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08 August 2021, Volume 48 Issue 8 Previous Issue    Next Issue

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One Hundred Years of the Party's Striving for the People's Health

Diagnosis, treatment and prognosis of human major exocrine ductal carcinoma Ma Pingchuan, Li Chunjie, Li Longjiang 2021, 48 (8):  449-455.  doi: 10.3760/cma.j.cn371439-20210602-00087 Abstract ( 199 )   HTML ( 19 )   PDF (5811KB) ( 120 )   Save Exocrine ductal carcinoma is an important part of malignant tumors of exocrine glands, including invasive breast ductal carcinoma, salivary duct carcinoma, pancreatic ductal adenocarcinoma and cholangiocarcinoma. Most of these diseases are aggressive, highly malignant and endanger human health. Early detection and diagnosis are the key to a good prognosis for exocrine ductal carcinoma. Different exocrine ductal carcinomas also have certain connections, and their molecular biological characteristics, pathological characteristics and molecular mechanisms have similarities. Surgical resection combined with adjuvant radiotherapy and chemotherapy is currently a common treatment method for exocrine ductal carcinoma. At the same time, its related targeted therapy and immunotherapy sites can also learn from each other. Human epidermal growth factor receptor-2 (HER-2) and the family markers have become breast ductal carcinoma and salivary duct carcinoma targeted therapy sites, and immunotherapy at programmed death ligand 1 (PD-L1) sites has also been involved in many studies, but there is no clear conclusion yet. References | Related Articles | Metrics

Original Articles

BRD4 inhibitor specifically inhibits the development of wild-type Kras differentiated thyroid carcinoma by regulating BRD4/miR-106b-5p/P21 axis Feng Zhiping, Yang Chuanzhou, Chen Ting, Zhu Jialun, Liu Chao, Lyu Juan, Lu Jianmei, Deng Zhiyong 2021, 48 (8):  463-472.  doi: 10.3760/cma.j.cn371439-20200528-00089 Abstract ( 278 )   HTML ( 20 )   PDF (26842KB) ( 123 )   Save Objective To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods The DTC cell line KrasWT TPC-1 was selected and the mutant KrasG12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of KrasWT TPC-1 cells. KrasWT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. KrasWT TPC-1 cells were divided into JQ-1+NC-OE group, JQ-1+p21-OE group (overexpression of p21) and JQ-1+p21-OE+miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into KrasWT group, KrasWT+JQ-1 group, KrasG12D group and KrasG12D+JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results JQ-1 inhibited the proliferation activity of KrasWT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences (t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in KrasWT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+NC-OE group, JQ-1+p21-OE group and JQ-1+p21-OE+miR-106b-5p mimic group, the proliferation activities at 24 h of KrasWT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 (F=8.720, P=0.017), and the proliferation activity of JQ-1+p21-OE group was significantly lower than that of the JQ-1+NC-OE group (P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 (F=8.347, P=0.018), and the number of cell invasion in the JQ-1+p21-OE group was significantly lower than that in the JQ-1+NC-OE group (P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% (F=37.764, P<0.001), and the apoptosis rate of the JQ-1+p21-OE group was significantly higher than that in the JQ-1+NC-OE group (P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+p21-OE+miR-106b-5p mimic group and JQ-1+NC-OE group (all P>0.05). In KrasWT group, KrasWT+JQ-1 group, KrasG12D group and KrasG12D+JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 (F=17.776, P<0.001). Compared with the KrasWT group, cell proliferation activity in the KrasWT+JQ-1 group was significantly decreased, while that in the KrasG12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 (F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the KrasWT+JQ-1 group was significantly decreased (P=0.002), and that in the KrasG12D group was significantly increased (P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% (F=119.170, P<0.001). Compared with the KrasWT group, the apoptosis rate in the KrasWT+JQ-1 group was significantly increased (P<0.001), and that in the KrasG12D group was significantly decreased (P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between KrasG12D+JQ-1 group and KrasG12D group (all P>0.05). Conclusion BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells. Figures and Tables | References | Related Articles | Metrics

TXNDC5-Prx2 axis regulates drug resistance of prostate cancer cells Zhang Yongli, Zhang Ruojia, Fan Huancai, Ge Luna, Wang Lin 2021, 48 (8):  473-478.  doi: 10.3760/cma.j.cn371439-20210324-00090 Abstract ( 315 )   HTML ( 16 )   PDF (4840KB) ( 114 )   Save Objective To study the effect of thioredoxin domain containing protein 5 (TXNDC5)-peroxiredoxin 2 (Prx2) on the drug resistance of prostate cancer cells.Methods Prostate cancer PC3 cells were cultured in vitro, treated with the chemotherapy drug cyclophosphamide (5, 10, 15 μmol/L) for 24 hours, and PC3 cells without any treatment was served as the control group. The expression levels of TXNDC5 in PC3 cells were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting. PC3 cells with TXNDC5 knocking down were exposed by cyclophosphamide and CCK-8 was used to detect the cell viability of siTXNDC5 group and siNC group. The content of reactive oxygen free radicals was determined by reactive oxygen detection kit. PC3 cells and its parental cyclophosphamide-resistant ones with TXNDC5 knocking down were treated by 10 μmol/L cyclophosphamide and subjected for CCK8 assay. The expression of Prx2 in PC3 cells was detected by Western blotting after TXNDC5 was silenced. Prx2 expression was silenced in PC3 cells overexpressing TXNDC5, and cell viability and reactive oxygen free radical content were detected in Vec-Ctrl group, pcTXNDC5 group, siNC group, siPrx2 group and pcTXNDC5+siPrx2 group.Results Compared with the control group, cyclophosphamide treatment significantly increased the expression of TXNDC5 at mRNA and protein levels in PC3 cells. After PC3 cells were treated with cyclophosphamide (10, 15 μmol/L) for 12 h, compared with the siNC group, the cell viability in the siTXNDC5 group was significantly suppressed (0.44±0.08 vs. 0.74±0.10, t=3.647, P=0.031; 0.30±0.04 vs. 0.53±0.06, t=6.115, P=0.006). When PC3 cells were treated with 10 μmol/L cyclophosphamide for 6 and 12 h, compared with the siNC group, the production of reactive oxygen free radicals in the siTXNDC5 group was significantly increased (2.68±0.19 vs. 1.58±0.26, t=-6.027, P=0.005; 4.56±0.37 vs. 2.73±0.26, t=-6.995, P=0.003). When PC3 cells and its cyclophosphamide-resistant ones were treated with 10 μmol/L cyclophosphamide for 12 h, compared with the siNC group, the cell viability was significantly inhibited in the siTXNDC5 group. Western blotting analysis showed that the expression of Prx2 was significantly reduced when TXNDC5 was silenced. Silencing Prx2 could significantly attenuate the increase of cell viability and the decrease of reactive oxygen content resulting from TXNDC5 overexpression. PC3 cells were treated with 10 μmol/L cyclophosphamide for 12 h, and the cell viabilities of the Vec-Ctrl group, pcTXNDC5 group, siNC group, siPrx2 group and pcTXNDC5+siPrx2 group were 0.52±0.07, 0.69±0.03, 0.56±0.05, 0.43±0.05, 0.58±0.07, respectively, and there was a statistically significant difference (F=8.868, P=0.003). Furthermore, the cell viability in the pcTXNDC5+siPrx2 group decreased significantly when compared to that of the pcTXNDC5 group (P=0.045). The contents of reactive oxygen free radicals in the above 5 groups were 3.26±0.46, 2.09±0.49, 3.16±0.38, 4.62±0.26, 2.87±0.36, respectively, and there was a statistically significant difference (F=16.037, P<0.001). The content of reactive oxygen radicals in the pcTXNDC5+siPrx2 group was higher than that of the pcTXNDC5 group (P=0.036).Conclusion TXNDC5 can reduce the level of reactive oxygen free radicals in prostate cancer cells by regulating the expression of Prx2, so as to promote the drug resistance of prostate cancer cells. Figures and Tables | References | Related Articles | Metrics

Clinical study of anlotinib combined with irinotecan in the third line treatment of metastatic esophageal cancer Zhao Huijuan, Ding Meiqian, Chen Wenting 2021, 48 (8):  479-483.  doi: 10.3760/cma.j.cn371439-20200527-00091 Abstract ( 422 )   HTML ( 24 )   PDF (3571KB) ( 157 )   Save Objective To investigate the clinical efficacy and adverse reactions of anlotinib combined with irinotecan in the third line treatment of metastatic esophageal cancer.Methods From October 2018 to October 2019, 52 patients with metastatic esophageal cancer who had developed distant metastasis after receiving standard concurrent chemoradiotherapy and failed second-line chemotherapy were selected from Lu'an Hospital of Traditional Chinese Medicine of Anhui Province. The patients were divided into experimental group and control group by random number table method, with 26 cases in each group. The control group was given intravenous chemotherapy with irinotecan. The experimental group was treated with oral erlotinib combined with intravenous chemotherapy of irinotecan. The clinical efficacy and adverse reactions of the two groups were evaluated after 2 cycles of treatment.Results Before treatment, there was no significant difference in Karnofsky performance status (KPS) score between the experimental group and the control group (76.15±7.52 vs. 74.62±8.59, t=-0.137, P=0.892). After treatment, there was no significant difference between the two groups (70.77±6.28 vs. 72.69±8.74, t=-1.761, P=0.084). However, after treatment, the KPS score in the experimental group was lower than that before treatment (t=3.035, P=0.006). There was no statistical significance in the KPS scores of the control group before and after treatment (t=1.000, P=0.327). Adverse reactions in the two groups were mainly grade 1-2. The incidences of grade 1-2 myelosuppression and diarrhea in the experimental group were 61.5% (16/26) and 46.2% (12/26), which were significantly higher than those in the control group (19.2%, 5/26 and 19.2%, 5/26), with statistically significant differences (χ2=9.665, P=0.002; χ 2=4.282, P=0.039). The disease control rate of the experimental group was 73.1% (19/26), which was significantly higher than that of the control group (46.2%, 12/26), and there was a statistically significant difference between the two groups (χ 2=3.914, P=0.048). The median progression-free survival of the experimental group and the control group was 52 days and 45 days, respectively, and there was a statistically significant difference (χ 2=4.692, P=0.032). Conclusion Anlotinib combined with irinotecan in the third-line treatment of metastatic esophageal cancer has obvious efficacy, but to a certain extent, it increases the incidence of grade 1-2 myelosuppression and diarrhea, and the KPS score is lower compared with before treatment. Figures and Tables | References | Related Articles | Metrics

Analysis of the clinical value of different radiotherapy schemes in patients with advanced esophageal squamous cell carcinoma Wang Bin, Zhou Jiangyun, Liu Xi 2021, 48 (8):  484-488.  doi: 10.3760/cma.j.cn371439-20200710-00092 Abstract ( 250 )   HTML ( 16 )   PDF (3612KB) ( 117 )   Save Objective To compare the clinical efficacy, adverse reactions and prognosis of different radiotherapy schemes in the treatment of advanced esophageal squamous cell carcinoma.Methods The clinical data of 60 patients with stage ⅣB esophageal squamous cell carcinoma who received radiotherapy in Rugao People's Hospital of Jiangsu Province from January 2015 to January 2020 were retrospectively analyzed. According to the radiation doses, the patients were divided into standard dose group (total radiation dose <50.4 Gy) and high dose group (total radiation dose ≥50.4 Gy), with 30 patients in each group. The scores of dysphagia before and after treatment were analyzed by Wilcoxon signed-rank test. The radiotherapy effective rate, remission rate of dysphagia and incidence of adverse reactions were analyzed by χ 2 test. Survival analysis was carried out by Kaplan-Meier and log-rank test was used to compare the prognosis of the two groups. Results There were no significant differences in dysphagia scores between standard dose group and high dose group before and after radiotherapy (Z=1.232, P=0.876; Z=1.506, P=0.278). The dysphagia symptoms were relieved after radiotherapy in all patients, and the dysphagia score was significantly higher than that before radiotherapy (Z=6.347, P<0.001). The radiotherapy effective rates in the standard dose group and high dose group were 76.7% (23/30) and 83.3% (25/30) respectively, with no statistically significant difference (χ2=0.417, P=0.519). The remission rates of dysphagia in the two groups were 80.0% (24/30) and 90.0% (27/30) respectively, with no statistically significant difference (χ 2=0.523, P=0.470). The incidences of adverse reactions in the two groups were 43.3% (13/30) and 83.3% (25/30) respectively, with a statistically significant difference (χ 2=10.335, P=0.001). The median overall survival in the standard dose group and high dose group were 11 months and 9 months respectively, with no statistically significant difference (χ 2=1.490, P=0.256). Conclusion There are no statistical differences in short-time efficacy, symptom remission and long-term prognosis between the standard dose group and the high dose group in patients with advanced esophageal squamous cell carcinoma. However, the incidence of adverse reactions in patients receiving standard dose radiotherapy is low, which is worthy of clinical application. Figures and Tables | References | Related Articles | Metrics

Reviews

Mechanism and application of hypoxia affecting immunotherapy drug resistance Chen Peiyao, Jia Junmei 2021, 48 (8):  489-493.  doi: 10.3760/cma.j.cn371439-20201105-00093 Abstract ( 322 )   HTML ( 18 )   PDF (3835KB) ( 167 )   Save Immunotherapy is a new anti-tumor method. The application of immune checkpoint inhibitor greatly improves the survival benefit for patients, but the drug resistance of immunotherapy affects the efficacy. Therefore, it is very important to explore the mechanism of drug resistance and solve the problem of drug resis-tance in tumor immunotherapy. Hypoxia in tumor microenvironment is the key factor of immune drug resistance. Hypoxia can inhibit the immune cells function and lead to immune escape through various mechanisms. It can be the breakthrough for overcoming the immunotherapy drug resistance that blocking pathway of hypoxia to promote immune resistance. By reviewing the mechanism of immunotherapy drug resistance induced by hypoxia, it is helpful to explore the development prospect of hypoxia-inducible factor-1α (HIF-1α) related targeted drugs in clinical application for immunotherapy. References | Related Articles | Metrics

Importance of recurrent laryngeal nerve lymph node in esophageal squamous cell carcinoma and the key points of dissection technique Zhao Fangchao 2021, 48 (8):  494-497.  doi: 10.3760/cma.j.cn371439-20210617-00094 Abstract ( 373 )   HTML ( 17 )   PDF (3252KB) ( 153 )   Save Recurrent laryngeal nerve lymph node (RLN LN) is not only the most common site of esophageal squamous cell carcinoma metastasis, but also a key factor affecting the prognosis of patients. RLN LN is a reliable predictor of cervical lymph node metastasis, and its status determines whether cervical lymph node dissection should be performed. However, because of its wide range of operations, large trauma and high incidence of postoperative complications, it is very important to screen out the beneficiaries. References | Related Articles | Metrics

Efficacy predictors of immune checkpoint inhibitors in the treatment of metastatic gastric cancer Hu Guangyue, Yin Hong, Zhang Hui, Luo Hong 2021, 48 (8):  498-501.  doi: 10.3760/cma.j.cn371439-20210104-00095 Abstract ( 280 )   HTML ( 14 )   PDF (3060KB) ( 146 )   Save In recent years, immunotherapy has been used more frequently for metastatic gastric cancer that has progressed after chemotherapy, the most commonly used of which are immune checkpoint inhibitors (ICIs). However, the efficacy of ICIs varies greatly among different patients. Therefore, more and more studies have been carried out on biomarkers that predict the efficacy of ICIs. Microsatellite instability and Epstein-Barr virus subtype are relatively accurate biomarkers indicating the response rate of ICIs treatment. The predictive roles of programmed death ligand-1 and tumor mutation burden are still controversial. Tumor infiltrating lymphocyte, tumor-associated macrophages, fibrinogen-like-protein 1, alternative promoters and other predictors are also being studied. References | Related Articles | Metrics

Application of non-coding RNAs in early diagnosis of colorectal cancer Wang Pei, Cui Manli, Zhang Mingxin 2021, 48 (8):  502-506.  doi: 10.3760/cma.j.cn371439-20210119-00096 Abstract ( 264 )   HTML ( 16 )   PDF (3627KB) ( 150 )   Save Non-coding RNAs (ncRNAs) is a kind of RNA without protein coding function. A large number of studies in recent years have shown that the occurrence and development of colorectal cancer (CRC) are closely related to the aberrant expression of ncRNAs. ncRNAs can be used as non-invasive biomarkers for early diagnosis of CRC. We review the research progress of ncRNAs in early diagnosis of CRC, and summarize the potential clinical value of ncRNAs detection, which can provide a theoretical basis for improving the early diagnosis rate of CRC. References | Related Articles | Metrics