Pub Date : 2023-06-05eCollection Date: 2023-01-01DOI: 10.3389/pore.2023.1610710
Jiayang Sun, Yushu Sun, Miniderima, Xiumei Wang
Background: The therapeutic efficacy of cytokine-induced killer (CIK) cells versus dendritic cells (DC) co-cultured with CIK cells (DC-CIK) in treating esophageal cancer (EC) remains unclear due to the absence of a direct comparison of these two regimens. This study evaluated the comparative efficacy and safety of CIK cells versus DC-CIK using network meta-analysis in treating EC. Material and methods: We identified eligible studies from previous meta-analyses, then conducted an updated search to retrieve additional trials between February 2020 and July 2021. The primary outcomes included overall survival (OS), objective response rate (ORR), and disease control rate (DCR), and the secondary outcomes included quality of life improved rate (QLIR) and adverse events (AEs). A network meta-analysis of 12 studies was conducted using ADDIS software. Results: Twelve studies were identified, including six comparing CIK or DC-CIK plus chemotherapy (CT) with CT alone. Immunotherapy plus CT significantly improved overall survival (OS) (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.23-13.69), objective response rate (ORR) (OR 2.72, 95% CI 1.79-4.11), disease control rate (DCR) (OR 3.45, 95% CI 2.32-5.14), and quality of life improvement rate (QLIR) (OR 3.54, 95% CI 2.31-5.41). DC-CIK+CT decreased the risk of leukopenia compared with CT alone. However, no statistical difference was detected between CIK-CT and DC-CIK+CT. Conclusion: Based on the available evidence, we concluded that CIK cell treatment is superior to CT alone, but CIK-CT and DC-CIK+CT may be comparable in treating EC. However, comparing CIK-CT and DC-CIK+CT is only based on indirect evidence, so it is undoubtedly necessary to conduct studies to compare CIK-CT with DC-CIK+CT in EC patients directly.
{"title":"Cytokine-induced killer cell treatment is superior to chemotherapy alone in esophageal cancer.","authors":"Jiayang Sun, Yushu Sun, Miniderima, Xiumei Wang","doi":"10.3389/pore.2023.1610710","DOIUrl":"10.3389/pore.2023.1610710","url":null,"abstract":"<p><p><b>Background:</b> The therapeutic efficacy of cytokine-induced killer (CIK) cells versus dendritic cells (DC) co-cultured with CIK cells (DC-CIK) in treating esophageal cancer (EC) remains unclear due to the absence of a direct comparison of these two regimens. This study evaluated the comparative efficacy and safety of CIK cells versus DC-CIK using network meta-analysis in treating EC. <b>Material and methods:</b> We identified eligible studies from previous meta-analyses, then conducted an updated search to retrieve additional trials between February 2020 and July 2021. The primary outcomes included overall survival (OS), objective response rate (ORR), and disease control rate (DCR), and the secondary outcomes included quality of life improved rate (QLIR) and adverse events (AEs). A network meta-analysis of 12 studies was conducted using ADDIS software. <b>Results:</b> Twelve studies were identified, including six comparing CIK or DC-CIK plus chemotherapy (CT) with CT alone. Immunotherapy plus CT significantly improved overall survival (OS) (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.23-13.69), objective response rate (ORR) (OR 2.72, 95% CI 1.79-4.11), disease control rate (DCR) (OR 3.45, 95% CI 2.32-5.14), and quality of life improvement rate (QLIR) (OR 3.54, 95% CI 2.31-5.41). DC-CIK+CT decreased the risk of leukopenia compared with CT alone. However, no statistical difference was detected between CIK-CT and DC-CIK+CT. <b>Conclusion:</b> Based on the available evidence, we concluded that CIK cell treatment is superior to CT alone, but CIK-CT and DC-CIK+CT may be comparable in treating EC. However, comparing CIK-CT and DC-CIK+CT is only based on indirect evidence, so it is undoubtedly necessary to conduct studies to compare CIK-CT with DC-CIK+CT in EC patients directly.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10277884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-30eCollection Date: 2023-01-01DOI: 10.3389/pore.2023.1611175
Lei Zhang, Xuefei Zhang, Bolin Wu, Xue Han, Cunli Guo, Bo Li, Hui Jing, Wen Cheng
Objective: The current study aimed to investigate the prognostic value of albumin-bilirubin (ALBI) score in predicting clinical outcomes of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Methods: This retrospective study included 90 pancreatic cancer patients after pancreatoduodenectomy with liver metastasis from January 2012 to December 2018. In this study, the Chi-square or Fisher's exact tests, the receiver operating characteristic (ROC) curve, Kaplan-Meier method and Log-rank test, univariate and multivariate Cox proportional hazard regression analyses, nomogram, calibration curves and decision curve analysis were used for all statistical analysis. Results: We analyzed the optimal cut-off value of ALBI by ROC curve, and the optimal cut-off value was -2.60. According to ALBI score, these patients were divided into two groups: low ALBI group (n = 33) and high ALBI group (n = 57). Patients with low ALBI score was significantly related to longer progression free survival (PFS) (p = 0.0002, HR: 3.039, 95% CI: 1.772-5.210) and overall survival (OS) (p = 0.0005, HR: 2.697, 95% CI: 1.539-4.720). The 1-, 3-, and 5-year PFS and OS rates in low ALBI group were higher than those in high ALBI group. ALBI was a potential independent prognostic factor for pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Moreover, the nomogram was used to predict the 1-, 3-, and 5-year survival probabilities of PFS and OS. The calibration curve shown that the prediction line matched the reference line well for postoperative 3-year PFS and OS. The DCA shown that nomogram model was better than the only ALBI, and indicated the ability for clinical decision-making, especially in 1-year PFS, and 3-, 5-year OS. Conclusion: ALBI is a potential independent factor for PFS and OS, and can predict the prognosis of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation.
{"title":"Prognostic value of albumin-bilirubin score in pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation.","authors":"Lei Zhang, Xuefei Zhang, Bolin Wu, Xue Han, Cunli Guo, Bo Li, Hui Jing, Wen Cheng","doi":"10.3389/pore.2023.1611175","DOIUrl":"10.3389/pore.2023.1611175","url":null,"abstract":"<p><p><b>Objective:</b> The current study aimed to investigate the prognostic value of albumin-bilirubin (ALBI) score in predicting clinical outcomes of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. <b>Methods:</b> This retrospective study included 90 pancreatic cancer patients after pancreatoduodenectomy with liver metastasis from January 2012 to December 2018. In this study, the Chi-square or Fisher's exact tests, the receiver operating characteristic (ROC) curve, Kaplan-Meier method and Log-rank test, univariate and multivariate Cox proportional hazard regression analyses, nomogram, calibration curves and decision curve analysis were used for all statistical analysis. <b>Results:</b> We analyzed the optimal cut-off value of ALBI by ROC curve, and the optimal cut-off value was -2.60. According to ALBI score, these patients were divided into two groups: low ALBI group (<i>n</i> = 33) and high ALBI group (<i>n</i> = 57). Patients with low ALBI score was significantly related to longer progression free survival (PFS) (<i>p</i> = 0.0002, HR: 3.039, 95% CI: 1.772-5.210) and overall survival (OS) (<i>p</i> = 0.0005, HR: 2.697, 95% CI: 1.539-4.720). The 1-, 3-, and 5-year PFS and OS rates in low ALBI group were higher than those in high ALBI group. ALBI was a potential independent prognostic factor for pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Moreover, the nomogram was used to predict the 1-, 3-, and 5-year survival probabilities of PFS and OS. The calibration curve shown that the prediction line matched the reference line well for postoperative 3-year PFS and OS. The DCA shown that nomogram model was better than the only ALBI, and indicated the ability for clinical decision-making, especially in 1-year PFS, and 3-, 5-year OS. <b>Conclusion:</b> ALBI is a potential independent factor for PFS and OS, and can predict the prognosis of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10263168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9711052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy. Methods: 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers. Results: PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (p < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (p = 0.046, and p = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs. Conclusion: This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.
{"title":"PD-1 and PD-L1 expression in rare lung tumors.","authors":"Marton Gyulai, Zsolt Megyesfalvi, Lilla Reiniger, Tunde Harko, Bence Ferencz, Luca Karsko, Laszlo Agocs, Janos Fillinger, Balazs Dome, Zoltan Szallasi, Judit Moldvay","doi":"10.3389/pore.2023.1611164","DOIUrl":"10.3389/pore.2023.1611164","url":null,"abstract":"<p><p><b>Background:</b> Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy. <b>Methods:</b> 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers. <b>Results:</b> PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (<i>p</i> < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (<i>p</i> = 0.046, and <i>p</i> = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs. <b>Conclusion:</b> This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-22eCollection Date: 2023-01-01DOI: 10.3389/pore.2023.1611083
Yan Chen, Tao Ma
Multiple myeloma (MM) is the second most common tumor of the hematologic system. MM remains incurable at this time. In this study, we used bioinformatics analysis to find key genes in the pathogenesis of MM. We first found that Lysosome associated membrane protein 5 (LAMP5) expression was sequentially increased in healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and newly diagnosed MM (NDMM), relapsed MM (RMM). We collected bone marrow from patients with NDMM, HD and post-treatment MM (PTMM) and performed qPCR analysis of LAMP5, and found that the expression of LAMP5 is stronger in NDMM than in HD, and decreases after treatment. Western blotting assay also found more expression of LAMP5 in NDMM than in HD. Patients with high LAMP5 expression have a higher DS (Durie-Salmon) stage and worse prognosis. We next verified the expression of LAMP5 in four MM cell lines and silenced LAMP5 expression in RPMI-8226 and AMO-1, and explored the effects of LAMP5 silencing on MM cell apoptosis and cell cycle by flow cytometry and western blotting. Knockdown of LAMP5 promoted apoptosis in MM cells, but had no effect on the cell cycle. Mechanistically, LAMP5 may exert its pro-tumor effects in MM in part through activation of p38 protein. We screened LAMP5 for the first time as a key gene for MM progression and recurrence, and found that LAMP5 may exert its pro-tumor effects in MM through activation of p38 protein.
多发性骨髓瘤(MM)是血液系统中第二常见的肿瘤。目前,多发性骨髓瘤仍无法治愈。在这项研究中,我们利用生物信息学分析找到了 MM 发病机制中的关键基因。我们首先发现,溶酶体相关膜蛋白5(LAMP5)的表达在健康供体(HD)、意义未定的单克隆抗体病(MGUS)、烟雾型多发性骨髓瘤(SMM)和新诊断的多发性骨髓瘤(NDMM)、复发的多发性骨髓瘤(RMM)中依次增加。我们采集了NDMM、HD和治疗后MM(PTMM)患者的骨髓,对LAMP5进行了qPCR分析,发现LAMP5在NDMM中的表达强于HD,且在治疗后有所下降。Western印迹检测也发现LAMP5在NDMM中的表达高于HD。LAMP5高表达的患者DS(Durie-Salmon)分期更高,预后更差。接下来,我们验证了LAMP5在四种MM细胞系中的表达,并沉默了LAMP5在RPMI-8226和AMO-1中的表达,通过流式细胞术和Western印迹法探讨了沉默LAMP5对MM细胞凋亡和细胞周期的影响。敲除LAMP5可促进MM细胞凋亡,但对细胞周期没有影响。从机理上讲,LAMP5可能部分通过激活p38蛋白在MM中发挥促瘤作用。我们首次将LAMP5作为MM进展和复发的关键基因进行了筛选,发现LAMP5可能通过激活p38蛋白在MM中发挥促癌作用。
{"title":"LAMP5 may promote MM progression by activating p38.","authors":"Yan Chen, Tao Ma","doi":"10.3389/pore.2023.1611083","DOIUrl":"10.3389/pore.2023.1611083","url":null,"abstract":"<p><p>Multiple myeloma (MM) is the second most common tumor of the hematologic system. MM remains incurable at this time. In this study, we used bioinformatics analysis to find key genes in the pathogenesis of MM. We first found that Lysosome associated membrane protein 5 (LAMP5) expression was sequentially increased in healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and newly diagnosed MM (NDMM), relapsed MM (RMM). We collected bone marrow from patients with NDMM, HD and post-treatment MM (PTMM) and performed qPCR analysis of LAMP5, and found that the expression of LAMP5 is stronger in NDMM than in HD, and decreases after treatment. Western blotting assay also found more expression of LAMP5 in NDMM than in HD. Patients with high LAMP5 expression have a higher DS (Durie-Salmon) stage and worse prognosis. We next verified the expression of LAMP5 in four MM cell lines and silenced LAMP5 expression in RPMI-8226 and AMO-1, and explored the effects of LAMP5 silencing on MM cell apoptosis and cell cycle by flow cytometry and western blotting. Knockdown of LAMP5 promoted apoptosis in MM cells, but had no effect on the cell cycle. Mechanistically, LAMP5 may exert its pro-tumor effects in MM in part through activation of p38 protein. We screened LAMP5 for the first time as a key gene for MM progression and recurrence, and found that LAMP5 may exert its pro-tumor effects in MM through activation of p38 protein.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9277950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-03eCollection Date: 2023-01-01DOI: 10.3389/pore.2023.1610983
Ni Zhao, Nan Mei, Ye Yi, Hongyan Wang, Yajian Wang, Yu Yao, Chunli Li
Objectives: Pancreatic undifferentiated carcinoma accounts for 2%-7% of pancreatic carcinomas. We aimed to investigate the pathological and genetic characteristics of pancreatic undifferentiated carcinoma with osteoclast-like giant cells and the key points of treatment. Methods: The clinical data and follow-up results of four patients diagnosed with pancreatic undifferentiated carcinoma with osteoclast-like giant cells between May 2015 and May 2020 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed. Results: Chief complaints included "pain and discomfort in the upper abdomen" (2/4), "nausea and vomiting" (1/4) or no symptoms (1/4). Preoperative mildly elevated tumor markers included carcinoembryonic antigen (1/4) and CA19-9 (1/4). The tumors were located in the tail of the pancreas in three patients and the head and neck in one patient. Tumor metastasis was found in pancreatic adipose tissue in two patients and lymph node metastasis in one patient, with microscopic heterogeneous mononuclear cells and scattered osteoclast-like giant cells of various sizes. One patient (1/4) had a mucinous cystic tumor of the pancreas, and two patients (2/4) had adenocarcinoma of the pancreatic duct. Only one patient received postoperative gemcitabine combined with albumin-bound paclitaxel chemotherapy. Conclusion: Currently, treatment guidelines are lacking for PUC-OGC, and prognosis varies markedly. More cases must be reported to clarify its origination. The long-term follow-up of diagnosed patients and genetic mutation testing can also contribute to improving treatment and prognosis of this disease.
{"title":"Case report: Pathological and genetic features of pancreatic undifferentiated carcinoma with osteoclast-like giant cells.","authors":"Ni Zhao, Nan Mei, Ye Yi, Hongyan Wang, Yajian Wang, Yu Yao, Chunli Li","doi":"10.3389/pore.2023.1610983","DOIUrl":"10.3389/pore.2023.1610983","url":null,"abstract":"<p><p><b>Objectives:</b> Pancreatic undifferentiated carcinoma accounts for 2%-7% of pancreatic carcinomas. We aimed to investigate the pathological and genetic characteristics of pancreatic undifferentiated carcinoma with osteoclast-like giant cells and the key points of treatment. <b>Methods:</b> The clinical data and follow-up results of four patients diagnosed with pancreatic undifferentiated carcinoma with osteoclast-like giant cells between May 2015 and May 2020 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed. <b>Results:</b> Chief complaints included \"pain and discomfort in the upper abdomen\" (2/4), \"nausea and vomiting\" (1/4) or no symptoms (1/4). Preoperative mildly elevated tumor markers included carcinoembryonic antigen (1/4) and CA19-9 (1/4). The tumors were located in the tail of the pancreas in three patients and the head and neck in one patient. Tumor metastasis was found in pancreatic adipose tissue in two patients and lymph node metastasis in one patient, with microscopic heterogeneous mononuclear cells and scattered osteoclast-like giant cells of various sizes. One patient (1/4) had a mucinous cystic tumor of the pancreas, and two patients (2/4) had adenocarcinoma of the pancreatic duct. Only one patient received postoperative gemcitabine combined with albumin-bound paclitaxel chemotherapy. <b>Conclusion:</b> Currently, treatment guidelines are lacking for PUC-OGC, and prognosis varies markedly. More cases must be reported to clarify its origination. The long-term follow-up of diagnosed patients and genetic mutation testing can also contribute to improving treatment and prognosis of this disease.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9145034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-09eCollection Date: 2023-01-01DOI: 10.3389/pore.2023.1610996
Dániel Sztankovics, Dorottya Moldvai, Gábor Petővári, Rebeka Gelencsér, Ildikó Krencz, Regina Raffay, Titanilla Dankó, Anna Sebestyén
Growing evidence propagates those alternative technologies (relevant human cell-based-e.g., organ-on-chips or biofabricated models-or artificial intelligence-combined technologies) that could help in vitro test and predict human response and toxicity in medical research more accurately. In vitro disease model developments have great efforts to create and serve the need of reducing and replacing animal experiments and establishing human cell-based in vitro test systems for research use, innovations, and drug tests. We need human cell-based test systems for disease models and experimental cancer research; therefore, in vitro three-dimensional (3D) models have a renaissance, and the rediscovery and development of these technologies are growing ever faster. This recent paper summarises the early history of cell biology/cellular pathology, cell-, tissue culturing, and cancer research models. In addition, we highlight the results of the increasing use of 3D model systems and the 3D bioprinted/biofabricated model developments. Moreover, we present our newly established 3D bioprinted luminal B type breast cancer model system, and the advantages of in vitro 3D models, especially the bioprinted ones. Based on our results and the reviewed developments of in vitro breast cancer models, the heterogeneity and the real in vivo situation of cancer tissues can be represented better by using 3D bioprinted, biofabricated models. However, standardising the 3D bioprinting methods is necessary for future applications in different high-throughput drug tests and patient-derived tumour models. Applying these standardised new models can lead to the point that cancer drug developments will be more successful, efficient, and consequently cost-effective in the near future.
越来越多的证据表明,替代技术(基于人体细胞的相关技术,如芯片上的器官或生物制造模型,或人工智能组合技术)有助于体外测试并更准确地预测医学研究中的人体反应和毒性。体外疾病模型的开发为减少和替代动物实验,建立基于人体细胞的体外测试系统,用于研究、创新和药物测试做出了巨大的努力。我们需要以人体细胞为基础的测试系统用于疾病模型和癌症实验研究;因此,体外三维(3D)模型复兴了,这些技术的重新发现和发展也越来越快。这篇最新论文总结了细胞生物学/细胞病理学、细胞、组织培养和癌症研究模型的早期历史。此外,我们还重点介绍了越来越多地使用三维模型系统和三维生物打印/生物制造模型的发展成果。此外,我们还介绍了新建立的三维生物打印管腔 B 型乳腺癌模型系统,以及体外三维模型(尤其是生物打印模型)的优势。根据我们的研究结果和对体外乳腺癌模型发展的回顾,使用三维生物打印、生物制造的模型可以更好地表现癌症组织的异质性和体内真实情况。然而,三维生物打印方法的标准化对于未来应用于不同的高通量药物测试和患者衍生肿瘤模型是非常必要的。在不久的将来,应用这些标准化的新模型可以使抗癌药物的研发更加成功、高效,从而提高成本效益。
{"title":"3D bioprinting and the revolution in experimental cancer model systems-A review of developing new models and experiences with <i>in vitro</i> 3D bioprinted breast cancer tissue-mimetic structures.","authors":"Dániel Sztankovics, Dorottya Moldvai, Gábor Petővári, Rebeka Gelencsér, Ildikó Krencz, Regina Raffay, Titanilla Dankó, Anna Sebestyén","doi":"10.3389/pore.2023.1610996","DOIUrl":"10.3389/pore.2023.1610996","url":null,"abstract":"<p><p>Growing evidence propagates those alternative technologies (relevant human cell-based-e.g., organ-on-chips or biofabricated models-or artificial intelligence-combined technologies) that could help <i>in vitro</i> test and predict human response and toxicity in medical research more accurately. <i>In vitro</i> disease model developments have great efforts to create and serve the need of reducing and replacing animal experiments and establishing human cell-based <i>in vitro</i> test systems for research use, innovations, and drug tests. We need human cell-based test systems for disease models and experimental cancer research; therefore, <i>in vitro</i> three-dimensional (3D) models have a renaissance, and the rediscovery and development of these technologies are growing ever faster. This recent paper summarises the early history of cell biology/cellular pathology, cell-, tissue culturing, and cancer research models. In addition, we highlight the results of the increasing use of 3D model systems and the 3D bioprinted/biofabricated model developments. Moreover, we present our newly established 3D bioprinted luminal B type breast cancer model system, and the advantages of <i>in vitro</i> 3D models, especially the bioprinted ones. Based on our results and the reviewed developments of <i>in vitro</i> breast cancer models, the heterogeneity and the real <i>in vivo</i> situation of cancer tissues can be represented better by using 3D bioprinted, biofabricated models. However, standardising the 3D bioprinting methods is necessary for future applications in different high-throughput drug tests and patient-derived tumour models. Applying these standardised new models can lead to the point that cancer drug developments will be more successful, efficient, and consequently cost-effective in the near future.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10792661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin-apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin-APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin-APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial-mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-β/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.
{"title":"Cancer apelin receptor suppresses vascular mimicry in malignant melanoma.","authors":"Koichi Inukai, Kazuyoshi Kise, Yumiko Hayashi, Weizhen Jia, Fumitaka Muramatsu, Naoki Okamoto, Hirotaka Konishi, Keigo Akuta, Hiroyasu Kidoya, Nobuyuki Takakura","doi":"10.3389/pore.2023.1610867","DOIUrl":"10.3389/pore.2023.1610867","url":null,"abstract":"<p><p>Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin-apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin-APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin-APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. <i>In vitro</i>, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial-mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-β/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9297151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/pore.2023.1611110
[This retracts the article DOI: 10.3389/pore.2021.1609761.].
[本文撤回文章DOI: 10.3389/pore.2021.1609761.]。
{"title":"Retraction: MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways.","authors":"","doi":"10.3389/pore.2023.1611110","DOIUrl":"https://doi.org/10.3389/pore.2023.1611110","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/pore.2021.1609761.].</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9617600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher's precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ2 = 6.632, p = 0.010; OS: χ2 = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram's predictive clinical utility for clinical decision was better than IOSS. Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.
目的:本研究旨在建立一种新的基于氧化应激指标的综合氧化应激评分系统(integrated oxidative stress score, IOSS)来预测III期胃癌的预后。方法:回顾性分析2014年1月至2016年12月期间接受手术治疗的III期胃癌患者。IOSS是一个基于可实现的氧化应激指数的综合指标,包括白蛋白、血尿素氮和直接胆红素。根据受试者工作特征曲线将患者分为低(IOSS≤2.00)和高(IOSS > 2.00)两组。分组变量采用卡方检验或Fisher精度概率检验。连续变量采用t检验。无病生存期(DFS)和总生存期(OS)采用Kaplan-Meier检验和Log-Rank检验。采用单因素Cox比例风险回归模型和逐步多因素Cox比例风险回归分析来评价DFS和OS的潜在预后因素。采用R软件对DFS和OS进行多因素分析,建立潜在预后因素的nomogram。为了评估模态图预测预后的准确性,我们制作了校准曲线和决策曲线分析,将观察结果与预测结果进行对比。结果:IOSS与DFS、OS显著相关,是影响III期胃癌患者预后的潜在因素。低iss患者生存期较长(DFS: χ2 = 6.632, p = 0.010;OS: χ2 = 6.519, p = 0.011),生存率较高。单因素和多因素分析表明,iiss是一个潜在的预后因素。对潜在的预后因素进行nomogram,以提高生存预测的准确性,评价III期胃癌患者的预后。校准曲线显示在1年、3年和5年的寿命率上有很好的一致性。决策曲线分析显示nomogram对临床决策的预测效用优于IOSS。结论:IOSS是基于氧化应激指数的非特异性肿瘤预测指标,低IOSS是III期胃癌预后较好的重要因素。
{"title":"Integrated oxidative stress score for predicting prognosis in stage III gastric cancer undergoing surgery.","authors":"Yu-Hang Liu, Rui Meng, Bing Zhu, Qi-Qi Zhan, Xin Yang, Guan-Yi Ding, Chun-Liang Jia, Qian-Yu Liu, Wei-Guo Xu","doi":"10.3389/pore.2023.1610897","DOIUrl":"https://doi.org/10.3389/pore.2023.1610897","url":null,"abstract":"<p><p><b>Objective:</b> This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. <b>Methods:</b> Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher's precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. <b>Results:</b> The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ<sup>2</sup> = 6.632, <i>p</i> = 0.010; OS: χ<sup>2</sup> = 6.519, <i>p</i> = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram's predictive clinical utility for clinical decision was better than IOSS. <b>Conclusion:</b> IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/pore.2023.1611038
Lifen Shen, Yen-Ling Chen, Chu-Chun Huang, Yu-Chiau Shyu, Richard E B Seftor, Elisabeth A Seftor, Mary J C Hendrix, Du-Shieng Chien, Yi-Wen Chu
CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G2/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.
{"title":"CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.","authors":"Lifen Shen, Yen-Ling Chen, Chu-Chun Huang, Yu-Chiau Shyu, Richard E B Seftor, Elisabeth A Seftor, Mary J C Hendrix, Du-Shieng Chien, Yi-Wen Chu","doi":"10.3389/pore.2023.1611038","DOIUrl":"https://doi.org/10.3389/pore.2023.1611038","url":null,"abstract":"<p><p>CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G<sub>2</sub>/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (<i>STK11</i> and <i>NF2</i>) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of <i>STK11</i> and <i>NF2</i> are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.</p>","PeriodicalId":19981,"journal":{"name":"Pathology & Oncology Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}