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28 December 2021, Volume 35 Issue 6
Cancer Surveillance
Characteristics and time trend of thyroid cancer incidence and mortality from 2012 to 2016 in cancer registration areas of Yunnan province
LIU Rui, CHEN Yang, SHI Qingping, YU Qiuli, ZHU Yunfang, WEN Hongmei
2021, 35(6):  489-494.  doi:10.11904/j.issn.1002-3070.2021.06.001
Abstract ( 124 )   PDF (11971KB) ( 43 )  
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Objective The aim of this study was to understand the incidence and mortality characteristics,and prevalence trends of thyroid cancer in the cancer registration areas of Yunnan province from 2012 to 2016,and to provide suggestions for the prevention and treatment of thyroid cancer. Methods The incidence and death of thyroid cancer cases(ICD-10 coded as C73)in Yunnan Cancer Registry from 2012 to 2016 were collected and sorted out.The incidence,mortality,standardized incidence,standardized mortality,truncation rate(35~64 years old),cumulative rate(0~74 years old),and annual percentage change(APC)of thyroid cancer were analyzed by urban and rural areas. Results The crude incidence of thyroid cancer from 2012 to 2016 in Yunnan cancer registration areas was 8.74/100,000.The China standardized rate was 7.51/100,000,the World standardized rate was 6.59/100,000,the cumulative rate was 0.64%,and the truncation rate was 13.89/100,000.The crude thyroid cancer death rate was 0.68/100,000,The China standardized rate was 2.44/100,000,the world standard rate was 2.39/100,000,the cumulative rate was 0.27%,and the cut-off rate was 3.74/100,000.The age-specific incidence was at a low level of 0~20 years old,and increased rapidly with age after 20 years old,peaks in the 50- years old group,and gradually decreased after 55 years old.The age-specific mortality was at a low level of the 0~40 years old age group,and increased rapidly after the 40 years old age group,reaching two peaks in the 65-years old and 85+ years old age groups,respectively.From 2012 to 2016,the total incidence of thyroid cancer,the women incidence,the crude incidence of thyroid cancer in rural areas(APC was 43.7%,42.3%,and 37.4%,respectively)and the standardized rate(APC was 42.4%,40.9%,and 36.5%,respectively)showed upward trend(P<0.05). Conclusion Thyroid cancer has become one of the common malignant tumors in Yunnan province,and the incidence is increasing rapidly year by year.Research on its risk factors should be strengthened and comprehensive prevention and treatment should be carried out.
Trend and prediction of gastric cancer burden in Beibei district of Chongqing city from 2013 to 2020
WU Liting, LI Dabing, DENG Xiaoxia, LI Baisong
2021, 35(6):  495-499.  doi:10.11904/j.issn.1002-3070.2021.06.002
Abstract ( 87 )   PDF (10197KB) ( 47 )  
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Objective The aim of this study was to understand the trend of the disease burden caused by gastric cancer in Beibei district of Chongqing city from 2013 to 2020,predict the mortality from 2021 to 2023,and provide the suggestion for prevention and treatment of gastric cancer. Methods The data on gastric cancer deaths in Beibei district,Chongqing city from 2013 to 2020 were collected from the “Population Death Information Registration Management System from China Disease Prevention and Control System”.The mortality,age-standard mortality,years of life lost due to early death(YLL),YLL rate,average years of life lost(AYLL)and years of life expectancy loss(YLEL)were calculated.A non-seasonal exponential smoothing model was used to predict mortality.The standardization rate was adopted the population structure of the 2010 national census.Chi-square test was used to compare the these rates.The annual percentage change(APC)and t test were used to analyze the changes of rates and trend. Results The mortality and age-standard mortality of gastric cancer in Beibei district decreased from 15.26/100,000 and 11.81/100,000 in 2013 to 10.66/100,000 and 6.75/100,000 in 2020.The APC were-6.29% and-8.79%,respectively,(t=-3.098,-4.690,P<0.05).The mortality of gastric cancer increased with age,with the lowest in the age group under 50(0.74/100,000 to 2.13/100,000),and the highest in the age group over 80(76.21/100,000 to 169.81/100,000).The YLL rate,AYLL,and YLEL decreased from 3.63‰,23.77,and 0.25 in 2013 to 2.31‰,21.66,and 0.16 in 2020,respectively.The APC was-7.60%,-1.39%,and-7.32%(t=-3.211,-2.308,-4.930,P<0.05).The simple non-seasonal model with exponential smoothing model was the optimal prediction model,and predicted to be 10.66/100,000 of gastric cancer mortality from 2021 to 2023. Conclusion The mortality rate of gastric cancer in Beibei district is on a downward trend.The burden of disease caused by early death of gastric cancer has decreased compared with the past,but the burden of disease is still heavy.It is necessary to continue to consolidate the comprehensive prevention and control of gastric cancer.
Basic Research
The effects of circRNA MYO1C on lung cancer cell autophagy and cancer stem cell differentiation
LUO Wen, JIA Li, ZHANG Jiawen, WANG Dongjie, KONG Yingjun
2021, 35(6):  500-505.  doi:10.11904/j.issn.1002-3070.2021.06.003
Abstract ( 86 )   PDF (12584KB) ( 39 )  
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Objective The aim of this study was to investigate the effects of circRNA MYO1C on autophagy and cancer stem cells(CSCs) differentiation of non-small cell lung cancer(NSCLC). Methods The levels of circRNA MYO1C in normal lung epithelial cells and NSCLC A549 cells were detected by RT-qPCR.A549 cells were divided into the control,NC and siMYO1C groups,and circRNA MYO1C was interfered by transfection with si-circRNA MYO1C plasmids.The cell growth viability and migration ability were detected by CCK-8 and Transwell assays.The expression of CSCs differentiation marker proteins(OCT4,SOX2 and NANOG)and autophagy marker proteins(P62 and IC3II/LC3I)was detected by Western blot. Results Compared with normal lung epithelial cells,the expression of circRNA MYO1C was significantly up-regulated in A549 cells(0.99±0.06 vs. 4.87±0.88,P=0.002).Compared with the NC group,the level of circRNA MYO1C,cell viability,cell migration,the levels of OCT4,SOX2,NANOG and IC3II/LC3I proteins in the siMYO1C group were significantly reduced,the level of P62 protein was significantly increased(P<0.001). Conclusion Down-regulating circRNA MYO1C can inhibit CSCs differentiation and autophagy-related protein expression of NSLCLC cells,and inhibit lung cancer cell migration.
The expression of UBQLN1 in cervical cancer and its effect on prognosis
WANG Lina, WANG Le, JIN Hong, LI Qi, CHENG Haiyan
2021, 35(6):  506-510.  doi:10.11904/j.issn.1002-3070.2021.06.004
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Objective The aim of this study was to investigate the expression of ubiquilin 1(UBQLN1)in cervical cancer and its correlation with prognosis. Methods The immunohistochemical method was used to detect the expression of UBQLN1 in 117 cervical cancer tissues and 32 paired adjacent tissues,and analyze the relationship between UBQLN1 expression and clinicopathological features,recurrence and metastasis,and survival time. Results The positive rate of UBQLN1 expression in cervical cancer tissues was 88.89%(104/117),and the positive rate of UBQLN1 expression in paired adjacent tissues was 56.25%(18/32).Its expression was related to age and histological grade(P<0.05).Kaplan-Meier survival analysis showed that higher expression of UBQN1 was related to the shorter overall survival(OS)and disease free survival(DFS)in patients with cervical cancer(P<0.05). Conclusion The overexpression of UBQLN1 is related to the poor prognosis of cervical cancer.UBQLN1 may play an important role in the occurrence and development of cervical cancer.
Comparison of dosimetry between H-IMRT and H-VMAT techniques in postoperative radiotherapy of breast cancer
XU Bingchen, CAO Yangsen, LI Jian
2021, 35(6):  511-516.  doi:10.11904/j.issn.1002-3070.2021.06.005
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Objective The aim of this study was to compare the dosimetric parameters of the mixed intensity-modulated plan(H-IMRT)and the mixed volume-modulated plan(H-VMAT)after radical mastectomy for left breast cancer(chest wall+supraclavicular+internal mammary area),and provide a certain reference for the design of complex breast cancer postoperative radiotherapy plans. Methods Twenty patients with left breast cancer who underwent radical surgery in our hospital from January 2018 to December 2020 were selected.All patients received radiotherapy on the chest wall,supra-clavicular lymph nodes,and internal mammary lymph nodes.Each patient was designed and made two radiotherapy plans:H-IMRT and H-VMAT.In the CRT field,a 2cm multi-leaf collimator(MLC)was placed in direction of the chest.The prescription dose of the target area was 50Gy,and the dose parameters of the target area and the organ at risk were compared through the dose calculation. Results The uniformity index for the target area of H-IMRT plan was(0.13±0.06),and the conformity index was(1.33±0.08).The uniformity index for the target area of H-VMAT plan was(0.12±0.04),and the conformity index is(1.24±0.07).The uniformity index and conformity index of the target area in the H-VMAT plan were higher than those in the H-IMRT plan(P<0.05).H-IMRT plan suffered from lung V5(48.99±2.91)% and V20(24.5±1.1)%;H-VMAT plan suffered from lung V5(45.87±3.53)% and V20(20.6±1.6)%.The doses of V5 and V20 suffered from lung in H-VMAT plan were lower than those of H-IMRT plan(P<0.05).H-IMRT plan suffered from heart V30(10.44±3.62)% and V40(6.59±3.53)%;H-VMAT plan suffered from heart V30(5.87±1.53)% and V40(4.9±2.8)%.H-VMAT plan heart V30 and V40 Lower than H-IMRT(P<0.05).The doses of V30 and V40 suffered from the heart in the H-VMAT were better than those of H-IMRT.H-IMRT plan for heart was Dmean(7.43±1.78)Gy and H-VMAT plan was Dmean(9.7±0.7)Gy.The Dmean of the heart in the H-VMAT was slightly higher than that of H-IMRT(P<0.05). Conclusion For the postoperative radiotherapy target area of breast cancer with internal mammary lymph nodes,H-VMAT has a better conformability than H-IMRT target area,and the exposure dose to the organs at risk is lower.
Clinical Research
Relationship between preoperative inflammation-related indicators and prognosis of patients with resectable gastric cancer
CHEN Yixin, SUN Yihua, CHENG Yangyang, HE Kaitong, GUO Ting
2021, 35(6):  517-522.  doi:10.11904/j.issn.1002-3070.2021.06.006
Abstract ( 103 )   PDF (11371KB) ( 48 )  
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Objective The aim of this study was to investigate the correlation among systemic immune-inflammation indexes(SII),neutrophils to lymphocytes ratio(NLR),platelets to lymphocytes ratio(PLR),prognosis of patients with resectable gastric cancer,and their clinical significance. Methods Clinicopathological data of 226 patients with gastric cancer treated in the Affiliated Cancer Hospital of Harbin Medical University from October 2013 to February 2015 were retrospectively analyzed.The prognostic values of SII,NLR and PLR in patients with resectable gastric cancer were evaluated and compared. Results The SII,NLR and PLR of the gastric cancer group were significantly higher than those of the healthy control group,and the differences were statistically significant(P<0.05).Multivariate Cox regression analysis showed that high SII(HR=2.947,95% CI:1.345~6.454,P=0.007),high NLR(HR=2.876,95% CI:1.445~5.724,P=0.003),high T staging(HR=5.885,95% CI:1.641~21.099,P=0.007)and presence of distant metastasis(HR=3.010,95% CI:1.472~6.154,P=0.003)were independent risk factors affecting the prognosis of patients with resectable gastric cancer.The area under the ROC curve of SII predicting the outcome of resectable gastric cancer patients was 0.840,the sensitivity was 86.6%,and the specificity was 68.0%,which was higher than NLR,PLR and CA199,and the difference was statistically significant(P<0.05). Conclusion SII is better than NLR and PLR in evaluating the survival outcomes of patients with resectable gastric cancer.
Efficacy and prognosis of SRT combined with lapatinib in the treatment of HER2-positive breast cancer brain metastasis
LUO Bo, ZHANG Qu, ZHENG Hongmei, LIANG Xinjun, ZHOU Xiaomei, WU Xinhong
2021, 35(6):  523-528.  doi:10.11904/j.issn.1002-3070.2021.06.007
Abstract ( 116 )   PDF (11341KB) ( 19 )  
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Objective The aim of this study was to investigate the efficacy and prognosis of stereotactic radiotherapy(stereotactic radiotherapy,SRT)combined with lapatinib in the treatment of HER2-positive breast cancer brain metastasis. Methods A total of 91 patients with HER2-positive breast cancer brain metastases receiving lapatinib targeted therapy and whole brain radiotherapy or SRT were retrospectively analyzed.Forty-two patients received SRT and lapatinib combined with capecitabine treatment(SRT group)and another 49 patients were treated with whole brain radiotherapy and lapatinib combined with capecitabine.Curative effect and toxicity were further evaluated.Regular follow-up The related prognostic factors of patients were analyzed by multivariate Cox ragression. Results The objective response rate of brain lesions in the SRT group was 92.86%(39/42)after the end of radiotherapy;the objective response rate of the whole brain radiotherapy group was 77.55%(38/49),and the SRT group was better than the whole brain radiotherapy group(χ2=4.070,P=0.044).The Irradiated lesions progression free survival rates of 12 months in the SRT group and whole brain group were 95.20% and 83.10%,respectively.The SRT group was better than the whole brain radiotherapy group(χ2=10.851,P=0.001).There was no significant difference in the intracranial metastasis rate between the SRT group and whole brain radiotherapy group.The 1-year survival rates of the SRT group and whole brain radiotherapy group were 85.70%,69.40%,and the 2-year survival rates were 66.70% and 55.10%,respectively.The median survival time of the two groups was 31 months and 25 months,respectively.The SRT group was better than that in the whole brain radiotherapy group(P=0.002).Cox multivariate analysis showed no extracranial metastasis(HR=0.527,95% CI:0.290~0.957,P=0.035),intracranial lesions ≤3(HR= 2.457,95% CI:1.223~4.933,P=0.012),The radiotherapy SRT(HR=1.746,95% CI:1.055-2.888,P=0.030)was an independent protective factors for the prognosis of radiotherapy for brain metastases from HER2-positive breast cancer. Conclusion SRT combined with lapatinib is superior to whole brain radiotherapy combined with lapatinib in terms of local control rate and survival.Few intracranial lesions and no extracranial metastases and radiotherapy SRT is a good prognostic factor for the treatment of brain metastases from HER2-positive breast cancer.
Review
Research progress of precision medical strategy for different subtypes of triple negative breast cancer
SHI Runze, LI Zhigao
2021, 35(6):  529-533.  doi:10.11904/j.issn.1002-3070.2021.06.008
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Triple negative breast cancer(TNBC)accounts for about 15% of the total number of breast cancer.There is no clear target for targeted therapy and endocrine therapy.The treatment method is relatively single,and the recurrence is early.The overall survival rate is poor.The main treatment methods of early TNBC are neoadjuvant chemotherapy and definitive surgery.The proposal of TNBC molecular typing makes the individualized treatment of TNBC enter the era of precision treatment.Precision medicine strategy based on the characteristics of TNBC subtypes can make patients get clinical benefits.This paper aims to review the research progress and clinical benefits of precision medicine strategy of TNBC subtypes.
The role of NK cell polarization in endometrial cancer
MU Guannan, MA Qiang
2021, 35(6):  534-537.  doi:10.11904/j.issn.1002-3070.2021.06.009
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Natural killer(NK)cells are a type of cytotoxic innate immune cells and are considered as cells of the main effector, but the function of NK cells has undergone tremendous changes in the process of tumor progression.Endometrial cancer(EC)is one of the most common tumors in the female reproductive system, and the immune escape mechanism is at the basis for the progress of EC.Recent studies have found that the microenvironment of EC can not only reduce the recruitment of cytotoxic NK cells to the tumor site, but also change its phenotype and reduce its killing function.Moreover, NK cells with cytotoxicity in the tumor microenvironment gradually shift to an immune tolerance phenotype, which promotes tumor growth and tumor angiogenesis.How to prevent the polarized microenvironment from damaging the toxicity of NK cells and inhibiting the NK cells that promote tumor growth has become the focus of our attention.
Research progress of metallothionein in colorectal cancer
ZHAO Xuan, LI Guodong, LIU Ming
2021, 35(6):  538-541.  doi:10.11904/j.issn.1002-3070.2021.06.010
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Metallothionein(MTs)is a small protein,rich in cysteine.MTs is mainly divided into four subtypes in the human body(MT1,MT2,MT3 and MT4).The main function of MTs is to scavenge free radicals and participate in the detoxification and homeostasis of heavy metals,resulting from antioxidant properties.Recent studies have found that MTs can participate in the repair of DNA damage,and participate in the occurrence and development of tumors,and are related to the drug resistance of tumor cells.This article will review the research progress of MTs in colorectal cancer.
Research progress in immunotherapy of nasopharyngeal carcinoma
YANG Kaiyan, WEI Yongchang, YANG Qiuyun, TANG Fengzhu
2021, 35(6):  542-546.  doi:10.11904/j.issn.1002-3070.2021.06.011
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Nasopharyngeal carcinoma is a malignant tumor with a high incidence in southern China.The treatment of nasopharyngeal carcinoma currently uses concurrent radiotherapy and chemotherapy as the main treatment.The prognosis of early nasopharyngeal carcinoma is better,while the prognosis of advanced nasopharyngeal carcinoma is poor.As a new method of treating malignant tumors,immunotherapy is more and more widely used clinically.It has achieved good results in the treatment for some malignant tumors,and has become a current clinical research hotspot.This article reviews the application of immunotherapy in nasopharyngeal carcinoma in order to discover existing problems and new research directions.
New progress in the regulation of colorectal cancer by metabolites derived from gut microbiota
WANG Langyue, ZHAO Qi, WU Huaxing
2021, 35(6):  547-551.  doi:10.11904/j.issn.1002-3070.2021.06.012
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Changes in the intestinal ecosystem will affect human health and even cause colorectal cancer.A large amount of evidence shows that a pathological imbalance of the microbiota is common in the intestines of patients with colorectal cancer,and metabolites derived from imbalanced microbiota can also affect the occurrence and development of colorectal cancer.This article reviews the ways which metabolites of specific gut microbiota trigger the progression of colorectal cancer,summarizes the latest progress in the contribution of metabolites from gut microbiota to colorectal cancer,and considers the accumulative effect of metabolites and the combination of multiple metabolites to predict and prevent colorectal cancer.
Dilemma and future direction of gastric cancer immunotherapy
YU Yuanyuan, MENG Qianhao, WANG Guangyu
2021, 35(6):  552-556.  doi:10.11904/j.issn.1002-3070.2021.06.013
Abstract ( 68 )   PDF (11216KB) ( 18 )  
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China is a country with a high incidence of gastric cancer.The number of new cases accounts for about 44% of the world.Moreover,the proportion of patients with advanced gastric cancer is large,the survival rate is low,and the economic burden is serious.Although chemotherapy regimens for advanced gastric cancer are constantly improving,the efficacy is still limited.Targeted drugs except trastuzumab have improved efficacy in HER2-positive advanced gastric cancer patients,and other targeted drugs have poor efficacy in advanced gastric cancer patients.In recent years,immunotherapy has set off a research boom in the field of gastric cancer,and it has also brought dawn to the treatment of gastric cancer.This article reviews the research progress of immunotherapy for advanced gastric cancer,and elaborates the current dilemmas and future exploration directions for immunotherapy for gastric cancer.
Research progress in molecular classification of liver cancer based on tumor immunological microenvironment
LIU Fei, SUI Hong
2021, 35(6):  557-561.  doi:10.11904/j.issn.1002-3070.2021.06.014
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Immunotherapy improves the overall treatment strategy of liver cancer. Its unique immune heterogeneity and high tolerance to immune microenvironment make immunotherapy enter the bottleneck stage.Therefore,it is necessary to classify molecular classifications of liver cancer patients who may benefit from immune checkpoint therapy.With the progress of next-generation sequencing technology,scientists have explored molecular classifications based on the abundance of infiltrating immune cells,the expression of immune checkpoints,multi-omics data,mutually exclusive mechanisms for immunosuppression and the heterogeneity of tumor microenvironment.It is not only the specific biological,molecular and clinicopathological characteristics of liver cancer associated with the tumor microenvironment,but it also shows the overlap with the molecular classifications of the transcriptome.It is beneficial to the diagnosis of liver cancer,the choice of treatment methods and the prediction of clinical outcomes,and promotes accurate individualized immunotherapy for liver cancer.
The latest research progress of long non-coding RNA in sorafenib resistance of hepatocellular carcinoma
JI Lei, JI Daolin, BAO Dongdong, TAN Gang
2021, 35(6):  562-567.  doi:10.11904/j.issn.1002-3070.2021.06.015
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Hepatocellular carcinoma(HCC)is one of the most common and deadly cancers in the world.Many patients with advanced stage are mainly treated with drugs.Sorafenib,as a unique targeted drug for advanced HCC,has been widely used in clinical practice.However,sorafenib targeted therapy is not only a single drug therapy with low efficiency,but also drug resistance is a big problem that needs to be solved urgently.Recent studies have shown that long non-coding RNA(lncRNA)is closely related to the occurrence,development,invasion and metastasis,prognosis and drug resistance of HCC,and it has become an emerging hot spot in the drug resistance research.This article reviews the latest findings of lncRNAs in the sorafenib resistance of HCC and specific mechanisms of regulating resistance.
Research progress of tumor mutational burden as an emerging biomarker for breast cancer immunotherapy
LI Xiang, HU Yang, ZHANG Qingyuan
2021, 35(6):  568-571.  doi:10.11904/j.issn.1002-3070.2021.06.016
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With the advent of the age of immunotherapy,breast cancer treatment has also opened a new treatment strategy.The application of immune checkpoint inhibitors(ICI)in the treatment of breast cancer has achieved remarkable success in clinical practice.However,because it is only effective for a small number of patients,immunotherapy may lead to the occurrence of immune-related adverse events.Therefore,the patient's treatment options must be optimized through the use of relevant biomarker.Recently,many studies have confirmed that tumor mutational burden(TMB)is an emerging biomarker that can predict the efficacy of breast cancer immunotherapy.The article reviews the predictive value and application status of TMB in immunotherapy for breast cancer patients.
Expression and clinical significance of heat shock protein 90 in esophageal squamous cell carcinoma
MENG Di, XU Qianwen, SUN Xiuwei
2021, 35(6):  572-575.  doi:10.11904/j.issn.1002-3070.2021.06.017
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Esophageal squamous cell carcinoma(ESCC)is the main pathological type of esophageal carcinoma in China.It is characterized by an insidious onset,rapid metastasis,and rapid drug resistance during treatment,resulting in an unsatisfactory prognosis.Many downstream proteins regulated by heat shock protein 90(HSP90)are involved in cell proliferation and other processes,so they often play an important role in the occurrence and development of malignant tumors.More and more studies have confirmed that HSP90 is highly expressed in a variety of malignant tumors and can affect tumor resistance.In recent years,the exploration relevant role of HSP90 in ESCC has also yielded many achievements worthy of attention.This article will review the expression and clinical significance of HSP90 in ESCC.
Research progress of hepatocellular carcinoma-related RNA binding protein
ZHAO Haoran, LI Man, ZHANG Yubao
2021, 35(6):  576-579.  doi:10.11904/j.issn.1002-3070.2021.06.018
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The incidence and mortality of primary liver cancer in China have been among the top five malignant tumors for many years,the recurrence rate is high and the prognosis is poor.In recent years,with the continuous in-depth research on gene expression,carcinogenesis and development,the scope of exploration is not limited to the study of coding RNA.Many non-coding RNAs have been gradually attracted the attention of researchers.RNA binding proteins,as the“transportation hub”involved in the regulation of these RNAs,play an important role.This article will describe the research progress of RNA-binding proteins related to hepatocellular carcinoma one by one,in order to provide valuable references and ideas for future research.
The role of NF-κB signaling pathway in chemotherapy resistance of malignant tumors
LI Na, DENG Qian, JIANG Jianjun
2021, 35(6):  580-584.  doi:10.11904/j.issn.1002-3070.2021.06.019
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Malignant tumors have become the main reason affecting people′s health.Chemotherapy is one of the most widely used and most effective anti-tumor treatments.However,with the use of chemotherapeutic drugs,tumor cells will develop drug resistance,which becomes the main reason that affects the effect of chemotherapy.The emergence of drug resistance may involve many mechanisms,including abnormal cell cycle regulation,blockage of apoptotic signaling pathways,and abnormal expression of drug resistance genes.Recent studies have shown that cell survival signaling pathways play an important role in tumor chemotherapy resistance.The abnormality of nuclear factor kappa B(NF-κB)signaling pathway is one of the main mechanisms of drug resistance in malignant tumors.Therefore,NF-κB signaling pathway may also become an effective target for overcoming drug resistance in malignant tumors.This review briefly summarizes the role of NF-κB signaling pathway in chemotherapy resistance of malignant tumors and its research progress.