Journal of International Oncology

PET probes of small molecule polypeptide immunosuppressive agents guiding tumor immunotherapy

Jiang Jinquan, Liu Teli, Xia Lei, Zhu Hua, Yang Zhi

2019, 46 (8): 449-452. doi: 10.3760/cma.j.issn.1673-422X.2019.08.001

Abstract ( 879 )

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Immunosuppressant targeting programmed death protein-1 and its ligand (PD-1/PD-L1) is a hot topic in solid tumor immunotherapy. Detection of PD-1/PD-L1 expression in solid tumor patients by molecular imaging can predict whether tumor patients can benefit from immunotherapy. Small molecular polypeptide inhibitors have the advantages of low molecular weight, fast diffusion in tumor microenvironment, uniform distribution and easy access to the deep part of solid tumor. Non-invasive, real-time and quantitative detection of PD-1/PD-L1 expression in tumor patients can be performed by radionuclide labeled small molecular polypeptide inhibitor molecular probe PET imaging. It is expected to provide new detection methods for patient screening, efficacy monitoring, treatment plan optimization and prognosis evaluation.

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Therapeutic effect and mechanism of regulating cellular immune function of chemotherapy combined with PD-1 inhibitor in the first-line treatment of Lewis xenografts

He Fang, Gao Yan, Qi Haiyan, Li Qin, Xu Chong′an

2019, 46 (8): 453-459. doi: 10.3760/cma.j.issn.1673-422X.2019.08.002

Abstract ( 773 )

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Objective To investigate the efficacy of chemotherapy combined with programmed death-1 (PD-1) inhibitor in the first-line treatment of Lewis xenografts and its possible mechanism of regulating cellular immune function. Methods Lewis xenografts mouse model was established. The mice were randomly divided into control, chemotherapy, immunotherapy and combination group according to the method of random number table (10 in each group), and each group separately received saline, cisplatinum, PD-1 inhibitor and cisplatinum combined with PD-1 inhibitor. The tumor growth and survival of each group were observed. Flow cytometry was used to detect and compare the proportion of CD8⁺ T cells and CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Treg cells). Results On the second day after treatment, the tumor volume of Lewis xenografts in control group, chemotherapy group, immunotherapy group and combination group were (1 662.0±209.0) mm³, (1 189.2±155.6) mm³, (991.1±146.6) mm³ and (761.7±141.8) mm³, with statistically significant difference (F=29.78, P<0.001). The tumor volume in the three treatment groups were significantly smaller than that in control group, combination group was significantly smaller than chemotherapy group and immunotherapy group, and immunotherapy group was significantly smaller than chemotherapy group (all P<0.05). Three mice died during the experiment (two in control group and one in chemotherapy group). The median survival time of mice in the four groups were 10, 12, 14 and 18 days, with statistically significant difference (χ²=26.06, P<0.001). The median survival time of mice in the three treatment groups were significantly longer than that in control group, combination group was significantly longer than chemotherapy group and immunotherapy group, and immunotherapy group was significantly longer than chemotherapy group (all P<0.05). The proportions of CD8⁺ T cells in the peripheral blood of the four groups were (28.5±1.2)%, (33.9±2.9)%, (34.0±2.5)% and (42.4±1.5)%, with statistically significant difference (F=21.32, P<0.001). The proportions of CD8⁺ T cells in the peripheral blood of the three treatment groups were significantly higher than that of control group, and combination group was significantly higher than chemotherapy group and immunotherapy group (all P<0.05). The proportions of CD8⁺T cells in the tumor microenvironment of the four groups were (23.5±1.3)%, (26.7±1.4)%, (34.2±2.8)% and (41.3±2.0)%, with statistically significant difference (F=61.65, P<0.001). The proportions of CD8⁺ T cells in the tumor microenvironment of the three treatment groups were significantly higher than that of control group, combination group was significantly higher than chemotherapy group and immunotherapy group, and immunotherapy group was significantly higher than chemotherapy group (all P<0.05). The proportions of CD4⁺CD25⁺FOXP3⁺ Treg cells in the spleen of the four groups were (8.6±0.5)%, (7.2±0.3)%, (6.3±0.4)% and (5.4±0.4)%, with statistically significant difference (F=37.06, P<0.001). The proportions of CD4⁺CD25⁺FOXP3⁺ Treg cells in the spleen of the three treatment groups were significantly lower than that of control group, combination group was significantly lower than chemotherapy group and immunotherapy group, and immunotherapy group was significantly lower than chemotherapy group (all P<0.05). Conclusion Chemotherapy and PD-1 inhibitor can enhance the anti-tumor effect of the body immune system by down-regulating the proportion of Treg cells and up-regulating the proportion of CD8⁺ T cells, etc. Chemotherapy combined with immunotherapy can improve the anti-tumor immune function, inhibit tumor growth and prolong the survival of mouse with xenograft, which were significantly better than chemotherapy and immunotherapy alone.

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Clinical epidemiological analysis of 2 403 cases of lung cancer

WANG Yu-Jin, HUANG Jing-Yu, HU Wei-Dong, LI Sheng, TANG Zheng, YANG Ze-Tian, SHEN Xiao-Yan, SONG Cong-Kuan, LI Fei

2019, 46 (8): 460-465. doi: 10.3760/cma.j.issn.1673-422X.2019.08.003

Abstract ( 774 )

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Objective To understand preliminaryly the epidemiological trend of lung cancer in recent years by retrospective analysis of 2 403 cases of lung cancer in Zhongnan Hospital of Wuhan University from 2013 to 2017. Methods The clinical data of patients with primary bronchogenic cancer diagnosed in Zhongnan Hospital of Wuhan University from 2013 to 2017 were collected. The clinical data such as gender, age, history of tobacco and alcohol, operation, pathological type, clinical stage and epidermal growth factor receptor (EGFR) gene mutation were analyzed statistically. Results A total of 2 403 cases of lung cancer were collected, including 1 766 males and 637 females. There was no significant difference in gender ratio between male and female in five years (χ²=8.481, P=0.075). There were 2 398 cases with age information, the male-to-female ratios of lung cancer patients aged less than 40, 40-49, 50-59, 60-69, 70-79, 80 and over were 0.9∶1.0, 1.4∶1.0, 2.4∶1.0, 3.6∶1.0, 3.4∶1.0 and 3.3∶1.0 respectively, and the difference was statistically significant (χ²=59.004, P＜0.001). The composition difference of adenocarcinoma was not statistically significant in five years (χ²=2.165, P=0.705). There was no statistically significant difference in the composition ratio of squamous cell carcinoma (χ²=4.788, P=0.310). Adenocarcinoma accounted for 43.15% (762/1 766) and 81.95% (522/637) of the pathological types of male and female patients respectively, and the difference was statistically significant (P＜0.001). Squamous cell carcinoma accounted for 39.01% (689/1 766) and 7.28% (47/637) respectively, and the difference was statistically significant (P＜0.001). The proportion of squamous cell carcinoma in smoking patients was 42.99% (583/1 356), which was significantly higher than that in non-smoking patients (14.61%, 153/1 047); the proportion of squamous cell carcinoma in drinking patients was 40.56% (277/683), which was higher than that in non-drinking patients (26.69%, 459/1 720), and the differences were statistically significant (both P＜0.001). A total of 1 252 patients underwent surgery, accounting for 52.10% (1 252/2 403) of the total cases. The surgical rate of small cell carcinoma was 21.72% (48/221), and that of non-small cell carcinoma was 55.18% (1 204/2 182). In five years, the surgical rates of lung cancer patients were 55.11% (221/401), 51.53% (252/489), 58.23% (244/419), 53.18% (276/519) and 45.04% (259/575) respectively, and there was significant difference in the proportion of surgical and non-surgical patients in each year (χ²=19.553, P=0.001). A total of 483 patients were tested for EGFR mutation, the EGFR mutation rate was 58.8% (251/427) in adenocarcinoma patients and 15.6% (5/32) in squamous cell carcinoma patients. Among lung cancer patients aged less than 40, 40-49, 50-59, 60-69, 70-79, 80 and over, the proportions of adenocarcinoma were 76.74% (33/43), 62.39% (136/218), 57.73% (381/660), 47.95% (455/949), 52.22% (235/450) and 52.56% (41/78) respectively, and the difference was statistically significant (χ²=33.078, P＜0.001); the proportions of squamous cell carcinoma were 9.30% (4/43), 21.56% (47/218), 28.03% (185/660), 34.14% (324/949), 32.44% (146/450) and 35.90% (28/78) respectively, and the difference was statistically significant (χ²=26.977, P＜0.001). The difference of composition ratio of TNM staging was statistically significant in five years (χ²=21.003, P=0.034). ConclusionThere has been no significant change of male-to-female ratio in patients with lung cancer in the past five years. With the increase of age, the male-to-female ratio increases first and then decreases. The proportion of adenocarcinoma and squamous cell carcinoma has not increased or decreased significantly in the past five years. Adenocarcinoma and squamous cell carcinoma are both common in male lung cancer patients, while the pathological type of female patients is mainly adenocarcinoma. Squamous cell carcinoma is highly prevalent in smokers and drinkers. The surgical rate of squamous cell carcinoma is higher than that of adenocarcinoma, and the surgical rate of non-small cell lung cancer is higher than that of small cell lung cancer. The EGFR mutation rate is higher in adenocarcinoma. With the increase of age, the proportion of adenocarcinoma in all pathological types tends to decrease, while that of squamous cell carcinoma tends to increase. The patients′ TNM staging has a downward trend, and the operation rate decreases slightly.

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Expression and clinical significance of HIF-1α and OPN in esophageal cancer tissues

Wang Miao, Liu Peijun

2019, 46 (8): 466-470. doi: 10.3760/cma.j.issn.1673-422X.2019.08.004

Abstract ( 715 )

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Objective To discuss the expression and clinical significance of hypoxia-inducible factor-1α (HIF-1α) and osteopontin (OPN) in esophageal cancer tissues. Methods A total of 100 patients with esophageal cancer in Enshi Tujia and Miao Autonomous Prefecture Central Hospital of Hubei Province from January 2015 to January 2017 were selected. The expressions of HIF-1α and OPN in esophageal cancer and adjacent tissues were detected by immunohistochemistry. The relationships between HIF-1α and OPN expressions and clinical pathological characteristics of esophageal cancer patients, as well as the correlation between them were analyzed. Results The positive rates of HIF-1α and OPN expression in esophageal cancer tissues were 70.00% (70/100) and 64.00% (64/100), which were significantly higher than the 14.00% (14/100) and 8.00% (8/100) in adjacent tissues, and the differences were statistically significant (χ²=64.368, P<0.001; χ²=68.056, P<0.001). The expression of HIF-1α was correlated with TNM stage, depth of invasion and lymph node metastasis (χ²=30.159, P<0.001; χ²=17.493, P<0.001; χ²=16.357, P<0.001), but it was not correlated with sex, age, tumor diameter and differentiation (all P>0.05). The expression of OPN was correlated with TNM stage, depth of invasion and lymph node metastasis (χ²=12.558, P=0.002; χ²=15.395, P<0.001; χ²=17.056, P<0.001), but it was not correlated with sex, age, tumor diameter and differentiation (all P>0.05). There was the positive correlation between HIF-1α and OPN expression in esophageal cancer tissues (χ²=61.144, P<0.001, C=0.616). The 2-year survival rates of HIF-1α and OPN positive patients in esophageal cancer tissues were 51.43% and 50.00% respectively, which were significantly lower than those of HIF-1α and OPN negative patients (80.00% and 77.78%), and the differences were statistically significant (χ²=7.143, P=0.008; χ²=7.407, P=0.006). Conclusion HIF-1α and OPN are highly expressed in esophageal cancer tissues, and their high expression may be related to poor survival prognosis of esophageal cancer.

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Correlation between pulmonary infection and preoperative pulmonary function indexes in patients with esophageal cancer undergoing thoracotomy

Hou Haisheng, Wang Qiuyan, Chen Shaochuan

2019, 46 (8): 471-474. doi: 10.3760/cma.j.issn.1673-422X.2019.08.005

Abstract ( 726 )

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Objective To explore the correlation between the occurrence of pulmonary infection after thoracotomy and preoperative pulmonary function indexes in patients with esophageal cancer, and to provide clinical theoretical basis for reducing the incidence of pulmonary infection after thoracotomy. Methods The clinical data of 80 patients with esophageal cancer who underwent thoracotomy from May 2017 to May 2018 in Qinhuangdao Military Industrial Hospital of Hebei Province were retrospectively analyzed. The patients were divided into infected group and uninfected group according to whether pulmonary infection occurred after operation. The preoperative maximal voluntary ventilation (MVV), MVV as a percentage of predicted value (MVV%pred), forced vital capacity (FVC), FVC as a percentage of predicted value (FVC%pred), forced expiratory volume in one second (FEV₁), FEV₁ as a percentage of predicted value (FEV₁%pred), peak expiratory flow (PEF), PEF as a percentage of predicted value (PEF%pred) of the two groups were compared and analyzed. Logistic regression was used to analyze the correlation between pulmonary function indexes and postoperative pulmonary infection. Results Postoperative pulmonary infection occurred in 24 out of 80 patients (30.00%). There was no correlation between gender (t=1.755, P=0.086), nationality (t=2.125, P=0.073) and the severity of pulmonary infection after operation. Age (t=4.084, P=0.024), smoking history (t=5.881, P=0.001), operation duration (t=3.583, P=0.041), intraoperative bleeding volume (t=5.115, P=0.003) and combined basic diseases (t=4.574, P=0.018) were significantly correlated with the severity of pulmonary infection after operation. MVV (χ²=4.242, P=0.039), MVV%pred (χ²=4.405, P=0.036), FVC (χ²=17.500, P<0.001), FVC%pred (χ²=12.382, P<0.001), FEV1 (χ²=12.070, P=0.001) were associated with pulmonary infection. FVC (OR=9.102, 95%CI: 2.691-28.213, P=0.027), FEV₁(OR=21.621, 95%CI: 8.956-81.145, P=0.002) and MVV%pred (OR=5.648, 95%CI: 2.979-15.248, P=0.001) were high risk factors for pulmonary infection. Conclusion Partial pulmonary function indexes are significantly associated with postoperative pulmonary infection. It is necessary to strengthen the detection and improvement of preoperative pulmonary function in order to reduce the incidence of pulmonary infection.

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Effects of calcium levofolinate and 5-fluorouracil combined with epirubicin on stress response and VEGF level in patients with gastric cancer

Liu Yanfeng, Guo Hui, Sun Xiyan

2019, 46 (8): 475-479. doi: 10.3760/cma.j.issn.1673-422X.2019.08.006

Abstract ( 487 )

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Objective To investigate the effects of calcium levofolinate and 5-fluorouracil combined with epirubicin on stress response and vascular endothelial growth factor (VEGF) level in patients with gastric cancer. Methods A total of 160 patients with gastric cancer treated in Huxi Hospital Affiliated to Jining Medical College from April 2016 to March 2018 were selected as research objects. All the patients were divided into two groups according to the random number table method and each group consisted of 80 cases. The control group was treated with epirubicin, while the study group was treated with calcium levofolinate and 5-fluorouracil combined with epirubicin. The clinical efficacy and adverse reactions of the two groups were observed and compared. The levels of VEGF and quality of life were compared before and after the treatment. The stress response indexes such as cortisol (Cor), norepinephrine (NE) and total antioxidant capacity (TAC) were detected, and the stress levels of the two groups were compared. Results The total effective rate of the study group was 67.5% (54/80), which was significantly better than that of the control group ［45.0% (36/80)］, and the difference was statistically significant (χ²=8.229, P=0.004). The quality of life of the two groups after the treatment was significantly higher than that before the treatment, and the quality of life scores of the study group were significantly higher than those of the control group (all P<0.001). After the treatment, the levels of Cor, NE and TAC of the study group were (239.27±19.63) μg/L, (258.46±18.31) ng/L, (11.01±0.77) KIU/L, which were significantly lower than those of the control group ［(286.35±20.63) μg/L, (294.18±21.95) ng/L, (12.73±1.58) KIU/L］, and the differences were statistically significant (t=10.003, P<0.001; t=9.476, P<0.001; t=6.984, P<0.001). After the treatment, the VEGF levels of the two groups were lower than those before the treatment, and the VEGF level of the study group was significantly lower than that of the control group ［(39.4±0.9) pg/ml vs. (42.3±1.1) pg/ml, t=18.251, P<0.001］. The total incidences of adverse reactions in the control group and the study group were 82.5% (66/80) and 48.8% (39/80), respectively. The incidence of adverse reactions in the control group was significantly higher than that in the study group, and the difference was statistically significant (χ²=20.197, P<0.001). Conclusion Calcium levofolinate and 5-fluorouracil combined with epirubicin has a good clinical effect in treating patients with gastric cancer. It can not only improve the level of VEGF in the serum of patients, but also can improve the quality of life of patients, reduce the incidence of adverse reactions and body stress response. It has broad application prospects and is worthy of further promotion and application in clinic.

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Value of perfusion CT quantitative analysis for predicting tumor regression grade after chemoradiotherapy in patients with rectal cancer

Song Zhe, Li Wei, Jia Nan, He Xiang, Zhou Wenyong

2019, 46 (8): 480-484. doi: 10.3760/cma.j.issn.1673-422X.2019.08.007

Abstract ( 815 )

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Objective To explore the value of perfusion CT quantitative analysis for predicting tumor regression grade (TRG) after chemoradiotherapy in patients with rectal cancer. Methods From June 2016 to June 2018, 94 rectal cancer patients diagnosed and treated in Cangzhou Central Hospital of Hebei Province were selected and were divided into reaction group (TRG 3-4) and nonreaction group (TRG 0-2) according to the results of surgical specimens. Perfusion CT was performed in both groups before treatment, and chemoradiotherapy and surgery were used. Baseline data and perfusion CT results including blood flow, blood volume, mean transit time (MTT), permeability surface (PS) were compared between the two groups, and receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of perfusion CT indexes for chemoradiotherapy responsiveness. Results In this study, a total of 23 cases (24.47%) were responsive to chemoradiotherapy, and 71 cases (75.53%) were not responsive to chemoradiotherapy. Blood flow in reaction group ［(38.60±7.13) ml·100 g^-1·min^-1］ was significantly lower than that in non-reaction group ［(67.39±11.33) ml·100 g-1·min-1, t=3.273, P=0.001］. MTT in reaction group was significantly longer than that in non-reaction group ［(11.12±2.19) s vs. (6.88±1.32) s, t=4.500, P＜0.001］. There was no significant difference in blood volume ［(4.62±0.73) ml/100 g vs. (5.01±1.04) ml/100 g］ and PS ［(13.72±3.82) ml·100 g^-1·min^-1 vs. (11.40±2.59) ml·100 g^-1·min^-1］ between the two groups (t=0.818, P=0.415; t=0.409, P=0.683). The best cut-off points of blood flow and MTT for predicting chemoradiotherapy responsiveness were 50.89 ml·100 g^-1·min^-1 and 8.99 s, the area under the curve (AUC) was 0.825 and 0.922, and the AUC of combined prediction of chemoradiotherapy responsiveness was 0.982, which was significantly better than that of single prediction (Z=2.868, P=0.004; Z=2.051, P=0.004). The accuracy (91.49%) and specificity (90.14%) of combined prediction of chemoradiotherapy responsiveness were significantly better than those of single prediction (blood flow: accuracy 75.53%, specificity 73.24%; MTT: accuracy 79.79%, specificity 78.87%), and the differences were statistically significant (χ²=8.800, P=0.012; χ²=6.766, P=0.034). Conclusion Blood flow and MTT in perfusion CT have great predictive value for chemoradiotherapy responsiveness in patients with rectal cancer.

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Prognostic value of red blood cell distribution width in tumors

Ye Jiannan, Sun Chao, Li Jianyong, Zhou Xin

2019, 46 (8): 485-488. doi: 10.3760/cma.j.issn.1673-422X.2019.08.008

Abstract ( 743 )

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Red blood cell distribution width (RDW) is a conventional digital index for diagnosis of anemia, and recent studies have found its new clinical significance: high RDW is closely related to prognosis and diagnosis of both solid tumors and hematological tumors in addition to acute and chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease. RDW, which is cheap and easily acquired, may offer a new direction for clinical diagnosis and prognosis of tumor though the relevant mechanism is unclear.

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Anti-tumor effect and mechanisms of shikonin on gliomas

Yi Lin, Qiu Shi

2019, 46 (8): 489-491. doi: 10.3760/cma.j.issn.1673-422X.2019.08.009

Abstract ( 721 )

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Shikonin has anti-tumor activity, and it not only can inhibit the proliferation, migration and infiltration of glioma cells, but also induce necroptosis of glioma cells via promoting the production of reactive oxygen species. Shikonin combined with endoplasmic reticulum stress inhibitors or regulatory tactics of micro-RNA expression may further enhance its killing effect on gliomas. Shikonin armed by nanoparticles shows increased targetability to gliomas. Shikonin combined with tumor-targeted therapeutic drugs or chemotherapeutic drugs is expected to overcome the drug resistance of glioma cells.

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