t=5.089, P=0.037) and lactic acid (t=8.573, P=0.013; t=13.364, P=0.006). ConclusionE2F1 is the target gene of miR320, and miR320 can regulate the glycometabolism of colorectal cancer cells by targeting E2F1 gene.

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Valuation of neutrophil to lymphocyte ratio in peripheral blood as a prognostic factor for patients with triple negative breast cancer

潘宇凯

2017, 44 (11): 824-827. doi: 10.3760/cma.j.issn.1673422X.2017.11.005

Abstract ( 462 )

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ObjectiveTo analyze the clinical features of patients with triplenegative breast cancer (TNBC) and prognostic factors, and to analyze the correlation between neutrophiltolymphocyte ratio (NLR) in peripheral blood before operation and the prognosis of TNBC patients and investigate the value of NLR as a prognostic index for patients with TNBC. MethodsThe clinical data of 87 patients with TNBC treated in People′s Hospital of Jiangyin of Jiangsu Province from January 2008 to January 2013 were analyzed retrospectively. The patients were divided into low NLR group (NLR≤4.39, n=58) and high NLR group (NLR＞4.39, n=29) according to the NLR in peripheral blood before operation. The correlations between NLR and clinicpathological features were analyzed. KaplanMeier method was used to estimate the survival. The univariate analysis was done and Cox proportional hazards regression model was used for multivariate analysis to explore the effect of the NLR in peripheral blood before operation on survival of TNBC patients. ResultsThe high NLR value was related with the clinical stage (χ2=8.628, P=0.005) and lymph node metastasis (χ2=4.911, P=0.027). However, NLR was not correlated with age (χ2=0.575, P=0.448), pathological types (χ2=0.687，P=0.709), tumor size (χ2=3.523, P=0.172), smoking (χ2=0.536， P=0.474), drinking (χ2=0.043, P=0.837) or inheritance (χ2=0.315, P=0.585). Univariate analysis showed that lymph node metastasis (HR=2.02, P=0.021), clinical stage (HR=2.69, P=0.007) and NLR value (HR=2.26, P=0.014) were related to the overall survival of patients with TNBC. Cox multivariate analysis showed that clinical stage (HR=4.10, P=0.033) and NLR value (HR=3.44, P=0.016) were independent predictors of prognosis in patients with TNBC. ConclusionIn TNBC, the NLR level is related to clinical tumor stage and lymph node metastasis significantly. Furthermore, the higher NLR value is a novel independent prognostic risk factor, which has important implications on prognosis of patients with TNBC.

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Analysis of cancer incidence and mortality in Heilongjiang province cancer registries, 2013

孙惠昕，陈王洋，张茂祥，宋冰冰

2017, 44 (11): 828-833. doi: 10.3760/cma.j.issn.1673-422X.2017.11.006

Abstract ( 514 )

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ObjectiveTo analyze the malignant tumor incidence and mortality in Heilongjiang province in 2013. MethodsTumor registration data of Heilongjiang province cancer registries in 2013 were collected. The malignant tumor incidence and mortality of registration data from 7 cancer registries were analyzed according to the criteria of quality control from National Central Cancer Registry (NCCR). ResultsThe crude incidence rate of cancer in Heilongjiang province was 234.34/105. Agestandardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 153.08/105 and 149.33/105 with the cumulative incidence rate (074 years old) of 17.17%. The cancer incidence and ASIRC were 258.42/105 and 157.00/105 in urban areas, whereas in rural areas, they were 190.95/105 and 145.44/105, respectively. The cancer mortality in Heilongjiang province was 147.62/105. Agestandardized mortality rates by ASIRC and by world standard population were 92.22/105 and 91.41/105 with the cumulative incidence rate (074 years old) of 10.44%. The cancer mortality and ASIRC were 171.85/105 and 97.85/105 in urban areas, whereas in rural areas, they were 103.95/105 and 78.48/105, respectively. Lung cancer, breast cancer, liver cancer, colorectal cancer and gastric cancer were the highincidence cancers in Heilongjiang province. Lung cancer, liver cancer, gastric cancer, colorectal cancer and breast cancer were the most death causes. ConclusionThe morbidity and mortality of lung cancer are the highest in Heilongjiang province in 2013. Lung cancer and digestive system malignancies are the most common cancers in Heilongjiang province. Dynamic monitoring tumor morbidity and mortality in Heilongjiang province is the basis of the cancer prevention and control work. The active and effective comprehensive control measures should be taken to curb the rising trend of malignant tumor burden.

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6-sulfo-LacNAc dendritic cells and tumors

陈邓林，陈俊民

2017, 44 (11): 834-837. doi: 10.3760/cma.j.issn.1673-422X.2017.11.007

Abstract ( 423 )

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6-sulfo-LacNAc dendritic cells (slanDCs), characterized by expressing the Fc receptors that absent in classic dendritic cells (DCs), have been identified as a novel subgroup of peripheral blood DCs. Hitherto, the majority researches of slanDCs are about inflammation and autoimmunity diseases, but a growing body of literature has shown that slanDCs may play important roles in antitumor immunity by inducing antibodydependent cellmediated cytotoxicity, releasing special cytokines, crosstalking with mesenchymal stem cells or natural killer cells, and signal transduction through Tolllike receptor pathway and mitogenactivated protein kinase pathway. slanDCs may be an ideal antitumor therapy tool.

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Salt-induced kinase 1 and tumors

刘大威，贺德

2017, 44 (11): 838-841. doi: 10.3760/cma.j.issn.1673-422X.2017.11.008

Abstract ( 499 )

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Salt-inducible kinase 1 (SIK1) is closely related to tumorigenesis. The expressions of SIK1 in hepatocellular carcinoma, pancreatic cancer, gastric cancer, lung cancer, ovarian cancer and other tumors are specific, and their abnormal expressions can inhibit or promote the occurrence, development and metastasis of tumor. Abnormal expressions of SIK1 are expected to provide a new method for the diagnosis and treatment of tumors, and provide guidance for clinical prognosis.

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Role of annexin A5 in tumor and basic research on the target of it

2017, 44 (11): 842-845.

Abstract ( 359 )

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Progress of the tumorigenic mechanism of neutrophil and its relevance to pre-metastatic niche

吴玉亮，程忠平

2017, 44 (11): 846-848. doi: 10.3760/cma.j.issn.1673-422X.2017.11.010

Abstract ( 449 )

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The tumorassociated neutrophils (TANs) are thought to be important and complicated character in tumor microenvironment. TANs play dual roles of antitumor or tumorpromoting in tumor microenvironment under different factors. TANs can not only play the antitumor effect by killing tumor cells directly and promoting immune response, but also can act as tumor promotors by promoting tumor angiogenesis and mediating tumor invasion and metastasis. Recent researches find that TANs are closely related to premetastatic niche (PMN), which can promote the construction and maintenance of PMN by means of changing the content of cell factors like interferon-γ.

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Co-stimulating molecule B7H3 and tumors

朱晓雯，王晶，克晓燕

2017, 44 (11): 849-852. doi: 10.3760/cma.j.issn.1673-422X.2017.11.011

Abstract ( 413 )

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B7-H3, a newly discovered co-stimulatory regulatory protein member of the B7 family. Its mRNA is ubiquitously expressed in a wide spectrum of tissues. As a co-stimulatory or co-inhibitory signal molecule which can regulate immune response, B7-H3 plays an important role in the immune system. Besides, B7-H3 can be also involved in cancer progression via nonimmunological. Recently, the aberrant expression of B7-H3 has been described in various malignancies, and significantly correlated with poor prognosis and cancer progression. Therefore, B7-H3 is considered as an early diagnostic and prognostic marker and therapeutic target for tumors, but the specific molecular mechanisms of B7-H3 regulation are poorly understood. The immune and gene therapy of tumor by target B7-H3 has made some progress.

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Wnt/β-catenin signaling pathway and cancer stem cells

郑佩

2017, 44 (11): 853-855. doi: 10.3760/cma.j.issn.1673-422X.2017.11.012

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Adult stem cells play important roles in the regeneration of human tissues, and they form cancer stem cells when malignant transformation occurs. Cancer stem cells are closely related to the occurrence of various tumors, chemotherapy resistance and recurrence. The Wnt/βcatenin signaling pathway regulates embryonic development and is evolutionarily conserved, and plays an important role in selfrenewal and differentiation of cancer stem cells. The Wnt/βcatenin signaling pathway and related regulatory proteins have become a hot target for cancer stem cell targeted therapy.

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Base excision repair and targeted therapy strategies

张天棋，王红兵

2017, 44 (11): 856-859. doi: 10.3760/cma.j.issn.1673-422X.2017.11.013

Abstract ( 802 )

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Base excision repair (BER) is an important pathway for DNA oxidative damage repair, and mutations in this pathway cause gene instability and increase cancer risk. A large number of studies have shown that abnormal expression of key proteins in the BER pathway in a variety of tumors, such as DNA glycosylase, apurinic/apyrimidinic endonuclease 1, DNA polymerase and so on. Single nucleotide polymorphisms of these proteins affect the repair activity of tumor cells, and are expected to be important indicators for the diagnosis, treatment and evaluation of prognosis.

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Adverse reactions and symptomatic treatment of immunological checkpoint inhibitors in tumor therapy

周丽娜，李红梅

2017, 44 (11): 860-863. doi: 10.3760/cma.j.issn.1673-422X.2017.11.014

Abstract ( 546 )

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Immunological checkpoint inhibitors include monoclonal antibodies of cytotoxic T lymphocyte antigen4 (CTLA4) and programmed cell death1 (PD1). AntiCTLA4 drug ezetimab (ipilimumab) and antiPD1 drug (pembrolizumab and nivolumab) are approved for the treatment of melanoma and nonsmall cell lung cancer. The effects of these drugs on renal cell carcinoma, bladder cancer, breast cancer, gastrointestinal cancer and other types of cancers are still in largescale clinical trials. These drugs have good effects in the clinical application, but they inevitably lead to many adverse reactions.

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Bevacizumab in the treatment of non-small-cell lung cancer with brain metastases

刘梦实，杨海燕，李红梅

2017, 44 (11): 864-865. doi: 10.3760/cma.j.issn.1673-422X.2017.11.015

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The occurrence of brain metastases in lung cancer affects the prognosis of patients. Following surgery, whole brain radiotherapy, stereotactic radiotherapy and chemotherapy, antiangiogenesis therapy has become a new treatment option for lung cancer patients with brain metastases. As an antiangiogenic drug, bevacizumab has a better effect of controlling peritumoral edema. Studies have shown that bevacizumab combined with chemotherapy, radiotherapy to treat nonsmall cell lung cancer with brain metastasis has a good efficacy and safety.

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MicroRNA and Helicobacter pylori-associated gastric carcinoma

李春霞，王学红

2017, 44 (11): 866-868. doi: 10.3760/cma.j.issn.1673-422X.2017.11.016

Abstract ( 410 )

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Helicobacter pylori infection can cause a series of microRNAs (miRNAs) disorders. These abnormal expressions of miRNAs can participate in the genesis and development of Helicobacter pyloriassociated gastric carcinoma through regulating cell proliferation, differentiation and apoptosis. Identifying the targets and regulatory pathways of various miRNAs in the development of Helicobacter pyloriassociated gastric cancer will provide a new direction for early diagnosis, prognosis and individualized treatment of gastric cancer.

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Drug therapy of late-stage gastric cancer

潘平生，庄红雯，沈玲

2017, 44 (11): 869-873. doi: 10.3760/cma.j.issn.1673-422X.2017.11.017

Abstract ( 423 )

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Gastric cancer is one of the most common cancers in the world, and it is also one of the most common causes of death due to cancer. Most patients have been in the late stage when coming for treatment, and drug therapy is the main scheme for most patients with advanced gastric cancer. In recent years, the progress of drug treatment for advanced gastric cancer has developed rapidly, from simple chemotherapy to targeted drug therapy, and a number of traditional or new treatment programs have shown the indispensability of drug treatment.

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