Pathology & Oncology Research最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Integrated oxidative stress score for predicting prognosis in stage III gastric cancer undergoing surgery.","authors":"Yu-Hang Liu,&nbsp;Rui Meng,&nbsp;Bing Zhu,&nbsp;Qi-Qi Zhan,&nbsp;Xin Yang,&nbsp;Guan-Yi Ding,&nbsp;Chun-Liang Jia,&nbsp;Qian-Yu Liu,&nbsp;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: χ² = 6.632, <i>p</i> = 0.010; OS: χ² = 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}

{"title":"CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.","authors":"Lifen Shen,&nbsp;Yen-Ling Chen,&nbsp;Chu-Chun Huang,&nbsp;Yu-Chiau Shyu,&nbsp;Richard E B Seftor,&nbsp;Elisabeth A Seftor,&nbsp;Mary J C Hendrix,&nbsp;Du-Shieng Chien,&nbsp;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 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 (<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}