Journal of International Oncology

Expressions of MDR-1 and P-gp in human nasopharyngeal squamous cell carcinoma CNE1 cell line after X-ray exposure

Huang Ting, Song Xuewei, An Shufen, Wang Zhibin, Liao Hehe

2018, 45 (6): 321-324. doi: 10.3760/cma.j.issn.1673-422X.2018.06.001

Abstract ( 462 )

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Objective To examine the expressions of multidrug resistance gene (MDR)-1 and P-glycoprotein (P-gp) in nasopharyngeal squamous cell carcinoma CNE1 cell line before and after X-ray exposure. Methods CNE1 cells were exposed to X-ray. After the irradiation, the CNE1 cells were cultured for 24 hours and tested. The mRNA expressions of MDR-1 in CNE1 cells were measured by semiquantitative realtime polymerase chain reaction (RT-PCR) before and after X-ray exposure, and the protein expressions of P-gp in CNE1 cells were detected by Western blotting. The protein expressions of Pgp in CNE1 cells were observed by confocal microscope before and after X-ray exposure. Results The results of RT-PCR showed that the absorbance (A) values of MDR1 mRNA in CNE1 cells were 0.17±0.01 and 0.34±0.03 before and after irradiation, and the difference was statistically significant (t=16.541, P＜0.001). The results of Western blotting showed that the A values of P-gp protein in CNE1 cells were 0.02±0.01 and 0.04±0.01, and the difference was statistically significant (t=4.612, P=0.016). The green fluorescence intensity of P-gp protein in CNE1 cells after X-ray irradiation was higher than that before X-ray irradiation by confocal microscope. Conclusion X-ray irradiation can cause the high expressions of MDR-1 and P-gp in CNE1 cells, suggesting that X-ray irradiation can induce the occurrence of multidrug resistance in CNE1 cells.

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Experimental study of allicin inhibiting the proliferation and invasion of human multiple myeloma cell

Wu Di, Liu Fang, Yu Yanli, Lu Rong, Zhang Wei

2018, 45 (6): 325-330. doi: 10.3760/cma.j.issn.1673-422X.2018.06.002

Abstract ( 537 )

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Objective To investigate the effect of allicin on the proliferation, apoptosis and invasion of human multiple myeloma (MM) cell line RPMI8226 in vitro, and to explore its mechanism. Methods The human MM cell line RPMI8226 cells were treated with different concentrations of allicin as 0, 5, 25, 125 μmol/L, wherein the control group was 0 μmol/L allicin treatment group. The proliferation of cells was calculated by cell counting kit-8 (CCK-8). The apoptosis and invasion ability of tumor cells were determined with flow cytometry and Transwell method respectively. The expressions of transforming growth factor-α (TGF-α), matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) protein were detected by Western blotting. ResultsThe proliferation rates of RPMI8226 cells in groups treated with 0, 5, 25 and 125 μmol/L allicin were 1.00%±0.02%, 0.98%±0.04%, 0.73%±0.22% and 0.44%±0.15% respectively, with a significant difference (F=329.2, P<0.001). The proliferation rates of RPMI8226 cells in the 25 and 125 μmol/L allicin treatment groups were significantly inhibited compared with control group (P<0.001; P<0.001); but there was no significant difference between 5 μmol/L treatment group and control group (P=0.395). The apoptosis rates of RPMI8226 cells treated with 0, 5, 25 and 125 μmol/L allicin were 3.05%±0.53%, 4.06%±0.29%, 12.17%±1.08% and 12.81%±1.78% respectively, with a significant difference (F=531.0, P<0.001). The apoptotic rates of RPMI8226 cells in the 25 and 125 μmol/L allicin treatment groups were significantly increased compared with control group (P=0.013; P=0.012); and there was no significant difference between 5 μmol/L treatment group and control group (P=0.211). The numbers of invasive cells in the 0, 5, 25 and 125 μmol/L allicin treatment groups were 112.5±1.9, 104.8±4.0, 76.9±2.6 and 52.5±3.7 respectively, with a significant difference (F=734.9, P<0.001). The abilities of cells invasiveness in 25 and 125 μmol/L allicin treatment groups were significantly decreased compared with control group (P<0.001; P<0.001), but 5 μmol/L allicin treatment group had no significant difference compared with the control group (P=0.160). Western blotting results showed that the expression levels of TGF-α, MMP-2, MMP-9 and TIMP-2 proteins were significantly different between groups treated with different concentrations of allicin (F=227.1, P<0.001; F=348.5, P<0.001; F=359.7, P<0.001; F=158.0, P<0.001). The protein expression levels of TGF-α, MMP-2 and MMP-9 were significantly decreased in the 25 and 125 μmol/L treatment groups compared with the control group (all P<0.001), and the expression of TIMP2 protein was significantly increased compared with the control group (all P<0.001), but there were no significant differences between the 5 μmol/L treatment group and the control group (P=0.349; P=0.744; P=0.613; P=0.567). Conclusion Allicin can significantly inhibit cell proliferation, invasive ability and induce apoptosis of human MM cell line RPMI8226 in vitro, and the mechanism may be related to inhibiting the expressions of TGF-α, MMP-2, MMP-9 and promoting the expression of TIMP-2 at the same time.

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Clinical study of intensity modulated radiation therapy for wholebrain radiotherapy with simultaneous integrated boost for brain metastases

Zhu Haisheng, Yan Haolin, Que Lilin, Gan Mei, Liang Leifeng, He Lin

2018, 45 (6): 331-336. doi: 10.3760/cma.j.issn.1673-422X.2018.06.003

Abstract ( 619 )

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Objective To evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for wholebrain radiotherapy with simultaneous integrated boost for brain metastases. MethodsFrom January 2015 to January 2017, 120 patients with brain metastases undergoing hospital radiotherapy at the First People′s Hospital and the Second People′s Hospital of Yulin City of Guangxi Zhuang Autonomous Region were randomly divided into three dimensional conformal radiation therapy (3DCRT) group (n=60) and IMRT group (n=60) by envelope method. The curative effects of the two groups and the changes of patient′s mental states before and after radiotherapy were compared. ResultsThe median survival times of patients in 3DCRT group was 11.5 months, and the 6 months and 1 year survival times rates were 83.3% and 35.0% respectively. The median survival times of patients in IMRT group was 12.9 months, and the 6 months and 1 year survival rates were 86.7% and 38.3% respectively. There was no significant difference in prognosis between the two groups (χ2=0.143, P=0.705). There were 8 cases with complete remission, 38 cases with partial remission, 11 cases with stable disease, 3 cases with progressive disease in 3DCRT group, and there were 9, 40, 9, 2 cases in IMRT group respectively. There was no statistically significant difference in shortterm efficacy between the two groups (Z=-0.641, P=0.520). Univariate analysis results showed that recursive partitioning analysis (RPA) classification (χ2=53.484, P＜0.001), extracranial lesions control (χ2=13.392, P＜0.001), whether the midline offset (χ2=4.427, P=0.035) were prognostic factors. Multivariate analysis results showed that RPA classification (HR=2.631, 95%CI: 1.8843.673, P＜0.001), extracranial lesions control (HR=1.697, 95%CI: 1.0342.786, P=0.037), whether the midline offset (HR=1.787, 95%CI: 1.1182.856, P=0.015) were the independent prognostic factors for the overall survival. According to the results of activities of minimental state examination, the scores of 3DCRT group before and after radiotherapy were 27.12±2.42 and 26.08±2.42 respectively, with a significant difference (t=2.723, P=0.009); and the scores of IMRT group before and after radiotherapy were 26.57±3.09 and 27.20±2.46 respectively, with no significant difference (t=-1.610, P=0.113). ConclusionIMRT for wholebrain radiotherapy with simultaneous integrated boost is an effective treatment for multiple brain metastases, which can relieve symptoms, prolong survival time and improve quality of life.

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Diagnostic value of serum tumor markers in bone metastasis of non-small cell lung cancer

Wu Qiong, Ma Haiyang, Wang Xuechen, Zhang Mingming, Zhang Yong

2018, 45 (6): 337-340. doi: 10.3760/cma.j.issn.1673-422X.2018.06.004

Abstract ( 611 )

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Objective To analyze the diagnostic value of serum tumor markers in bone metastasis of non-small cell lung cancer (NSCLC). Methods The clinical data and follow up data of 160 patients with NSCLC from March 2013 to September 2015 in Tangshan People′s Hospital were retrospectively analyzed. According to the status of bone metastasis, the patients were divided into the observation group with bone metastasis (n=114) and the control group without bone metastasis (n=46). The positive rates and concentrations of 4 tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen CA125, CA19-9 and Ferritin were analyzed and compared. And their sensitivities and specificities to the diagnosis of NSCLC bone metastasis were analyzed. The Youden index was calculated to capture the performance of the diagnostic test. Results The concentrations of CEA, CA125, CA19-9 and Ferritin in the observation group were (19.74±6.71) μg/L, (45.62±19.53) kU/L, (35.89±15.66) kU/L and (334.02±79.43) μg/L respectively, which were higher than those in the control group ［(2.36±0.92) μg/L, (14.37±5.43) kU/L, (15.31±7.22) kU/L, (122.58±69.46) μg/L］, and the differences were statistically significant (t=7.200, P＜0.001; t=7.180, P＜0.001; t=6.032, P＜0.001; t=11.152, P＜0.001). The positive rates of CEA, CA125, CA19-9 and Ferritin in the observation group were 78.95%, 68.42%, 52.63% and 73.68% respectively, which were higher than those in the control group (8.70%, 4.35%, 4.35% and 13.04%), and the differences were statistically significant (χ2=66.746, P＜0.001; χ2=53.822, P＜0.001; χ2=32.193, P＜0.001; χ2=48.975, P＜0.001). The sensitivities of CEA, CA125, CA199 and Ferritin were 78.94%, 68.42%, 52.63% and 73.68% respectively, and the specificities of them were 91.30%, 95.65%, 95.65% and 86.96% respectively. The Youden indexes were 70.24%, 64.07%, 48.28% and 60.64% respectively. The sensitivity and specificity of multifactorial combination were 99.17% and 72.63%, and the Youden index was 71.80%. Conclusion Four tumor markers including CEA, CA125, CA19-9 and Ferritin were correlated with NSCLC, and combined detection has better performance of dignosis than single factor.

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Association of the prognostic nutrition index with overall survival time of the patients with brain metastases of lung adenocarcinoma

Xue Ruiqi, Li Hongwei, Zhang Xiaqin, Song Xin, Peng Hua, Zhou Wei, Zhang Changcheng

2018, 45 (6): 341-346. doi: 10.3760/cma.j.issn.1673-422X.2018.06.005

Abstract ( 468 )

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Objective To explore the effect of prognostic nutrition index (PNI) on the overall survival time of patients with brain metastases of lung adenocarcinoma. Methods A retrospective analysis was performed on the clinic data of 274 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma from May 2013 to May 2016. The prognosic factors for brain metastases such as PNI, gender, age, smoking history, epidermal growth factor receptor (EGFR) mutation status, Karnofsky performance status (KPS) score, the number of brain lesions, treatment of brain lesions, extracranial metastases and the status of primary disease were analyzed. The receiver operating characteristic (ROC) curve was drawn to determine the optimal cutoff value of PNI, and the patients were divided into high PNI group and low PNI group. The univariate and multivariate prognostic analyses were performed by the Logrank test and the Cox proportional hazards model. Results The patients were divided into high PNI (＞50.45) group (n=72) and low PNI (≤50.45) group (n=202). The median overall survival (OS) was 11.20 months in all patients with brain metastases, and the median OS of the low PNI group and high PNI group were 10.13 months and 15.17 months respectively. The univariate analysis results showed that gender (χ2=5.459, P=0.019), age (χ2=3.986, P=0.046), smoking or not (χ2=6.878, P=0.009), EGFR mutation status (χ2=20.484, P＜0.001), KPS score (χ2=126.573, P＜0.001), extracranial metastases or not (χ2=4.403, P=0.036), treatment on the brain lesions (χ2=40.444, P＜0.001) and PNI (χ2=7.972,P=0.005) were related to the prognosis. The Cox multivariate analysis results showed that age (HR=1.580, 95%CI: 1.1042.295, P=0.012), EGFR mutation status (HR=0.549, 95%CI: 0.4080.738, P＜0.001), KPS score (HR=0.077, 95%CI: 0.0450.134, P＜0.001), treatment on brain metastases (HR=0.882, 95%CI: 0.7890.987, P=0.029) and PNI (HR=0.614, 95%CI: 0.4370.861, P=0.005) were related to the prognosis. Conclusion PNI is an independent prognostic predictor of brain metastases in patients with lung adenocarcinoma, and the highPNI is correlated to the long OS of patients with brain metastases of lung adenocarcinoma, which has certain clinical practical value.

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Correlations between peripheral absolute lymphocyte count and clinicopathological characteristics of the elderly patients with multiple myeloma and its prognosis

Yao Yixuan, Wang Huan, Xia Jun, Wang Jing, Sun Chao, Sun Hongli, Zhou Xin

2018, 45 (6): 347-351. doi: 10.3760/cma.j.issn.1673-422X.2018.06.006

Abstract ( 622 )

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Objective To investigate the correlations between peripheral absolute lymphocyte count (ALC) and clinicopathological characteristics of newly diagnosed elderly patients with multiple myeloma (MM) and its prognosis. MethodsA total of 57 elderly patients with MM were selected in Wuxi People′s Hospital Affiliated to Nanjing Medical University from January 1, 2007 to December 31, 2015. The patients were grouped as ALC≥1.3×109/L (n=24) and ALC＜1.3×109/L (n=33). The ALC and clinical characteristics of the patients were collected. The chisquare test, rank sum test, Cox regression analysis, Kaplan-Meier analysis and Logrank test were used to analyze the correlation of ALC with clinicopathological characteristics, curative effect and prognosis of elderly patients with MM. ResultsThe peripheral ALC of elderly MM patients was related to hemoglobin content (χ2=6.915, P=0.009), but it was not related to the sex, age, DurieSalmon stage, international staging system stage, creatinine content, lactate dehydrogenase content, albumin content, concentration of Ca2+, performance status and classification (all P＞0.05). There was no significant difference in efficacy between ALC≥1.3×109/L group and ALC＜1.3×109/L group (Z=0.464, P=0.642). In univariate analysis, age (RR=2.843, 95%CI: 1.3855.835, P=0.004), sex (RR=2.092, 95%CI: 1.0344.231, P=0.040), ALC (RR=3.562, 95%CI: 1.5398.244, P=0.003), hemoglobin content (RR=3.583, 95%CI: 1.08711.811, P=0.036), lactate dehydrogenase content (RR=3.192, 95%CI: 1.5806.452, P=0.001) and curative effect (RR=5.202, 95%CI: 1.18422.864, P=0.029) were related to the prognosis of patients. Multivariate analysis results revealed that age (RR=2.672, 95%CI: 1.2355.782, P=0.013) and ALC (RR=2.613, 95%CI: 1.0926.250, P=0.031) were independent predictive factors for patients with MM. KaplanMeier analysis indicated that the median overall survival of ALC≥1.3×109/L group was significantly longer than that of ALC＜1.3×109/L group (69 months vs. 24 months; χ2=10.171, P=0.001). ConclusionThe peripheral ALC in elderly patients with MM is related to hemoglobin content. ALC is an independent prognostic factor for the elderly patients with newly diagnosed MM, and has clinical value for the prognosis of MM.

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Research progress of circulating tumor DNA detection in radiotherapy

Wang Tuo, Li Guixiang

2018, 45 (6): 352-354. doi: 10.3760/cma.j.issn.1673-422X.2018.06.007

Abstract ( 494 )

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Circulating tumor DNA (ctDNA) refers to the DNA segment of the free tumor located in the peripheral circulation, which carries the biologic information derived from the tumor. In recent years, the innovation of the second generation sequencing technology has expanded the prospect of the clinical application of ctDNA analysis. Detection of ctDNA has made a great progress in the field of radiation therapy, especially in the aspect of evaluating the sensitivity of radiotherapy. ctDNA in peripheral blood is characterized by convenient extraction and high specificity. Detection of ctDNA is not only conducive to find minimal residual disease and metastasis, but also help clinicians better evaluate the curative effect and judge prognosis after radiotherapy, which will provide a new way of thinking for the diagnosis and treatment strategy of tumor.

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Role of microRNA-373 in tumor

Shen Kai, Shao Fang, Feng Tongbao, Qi Chunjian

2018, 45 (6): 355-357. doi: 10.3760/cma.j.issn.1673-422X.2018.06.008

Abstract ( 373 )

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MicroRNAs are non-coding small RNAs that participate in the regulation of post transcriptional gene expression. MicroRNAs play the roles of inhibiting cancer or promoting cancer in different tumors. MicroRNA-373 is one of the members of the microRNA-520/373 family, which is involved in cancer anoxic response and DNA damage repair. MicroRNA-373 is abnormal expressed in breast cancer, glioma, lung cancer, prostate cancer and other tumors, which may play an important role in tumor development process, especially in tumor invasion and migration.

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Evaluation criteria for tumor efficacy in the times of immunotherapy

Bai Rilan, Guo Hanfei, Cui Jiuwei

2018, 45 (6): 358-361. doi: 10.3760/cma.j.issn.1673-422X.2018.06.009

Abstract ( 691 )

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With the advent of the times of immunotherapy and the emergence of a variety of unconventional response patterns such as delayed response and pseudoprogressive disease, a variety of immunerelated efficacy evaluation criteria such as immunerelated response criteria, immunerelated response evaluation criteria in solid tumor and immune response evaluation criteria in solid tumor have been proposed successively. The evaluation principles and judgment results of these criteria are distinctly different from the traditional response evaluation criteria. In particular, the newly proposed immune response evaluation criteria in solid tumor introduces two new concepts of unconfirmed progressive disease and confirmed progressive disease and provides a new response evaluation model for solid tumors, which is expected to provide solutions to some of the most urgent clinical problems under the times of cancer immunotherapy.

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Mechanism of microRNA-495 in glioma

Zhang Yuanyuan, Zhu Shuxia

2018, 45 (6): 362-364. doi: 10.3760/cma.j.issn.1673-422X.2018.06.010

Abstract ( 411 )

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MicroRNA-495 (miR-495) is abnormally expressed in many tumors, especially in glioma. It involves in the proliferation, apoptosis, cycle regulation, metabolism, invasion and metastasis of tumor cells by regulating cyclin dependent kinase 6 signaling pathway, glucose transporter type 1 signaling pathway, MYB signaling pathway, growth factor independent 1 signaling pathway and high mobility group nucleosome binding domain 5 signaling pathway. Further study of miRNA-495 might provide a novel direction for clarifying the pathogenesis, diagnosis and treatment of glioma.

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