Pub Date : 2022-02-28DOI: 10.21147/j.issn.1000-9604.2022.01.06
Zichen Zhao, J. Gu
The benefits and popularity of minimally invasive surgery are undeniable around the globe. However, open surgery is necessary and learning open surgery skills is still a necessity. Open surgery allows for better exposure to the surgical field and provides tactile sensation to facilitate the stereo visual assessment to precisely remove the lesion. Open surgery is still the key to surgical training, and the skills learned from open surgeries remain crucial for unforeseen circumstances and certain conditions like emergencies, challenge cases, or patients with compromised status.
{"title":"Open surgery in the era of minimally invasive surgery","authors":"Zichen Zhao, J. Gu","doi":"10.21147/j.issn.1000-9604.2022.01.06","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.06","url":null,"abstract":"The benefits and popularity of minimally invasive surgery are undeniable around the globe. However, open surgery is necessary and learning open surgery skills is still a necessity. Open surgery allows for better exposure to the surgical field and provides tactile sensation to facilitate the stereo visual assessment to precisely remove the lesion. Open surgery is still the key to surgical training, and the skills learned from open surgeries remain crucial for unforeseen circumstances and certain conditions like emergencies, challenge cases, or patients with compromised status.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"63 - 65"},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46996801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 10.21147/j.issn.1000-9604.2022.01.04
Yanqi Huang, Lan He, Zhenhui Li, Xin Chen, Chu Han, Ke Zhao, Yuan Zhang, Jin Qu, Y. Mao, C. Liang, Zaiyi Liu
Objective This study aimed to establish a method to predict the overall survival (OS) of patients with stage I−III colorectal cancer (CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification. Methods We retrospectively identified 161 consecutive patients with stage I−III CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction. Results The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio (HR)=6.670; 95% confidence interval (95% CI): 3.433−12.956; P<0.001), external validation cohort 1 (HR=2.866; 95% CI: 1.646−4.990; P<0.001) and external validation cohort 2 (HR=3.342; 95% CI: 1.289−8.663; P=0.002). Incorporating the EcoRad signature into the prediction model presented a higher prediction ability (P<0.001) with respect to the C-index (0.813, 95% CI: 0.804−0.822 in the training cohort; 0.758, 95% CI: 0.751−0.765 in the external validation cohort 1; and 0.746, 95% CI: 0.722−0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis (TNM) system, as well as a better calibration, improved reclassification and superior clinical usefulness. Conclusions This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage I−III CRC patients.
{"title":"Coupling radiomics analysis of CT image with diversification of tumor ecosystem: A new insight to overall survival in stage I−III colorectal cancer","authors":"Yanqi Huang, Lan He, Zhenhui Li, Xin Chen, Chu Han, Ke Zhao, Yuan Zhang, Jin Qu, Y. Mao, C. Liang, Zaiyi Liu","doi":"10.21147/j.issn.1000-9604.2022.01.04","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.04","url":null,"abstract":"Objective This study aimed to establish a method to predict the overall survival (OS) of patients with stage I−III colorectal cancer (CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification. Methods We retrospectively identified 161 consecutive patients with stage I−III CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction. Results The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio (HR)=6.670; 95% confidence interval (95% CI): 3.433−12.956; P<0.001), external validation cohort 1 (HR=2.866; 95% CI: 1.646−4.990; P<0.001) and external validation cohort 2 (HR=3.342; 95% CI: 1.289−8.663; P=0.002). Incorporating the EcoRad signature into the prediction model presented a higher prediction ability (P<0.001) with respect to the C-index (0.813, 95% CI: 0.804−0.822 in the training cohort; 0.758, 95% CI: 0.751−0.765 in the external validation cohort 1; and 0.746, 95% CI: 0.722−0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis (TNM) system, as well as a better calibration, improved reclassification and superior clinical usefulness. Conclusions This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage I−III CRC patients.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"40 - 52"},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42035376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective Cleavage and polyadenylation specific factor 6 (CPSF6) has been documented as an oncoprotein in different types of cancer. However, functions of CPSF6 have not been investigated yet in esophageal squamous cell carcinoma (ESCC). Here, we aimed to investigate the potential clinical values and biological functions of CPSF6 in ESCC. Methods For determining the expression level of CPSF6 in ESCC patients, we analyzed published data, performed quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. Kaplan-Meier curves and log-rank tests were used for survival analyses. GO and KEGG analyses were done for CPSF6-related genes. Cell proliferation, colony formation and xenograft assays were conducted to verify the effects of CPSF6 on ESCC. In addition, cell cycle and apoptosis assays were also performed to manifest the functions of CPSF6 and circCPSF6. RNA pulldown and radioimmunoprecipitation (RIP) assays were used for confirming the interaction between circCPSF6 (hsa_circ_0000417) and CPSF6 protein. The regulatory relationship between CPSF6 protein and circCPSF6 was determined by RT-qPCR. Results We found that CPSF6 was upregulated in ESCC tissues and overexpression of cytoplasmic CPSF6 was associated with poor prognosis. GO and KEGG analyses suggested that CPSF6 could mainly affect cell division in ESCC. Further experiments manifested that CPSF6 promoted cell proliferation and colony formationin vitro. Xenograft assay showed that knockdown of CPSF6 significantly decreased tumor growth rate in vivo. Subsequently, we verified that depletion of CPSF6 led to cell cycle arrest and apoptosis. Finally, we validated that CPSF6, as a circRNA-binding protein, interacted with and regulated its circular isoform circCPSF6 (hsa_circ_0000417), of which depletion also resulted in cell cycle arrest and cell apoptosis in ESCC. Conclusions These findings gave us insight that overexpression of cytoplasmic CPSF6 protein is associated with poor prognosis in ESCC and CPSF6 may function as an oncoprotein, at least in part, through regulating circCPSF6 expression.
{"title":"Deregulated expression and subcellular localization of CPSF6, a circRNA-binding protein, promote malignant development of esophageal squamous cell carcinoma","authors":"Shichao Guo, Guang-li Wang, Zitong Zhao, Dan Li, Yongmei Song, Q. Zhan","doi":"10.21147/j.issn.1000-9604.2022.01.02","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.02","url":null,"abstract":"Objective Cleavage and polyadenylation specific factor 6 (CPSF6) has been documented as an oncoprotein in different types of cancer. However, functions of CPSF6 have not been investigated yet in esophageal squamous cell carcinoma (ESCC). Here, we aimed to investigate the potential clinical values and biological functions of CPSF6 in ESCC. Methods For determining the expression level of CPSF6 in ESCC patients, we analyzed published data, performed quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. Kaplan-Meier curves and log-rank tests were used for survival analyses. GO and KEGG analyses were done for CPSF6-related genes. Cell proliferation, colony formation and xenograft assays were conducted to verify the effects of CPSF6 on ESCC. In addition, cell cycle and apoptosis assays were also performed to manifest the functions of CPSF6 and circCPSF6. RNA pulldown and radioimmunoprecipitation (RIP) assays were used for confirming the interaction between circCPSF6 (hsa_circ_0000417) and CPSF6 protein. The regulatory relationship between CPSF6 protein and circCPSF6 was determined by RT-qPCR. Results We found that CPSF6 was upregulated in ESCC tissues and overexpression of cytoplasmic CPSF6 was associated with poor prognosis. GO and KEGG analyses suggested that CPSF6 could mainly affect cell division in ESCC. Further experiments manifested that CPSF6 promoted cell proliferation and colony formationin vitro. Xenograft assay showed that knockdown of CPSF6 significantly decreased tumor growth rate in vivo. Subsequently, we verified that depletion of CPSF6 led to cell cycle arrest and apoptosis. Finally, we validated that CPSF6, as a circRNA-binding protein, interacted with and regulated its circular isoform circCPSF6 (hsa_circ_0000417), of which depletion also resulted in cell cycle arrest and cell apoptosis in ESCC. Conclusions These findings gave us insight that overexpression of cytoplasmic CPSF6 protein is associated with poor prognosis in ESCC and CPSF6 may function as an oncoprotein, at least in part, through regulating circCPSF6 expression.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"11 - 27"},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49348836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 10.21147/j.issn.1000-9604.2022.01.01
Dong-dong Ti, Xin Yan, Jianshu Wei, Zhiqiang Wu, Yao Wang, W. Han
Immunotherapy has revolutionized cancer treatment and substantially improved patient outcomes with respect to multiple types of tumors. However, most patients cannot benefit from such therapies, mainly due to the intrinsic low immunogenicity of cancer cells (CCs) that allows them to escape recognition by immune cells of the body. Immunogenic cell death (ICD), which is a form of regulated cell death, engages in a complex dialogue between dying CCs and immune cells in the tumor microenvironment (TME), ultimately evoking the damage-associated molecular pattern (DAMP) signals to activate tumor-specific immunity. The ICD inducers mediate the death of CCs and improve both antigenicity and adjuvanticity. At the same time, they reprogram TME with a “cold-warm-hot” immune status, ultimately amplifying and sustaining dendritic cell- and T cell-dependent innate sensing as well as the antitumor immune responses. In this review, we discuss how to stimulate ICD based upon the biological properties of CCs that have evolved under diverse stress conditions. Additionally, we highlight how this dynamic interaction contributes to priming tumor immunogenicity, thereby boosting anticancer immune responses. We believe that a deep understanding of these ICD processes will provide a framework for evaluating its vital role in cancer immunotherapy.
{"title":"Inducing immunogenic cell death in immuno-oncological therapies","authors":"Dong-dong Ti, Xin Yan, Jianshu Wei, Zhiqiang Wu, Yao Wang, W. Han","doi":"10.21147/j.issn.1000-9604.2022.01.01","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.01","url":null,"abstract":"Immunotherapy has revolutionized cancer treatment and substantially improved patient outcomes with respect to multiple types of tumors. However, most patients cannot benefit from such therapies, mainly due to the intrinsic low immunogenicity of cancer cells (CCs) that allows them to escape recognition by immune cells of the body. Immunogenic cell death (ICD), which is a form of regulated cell death, engages in a complex dialogue between dying CCs and immune cells in the tumor microenvironment (TME), ultimately evoking the damage-associated molecular pattern (DAMP) signals to activate tumor-specific immunity. The ICD inducers mediate the death of CCs and improve both antigenicity and adjuvanticity. At the same time, they reprogram TME with a “cold-warm-hot” immune status, ultimately amplifying and sustaining dendritic cell- and T cell-dependent innate sensing as well as the antitumor immune responses. In this review, we discuss how to stimulate ICD based upon the biological properties of CCs that have evolved under diverse stress conditions. Additionally, we highlight how this dynamic interaction contributes to priming tumor immunogenicity, thereby boosting anticancer immune responses. We believe that a deep understanding of these ICD processes will provide a framework for evaluating its vital role in cancer immunotherapy.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"1 - 10"},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42578044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 10.21147/j.issn.1000-9604.2022.01.03
Jun Lu, T. Chu, Hongyu Liu, Min-juan Hu, Y. Lou, Yanwei Zhang, Zhi-qiang Gao, Wei Zhang, Xueyan Zhang, Huimin Wang, H. Zhong, B. Han
Objective Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer (NSCLC). Here, we aim to update the equivalent efficacy assessment between QL1101 and bevacizumab based on two-year follow-up data. Methods In total, 535 eligible NSCLC patients were enrolled in this randomized controlled trial. Patients were randomly assigned 1:1 to the QL1101 group and the bevacizumab group. The full end time of this study was defined as 24 months after the last enrolled patient was randomized. The primary endpoint was the objective response rate (ORR); equivalence was confirmed if the two-sided 90% confidence interval (90% CI) of the relative risk was within the range of 0.75−1.33. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results The two-year updated data showed similar ORR (QL1101 vs. bevacizumab: 53.1% vs. 54.3%; relative risk=0.977; 90% CI: 0.838−1.144), PFS (235 d vs. 254 d, log-rank P=0.311), and OS (577 d vs. 641 d, log-rank P=0.099) results between the QL1101 group and the bevacizumab group. The mean shrinkage ratio of targeted lesions was also similar between the QL1101 group and the bevacizumab group (22.5% vs. 23.5%). For patients who received QL1101 maintenance therapy, similar results were shown between the QL1101 group (n=157) and the bevacizumab group (n=148) (PFS: 253 d vs. 272 d, log-rank P=0.387; OS: 673 d vs. 790 d, log-rank P=0.101; mean tumor shrinkage rate: 26.6% vs. 27.5%). Conclusions This study reported that QL1101 had similar efficacy in treating nonsquamous NSCLC in terms of ORR, PFS and OS based on two-year updated data, providing a basis for the clinical application of QL1101.
目的抗血管内皮生长因子(VEGF)单克隆抗体是治疗非小细胞肺癌(NSCLC)的有效手段。在这里，我们的目标是基于两年随访数据更新QL1101和贝伐单抗之间的等效疗效评估。方法本随机对照试验共纳入535例符合条件的非小细胞肺癌患者。患者按1:1的比例随机分配到QL1101组和贝伐单抗组。本研究的完整结束时间定义为最后一名入组患者随机化后的24个月。主要终点为客观缓解率(ORR);如果相对风险的双侧90%置信区间(90% CI)在0.75 - 1.33范围内，则确认等效性。次要终点是无进展生存期(PFS)和总生存期(OS)。结果两年更新的数据显示相似的ORR (QL1101 vs.贝伐单抗:53.1% vs. 54.3%;相对危险度= 0.977;QL1101组和贝伐单抗组之间的90% CI: 0.838−1.144)、PFS (235 d vs. 254 d, log-rank P=0.311)和OS (577 d vs. 641 d, log-rank P=0.099)结果。QL1101组和贝伐单抗组的目标病灶平均收缩率也相似(22.5% vs 23.5%)。对于接受QL1101维持治疗的患者，QL1101组(n=157)和贝伐单抗组(n=148)的结果相似(PFS: 253 d vs 272 d, log-rank P=0.387;OS: 673 d vs. 790 d, log-rank P=0.101;平均肿瘤收缩率:26.6% vs. 27.5%)。结论本研究基于2年更新数据，报告了QL1101治疗非鳞状NSCLC在ORR、PFS和OS方面具有相似的疗效，为QL1101的临床应用提供了依据。
{"title":"Equivalent efficacy assessment of QL1101 and bevacizumab in nonsquamous non-small cell lung cancer patients: A two-year follow-up data update","authors":"Jun Lu, T. Chu, Hongyu Liu, Min-juan Hu, Y. Lou, Yanwei Zhang, Zhi-qiang Gao, Wei Zhang, Xueyan Zhang, Huimin Wang, H. Zhong, B. Han","doi":"10.21147/j.issn.1000-9604.2022.01.03","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.03","url":null,"abstract":"Objective Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer (NSCLC). Here, we aim to update the equivalent efficacy assessment between QL1101 and bevacizumab based on two-year follow-up data. Methods In total, 535 eligible NSCLC patients were enrolled in this randomized controlled trial. Patients were randomly assigned 1:1 to the QL1101 group and the bevacizumab group. The full end time of this study was defined as 24 months after the last enrolled patient was randomized. The primary endpoint was the objective response rate (ORR); equivalence was confirmed if the two-sided 90% confidence interval (90% CI) of the relative risk was within the range of 0.75−1.33. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results The two-year updated data showed similar ORR (QL1101 vs. bevacizumab: 53.1% vs. 54.3%; relative risk=0.977; 90% CI: 0.838−1.144), PFS (235 d vs. 254 d, log-rank P=0.311), and OS (577 d vs. 641 d, log-rank P=0.099) results between the QL1101 group and the bevacizumab group. The mean shrinkage ratio of targeted lesions was also similar between the QL1101 group and the bevacizumab group (22.5% vs. 23.5%). For patients who received QL1101 maintenance therapy, similar results were shown between the QL1101 group (n=157) and the bevacizumab group (n=148) (PFS: 253 d vs. 272 d, log-rank P=0.387; OS: 673 d vs. 790 d, log-rank P=0.101; mean tumor shrinkage rate: 26.6% vs. 27.5%). Conclusions This study reported that QL1101 had similar efficacy in treating nonsquamous NSCLC in terms of ORR, PFS and OS based on two-year updated data, providing a basis for the clinical application of QL1101.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"28 - 39"},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44258412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-08DOI: 10.21147/j.issn.1000-9604.2022.01.05
Z. Ying, T. He, Shanzhao Jin, Xiao-pei Wang, W. Zheng, N. Lin, M. Tu, Yan Xie, L. Ping, Weiping Liu, L. Deng, Yanping Ding, Xu-dong Hu, B. Bu, Xin-an Lu, Yuqin Song, Jun Zhu
Objective Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor (CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells, especially the lower incidence rate of severe adverse events. However, the median progression-free survival (mPFS) of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta (2.9 monthsvs. 5.9 months), suggesting that Kymriah was limited in the long-term efficacy. Thus, a safe and durable 4-1BB-based CD19 CAR-T needs to be developed. Methods We designed a CD19-targeted CAR-T (named as IM19) which consisted of an FMC63 scFv, 4-1BB and CD3ζ intracellular domain and was manufactured into a memory T-enriched formulation. A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory (r/r) B cell non-Hodgkin lymphoma (B-NHL). Dose-escalation investigation (at a dose of 5×105/kg, 1×106/kg and 3×106/kg) was performed in 22 r/r B-NHL patients. All patients received a single infusion of IM19 after 3-day conditional regimen. Results At month 3, the overall response rate (ORR) was 59.1%, the complete response rate (CRR) was 50.0%. The mPFS was 6 months and the 1-year overall survival rate was 77.8%. Cytokine release syndrome (CRS) occurred in 13 patients (59.1%), with 54.5% of grade 1−2 CRS. Only one patient (4.5%) experienced grade 3 CRS and grade 3 neurotoxicity. Conclusions These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T, IM19, which is promising for further development and clinical investigation.
{"title":"A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma","authors":"Z. Ying, T. He, Shanzhao Jin, Xiao-pei Wang, W. Zheng, N. Lin, M. Tu, Yan Xie, L. Ping, Weiping Liu, L. Deng, Yanping Ding, Xu-dong Hu, B. Bu, Xin-an Lu, Yuqin Song, Jun Zhu","doi":"10.21147/j.issn.1000-9604.2022.01.05","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.05","url":null,"abstract":"Objective Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor (CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells, especially the lower incidence rate of severe adverse events. However, the median progression-free survival (mPFS) of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta (2.9 monthsvs. 5.9 months), suggesting that Kymriah was limited in the long-term efficacy. Thus, a safe and durable 4-1BB-based CD19 CAR-T needs to be developed. Methods We designed a CD19-targeted CAR-T (named as IM19) which consisted of an FMC63 scFv, 4-1BB and CD3ζ intracellular domain and was manufactured into a memory T-enriched formulation. A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory (r/r) B cell non-Hodgkin lymphoma (B-NHL). Dose-escalation investigation (at a dose of 5×105/kg, 1×106/kg and 3×106/kg) was performed in 22 r/r B-NHL patients. All patients received a single infusion of IM19 after 3-day conditional regimen. Results At month 3, the overall response rate (ORR) was 59.1%, the complete response rate (CRR) was 50.0%. The mPFS was 6 months and the 1-year overall survival rate was 77.8%. Cytokine release syndrome (CRS) occurred in 13 patients (59.1%), with 54.5% of grade 1−2 CRS. Only one patient (4.5%) experienced grade 3 CRS and grade 3 neurotoxicity. Conclusions These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T, IM19, which is promising for further development and clinical investigation.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"53 - 62"},"PeriodicalIF":5.1,"publicationDate":"2021-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48108525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-04Epub Date: 2019-09-16DOI: 10.1098/rsta.2019.0010
Barbara Amaral
In addition to the important role of contextuality in foundations of quantum theory, this intrinsically quantum property has been identified as a potential resource for quantum advantage in different tasks. It is thus of fundamental importance to study contextuality from the point of view of resource theories, which provide a powerful framework for the formal treatment of a property as an operational resource. In this contribution, we review recent developments towards a resource theory of contextuality and connections with operational applications of this property. This article is part of the theme issue 'Contextuality and probability in quantum mechanics and beyond'.
{"title":"Resource theory of contextuality.","authors":"Barbara Amaral","doi":"10.1098/rsta.2019.0010","DOIUrl":"10.1098/rsta.2019.0010","url":null,"abstract":"<p><p>In addition to the important role of contextuality in foundations of quantum theory, this intrinsically quantum property has been identified as a potential resource for quantum advantage in different tasks. It is thus of fundamental importance to study contextuality from the point of view of resource theories, which provide a powerful framework for the formal treatment of a property as an operational resource. In this contribution, we review recent developments towards a resource theory of contextuality and connections with operational applications of this property. This article is part of the theme issue 'Contextuality and probability in quantum mechanics and beyond'.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"20 1","pages":"20190010"},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74821292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-01DOI: 10.21147/j.issn.1000-9604.2019.05.07
Han-Chen Huang, X. Wen, Hua Xue, Run-sheng Chen, J. Ji, Lei Xu
Objective Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer (GC) challenging. Here, we aimed to identify prognostic genes of GC using computational analysis. Methods We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase (GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state (E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition (EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets. Results We found that higher expression of GPI in GC correlated with prolonged survival of patients. Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage II/III. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells. Conclusions Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis, allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.
{"title":"Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer","authors":"Han-Chen Huang, X. Wen, Hua Xue, Run-sheng Chen, J. Ji, Lei Xu","doi":"10.21147/j.issn.1000-9604.2019.05.07","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.05.07","url":null,"abstract":"Objective Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer (GC) challenging. Here, we aimed to identify prognostic genes of GC using computational analysis. Methods We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase (GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state (E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition (EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets. Results We found that higher expression of GPI in GC correlated with prolonged survival of patients. Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage II/III. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells. Conclusions Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis, allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"31 1","pages":"771 - 784"},"PeriodicalIF":5.1,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44744918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-01DOI: 10.21147/j.issn.1000-9604.2019.05.02
Weiping Liu, Jun Zhu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China Correspondence to: Jun Zhu. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital &Institute, Beijing 100142, China. Email: zhu-jun2017@outlook.com.
{"title":"Comments on Chinese guidelines for diagnosis and treatment of malignant lymphoma 2018 (English version)","authors":"Weiping Liu, Jun Zhu","doi":"10.21147/j.issn.1000-9604.2019.05.02","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.05.02","url":null,"abstract":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China Correspondence to: Jun Zhu. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital &Institute, Beijing 100142, China. Email: zhu-jun2017@outlook.com.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"31 1","pages":"738 - 739"},"PeriodicalIF":5.1,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48905019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-01DOI: 10.21147/j.issn.1000-9604.2019.05.10
Z. Ye, Hanyu Jiang, Jie Chen, Xijiao Liu, Yi Wei, C. Xia, Ting Duan, Likun Cao, Zhen Zhang, B. Song
Objective To investigate the value of whole-lesion texture analysis on preoperative gadoxetic acid enhanced magnetic resonance imaging (MRI) for predicting tumor Ki-67 status after curative resection in patients with hepatocellular carcinoma (HCC). Methods This study consisted of 89 consecutive patients with surgically confirmed HCC. Texture features were extracted from multiparametric MRI based on whole-lesion regions of interest. The Ki-67 status was immunohistochemical determined and classified into low Ki-67 (labeling index ≤15%) and high Ki-67 (labeling index >15%) groups. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were applied for generating the texture signature, clinical nomogram and combined nomogram. The discrimination power, calibration and clinical usefulness of the three models were evaluated accordingly. Recurrence-free survival (RFS) rates after curative hepatectomy were also compared between groups. Results A total of 13 texture features were selected to construct a texture signature for predicting Ki-67 status in HCC patients (C-index: 0.878, 95% confidence interval: 0.791−0.937). After incorporating texture signature to the clinical nomogram which included significant clinical variates (AFP, BCLC-stage, capsule integrity, tumor margin, enhancing capsule), the combined nomogram showed higher discrimination ability (C-index: 0.936vs. 0.795, P<0.001), good calibration (P>0.05 in Hosmer-Lemeshow test) and higher clinical usefulness by decision curve analysis. RFS rate was significantly lower in the high Ki-67 group compared with the low Ki-67 group after curative surgery (63.27%vs. 85.00%, P<0.05). Conclusions Texture analysis on gadoxetic acid enhanced MRI can serve as a noninvasive approach to preoperatively predict Ki-67 status of HCC after curative resection. The combination of texture signature and clinical factors demonstrated the potential to further improve the prediction performance.
{"title":"Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study","authors":"Z. Ye, Hanyu Jiang, Jie Chen, Xijiao Liu, Yi Wei, C. Xia, Ting Duan, Likun Cao, Zhen Zhang, B. Song","doi":"10.21147/j.issn.1000-9604.2019.05.10","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.05.10","url":null,"abstract":"Objective To investigate the value of whole-lesion texture analysis on preoperative gadoxetic acid enhanced magnetic resonance imaging (MRI) for predicting tumor Ki-67 status after curative resection in patients with hepatocellular carcinoma (HCC). Methods This study consisted of 89 consecutive patients with surgically confirmed HCC. Texture features were extracted from multiparametric MRI based on whole-lesion regions of interest. The Ki-67 status was immunohistochemical determined and classified into low Ki-67 (labeling index ≤15%) and high Ki-67 (labeling index >15%) groups. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were applied for generating the texture signature, clinical nomogram and combined nomogram. The discrimination power, calibration and clinical usefulness of the three models were evaluated accordingly. Recurrence-free survival (RFS) rates after curative hepatectomy were also compared between groups. Results A total of 13 texture features were selected to construct a texture signature for predicting Ki-67 status in HCC patients (C-index: 0.878, 95% confidence interval: 0.791−0.937). After incorporating texture signature to the clinical nomogram which included significant clinical variates (AFP, BCLC-stage, capsule integrity, tumor margin, enhancing capsule), the combined nomogram showed higher discrimination ability (C-index: 0.936vs. 0.795, P<0.001), good calibration (P>0.05 in Hosmer-Lemeshow test) and higher clinical usefulness by decision curve analysis. RFS rate was significantly lower in the high Ki-67 group compared with the low Ki-67 group after curative surgery (63.27%vs. 85.00%, P<0.05). Conclusions Texture analysis on gadoxetic acid enhanced MRI can serve as a noninvasive approach to preoperatively predict Ki-67 status of HCC after curative resection. The combination of texture signature and clinical factors demonstrated the potential to further improve the prediction performance.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"31 1","pages":"806 - 817"},"PeriodicalIF":5.1,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47482319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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