Pub Date : 2024-02-01Epub Date: 2024-01-10DOI: 10.14740/wjon1739
Rui Wang, Aashiq Hussain, Quan Quan Guo, Xiao Wei Jin, Miao Miao Wang
The dynamic changes between glycolysis and oxidative phosphorylation (OXPHOS) for adenosine triphosphate (ATP) output, along with glucose, glutamine, and fatty acid utilization, etc., lead to the maintenance and selection of growth advantageous to tumor cell subgroups in an environment of iron starvation and hypoxia. Iron plays an important role in the three major biochemical reactions in nature: photosynthesis, nitrogen fixation, and oxidative respiration, which all require the participation of iron-sulfur proteins, such as ferredoxin, cytochrome b, and the complex I, II, III in the electron transport chain, respectively. Abnormal iron-sulfur cluster synthesis process or hypoxia will directly affect the function of mitochondrial electron transfer and mitochondrial OXPHOS. More research results have indicated that iron metabolism, oxygen availability and hypoxia-inducible factor mutually regulate the shift between glycolysis and OXPHOS. In this article, we make a perspective review to provide novel opinions of the regulation of glycolysis and OXPHOS in tumor cells.
糖酵解和氧化磷酸化(OXPHOS)输出三磷酸腺苷(ATP)之间的动态变化,以及葡萄糖、谷氨酰胺和脂肪酸的利用等,导致肿瘤细胞亚群在铁饥饿和缺氧环境中维持和选择有利的生长。铁在自然界的三大生化反应中发挥着重要作用:光合作用、固氮作用和氧化呼吸作用,这些反应都需要铁硫蛋白的参与,如铁氧还蛋白、细胞色素 b 和电子传递链中的复合体 I、II、III。铁硫簇合成过程异常或缺氧会直接影响线粒体电子传递和线粒体 OXPHOS 的功能。更多的研究结果表明,铁代谢、氧供应和缺氧诱导因子相互调控糖酵解和 OXPHOS 之间的转变。本文将对肿瘤细胞中糖酵解和 OXPHOS 的调控进行综述,以提供新的观点。
{"title":"Oxygen and Iron Availability Shapes Metabolic Adaptations of Cancer Cells.","authors":"Rui Wang, Aashiq Hussain, Quan Quan Guo, Xiao Wei Jin, Miao Miao Wang","doi":"10.14740/wjon1739","DOIUrl":"10.14740/wjon1739","url":null,"abstract":"<p><p>The dynamic changes between glycolysis and oxidative phosphorylation (OXPHOS) for adenosine triphosphate (ATP) output, along with glucose, glutamine, and fatty acid utilization, etc., lead to the maintenance and selection of growth advantageous to tumor cell subgroups in an environment of iron starvation and hypoxia. Iron plays an important role in the three major biochemical reactions in nature: photosynthesis, nitrogen fixation, and oxidative respiration, which all require the participation of iron-sulfur proteins, such as ferredoxin, cytochrome b, and the complex I, II, III in the electron transport chain, respectively. Abnormal iron-sulfur cluster synthesis process or hypoxia will directly affect the function of mitochondrial electron transfer and mitochondrial OXPHOS. More research results have indicated that iron metabolism, oxygen availability and hypoxia-inducible factor mutually regulate the shift between glycolysis and OXPHOS. In this article, we make a perspective review to provide novel opinions of the regulation of glycolysis and OXPHOS in tumor cells.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-01-10DOI: 10.14740/wjon1714
Hong Yu Deng, Li Wen Zhang, Fa Qing Tang, Ming Zhou, Meng Na Li, Lei Lei Lu, Ying Hua Li
Background: Ovarian cancer is an extremely deadly gynecological malignancy, with a 5-year survival rate below 30%. Among the different histological subtypes, serous ovarian cancer (SOC) is the most common. Anoikis significantly contributes to the progression of ovarian cancer. Therefore, identifying an anoikis-related signature that can serve as potential prognostic predictors for SOC is of great significance.
Methods: We intersected 308 anoikis-related genes (ARGs) and identified those significantly associated with SOC prognosis using univariate Cox regression. A LASSO Cox regression model was constructed and evaluated using Kaplan-Meier and receiver operating characteristic (ROC) analyses in TCGA (The Cancer Genome Atlas) and GSE26193 cohorts. We conducted quantitative real-time polymerase chain reaction (qPCR) to assess mRNA levels and applied bioinformatics to investigate the correlation between risk groups and gene expression, mutations, pathways, tumor immune microenvironment (TIME), and drug sensitivity in SOC.
Results: Among 308 ARGs, 28 were significantly associated with SOC prognosis. A 13-gene prognostic model was established through LASSO Cox regression in TCGA cohort. High-risk group had poorer prognosis than low-risk group (median overall survival (mOS): 34.2 vs. 57.1 months, hazard ratio (HR): 2.590, 95% confidence interval (CI): 0.159 - 6.00, P < 0.001). The area under the curve (AUC) values of 0.63, 0.65, and 0.74 reflected the predictive performance for 3-, 5-, and 8-year overall survival (OS) in GSE26193 validation cohort. Functional enrichment, pathway analysis, and TIME analysis identified distinct characteristics between risk groups. Drug sensitivity analysis revealed potential drug advantages for each group. Furthermore, qPCR validation once again confirmed the effectiveness of the risk model in SOC patients.
Conclusions: We developed and validated a robust ARG model, which could be used to predict OS in SOC patients. By systematically analyzing the correlation between the risk score of the ARGs signature model and various patterns, including the TIME and drug sensitivity, our findings suggest that this prognostic model contributes to the advancement of personalized and precise therapeutic strategies. Nevertheless, further validation studies and investigations into the underlying mechanisms are warranted.
{"title":"Identification and Validation of a Novel Anoikis-Related Gene Signature for Predicting Survival in Patients With Serous Ovarian Cancer.","authors":"Hong Yu Deng, Li Wen Zhang, Fa Qing Tang, Ming Zhou, Meng Na Li, Lei Lei Lu, Ying Hua Li","doi":"10.14740/wjon1714","DOIUrl":"10.14740/wjon1714","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is an extremely deadly gynecological malignancy, with a 5-year survival rate below 30%. Among the different histological subtypes, serous ovarian cancer (SOC) is the most common. Anoikis significantly contributes to the progression of ovarian cancer. Therefore, identifying an anoikis-related signature that can serve as potential prognostic predictors for SOC is of great significance.</p><p><strong>Methods: </strong>We intersected 308 anoikis-related genes (ARGs) and identified those significantly associated with SOC prognosis using univariate Cox regression. A LASSO Cox regression model was constructed and evaluated using Kaplan-Meier and receiver operating characteristic (ROC) analyses in TCGA (The Cancer Genome Atlas) and GSE26193 cohorts. We conducted quantitative real-time polymerase chain reaction (qPCR) to assess mRNA levels and applied bioinformatics to investigate the correlation between risk groups and gene expression, mutations, pathways, tumor immune microenvironment (TIME), and drug sensitivity in SOC.</p><p><strong>Results: </strong>Among 308 ARGs, 28 were significantly associated with SOC prognosis. A 13-gene prognostic model was established through LASSO Cox regression in TCGA cohort. High-risk group had poorer prognosis than low-risk group (median overall survival (mOS): 34.2 vs. 57.1 months, hazard ratio (HR): 2.590, 95% confidence interval (CI): 0.159 - 6.00, P < 0.001). The area under the curve (AUC) values of 0.63, 0.65, and 0.74 reflected the predictive performance for 3-, 5-, and 8-year overall survival (OS) in GSE26193 validation cohort. Functional enrichment, pathway analysis, and TIME analysis identified distinct characteristics between risk groups. Drug sensitivity analysis revealed potential drug advantages for each group. Furthermore, qPCR validation once again confirmed the effectiveness of the risk model in SOC patients.</p><p><strong>Conclusions: </strong>We developed and validated a robust ARG model, which could be used to predict OS in SOC patients. By systematically analyzing the correlation between the risk score of the ARGs signature model and various patterns, including the TIME and drug sensitivity, our findings suggest that this prognostic model contributes to the advancement of personalized and precise therapeutic strategies. Nevertheless, further validation studies and investigations into the underlying mechanisms are warranted.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-09DOI: 10.14740/wjon1701
Nadya Keumala Fitri, Bahagia Willibrordus Maria Nainggolan, Naufal Nandita Firsty, Andika Pradana, Dina Keumala Sari
Background: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent types of cancer worldwide, driving extensive research in oncologic therapeutic approaches. Atezolizumab, among the treatments under scrutiny, is undergoing evaluation as a potential first-line therapy for NSCLC. This review aims to assess the efficacy of atezolizumab in treating patients with NSCLC and to shed light on the ongoing quest for the most effective treatment.
Methods: Multiple scientific databases, including PubMed, Cochrane, and ScienceDirect, were consulted. The literature identification utilized the strategic Boolean term method of keywords relating to "non-small cell lung cancer" and "atezolizumab" to suggest the analyzed population in our review without restricting the potential outcomes. The primary inclusion criterion is clinical studies that attempted to determine the efficacy of atezolizumab in NSCLC patients.
Results: We included four trials to be analyzed in the final analysis, which we stratified into the programmed cell death-ligand 1 (PD-L1) expressivity status aside from the pooled intention-to-treat (ITT) population. We found the addition of atezolizumab may significantly improve the overall survival (OS) in the respective arm, remarkably among the high PD-L1 expression group (TC3 or IC3). The result of our meta-analysis presented the pooled OS of 0.79 (0.72, 0.87) in 95% confidence interval (CI) with a P value of < 0.05. Sub-analysis of the PD-L1's expression revealed TC3 population benefits the most (hazard ratio (HR): 0.55, 95% CI (0.42, 0.73)), compared to low (HR: 0.80, 95% CI (0.68, 0.93)) and negative expression (HR: 0.79, 95% CI (0.68, 0.93)); which is statistically meaningful (P < 0.05). Similar result was also observed in progression-free survival (PFS) analysis with the HR value of 0.63 (0.55, 0.72), with P value of < 0.05, favoring atezolizumab arm.
Conclusions: Upon examination, the study reveals that the addition of atezolizumab demonstrates notable improvements in both OS and PFS among NSCLC patients. These findings present promising attributes for atezolizumab as a viable treatment for NSCLC. However, it is important to acknowledge that the future holds further revelations in this realm, and more insights are yet to be uncovered.
{"title":"The Addition of Atezolizumab to Chemotherapy in Non-Small Cell Lung Cancer: A Trial-Based Review and Meta-Analysis.","authors":"Nadya Keumala Fitri, Bahagia Willibrordus Maria Nainggolan, Naufal Nandita Firsty, Andika Pradana, Dina Keumala Sari","doi":"10.14740/wjon1701","DOIUrl":"10.14740/wjon1701","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) stands as one of the most prevalent types of cancer worldwide, driving extensive research in oncologic therapeutic approaches. Atezolizumab, among the treatments under scrutiny, is undergoing evaluation as a potential first-line therapy for NSCLC. This review aims to assess the efficacy of atezolizumab in treating patients with NSCLC and to shed light on the ongoing quest for the most effective treatment.</p><p><strong>Methods: </strong>Multiple scientific databases, including PubMed, Cochrane, and ScienceDirect, were consulted. The literature identification utilized the strategic Boolean term method of keywords relating to \"non-small cell lung cancer\" and \"atezolizumab\" to suggest the analyzed population in our review without restricting the potential outcomes. The primary inclusion criterion is clinical studies that attempted to determine the efficacy of atezolizumab in NSCLC patients.</p><p><strong>Results: </strong>We included four trials to be analyzed in the final analysis, which we stratified into the programmed cell death-ligand 1 (PD-L1) expressivity status aside from the pooled intention-to-treat (ITT) population. We found the addition of atezolizumab may significantly improve the overall survival (OS) in the respective arm, remarkably among the high PD-L1 expression group (TC3 or IC3). The result of our meta-analysis presented the pooled OS of 0.79 (0.72, 0.87) in 95% confidence interval (CI) with a P value of < 0.05. Sub-analysis of the PD-L1's expression revealed TC3 population benefits the most (hazard ratio (HR): 0.55, 95% CI (0.42, 0.73)), compared to low (HR: 0.80, 95% CI (0.68, 0.93)) and negative expression (HR: 0.79, 95% CI (0.68, 0.93)); which is statistically meaningful (P < 0.05). Similar result was also observed in progression-free survival (PFS) analysis with the HR value of 0.63 (0.55, 0.72), with P value of < 0.05, favoring atezolizumab arm.</p><p><strong>Conclusions: </strong>Upon examination, the study reveals that the addition of atezolizumab demonstrates notable improvements in both OS and PFS among NSCLC patients. These findings present promising attributes for atezolizumab as a viable treatment for NSCLC. However, it is important to acknowledge that the future holds further revelations in this realm, and more insights are yet to be uncovered.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-01-10DOI: 10.14740/wjon1747
Tian Tian Dai, Yi Ze Li, Hui Ting Hu, Yong Mei Zhao, Hong Yan Peng, Wen Dong Bai, Jing Wen Wang
Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown.
Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition.
Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression.
Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.
{"title":"Inhibiting the m<sup>6</sup>A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.","authors":"Tian Tian Dai, Yi Ze Li, Hui Ting Hu, Yong Mei Zhao, Hong Yan Peng, Wen Dong Bai, Jing Wen Wang","doi":"10.14740/wjon1747","DOIUrl":"10.14740/wjon1747","url":null,"abstract":"<p><strong>Background: </strong>The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m<sup>6</sup>A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown.</p><p><strong>Methods: </strong>The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition.</p><p><strong>Results: </strong>IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in <i>in vivo</i> experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression.</p><p><strong>Conclusion: </strong>All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-09DOI: 10.14740/wjon1748
Abdulla Alzibdeh, Issa Mohamad, Maysa Al-Hussaini, Samer Salah, Abdalgani Jaradat, Ramiz Abuhijlih, Fawzi Abuhijla
Uterine leiomyosarcoma is a high-grade sarcoma that might be associated with dismal outcome. There are no hematological markers that can be used to follow up the recurrence and/or progression of the tumor. We present a case of a 44-year-old female, who was diagnosed with uterine leiomyosarcoma. During her management course, serum beta human chorionic gonadotropin (β-hCG) elevation was correlated with clinical and radiological disease progression on two separate occasions. This correlation should be further investigated to potentially integrate serum β-hCG as a predictive tool for clinical behavior and treatment response.
{"title":"Significance of Beta Human Chorionic Gonadotropin in Predicting Disease Progression in Uterine Leiomyosarcoma.","authors":"Abdulla Alzibdeh, Issa Mohamad, Maysa Al-Hussaini, Samer Salah, Abdalgani Jaradat, Ramiz Abuhijlih, Fawzi Abuhijla","doi":"10.14740/wjon1748","DOIUrl":"10.14740/wjon1748","url":null,"abstract":"<p><p>Uterine leiomyosarcoma is a high-grade sarcoma that might be associated with dismal outcome. There are no hematological markers that can be used to follow up the recurrence and/or progression of the tumor. We present a case of a 44-year-old female, who was diagnosed with uterine leiomyosarcoma. During her management course, serum beta human chorionic gonadotropin (β-hCG) elevation was correlated with clinical and radiological disease progression on two separate occasions. This correlation should be further investigated to potentially integrate serum β-hCG as a predictive tool for clinical behavior and treatment response.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-07-12DOI: 10.14740/wjon1590
Haitham Abdelmoaty, Sonya Good, Tuan Phan
Background: There is no literature report on how metformin and adenosine monophosphate-activated protein kinase (AMPK) inhibitor affect normal and cancer bladder cells under the presence of nitrate.
Methods: Various treatment concentrations and methods were used to study the effects of nitrate, metformin, and/or AMPK inhibitor on normal and/or cancer bladder cells. Normal bladder cells were exposed to nitrate or metformin alone or in combination. The effects of AMPK on normal bladder cells were investigated with nitrate and metformin pretreatment. The effects of varying metformin concentrations on cancer bladder cells were examined as well.
Results: Metformin has produced almost no changes in cell viability of normal cells with various concentrations. Addition of both nitrate and metformin at the same time resulted in less than 17% cell viability as compared to the controlled values; however, this value is about 10% better than nitrate alone for 24 h and approximate 27% better for 48 h. Pre-treatment of normal cells with AMPK inhibitor for 6 h prior to addition of metformin and nitrate reduced the cell viability greatly. The treatment of cancer bladder cells with metformin indicated an inverse relationship between metformin concentration and cancer bladder cell viability.
Conclusion: Metformin assisted normal bladder cells in surviving in the presence of nitrate, but its total survival was greatly reduced by AMPK inhibitors. Metformin inhibited the growth of bladder cancer cells.
{"title":"Viability Profiles of Normal and Cancer Bladder Cells With Metformin, Nitrate and Adenosine Monophosphate-Activated Protein Kinase Inhibitor.","authors":"Haitham Abdelmoaty, Sonya Good, Tuan Phan","doi":"10.14740/wjon1590","DOIUrl":"10.14740/wjon1590","url":null,"abstract":"<p><strong>Background: </strong>There is no literature report on how metformin and adenosine monophosphate-activated protein kinase (AMPK) inhibitor affect normal and cancer bladder cells under the presence of nitrate.</p><p><strong>Methods: </strong>Various treatment concentrations and methods were used to study the effects of nitrate, metformin, and/or AMPK inhibitor on normal and/or cancer bladder cells. Normal bladder cells were exposed to nitrate or metformin alone or in combination. The effects of AMPK on normal bladder cells were investigated with nitrate and metformin pretreatment. The effects of varying metformin concentrations on cancer bladder cells were examined as well.</p><p><strong>Results: </strong>Metformin has produced almost no changes in cell viability of normal cells with various concentrations. Addition of both nitrate and metformin at the same time resulted in less than 17% cell viability as compared to the controlled values; however, this value is about 10% better than nitrate alone for 24 h and approximate 27% better for 48 h. Pre-treatment of normal cells with AMPK inhibitor for 6 h prior to addition of metformin and nitrate reduced the cell viability greatly. The treatment of cancer bladder cells with metformin indicated an inverse relationship between metformin concentration and cancer bladder cell viability.</p><p><strong>Conclusion: </strong>Metformin assisted normal bladder cells in surviving in the presence of nitrate, but its total survival was greatly reduced by AMPK inhibitors. Metformin inhibited the growth of bladder cancer cells.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-21DOI: 10.14740/wjon1681
Rui Wang, Shu Ling Liu, Quan Quan Guo, Xiao Hong Shi, Mei Mei Ma
Background: Proteasome inhibitors, such as bortezomib, have demonstrated efficacy in the therapeutic management of multiple myeloma (MM). However, it is important to note that these inhibitors also elicit endoplasmic reticulum stress, which subsequently triggers the unfolded protein response (UPR) and autophagy, which have been shown to facilitate the survival of tumor cells. The disruption of the circadian clock is considered a characteristic feature of cancer. However, how disrupted circadian clock intertwines with tumor metabolism and drug resistance is not clearly clarified. This work explores the antitumor effectiveness of bortezomib and the circadian clock agonist SR9009, elucidating their impact on glucose-regulated protein 78 (GRP78), the autophagy process, and lipogenesis.
Methods: The antitumor effects of bortezomib and SR9009 were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo nonobese diabetic/severe combined immunodeficient (NOD/SCID) murine xenograft MM model. The assessment of cell viability was conducted using the cell counting kit-8 (CCK8) method, whereas the measurement of cell proliferation was performed with the inclusion of EdU (5-ethynyl-2'-deoxyuridine). Apoptosis was assessed by flow cytometry. The cells were transduced using adenovirus-tf-LC3, which was labeled with dual fluorescence. Subsequently, confocal imaging was employed to observe and examine the autophagosomes. REV-ERBα knockdown leads to upregulation of ATG5 and BENC1 at the protein level with immunoblot. Changes in the expression levels of GRP78, LC3, stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FASN) were assessed through the utilization of quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting.
Results: Our results showed that both bortezomib and circadian clock REV-ERBs agonist SR9009 decreased MM viability, proliferation rate and induced an apoptotic response in a dose-dependent manner in vitro. However, the two differ greatly in their mechanisms of action. Bortezomib upregulated GRP78 and autophagy LC3, while circadian clock agonist SR9009 inhibited GRP78 and autophagy LC3. Combined SR9009 with bortezomib induced synergistic cytotoxicity against MM cells. REV-ERBα knockdown lead to upregulation of ATG5, BENC1 and significant upregulation of FASN, and SCD1. Mechanically, SR9009 inhibited the core autophagy gene ATG5 and BECN1, and two essential enzymes for de novo lipogenesis FASN and SCD1. SR9009 had synergistic effect with bortezomib and slowed down murine xenograft models of human MM tumor growth in vivo.
Conclusions: Taken together, these results demonstrated that the circadian clock component REV-ERBs agonist SR9009 could inhibit GRP78-induced autophagy and de novo lipogenesis processes and had a synergistic effect with proteasome inhibitors
{"title":"Circadian Clock REV-ERBs Agonist SR9009 Induces Synergistic Antitumor Activity in Multiple Myeloma by Suppressing Glucose-Regulated Protein 78-Dependent Autophagy and Lipogenesis.","authors":"Rui Wang, Shu Ling Liu, Quan Quan Guo, Xiao Hong Shi, Mei Mei Ma","doi":"10.14740/wjon1681","DOIUrl":"https://doi.org/10.14740/wjon1681","url":null,"abstract":"<p><strong>Background: </strong>Proteasome inhibitors, such as bortezomib, have demonstrated efficacy in the therapeutic management of multiple myeloma (MM). However, it is important to note that these inhibitors also elicit endoplasmic reticulum stress, which subsequently triggers the unfolded protein response (UPR) and autophagy, which have been shown to facilitate the survival of tumor cells. The disruption of the circadian clock is considered a characteristic feature of cancer. However, how disrupted circadian clock intertwines with tumor metabolism and drug resistance is not clearly clarified. This work explores the antitumor effectiveness of bortezomib and the circadian clock agonist SR9009, elucidating their impact on glucose-regulated protein 78 (GRP78), the autophagy process, and lipogenesis.</p><p><strong>Methods: </strong>The antitumor effects of bortezomib and SR9009 were evaluated using human MM cell lines (RPMI8226 and U266) <i>in vitro</i> and <i>in vivo</i> nonobese diabetic/severe combined immunodeficient (NOD/SCID) murine xenograft MM model. The assessment of cell viability was conducted using the cell counting kit-8 (CCK8) method, whereas the measurement of cell proliferation was performed with the inclusion of EdU (5-ethynyl-2'-deoxyuridine). Apoptosis was assessed by flow cytometry. The cells were transduced using adenovirus-tf-LC3, which was labeled with dual fluorescence. Subsequently, confocal imaging was employed to observe and examine the autophagosomes. REV-ERBα knockdown leads to upregulation of ATG5 and BENC1 at the protein level with immunoblot. Changes in the expression levels of GRP78, LC3, stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FASN) were assessed through the utilization of quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting.</p><p><strong>Results: </strong>Our results showed that both bortezomib and circadian clock REV-ERBs agonist SR9009 decreased MM viability, proliferation rate and induced an apoptotic response in a dose-dependent manner <i>in vitro</i>. However, the two differ greatly in their mechanisms of action. Bortezomib upregulated GRP78 and autophagy LC3, while circadian clock agonist SR9009 inhibited GRP78 and autophagy LC3. Combined SR9009 with bortezomib induced synergistic cytotoxicity against MM cells. REV-ERBα knockdown lead to upregulation of ATG5, BENC1 and significant upregulation of FASN, and SCD1. Mechanically, SR9009 inhibited the core autophagy gene <i>ATG5</i> and <i>BECN1</i>, and two essential enzymes for <i>de novo</i> lipogenesis FASN and SCD1. SR9009 had synergistic effect with bortezomib and slowed down murine xenograft models of human MM tumor growth <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Taken together, these results demonstrated that the circadian clock component REV-ERBs agonist SR9009 could inhibit GRP78-induced autophagy and <i>de novo</i> lipogenesis processes and had a synergistic effect with proteasome inhibitors ","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The aim of this study was to investigate whether the robotic platform can have a positive impact on the rate of sphincter preservation in patients with rectal tumors, undergoing robotic total mesorectal excision (TME), in comparison with laparoscopic or open TME. We also analyzed and compared short-term outcomes.
Methods: A prospectively collected robotic database was reviewed and compared with the trust and national data. Three groups were designed according to the surgical technique: open, laparoscopic and robotic. This includes all resections for mid and low rectal cancer which were performed with the robotic platform, over a period of 4 years, versus the trust data for the same period.
Results: Two hundred ninety-seven patients with mid and low rectal cancers were analyzed. Demographics for the groups (gender, age, and body mass index) were similar but distance from anal verge was shorter in the robotic group (7 vs. 8.5 cm, P < 0.001). The percentage of abdominoperineal resection (APR) rate was significantly lower in the robotic group (13.5% vs. 39.6% vs. 52.4% for the open group, P < 0.001). Median length of stay, complication rate, and positive circumferential resection margin (CRM) rate for the robotic group were also statistically significantly lower than those for both laparoscopic and open groups.
Conclusion: Robotic surgery for mid and low rectal cancer is safe and feasible, and could help surgeons perform ultra-low anterior resections, rather than APRs and save patients' sphincters. Positive CRM is low, which could lead to improved oncological outcomes.
背景:本研究的目的是探讨与腹腔镜或开放式全肠系膜切除术(TME)相比,机器人平台是否对直肠肿瘤患者接受机器人全肠系膜切除术(TME)的括约肌保存率有积极影响。我们还分析和比较了短期结果。方法:对前瞻性收集的机器人数据库进行审查,并与信托和国家数据进行比较。根据手术技术分为开放组、腹腔镜组和机器人组。这包括在4年期间使用机器人平台进行的所有中低位直肠癌切除术,与同期的信任数据相比。结果:分析了297例中低位直肠癌患者。两组的人口统计数据(性别、年龄和体重指数)相似,但机器人组与肛门边缘的距离更短(7厘米比8.5厘米,P < 0.001)。机器人组的腹会阴切除术(APR)率明显低于开放组(13.5% vs. 39.6% vs. 52.4%, P < 0.001)。机器人组的中位住院时间、并发症发生率和阳性环切缘(CRM)率也显著低于腹腔镜组和开放组。结论:机器人手术治疗中低位直肠癌是安全可行的,可以帮助外科医生进行超低前切除术,而不是APRs手术,挽救患者的括约肌。阳性的CRM较低,这可能导致肿瘤预后的改善。
{"title":"Efficiency of the Robotic Platform in Improving the Rate of Sphincter Preservation in Patients With Mid and Low Rectal Cancer.","authors":"Thalia Petropoulou, Kassiani Theodoraki, Panagiota Kitsanta, Shwan Amin","doi":"10.14740/wjon1581","DOIUrl":"https://doi.org/10.14740/wjon1581","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to investigate whether the robotic platform can have a positive impact on the rate of sphincter preservation in patients with rectal tumors, undergoing robotic total mesorectal excision (TME), in comparison with laparoscopic or open TME. We also analyzed and compared short-term outcomes.</p><p><strong>Methods: </strong>A prospectively collected robotic database was reviewed and compared with the trust and national data. Three groups were designed according to the surgical technique: open, laparoscopic and robotic. This includes all resections for mid and low rectal cancer which were performed with the robotic platform, over a period of 4 years, versus the trust data for the same period.</p><p><strong>Results: </strong>Two hundred ninety-seven patients with mid and low rectal cancers were analyzed. Demographics for the groups (gender, age, and body mass index) were similar but distance from anal verge was shorter in the robotic group (7 vs. 8.5 cm, P < 0.001). The percentage of abdominoperineal resection (APR) rate was significantly lower in the robotic group (13.5% vs. 39.6% vs. 52.4% for the open group, P < 0.001). Median length of stay, complication rate, and positive circumferential resection margin (CRM) rate for the robotic group were also statistically significantly lower than those for both laparoscopic and open groups.</p><p><strong>Conclusion: </strong>Robotic surgery for mid and low rectal cancer is safe and feasible, and could help surgeons perform ultra-low anterior resections, rather than APRs and save patients' sphincters. Positive CRM is low, which could lead to improved oncological outcomes.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-03DOI: 10.14740/wjon1702
Chang Jun Chen, Xin Zhao, Jing Wen Zhao, Xiao Jie Ma, Wei Hua Xu, Yu Bin Qi, Jing Kun Li, Qing Wei Ma, Lei Zhang, Yun Yang
Osteoblastic bone reaction, the occurrence of new osteoblastic lesions, is a paradoxical phenomenon during the treatment of cancers and can be defined as disease progression or bone metastases. Osteoblastic bone reactions usually occur in patients who receive treatments such as chemotherapy or hormonal or targeted therapy; however, it is difficult to differentiate them from disease progression or an increase in osteoblastic activity in response to therapy. Although osteoblastic bone reaction in lung cancer has been described in a few reports, it has never been reported in patients with KRASG12V-mutant lung adenocarcinoma treated with immunotherapy and antiangiogenesis. Here, we describe a case of a 77-year-old male with KRASG12V-mutant lung adenocarcinoma whose osteoblastic bone response was found during treatment with sintilimab and bevacizumab. We showed the course of the disease as well as systematic imaging manifestations of lung cancer with osteoblastic bone reaction and discussed their mechanisms.
{"title":"Osteoblastic Bone Reaction Developing During Treatment With Sintilimab and Bevacizumab in a Patient With <i>KRAS</i><sup>G12V</sup>-Mutant Lung Adenocarcinoma.","authors":"Chang Jun Chen, Xin Zhao, Jing Wen Zhao, Xiao Jie Ma, Wei Hua Xu, Yu Bin Qi, Jing Kun Li, Qing Wei Ma, Lei Zhang, Yun Yang","doi":"10.14740/wjon1702","DOIUrl":"https://doi.org/10.14740/wjon1702","url":null,"abstract":"<p><p>Osteoblastic bone reaction, the occurrence of new osteoblastic lesions, is a paradoxical phenomenon during the treatment of cancers and can be defined as disease progression or bone metastases. Osteoblastic bone reactions usually occur in patients who receive treatments such as chemotherapy or hormonal or targeted therapy; however, it is difficult to differentiate them from disease progression or an increase in osteoblastic activity in response to therapy. Although osteoblastic bone reaction in lung cancer has been described in a few reports, it has never been reported in patients with <i>KRAS</i><sup>G12V</sup>-mutant lung adenocarcinoma treated with immunotherapy and antiangiogenesis. Here, we describe a case of a 77-year-old male with <i>KRAS</i><sup>G12V</sup>-mutant lung adenocarcinoma whose osteoblastic bone response was found during treatment with sintilimab and bevacizumab. We showed the course of the disease as well as systematic imaging manifestations of lung cancer with osteoblastic bone reaction and discussed their mechanisms.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-21DOI: 10.14740/wjon1691
Aki Kimura, Akimitsu Yamada, Masanori Oshi, Mina Nakayama, Naohiro Komura, Teruyasu Sugano, Shinya Yamamoto, Kazutaka Narui, Itaru Endo
A 47-year-old woman diagnosed with stage IV left-sided breast cancer (T3N3aM1; OSS, HEP, LYM) 6 months back presented with respiratory distress. On admission, she developed respiratory failure, requiring 4 L of oxygen support. Pulmonary embolism was ruled out because computed tomography revealed no obvious pulmonary artery thrombus. Transthoracic echocardiography revealed a significant enlargement of the right ventricle and atrium. Pulmonary hypertension was confirmed via right heart catheterization. Pulmonary artery wedge aspiration cytology revealed adenocarcinoma cells. Based on these findings, we diagnosed the patient with pulmonary tumor thrombotic microangiopathy (PTTM) caused by breast cancer. Immediate chemotherapy (paclitaxel and bevacizumab) for breast cancer and concurrent treatment for pulmonary hypertension and disseminated intravascular coagulation were initiated. We could successfully control her condition with paclitaxel and bevacizumab for a year, and the patient survived for 1 year and 8 months. PTTM is a rare disease characterized by pulmonary hypertension and hypoxemia arising due to tumor embolization of the peripheral pulmonary arteries. PTTM is a rapidly progressing condition with no established treatment guidelines; its pathogenesis involves vascular endothelial growth factor (VEGF). This report highlighted the potential of bevacizumab, known for its anti-VEGF effect, in improving the pathological condition of patients with PTTM caused by breast cancer.
{"title":"Dramatic Improvement of Pulmonary Tumor Thrombotic Microangiopathy in a Breast Cancer Patient Treated With Bevacizumab.","authors":"Aki Kimura, Akimitsu Yamada, Masanori Oshi, Mina Nakayama, Naohiro Komura, Teruyasu Sugano, Shinya Yamamoto, Kazutaka Narui, Itaru Endo","doi":"10.14740/wjon1691","DOIUrl":"https://doi.org/10.14740/wjon1691","url":null,"abstract":"<p><p>A 47-year-old woman diagnosed with stage IV left-sided breast cancer (T3N3aM1; OSS, HEP, LYM) 6 months back presented with respiratory distress. On admission, she developed respiratory failure, requiring 4 L of oxygen support. Pulmonary embolism was ruled out because computed tomography revealed no obvious pulmonary artery thrombus. Transthoracic echocardiography revealed a significant enlargement of the right ventricle and atrium. Pulmonary hypertension was confirmed via right heart catheterization. Pulmonary artery wedge aspiration cytology revealed adenocarcinoma cells. Based on these findings, we diagnosed the patient with pulmonary tumor thrombotic microangiopathy (PTTM) caused by breast cancer. Immediate chemotherapy (paclitaxel and bevacizumab) for breast cancer and concurrent treatment for pulmonary hypertension and disseminated intravascular coagulation were initiated. We could successfully control her condition with paclitaxel and bevacizumab for a year, and the patient survived for 1 year and 8 months. PTTM is a rare disease characterized by pulmonary hypertension and hypoxemia arising due to tumor embolization of the peripheral pulmonary arteries. PTTM is a rapidly progressing condition with no established treatment guidelines; its pathogenesis involves vascular endothelial growth factor (VEGF). This report highlighted the potential of bevacizumab, known for its anti-VEGF effect, in improving the pathological condition of patients with PTTM caused by breast cancer.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}