Journal of International Oncology

Construction of overexpression lentiviral vector and its expression in lung cancer A549 cells of AMPactivated protein kinase

Zhang Xiangmin, Liu Lianbin, Zeng Wen, Zhou Maohua, Ye Guilin, Ye Yongqiang, Wang Gang, Li Shaojin

2017, 44 (10): 721-726. doi: 10.3760/cma.j.issn.1673-422X.2017.10.001

Abstract ( 453 )

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ObjectiveTo establish a stable lung cancer A549 cell line transfected by AMPactivated protein kinase (AMPK) expression vector, and to observe the effect of AMPK on proliferation as well as on the invasive ability of A549 cells. MethodsFulllength of AMPK gene was amplified and its target gene was digested, then inserted into the GV358 plasmid. Cotranfected 293T cells were subjected to the lentivirus equipment package. Subsequently, we collected the lentivirus supernatant to infect the A549 cells and establish a stably, overexpressed cell line A549. The mRNA and protein of AMPK were examined by realtime quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and Western blotting. The proliferation and invasion abilities of A549 cells were detected by methyl thiazolyl thiazolium (MTT) and Transwell assay. ResultsGV358AMPK lentivirus vectors was successfully constructed by restrictive enzyme digestion and plasmid sequencing. There were significantly increased expressions of AMPK protein (5.87 times, P=0.002) and mRNA (16.12 times, P＜0.001) after transfected with GV358AMPK compared with the Vector group. Meanwhile, AMPK overexpression showed significantly lower proliferation (the forth day: 0.53±0.03 vs. 0.64±0.05, P=0.021; the fifth day: 0.58±0.04 vs. 0.80±0.07, P=0.002) and weaken invasive ability ［(1.6±0.5)×105 vs. (3.4±0.3)×105, P=0.004］ of A549 cells. ConclusionThe lentiviral AMPK expression vector and its A549 cell line is successfully constructed. AMPK overexpression inhibits the proliferation and invasive ability of A549 cells.

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Clinical significance of detection of mtMSI and Hp in the diagnosis of esophageal squamous cell carcinoma

Peng Qianqian, Deng Sanhua, Chen Peisheng, He Fengjian, Xu Shenghao

2017, 44 (10): 727-730. doi: 10.3760/cma.j.issn.1673-422X.2017.10.002

Abstract ( 481 )

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ObjectiveTo detect the mitochondrial microsatellite instability (mtMSI) and Helicobacter pylori (Hp) infection status in esophageal squamous cell carcinoma (ESCC), and to analyze their clinical significance in the diagnosis of ESCC. MethodsThe mtMSI and Hp infection status were examined by immunohistochemical SP method in 93 cases of ESCC and their normal control tissues. The relationship between Hp and mtMSI and their correlations with the clinicopathological features of ESCC were analyzed. ResultsThe Hp positive rates of ESCC group and control group were 61.3% (57/93) and 20.4% (19/93) respectively, and there was statistically significant difference between the two groups (χ2=32.127, P＜0.001). The mtMSI positive rates of ESCC group and control group were 34.4% (32/93) and 0 (0/93) respectively, and there was statistically significant difference between the two groups (χ2=38.649, P＜0.001). The Hp infection was correlated with tumor infiltrating degree (χ2=22.213, P＜0.001) and lymph node metastasis (χ2=8.318, P=0.004), but was not correlated with gender (χ2=0.330, P=0.565), major axis of tumor (χ2=0.692, P=0.406), gross type (χ2=1.006, P=0.316), differentiated degree (χ2=0.665, P=0.415). The mtMSI was not correlated with gender (χ2=0.163, P=0.686), major axis of tumor (χ2=0.384, P=0.530), gross type (χ2=0.422, P=0.516), differentiated degree (χ2=0.213, P=0.645), infiltrating degree (χ2=0.001, P=0.979) or lymph node metastasis (χ2=0.039, P=0.843). The Hp infection was positively associated with mtMSI in ESCC (r=0.864, P=0.006). ConclusionThe positive rates of Hp and mtMSI in ESCC are higher than those in normal tissues, and there is a close relationship between Hp and mtMSI. Hp is also associated with the progression of ESCC.

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Significance of miR145 expression in peripheral blood in shortterm efficacy evaluation of radiotherapy for esophageal carcinoma

Wang Zhaojian, Lu Haijun, Ding Xiao, He Xinjia

2017, 44 (10): 731-735. doi: 10.3760/cma.j.issn.1673-422X.2017.10.003

Abstract ( 369 )

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ObjectiveTo investigate the relationship between the expression level of microRNA145 (miR145) in peripheral blood and clinicopathological characteristics of esophageal cancer patients and evaluate its significance in shortterm efficacy of radiotherapy. MethodsA total of 52 patients with esophageal cancer diagnosed in Affiliated Hospital of Qingdao University were collected, and all of the patients received radiotherapy alone. The relative expression level of miR145 in peripheral blood was detected by using the method of reverse transcriptase polymerase chain reaction (RTPCR) before radiotherapy. The correlations between the expression of miR145 and pathological characteristics as well as shortterm efficacy of radiotherapy were analyzed. ResultsIn the 52 patients, the relative expression of miR145 ［M(QR)］ in peripheral blood of clinical stage ⅠⅡ was 3.14 (1.44), higher than that of stage ⅢⅣ ［1.71 (0.48)］, and the difference was statistically significant (Z=-3.002, P=0.003). The expression level of miR145 was not related with the age (Z=-0.403, P=0.687), gender (Z=-1.179, P=0.238) and history of drinking (Z=-0.389, P=0.697). The expression levels of miR145 in complete response (CR), partial response (PR) and no change (NC) groups were 3.27 (1.64), 1.83 (1.26) and 1.40 (2.51), respectively, and the difference was statistically significant (H=6.567, P=0.038). ConclusionThe expression level of miR145 in peripheral blood is significantly correlated with the clinical stage of esophageal cancer. Its expression level is positively correlated with the shortterm efficacy of esophageal cancer radiotherapy. High expression of miR145 shows a better shortterm efficacy of radiotherapy.

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Phase Ⅱ clinical study of paclitaxel and cisplatin combined with concurrent radiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma

An Cheng, Zhang Huanjiang

2017, 44 (10): 736-739. doi: 10.3760/cma.j.issn.1673-422X.2017.10.004

Abstract ( 430 )

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ObjectiveTo study the phase Ⅱ clinical efficacy of paclitaxel and cisplatin combined with concurrent radiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma. MethodsSixtythree cases of locally advanced esophageal squamous cell carcinoma patients were selected from January 2014 to January 2016 in our hospital. All patients were randomly divided into the study group (32 cases) and control group (31 cases) according to random number table method. All patients were treated with threedimensional conformal radiotherapy, the control group was treated with 5fluorouracil and cisplatin, and study group was treated with paclitaxel combined with cisplatin, 21 days for a course of treatment, continuous 2 cycles of chemotherapy. The therapeutic effects and adverse reactions of the two groups of patients were evaluated. The levels of tumor markers such as carcino embryonic antigen (CEA), CA125 and CA50 were detected in the two groups before and after chemotherapy. The patients were followed up, and the survival rates were recorded. ResultsThe effective rate of the patients in the study group was 93.75%, higher than that of the control group (74.19%, χ2=4.510, P=0.034). Compared with the control group, the radiation esophagitis (Z=2.076, P=0.038), neurotoxicity (Z=3.806, P＜0.001), gastrointestinal reactions (Z=2.374, P=0.018), leukopenia (Z=1.979, P=0.048) were significantly lighter in the study group. After chemotherapy, the levels of CEA, CA125, CA50 of study group and control group were significantly lower than those before chemotherapy (all P＜0.05), and the levels of study group after chemotherapy were significantly lower than those of the control group (all P＜0.05). The 1year survival rate of the patients in the study group was 90.63%, which was significantly higher than that in the control group (70.97%), and the difference was statistically significant (χ2=4.287, P=0.038). ConclusionPaclitaxel and cisplatin combined with concurrent radiotherapy can improve the phase Ⅱ therapeutic effect of locally advanced esophageal squamous cell carcinoma, the toxicity of chemotherapy in patients is low, effectively improve the shortterm survival rate, with better clinical value.

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Curative effect of iodine125 brachytherapy and concurrent chemoradiotherapy for middle and advanced stage nonsmall cell lung cancer

Sun Ying, Wang Ning, Guo Zhanwen, Yan Ying

2017, 44 (10): 740-744. doi: 10.3760/cma.j.issn.1673-422X.2017.10.005

Abstract ( 436 )

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ObjectiveTo review the efficacy and safety of combination of iodine125 brachytherapy and concurrent chemoradiotherapy for middle and advanced stage nonsmall cell lung cancer (NSCLC). MethodsEightytwo cases of peripheral NSCLC patients were divided into the experimental group (n=32) and the control group (n=50) by different treatment methods. The patients in experimental group were treated by iodine125 brachytherapy combined with concurrent chemoradiotherapy, and the patients in control group were treated by concurrent chemoradiotherapy. The two groups were treated with helical tomotherapy, and the chemotherapy regimen was PC regimen (paclitaxel + cisplatin) or TP regimen (taxotere + cisplatin). The response rate (RR), progression free survival (PFS), overall survival (OS) and adverse reactions were observed. ResultsThe RR of experimental group and control group was 87.5% and 76.0%, and the difference was not statistically significant (χ2=0.992, P=0.319). The median PFS was 16 months and 11 months, and the difference was statistically significant (χ2=5.216, P=0.022). The median OS was 26 months and 19 months, and the difference was not statistically significant (χ2=1.085, P=0.298). There were no statistically significant differences of the occurrence rates of adverse reactions in the experimental group and the control group such as radioactive pneumonia (18.75% vs. 24.00%, χ2=0.314, P=0.575), radiation esophagitis (25.00% vs. 30.00%, χ2=0.242, P=0.623), digestive tract reaction (21.88% vs. 26.00%, χ2=0.180, P=0.671), bone marrow suppression (12.50% vs. 16.00%, χ2=0.014, P=0.907) and hemopneumothorax (6.25% vs. 0, P=0.149). ConclusionThe combination of iodine125 brachytherapy with concurrent chemoradiotherapy is a safe and effective treatment for middle and advanced stage NSCLC, which is worthy of further research and promotion.

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Efficacy of recombinant human endostatin combined with TP regimen on patients with advanced EGFR wild type squamous cell lung carcinoma

Wang Wei, Ren Biyong

2017, 44 (10): 745-748. doi: 10.3760/cma.j.issn.1673-422X.2017.10.006

Abstract ( 497 )

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ObjectiveTo evaluate the efficacy of recombinant human endostatin combined with TP (paclitaxel + cisplatin) in the treatment of advanced epidermal growth factor receptor (EGFR) squamous cell lung carcinoma. MethodsFrom January 2012 to February 2015, 100 patients with squamous cell lung carcinoma in Chongqing Three Gorges Central Hospital for medical treatment were selected as the subjects. According to different treatment methods, they were divided into single group (n=50) and combined group (n=50). The single group used the TP protocol and the combined group was treated with recombinant human endostatin on the basis of the TP protocol. The therapeutic effect was evaluated according to the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1). The shortterm effects, longterm effects, adverse reactions, hospitalization time and expenses were also analyzed. ResultsThe objective effective rate in the combined group ［52.0% (26/50)］ was significantly higher than that in the single group ［16.0% (8/50)］, with a significant difference (χ2=14.429, P=0.007). The disease control rate in the combined group was higher than that in the single group (80.0% vs. 52.0%), with a significant difference (χ2=8.734, P=0.009). Compared with the patients in the single group, the median progression free survival (8.4 months vs. 6.3 months) and overall survival (17.7 months vs. 11.5 months) in the combined group were prolonged obviously, with significant differences (χ2=5.390, P=0.025; χ2=3.993, P=0.035). The incidence rates of adverse reactions in single group were basically the same compared with the combined group, and the difference was not statistically significant (all P>0.05). Compared with the single group, the hospitalization time in combined group was longer ［(23.5±2.8) weeks vs. (18.2±3.5) weeks］, and the expenses in combined group was higher ［(112 453.9±994.9) yuan vs. (87 821.4±943.2) yuan］, with significant differences (t=8.361, P＜0.001; t=127.051, P＜0.001). But the satisfaction of patients in combined group was significantly higher than that in single group (88.0% vs. 64.0%, χ2=4.210, P=0.017). ConclusionRecombinant human endostatin combined with TP regimen is effective in the treatment of advanced EGFR wildtype squamous cell lung carcinoma, and has a low incidence of adverse reactions. It is suitable for clinical application.

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Application of preoperative neoadjuvant chemotherapy in cervical cancer patients undergoing surgical treatment

Chen Yue, Xiao Su, Pan Wei

2017, 44 (10): 749-753. doi: 10.3760/cma.j.issn.1673-422X.2017.10.007

Abstract ( 487 )

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ObjectiveTo explore the clinical effect of preoperative neoadjuvant chemotherapy on locally advanced cervical cancer. MethodsFrom March 2010 to November 2013, 284 cases of stage ⅠB2 and stage ⅡA2 cervical cancer who underwent radical operation in our hospital were divided into experimental group (n=172) and control group (n=112) according to the patients′ will. The experimental group was treated by neoadjuvant chemotherapy (paclitaxel combined with oxaliplatin) before surgery, while the control group was treated by surgery alone. The effect of chemotherapy of experimental group was evaluated, and the operative time, blood loss, adjuvant therapy rates after operation, positive rates of resection margin, pathological characteristics, overall survival (OS) and relapse free survival (RFS) of the two groups were compared. ResultsThe effective rate of neoadjuvant chemotherapy was 76.74% (132/172), while the effective rate in ⅠB2 patients was 82.80% (77/93) and in ⅡA2 patients was 69.62% (55/79), with a statistically significant difference (χ2=4.155, P=0.042). The operation time of experimental group ［(231.71±29.04) min］ was shorter than that of control group ［(253.12±30.97) min, t=5.914, P<0.001］. The adjuvant therapy rate after operation of experimental group was lower than that of control group (61.05% vs. 76.79%, χ2=7.630, P=0.006). There was no significant difference in bleeding volume between the two groups ［(614.33±120.19) ml vs. (622.84±131.27) ml, t=0.562, P=0.574］, and there were no positive cases of vaginal incision in the two groups. The rates of deep cervical stromal invasion (χ2=6.752, P=0.009), parametrial metastasis (χ2=4.359, P=0.037), vascular infiltration (χ2=5.310, P=0.021), cervical canal involving (χ2=11.022, P<0.001) and lymph node metastasis (χ2=6.830, P=0.009) of experimental group were significantly lower than those of control group. The median followup was 31.5 (4.542.0) months and 33.4 (4.542.0) months in control and experimental group. There were no significant differences in 3year RFS (52.68% vs. 60.47%, HR=0.746, 95%CI: 0.5071.067, P=0.109) and 3year OS (79.46% vs. 81.40%, HR=0.732, 95%CI: 0.4361.203, P=0.214) between the two groups. ConclusionThe preoperative neoadjuvant chemotherapy is effective for patients with cervical cancer. It can shorten the operation time, improve the pathologic features and decrease the lymph node metastasis rate. But it can not significantly reduce the longterm recurrence rate or improve the longterm survival rate.

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Antitumor effect of histone deacetylase inhibitors

Xiao Sa, Li Ling, Zhang Mingzhi

2017, 44 (10): 754-757. doi: 10.3760/cma.j.issn.1673-422X.2017.10.008

Abstract ( 505 )

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Histone deacetylase (HDAC) is a kind of protease, which plays an important role in the structural modification of chromosomes and the regulation of gene expression. Its excessive expression in cancer cells causes acetylation imbalance, which is closely related to the occurrence of tumor. The high efficiency and low toxicity of histone deacetylase inhibitor (HDACi) has been widely recognized as antitumor drug with the deepening of the study in epigenetics. It is expected to bring more breakthroughs in the treatment of tumor.

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Reversal of Pglycoproteinmediated multidrug resistance mechanism by curcumin

Liu Lan, Zhang Zhimin, Peng Wenmiao, Fu Hongxing, Rao Zhiguo

2017, 44 (10): 758-761. doi: 10.3760/cma.j.issn.1673-422X.2017.10.009

Abstract ( 500 )

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Multidrug resistance (MDR) is one of the important reasons for the failure of clinical anticancer drugs, involving multiple mechanisms. Among them, the classical MDR mechanism mediated by Pglycoprotein (Pgp) is closely related to the formation of MDR, which can excrete intracellular chemotherapeutic drugs through the "drug pump" effect and significantly reduce the therapeutic effect. Curcumin is mainly extracted from the underground rhizome of Chinese medicine turmeric, with a wide range of pharmacological activity. Recent studies have found that curcumin also has a role in reversing the MDR of the tumor, by inhibiting both Pgp function and expression, and this process involves a variety of signal paths.

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Warburg effect on tumor

Zhou Yuhui, Wei Jiufeng, Li Guodong, Liu Ming

2017, 44 (10): 762-766. doi: 10.3760/cma.j.issn.1673-422X.2017.10.010

Abstract ( 1492 )

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Tumor cells can escape from the normal apoptosis process and enhance the ability of proliferation and migration via an abnormal glucose metabolism. This abnormal glucose metabolism is named the Warburg effect, which plays a key role in the incidence of tumor. The Warburg effect is that, under aerobic condition, attenuating aerobic respiration of tumor cells via a series of molecular mechanisms, and exhibiting higher glycolysis metabolism and adenosine triphosphate (ATP) production, and meanwhile, creating the microenvironment that suitable for tumor cell survival, inducing proliferation advantages for tumor cells. In addition, the Warburg effect induced regional hypoxia reduces monitoring effect and lethality of Tlymphocytes, and thus induces immune escape of tumor cells. By inhibiting related pathways of Warburg effect, some drugs such as 2deoxyDglucose and dichloroacetic acid have effective ability to inhibit Warburg effectcaused proliferation advantages and immune escape of tumor cells, and thus inhibit tumor cells growth and promote tumor cells death. Moreover, health diet also effectively inhibits the Warburg effect. However, there are also some problems to be solved. As the development of researches on the Warburg effect, the effect of various antitumor drugs will be revalued, and these will provide new theoretical basis and research direction for tumor prevention and therapy.

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Diagnosis and treatment of recurrent high grade glioma

Liu Xue, Ren Qinglan

2017, 44 (10): 767-770. doi: 10.3760/cma.j.issn.1673-422X.2017.10.011

Abstract ( 535 )

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High grade glioma is a kind of malignant brain tumor with strong invasiveness, which progresses commonly after initial treatments and shows high mortality. Early diagnosis of tumor recurrence and highlyindividualized systemic treatment mean significance to prolong survival. Multimode magnetic resonance imaging and molecular imaging play important roles in differential diagnosis and prognosis evaluation for recurrence. Therapeutic strategies like reoperation, reirradiation, electric field technology, chemotherapy, targeted therapies and immunotherapeutic approaches are expected to bring survival benefits for patients with recurrent high grade glioma.

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Application of diffusion weighted imaging in the diagnosis and treatment of nasopharyngeal carcinoma

Xu Jinpeng, Ren Ruimei, Liu Xiguang, Zhou Jing, Liu Zhicheng

2017, 44 (10): 771-774. doi: 10.3760/cma.j.issn.1673-422X.2017.10.012

Abstract ( 380 )

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The judgment of early curative effect is important to the treatment of nasopharyngeal carcinoma and the prognosis of the patients. As a rapid imaging technique, magnetic resonance diffusion weighted imaging (DWI) is used to quantitatively analyze the changes of water molecules in the tissue by means of apparent diffusion coefficient (ADC), so as to diagnose the small lesions of nasopharyngeal carcinoma accurately, evaluate the early curative effect and observe the prognosis. With the continuous improvement and progress of MRI and data analysis technology, DWI in the diagnosis and treatment of nasopharyngeal carcinoma shows a broader application prospect.

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Histone modification in breast cancer

Fang Jiahui, Wang Changshan, Jia Yongfeng

2017, 44 (10): 775-778. doi: 10.3760/cma.j.issn.1673-422X.2017.10.013

Abstract ( 479 )

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Epigenetic regulation plays an important role in breast cancer research. The epigenetic modification of histone mainly affects the occurrence and development of breast cancer by adding and removing methyl, acetyl and phosphate groups under the action of various enzymes. Because of its reversible regulatory process, it can provide advantage for the affected region to return to the normal genome state. Clinically, this can be used to develop a variety of drugs for patient diagnosis and treatment and to provide treatment targets.

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Application of circulating tumor DNA in endocrine therapy resistance of breast cancer

Liu Binliang, Ma Fei, Zeng Yixin

2017, 44 (10): 779-782. doi: 10.3760/cma.j.issn.1673-422X.2017.10.014

Abstract ( 386 )

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Although most hormonereceptor positive breast cancer patients initially respond to endocrine treatment, they will eventually acquire resistance to endocrine therapy. Therefore, during clinical treatment, it is of great importance to continuously monitor for resistant mutations. Circulating tumor DNA (ctDNA) has become more prevalent because it is noninvasive, convenient, rapid, and can quickly assess the overall situation of the tumor. With the maturity of nextgeneration sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR), the establishment of endocrine treatment resistance mutation monitoring system has become possible.

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ROS1 fusion gene in targeted therapy of nonsmall cell lung cancer

Chuang Xin, Jin Bo

2017, 44 (10): 783-786. doi: 10.3760/cma.j.issn.1673-422X.2017.10.015

Abstract ( 442 )

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The molecular target therapy of nonsmall cell lung cancer (NSCLC) has become a hot research direction in the field of medicine. Following the discovery of wellknown tumordriven genes such as epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene (KRAS) and anaplastic lymphoma kinase (ALK) genes, more and more scholars have shifted focus to ROS1 fusion gene. The protein encoded by ROS1 is a member of the receptor tyrosine kinase super family, and it plays an important role in cell growth and cell survival. ROS1 fusion gene plays a vital role in the occurrence, development and clinical treatment of NSCLC.

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Roles of interleukin6 in occurrence, development and prognosis of hepatocellular carcinoma

Zhang Bin, Shi Dongmei, Qiao Sen

2017, 44 (10): 787-789. doi: 10.3760/cma.j.issn.1673-422X.2017.10.016

Abstract ( 506 )

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Interleukin6 (IL6) involves in a variety of inflammatory responses and immune regulation, showing closely correlations to tumor progression. Recent studies reveal that IL6 may play an important role in constituting tumor microenvironment, activating related signal pathway, regulating downstream transcription factors, to affect the proliferation, invasion and metastasis of tumor cells. IL6 has important potential value in the targeted therapy for hepatocellular carcinoma.

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Relationship between insulin resistance related factors and colon cancer stem cells

Wan Lijuan, Chen Mingwei

2017, 44 (10): 790-793. doi: 10.3760/cma.j.issn.1673-422X.2017.10.017

Abstract ( 453 )

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Colon cancer stem cells have uncontrolled selfrenewal capabilities, a potential of forming colon cancer and resistance to conventional antitumor therapy. Insulin resistance related factors mainly include adiponectin, leptin and various inflammatory factors. Various insulin resistance related factors have different effects on the proliferation, apoptosis, migration, carcinogenesis of colon cancer stem cells through different mechanisms. Understanding the relationship between various insulin resistance related factors and colon cancer stem cells can provide a new treatment for colon cancer.

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