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Chinese Journal of Oncology Prevention and Treatment

Table of Content

    25 December 2023, Volume 15 Issue 6 Previous Issue    Next Issue
    DNA mismatch repair gene variants/mutations and cancer treatment response
    TANG Shaomei, YU Hongping, WEI Qingyi
    2023, 15 (6):  593-601.  doi: 10.3969/j.issn.1674-5671.2023.06.01
    Abstract ( 190 )   PDF   Save
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    Multifaceted hand of tumor stress : glutamate dehydrogenase 1 (GLUD1)
    DUAN Haibo, LIU Yuhang, WANG Xiongjun
    2023, 15 (6):  602-609.  doi: 10.3969/j.issn.1674-5671.2023.06.02
    Abstract ( 317 )   PDF   Save
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    Vitexicarpin inhibits the proliferation of liver cancer cells by regulating glucose metabolism reprogramming
    DONG Jiaqi, FANG Tao, OU Yong, WEI Jingyi, HU Longquan, LI Yuanyuan, CHAO Xu
    2023, 15 (6):  615-622.  doi: 10.3969/j.issn.1674-5671.2023.06.04
    Abstract ( 148 )   PDF   Save
    Objective To investigate the effects of Vitexicarpin on the proliferation of liver cancer cells and its molecular mechanisms. Methods MTS assay and clonogenic formation assay were used to detect the effects of different concentrations of Vitexicarpin (0.5, 1.0 and 2.0 μmol/L, respectively) on the growth of liver cancer cell lines SNU⁃368 and SNU⁃739, as well as human liver immortalized cells THLE⁃2, the appropriate concentration of Vitexicarpin in treatment of liver cancer cells was selected at the same time. Liver cancer cell lines SNU⁃368 and SNU⁃739 were infected with HIF⁃1α overexpressing lentivirus and its negative control lentivirus, while the liver cancer cells overexpressing HIF⁃1α were treated with the appropriate concentration of Vitexicarpin. The expressions of HIF⁃1α, C⁃MYC, and P53 in liver cancer cell lines were detected by qRT⁃PCR and Western blot. The conditions of glycolysis and oxidative phosphorylation in liver cancer cells were analyzed by glucose uptake level, lactate production level, extracellular pH, and cellular oxygen consumption test. The proliferation of the cells was detected by MTS assay and clone formation assay. Results The proliferation of SNU⁃368 and SNU⁃739 cells was inhibited by Vitexicarpin with a dose and time dependent manner. After treatment with 1.0 μmol/L Vitexicarpin, the value of glucose uptake and lactate production in SNU⁃368 and SNU⁃739 liver cancer cells were reduced (all P<0.01), while the extracellular pH and cellular oxygen consumption rate were increased (all P<0.01), and the expression of HIF⁃1α was inhibited (P<0.05). Overexpression of HIF⁃1α could promote the glycolysis of liver cancer cells, inhibit oxidative phosphorylation, and enhance cell proliferation (all P<0.05), while the Vitexicarpin could reverse the growth⁃promoting effect of HIF⁃1α overexpression in liver cancer cells (all P<0.05). Conclusions Vitexicarpin can inhibit the proliferation of cell glycolysis and enhance oxidative phosphorylation by inhibiting the expression of HIF⁃1α, thereby inhibiting the proliferation of liver cancer cells.
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    Paeoniflorin inhibiting the migration and invasion of endometrial cancer and its mechanism 
    XIAO Hui, QIN Hongen, YAO Ziyu, ZHOU Hui, MA Ronghe
    2023, 15 (6):  623-630.  doi: 10.3969/j.issn.1674-5671.2023.06.05
    Abstract ( 123 )   PDF   Save
    Objective To investigate the effect of Paeoniflorin in inhibiting the progression of endometrial cancer and its mechanism. Methods  The target gene of Paeoniflorin was predicted by TargetNet and Swiss target prediction online databases, the expression of Paeoniflorin target gene in endometrial cancer was analyzed by UALCAN database, and the expression of Paeoniflorin target gene in patients with different clinicopathological characteristics was analyzed by TCGA database. The endometrial cancer cell lines HEC108 and Ishikawa were cultured in vitro, and were divided into the Control group/Vector group (no treatment), the AURKA group (transfected with AURKA plasmid), the Paeoniflorin group and the Paeoniflorin+AURKA group (treated with Paeoniflorin and transfected with AURKA plasmid). The target gene of Paeoniflorin was predicted by bioinformatics. The cells were treated with Paeoniflorin at different concentrations. The cells activity was detected by CCK⁃8 assay. The cells migration and invasion were detected by Transwell assay. The activity of lactate dehydrogenase (LDH) was detected by the enzyme⁃linked immunosorbent assay. The cells proliferation inhibited by Paeoniflorin in vivo was detected by the transplanted tumor assay in nude mice. The proliferating cell antigen (Ki⁃67) was detected by immunohistochemistry. The expression of AURKA, migration⁃related proteins and epithelial mesenchymal transition (EMT)⁃related proteins were detected by Western Blot. Results Bioinformatics showed that AURKA was the target of Paeoniflorin, which was highly expressed in endometrial cancer tissues and related to clinical adverse phenotypes (P<0.05). The vitro experiment results showed that Paeoniflorin could inhibit cells proliferation, migration and invasion of HEC108 and Ishikawa cells, increase LDH activity, inhibit Ki⁃67 expression (all P<0.05), the levels of migration⁃related proteins (MMP2, MMP9) in cells, and regulate the levels of EMT⁃related proteins (Vimentin, N⁃cadherin, Snail, E⁃cadherin) in cells (all P<0.05).  Paeoniflorin could inhibit the growth of volume and the weight of transplanted tumors in nude mice (all P<0.05), as well as the expression of AURKA protein in concentration⁃ and time⁃dependent manners (all P<0.05). The high expression of AURKA could promote cells proliferation and reduce LDH activity (all P<0.05). Conclusions Paeoniflorin inhibited the expression of Proliferation, migration and invasion of endometrial cancer cells in vitro and the growth of transplanted tumor in nude mice in vivo. The mechanism may be that Paeoniflorin inhibits the development of endometrial cancer by down⁃regulating AURKA expression.
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    Construction and identification of macrophage-conditional GP73 gene knockout mice
    HUANG Qing, ZHEN Lan, ZHAO Guilin, ZHAO Ruzhou, YE Xinping, WU Feixiang
    2023, 15 (6):  630-636.  doi: 10.3969/j.issn.1674-5671.2023.06.06
    Abstract ( 242 )   PDF   Save
    Objective To construct and identify macrophage⁃conditional Golgi protein 73(GP73) gene knockout mice, and to provide an animal model for exploring the effect of GP73 on the occurrence and development of neoplastic diseases by regulating the function of macrophages. Methods The GP73 flox/+ mice were constructed based on the Cre/LoxP recombination system. GP73flox/flox mice were obtained by self⁃cross of GP73flox/+mice. GP73flox/flox mice were crossed with Lyz2⁃Cre+ mice to obtain GP73flox/+Lyz2⁃Cre+ mice, and then crossed with GP73flox/flox mice to obtain the macrophage⁃conditional GP73 gene knockout mice, referred to as GP73flox/floxLyz2⁃Cre+ mice(MKO mice). The GP73flox/floxLyz2⁃Cre- (GP73fl/fl) mice were used as the control mice. The genotypes of flox and Cre were identified by PCR and agarose gel electrophoresis. Real⁃time fluorescence quantitative PCR (qPCR) and Western blot were used to verify the knockout efficiency and tissue specificity of macrophages GP73 at mRNA and protein levels, respectively. The ratio of tissue weight to body weight was calculated to analyze the growth and development of mice, and the blood biochemical indicators of mice were detected. Results The successful construction of macrophage⁃conditional GP73 gene knockout mice was confirmed by genotype identification, mRNA, and protein level analysis. qPCR tests showed that, compared with GP73fl/fl mice, the GP73 mRNA levels in bone marrow⁃derived macrophages (BMDMs) and peritoneal macrophages (PM) of MKO mice were decreased (P<0.0001). Western blot detection showed that compared with GP73fl/fl mice, the expression levels of GP73 protein in BMDMs and PM in MKO mice were significantly decreased, though no significant differences were found in the expression levels of GP73 protein in liver, kidney and thymus tissues. Compared with GP73fl/fl mice, the ratio of body weight to tissue weight of heart, liver, spleen, lung, kidney, brown adipose and white adipose in MKO mice was not significantly different, and there was no significant morphological difference among the tissues. The results of blood biochemical indicators showed that there were no significant difference in blood biochemical indexes between the MKO mice and GP73fl/fl mice (P>0.05). Conclusions  The mouse model of macrophage⁃conditional GP73 gene knockout is successfully constructed, providing a valuable animal model for the further study of the role and mechanism of GP73 in regulating macrophage in neoplastic diseases.oxP recombination system; Conditional knockout; Genotype identification; Mouse model
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    Clinical study of single-center CCLG-ALL 2018 regimen in the treatment of MLL-rearrangement childhood acute lymphoblastic leukemia
    LI Chen, LIU Wei, WANG Yafeng, WANG Tianyou
    2023, 15 (6):  637-643.  doi: 10.3969/j.issn.1674-5671.2023.06.07
    Abstract ( 177 )   PDF   Save
    Objective To investigate the efficacy and prognostic factors of single⁃center CCLG⁃ALL 2018 regimen in the treatment of children with MLL⁃rearrangement acute lymphoblastic leukemia (MLL⁃r ALL). Methods A total of 19 newly diagnosed children with MLL⁃r ALL who received CCLG⁃ALL 2018 regimen in Children's Hospital Affiliated to Zhengzhou University from April 2018 to July 2022 were retrospectively analyzed. Results Among the 19 children with MLL⁃r ALL, 12 (63.2%) were males and 7 (36.8%) were females; 15 (78.9%) aged ≤1 year old, and 4 (21.1%) aged>1 year old. The median age at diagnosis was 10.2 months (range: 0.5-156.0 months). There were 18 (94.7%)  cases of BCP⁃ALL and 1(5.3%) case of T⁃ALL. MLL⁃AF4 was the most common fusion genotype (7/19). The median follow⁃up time was 19.0 months (range: 0.1-62.0 months), and 1 patient died 5 days after diagnosis, with a complete response rate of 61.1% on the 33rd day of induction chemotherapy. In total, 9 of 19 children died (47.4%), including 3 cases of treatment⁃related complications (1 case of pulmonary hemorrhage and 2 cases of severe infection). One case died of leukemia without remission, 5 cases died of recurrence with a recurrence rate of 26.3% (5/19), and all these cases were early bone marrow recurrence, with a median recurrence time of 6 months (range: 5-9 months). Kaplan⁃Meier showed that the 2⁃year overall survival (OS) and event⁃free survival (EFS) rates of 19 children were 57.9 % and 52.6%, respectively. The results of univariable analysis showed that there were significant differences in 2⁃year OS rate between the <1×10-3 group and ≥1×10-3 group on the 15th day of minimal residual disease (MRD), between the MLL rearrangement gene negative and non⁃negative groups on the 33rd day, and between the MLL⁃AF4 group and the non⁃MLL⁃AF4 group (all P<0.05). Multivariable analysis of Cox model showed that MLL⁃AF4 was an independent adverse prognostic factor affecting the OS in children with MLL⁃r ALL (P=0.032). Conclusions CCLG⁃ALL 2018 regimen could achieve remission in some of children with MLL⁃rearrangement, but the overall prognosis is poor, prone to recurrence and high mortality rate at recurrence. The MLL⁃AF4 rearrangement is the adverse factor affecting the treatment effect of CCLG⁃ALL 2018 regimen in children with MLL⁃r ALL.
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    Factors influencing the efficacy and safety of surgery for hilar cholangiocarcinoma
    YANG Dalong, LU Haiming, ZHONG Jianhong, QI Lunan, CHEN Zushun, XIANG Bangde, LI Lequn, MA Liang
    2023, 15 (6):  644-649.  doi: 10.3969/j.issn.1674-5671.2023.06.08
    Abstract ( 135 )   PDF   Save
    Objective To investigate the risk factors of surgical complications of grade ≥Ⅲa and the overall survival rate of hilar cholangiocarcinoma (HC) after resection. Methods The clinical data of 62 patients with HC who underwent surgical resection in the Guangxi Medical University Cancer Hospital from June 2010 to March 2022 were retrospectively analyzed. The risk factors of postoperative complications of grade ≥Ⅲa were analyzed by virtue of logistic regression analysis, and Cox regression model was used to analyze the factors influencing overall survival. Results The incidence of postoperative complications in HC patients was 73.5%(36/49), among which the incidence of ≥Ⅲa complications and the perioperative mortality accounted for 46.9%(23/49) and 10.2%(5/49), respectively. Intraoperative blood loss >500 mL and AJCC stage Ⅲ/Ⅳ were independent risk factors for postoperative complications grade ≥Ⅲa in HC patients (all P<0.05). The median survival of HC patients was 24.0 months, and the 1⁃year, 3⁃year and 5⁃year overall survival rates were 73%, 49% and 20%, respectively. Preoperative CA19⁃9≥150 U/L and total caudate lobed resection were independent factors affecting the overall survival rate (all P<0.05). Conclusions AJCC stage Ⅲ/Ⅳ and intraoperative blood loss >500 mL are risk factors for perioperative complications ≥ grade Ⅲa after HC resection. Preoperative CA19⁃9≥150 U/L is a risk factor for postoperative overall survival, and total caudate lobectomy is a protective factor for postoperative overall survival.
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    Analysis of risk factors of prognosis,recurrence and metastasis of breast cancer patients with  non-pathologic complete response after neoadjuvant chemotherapy
    GAO Fangfang, CHEN Binjie, TAN Qixing, HUANG Zhen, LU Weifeng, WEI Changyuan
    2023, 15 (6):  650-656.  doi: 10.3969/j.issn.1674-5671.2023.06.09
    Abstract ( 145 )   PDF   Save
    Objective To investigate the risk factors of prognosis, recurrence and metastasis of breast cancer patients with non⁃pathologic complete response (non⁃pCR)  after neoadjuvant chemotherapy. Methods The clinical characteristics of 500 patients with breast cancer diagnosed and treated with neoadjuvant chemotherapy, in the Breast Surgery Department of Guangxi Medical University Cancer Hospital from January 2016 to December 2020 and the First Affiliated Hospital of Hainan Medical University from  January 2020 to December 2022, were retrospectively analyzed. Compare the disease⁃free survival (DFS) and overall survival (OS) of pathologic complete response (pCR) and non⁃pCR patients, respectively. Cox regression analysis was used to screen independent risk factors for recurrence and metastasis of non⁃pCR patients after neoadjuvant chemotherapy. Results The median follow⁃up time was 38 months (range: 6-81 months) in the study cohort, and the median DFS and OS were not reached. The pCR rate after neoadjuvant chemotherapy was 19.4% (97/500). The 5⁃year DFS of pCR and non⁃pCR patients were 91.9 % and 81.2%, respectively (P=0.003), and their 5⁃year OS were 96.1% and 81.6%, respectively (P=0.007). A total of 71 patients experienced recurrence and metastasis after neoadjuvant chemotherapy, including 4 patients with pCR and 67 patients with non⁃pCR. Cox regression analysis showed that age > 35 years (HR=0.393, 95%CI: 0.220-0.701) was the protective factor for recurrence and metastasis in non⁃pCR patients, while the histological grade 3 (HR=3.568, 95%CI: 2.050-6.210), high Ki⁃67 index (HR=2.742, 95%CI: 1.528-4.921), elevated postoperative Ki⁃67 index (HR=5.349, 95%CI: 2.470-11.586) and high pN stage (HR=6.716, 95%CI: 2.922-15.436) were independent risk factors for recurrence and metastasis in non⁃pCR patients. Conclusions Achieving pCR after neoadjuvant chemotherapy can improve the DFS and OS of the patients. Age≤35 years, histological grade 3, Ki⁃67>30%, elevated postoperative Ki⁃67 index and high pN stage are independent risk factors of recurrence and metastasis in non⁃pCR patients. 
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    Application of neuronavigation combined with fluorescein sodium in intraoperative imaging-assisted resection of brain metastases
    ZHU Lei, LEI Yi, MO Ligen, LING Guoyuan, DENG Teng, HUANG Qianrong, JIANG Qian, SHI Liu
    2023, 15 (6):  657-662.  doi: 10.3969/j.issn.1674-5671.2023.06.10
    Abstract ( 119 )   PDF   Save
    Objective To investigate the efficacy of neuronavigation combined with fluorescein sodium (FLS) in intraoperative imaging⁃assisted resection of brain metastases. Methods The clincal data of 125 surgical patients with brain metastasis (BM) treated in neurosurgery department of Guangxi Medical University Cancer Hospital from January 2019 to October 2022 were retrospectively analyzed. Among these BM patients, 87 patients who underwent neuronavigation combined with FLS intraoperative imaging⁃assisted resection were classified into the neuronavigation combined with FLS group, and 38 patients who underwent surgical resection under neuronavigation alone were classified into the neuronavigation group. The degree of tumor resection, surgical time, blood bleeding, complications, and 1⁃month postoperative karnofsky scale (KPS) scores were compared between the two groups. Results The total resection rate of the neuronavigation combined with FLS group was 85.1%, which was significantly higher than that (65.8%) of the neuronavigation group (P=0.028). After adjusting for possible confounding factors, the total resection rate of the neuronavigation combined with FLS group was 1.849 times higher than that of the neuronavigation group (OR=1.849, 95% CI: 1.130~3.026, P=0.014). The KPS scores of the neuronavigation combined with FLS group was significantly higher than that of the neuronavigation group at 1 month after surgery (78.96±13.81 vs 65.00±18.56, P<0.001). The difference between the two groups was statistically significant (P<0.001). The surgical time and blood bleeding of the neuronavigation combined with FLS group were lower than those of the neuronavigation group (all P<0.05), though no significant difference in complications was found between the two groups (P>0.05). Conclusions Neuronavigation combined with FLS assisted BM resection surgery can improve the total tumor resection rate and the short⁃term life quality of patients with safety.
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    An analysis of hospitalized death cases of malignant tumors in a tertiary hospital in Guangxi from 2010 to 2020
    LIANG Xiumei, CHEN Weiyi, MA Liang, CHEN Lijun, GONG Wenfeng, YU Hongping, LIU Yingchun
    2023, 15 (6):  662-666.  doi: 10.3969/j.issn.1674-5671.2023.06.11
    Abstract ( 242 )   PDF   Save
    Objective To analyze the distribution characteristics and the causes of hospitalized death cases with malignant tumors in a tertiary hospital, and to provide the reference for hospital management and discipline construction. Methods Based on the clinical information data of 1, 834 hospitalized death cases with malignant tumors in Guangxi Medical University Cancer Hospital from January 1, 2010 to December 31, 2020, the trend of fatality rate, gender and age distribution, and the rank of death in malignant tumors were analyzed.  Results The fatality rate of hospitalized patients with malignant tumors showed a decreasing trend, with higher fatality rate in male than in female (χ2=141.487, P<0.001). The fatality rate of hospitalized patients with malignancies in different age groups was statistically significant  (χ2=389.637, P<0.001) and increased with age. The top 10 cancer causes of death were lung cancer, liver cancer, colorectal cancer, breast cancer, gastric cancer, lymphoma, oesophageal cancer, nasopharyngeal cancer, ovarian cancer, and pancreatic cancer. Conclusions  The fatality rate of hospitalized patients with malignant tumors decrease gradually; lung cancer and liver cancer are the main causes of death diseases. Hospitals need to further optimize the allocation of medical resources, and strengthen the construction of corresponding disciplines, continuously improving the quality of medical treatment and reducing the fatality rate of tumors.

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    Research status of mitochondrial retrograde signaling in tumor progression 
    XU Xiaojun, LIAO Dawen, WANG Xingchen, WEI Yuanyuan, HUANG Qichao, DU Yulu
    2023, 15 (6):  672-676.  doi: 10.3969/j.issn.1674-5671.2023.06.13
    Abstract ( 157 )   PDF   Save
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     Research progress of spatial transcriptomics technology in digestive system tumors
    ZHAO Lili, LONG Lin, ZANG Jianhua, XU Lijuan, TIAN Jin, LIU Wei, ZHAO Wen, XIAO Jun
    2023, 15 (6):  696-702.  doi: 10.3969/j.issn.1674-5671.2023.06.17
    Abstract ( 142 )   PDF   Save
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    Research progress of spatial transcriptomics technology in digestive system tumors
    XUAN Chenyi, NIU Xudong, CHUN Yujie, WANG Shaoqing, WANG Xianyan
    2023, 15 (6):  702-710.  doi: 10.3969/j.issn.1674-5671.2023.06.18
    Abstract ( 156 )   PDF   Save
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