Pub Date : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2023.043922
Yan Zhang, Heyang Zhang, Jing Wang, Xin Wei, Y I Qu, Feng Xu, Lijun Zhang
Background: Bortezomib results in peripheral neuropathy (PN) in approximately 50% of patients, during multiple myeloma (MM) treatment, a complication known as Bortezomib-induced peripheral neuropathy (BIPN). The drug response varies among individuals. Genetic factor may play an important role in BIPN.
Methods: A next-generation sequencing (NGS) panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy. mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR (RT-qPCR). Serum homocysteine (Hcy) levels were detected in 40 samples by chemiluminescent microparticle immunoassay (CMIA).
Results: Compared with the non-BIPN group (n = 89), a total of 8 significantly associated single nucleotide polymorphisms (SNPs) were identified in the BIPN group (n = 115): MTHFR (rs1801131, rs1801133, rs17421511), EPHX1 (rs1051740), MME (rs2016848), ALDH1A1 (rs6151031), HTR7 (rs1935349) and CYP2A6 (rs8192720). The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment (NP group) was lower than that of newly diagnosed patients without peripheral neuritis after treatment (NnP group) (1.70 ± 0.77 vs. 2.81 ± 0.97, p= 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 μmol/L vs. 8.52 ± 3.29 μmol/L, p= 0.016) and healthy controls (11.66 ± 1.79 μmol/L vs. 8.55 ± 2.13 μmol/L, p≤ 0.001).
Conclusion: CYP2A6, EPHX1, MTHFR, ALDH1A1, HTR7, MME and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower MTHFR mRNA expression, which might result in higher serum Hcy levels.
{"title":"A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients.","authors":"Yan Zhang, Heyang Zhang, Jing Wang, Xin Wei, Y I Qu, Feng Xu, Lijun Zhang","doi":"10.32604/or.2023.043922","DOIUrl":"https://doi.org/10.32604/or.2023.043922","url":null,"abstract":"<p><strong>Background: </strong>Bortezomib results in peripheral neuropathy (PN) in approximately 50% of patients, during multiple myeloma (MM) treatment, a complication known as Bortezomib-induced peripheral neuropathy (BIPN). The drug response varies among individuals. Genetic factor may play an important role in BIPN.</p><p><strong>Methods: </strong>A next-generation sequencing (NGS) panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy. mRNA expression of <i>MTHFR</i> and <i>ALDH1A1</i> in 62 peripheral blood samples was detected by real-time quantitative PCR (RT-qPCR). Serum homocysteine (Hcy) levels were detected in 40 samples by chemiluminescent microparticle immunoassay (CMIA).</p><p><strong>Results: </strong>Compared with the non-BIPN group (n = 89), a total of 8 significantly associated single nucleotide polymorphisms (SNPs) were identified in the BIPN group (n = 115): <i>MTHFR</i> (rs1801131, rs1801133, rs17421511), <i>EPHX1</i> (rs1051740), <i>MME</i> (rs2016848), <i>ALDH1A1</i> (rs6151031), <i>HTR7</i> (rs1935349) and <i>CYP2A6</i> (rs8192720). The mRNA expression level of <i>MTHFR</i> in newly diagnosed patients with peripheral neuritis after treatment (NP group) was lower than that of newly diagnosed patients without peripheral neuritis after treatment (NnP group) (1.70 ± 0.77 <i>vs</i>. 2.81 ± 0.97, <b><i>p</i></b>= 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 μmol/L <i>vs</i>. 8.52 ± 3.29 μmol/L, <b><i>p</i></b>= 0.016) and healthy controls (11.66 ± 1.79 μmol/L <i>vs</i>. 8.55 ± 2.13 μmol/L, <b><i>p</i></b>≤ 0.001).</p><p><strong>Conclusion: </strong><i>CYP2A6, EPHX1, MTHFR, ALDH1A1, HTR7, MME</i> and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower <i>MTHFR</i> mRNA expression, which might result in higher serum Hcy levels.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855690","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2023.044775
Jianbo Zhou, Feng Wan, Bin Xiao, Xin Li, Cheng Peng, F U Peng
Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men, respectively, worldwide. Although the antitumor activity of chalcones has been extensively studied, the molecular mechanisms of isoliquiritigenin analog 2', 4', 4-trihydroxychalcone (metochalcone; TEC) against carcinomas remain less well understood. In this study, we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner. TEC induced cell cycle arrest in the S-phase, cell migration inhibition in vitro, and reduced tumor growth in vivo. Moreover, transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways. TEC triggered the senescence-associated secretory phenotype (SASP) by repressing the JAK2/STAT3 axis. The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway, highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.
{"title":"Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer.","authors":"Jianbo Zhou, Feng Wan, Bin Xiao, Xin Li, Cheng Peng, F U Peng","doi":"10.32604/or.2023.044775","DOIUrl":"https://doi.org/10.32604/or.2023.044775","url":null,"abstract":"<p><p>Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men, respectively, worldwide. Although the antitumor activity of chalcones has been extensively studied, the molecular mechanisms of isoliquiritigenin analog 2', 4', 4-trihydroxychalcone (metochalcone; TEC) against carcinomas remain less well understood. In this study, we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner. TEC induced cell cycle arrest in the S-phase, cell migration inhibition <i>in vitro</i>, and reduced tumor growth <i>in vivo</i>. Moreover, transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways. TEC triggered the senescence-associated secretory phenotype (SASP) by repressing the JAK2/STAT3 axis. The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway, highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863750","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}
Ovarian cancer is among the most lethal gynecological cancers, primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy. Drug resistance (DR) poses the most significant challenge in treating patients with existing drugs. The Food and Drug Administration (FDA) has recently approved three new therapeutic drugs, including two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and niraparib) and one vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) for maintenance therapy. However, resistance to these new drugs has emerged. Therefore, understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management. In this review, we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.
卵巢癌是致死率最高的妇科癌症之一,主要原因是缺乏导致晚期诊断的特异性症状以及对化疗的耐药性。耐药性(DR)是现有药物治疗患者的最大挑战。美国食品和药物管理局(FDA)最近批准了三种新的治疗药物,包括两种多聚(ADP-核糖)聚合酶(PARP)抑制剂(奥拉帕利和尼拉帕利)和一种血管内皮生长因子(VEGF)抑制剂(贝伐珠单抗),用于维持治疗。然而,这些新药的耐药性已经出现。因此,了解 DR 的机制并探索克服这些机制的新方法对于有效治疗至关重要。在这篇综述中,我们总结了 DR 的主要分子机制,并讨论了对抗 DR 的新策略。
{"title":"Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review.","authors":"Effat Alemzadeh, Leila Allahqoli, Afrooz Mazidimoradi, Esmat Alemzadeh, Fahimeh Ghasemi, Hamid Salehiniya, Ibrahim Alkatout","doi":"10.32604/or.2024.031006","DOIUrl":"10.32604/or.2024.031006","url":null,"abstract":"<p><p>Ovarian cancer is among the most lethal gynecological cancers, primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy. Drug resistance (DR) poses the most significant challenge in treating patients with existing drugs. The Food and Drug Administration (FDA) has recently approved three new therapeutic drugs, including two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and niraparib) and one vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) for maintenance therapy. However, resistance to these new drugs has emerged. Therefore, understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management. In this review, we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855463","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2024.047042
Nilam Bhusare, Maushmi Kumar
Glioblastoma, the most aggressive form of brain tumor, poses significant challenges in terms of treatment success and patient survival. Current treatment modalities for glioblastoma include radiation therapy, surgical intervention, and chemotherapy. Unfortunately, the median survival rate remains dishearteningly low at 12-15 months. One of the major obstacles in treating glioblastoma is the recurrence of tumors, making chemotherapy the primary approach for secondary glioma patients. However, the efficacy of drugs is hampered by the presence of the blood-brain barrier and multidrug resistance mechanisms. Consequently, considerable research efforts have been directed toward understanding the underlying signaling pathways involved in glioma and developing targeted drugs. To tackle glioma, numerous studies have examined kinase-downstream signaling pathways such as RAS-RAF-MEK-ERK-MPAK. By targeting specific signaling pathways, heterocyclic compounds have demonstrated efficacy in glioma therapeutics. Additionally, key kinases including phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase, cytoplasmic tyrosine kinase (CTK), receptor tyrosine kinase (RTK) and lipid kinase (LK) have been considered for investigation. These pathways play crucial roles in drug effectiveness in glioma treatment. Heterocyclic compounds, encompassing pyrimidine, thiazole, quinazoline, imidazole, indole, acridone, triazine, and other derivatives, have shown promising results in targeting these pathways. As part of this review, we propose exploring novel structures with low toxicity and high potency for glioma treatment. The development of these compounds should strive to overcome multidrug resistance mechanisms and efficiently penetrate the blood-brain barrier. By optimizing the chemical properties and designing compounds with enhanced drug-like characteristics, we can maximize their therapeutic value and minimize adverse effects. Considering the complex nature of glioblastoma, these novel structures should be rigorously tested and evaluated for their efficacy and safety profiles.
{"title":"A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases.","authors":"Nilam Bhusare, Maushmi Kumar","doi":"10.32604/or.2024.047042","DOIUrl":"10.32604/or.2024.047042","url":null,"abstract":"<p><p>Glioblastoma, the most aggressive form of brain tumor, poses significant challenges in terms of treatment success and patient survival. Current treatment modalities for glioblastoma include radiation therapy, surgical intervention, and chemotherapy. Unfortunately, the median survival rate remains dishearteningly low at 12-15 months. One of the major obstacles in treating glioblastoma is the recurrence of tumors, making chemotherapy the primary approach for secondary glioma patients. However, the efficacy of drugs is hampered by the presence of the blood-brain barrier and multidrug resistance mechanisms. Consequently, considerable research efforts have been directed toward understanding the underlying signaling pathways involved in glioma and developing targeted drugs. To tackle glioma, numerous studies have examined kinase-downstream signaling pathways such as RAS-RAF-MEK-ERK-MPAK. By targeting specific signaling pathways, heterocyclic compounds have demonstrated efficacy in glioma therapeutics. Additionally, key kinases including phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase, cytoplasmic tyrosine kinase (CTK), receptor tyrosine kinase (RTK) and lipid kinase (LK) have been considered for investigation. These pathways play crucial roles in drug effectiveness in glioma treatment. Heterocyclic compounds, encompassing pyrimidine, thiazole, quinazoline, imidazole, indole, acridone, triazine, and other derivatives, have shown promising results in targeting these pathways. As part of this review, we propose exploring novel structures with low toxicity and high potency for glioma treatment. The development of these compounds should strive to overcome multidrug resistance mechanisms and efficiently penetrate the blood-brain barrier. By optimizing the chemical properties and designing compounds with enhanced drug-like characteristics, we can maximize their therapeutic value and minimize adverse effects. Considering the complex nature of glioblastoma, these novel structures should be rigorously tested and evaluated for their efficacy and safety profiles.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869222","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2023.042447
Jingjing Tian, Xibao Hu, Xinrong Zhang
To confirm the relationship between Circ_0003855 and EC, we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC, and the expression levels of Circ_0003855, miR-622, and FLOT1 were detected. The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells, while miR-622 was lowly expressed (p < 0.05). Subsequently, Circ_0003855 small interfering RNA (si-Circ_0003855) and its negative control (si-NC) were used to detect changes in cellular biological behaviors. We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855, and miR-622 expression was elevated, while FLOT1 was decreased (p < 0.05). Additionally, si-Circ_0003855 and miR-622 inhibitor sequence (miR-622-inhibition) were co-transfected into cells with miR-622-inhibition alone, and untreated Eca109 cells were used as a control to detect the expression of FLOT1. Co-transfection of si-Circ_0003855 and miR-622-inhibition showed no significant difference in FLOT1 expression compared to the control cells (p > 0.05). Synthesizing the results of these experiments above, we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells, and its mechanism is related to miR-622 and FLOT1.
{"title":"Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1.","authors":"Jingjing Tian, Xibao Hu, Xinrong Zhang","doi":"10.32604/or.2023.042447","DOIUrl":"https://doi.org/10.32604/or.2023.042447","url":null,"abstract":"<p><p>To confirm the relationship between Circ_0003855 and EC, we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC, and the expression levels of Circ_0003855, miR-622, and FLOT1 were detected. The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells, while miR-622 was lowly expressed (<i>p</i> < 0.05). Subsequently, Circ_0003855 small interfering RNA (si-Circ_0003855) and its negative control (si-NC) were used to detect changes in cellular biological behaviors. We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855, and miR-622 expression was elevated, while FLOT1 was decreased (<i>p</i> < 0.05). Additionally, si-Circ_0003855 and miR-622 inhibitor sequence (miR-622-inhibition) were co-transfected into cells with miR-622-inhibition alone, and untreated Eca109 cells were used as a control to detect the expression of FLOT1. Co-transfection of si-Circ_0003855 and miR-622-inhibition showed no significant difference in FLOT1 expression compared to the control cells (<i>p</i> > 0.05). Synthesizing the results of these experiments above, we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells, and its mechanism is related to miR-622 and FLOT1.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852481","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2024.048948
Marko Skelin, Bruna Perkov-Stipičin, Sanja Vušković, Marina Šandrk Plehaček, Ane Bašić, David Šarčević, Maja Ilić, Ivan Krečak
Background: The European Society for Medical Oncology (ESMO) guidelines are among the most comprehensive and widely used clinical practice guidelines (CPGs) globally. However, the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated. This study assessed ESMO CPG levels of evidence (LOE) and grades of recommendations (GOR), as well as their trends over time across various cancer settings.
Methods: We manually extracted every recommendation with the Infectious Diseases Society of America (IDSA) classification from each CPG. We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.
Results: Among the 1,823 recommendations in the current CPG, 30% were classified as LOE I, and 43% were classified as GOR A. Overall, there was a slight decrease in LOE I (-2%) and an increase in the proportion of GOR A (+1%) in the current CPG compared to previous versions. The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials (LOE I-II) shows a decrease (71% vs. 63%, p = 0.009) while recommendations based on lower levels of evidence (LOE III-V) show an increase (29% vs. 37%, p = 0.01) between previous and current version. In the current versions, the highest proportion of LOE I (42%) was found in recommendations related to pharmacotherapy, while the highest proportion of GOR A recommendations was found in the areas of pathology (50%) and diagnostic (50%) recommendations. Significant variability in LOE I and GOR A recommendations and their changes over time was observed across different cancer types.
Conclusion: One-third of the current ESMO CPG recommendations are supported by the highest level of evidence. More well-designed randomized clinical trials are needed to increase the proportion of LOE I and GOR A recommendations, ultimately leading to improved outcomes for cancer patients.
背景:欧洲肿瘤内科学会(ESMO)指南是全球最全面、使用最广泛的临床实践指南(CPG)之一。然而,支持ESMO CPG建议的科学证据水平尚未得到系统研究。本研究评估了ESMO CPG的证据水平(LOE)和建议等级(GOR),以及它们在不同癌症环境下的发展趋势:方法:我们手动提取了每份 CPG 中符合美国传染病学会(IDSA)分类的每条建议。我们研究了所有ESMO CPG指南中LOE和GOR在不同主题和癌症类型中的分布情况:总体而言,与之前的版本相比,现行CPG中LOE I的比例略有下降(-2%),GOR A的比例有所上升(+1%)。基于随机试验等较高证据级别(LOE I-II)的 GOR A 推荐比例有所下降(71% vs. 63%,p = 0.009),而基于较低证据级别(LOE III-V)的推荐比例则有所上升(29% vs. 37%,p = 0.01)。在当前版本中,LOE I比例最高(42%)的是与药物治疗相关的建议,而GOR A比例最高的是病理(50%)和诊断(50%)方面的建议。不同癌症类型的LOE I和GOR A建议及其随时间的变化存在显著差异:结论:三分之一的ESMO CPG建议得到了最高级别证据的支持。需要更多设计良好的随机临床试验来提高 LOE I 和 GOR A 建议的比例,最终改善癌症患者的预后。
{"title":"Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines.","authors":"Marko Skelin, Bruna Perkov-Stipičin, Sanja Vušković, Marina Šandrk Plehaček, Ane Bašić, David Šarčević, Maja Ilić, Ivan Krečak","doi":"10.32604/or.2024.048948","DOIUrl":"https://doi.org/10.32604/or.2024.048948","url":null,"abstract":"<p><strong>Background: </strong>The European Society for Medical Oncology (ESMO) guidelines are among the most comprehensive and widely used clinical practice guidelines (CPGs) globally. However, the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated. This study assessed ESMO CPG levels of evidence (LOE) and grades of recommendations (GOR), as well as their trends over time across various cancer settings.</p><p><strong>Methods: </strong>We manually extracted every recommendation with the Infectious Diseases Society of America (IDSA) classification from each CPG. We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.</p><p><strong>Results: </strong>Among the 1,823 recommendations in the current CPG, 30% were classified as LOE I, and 43% were classified as GOR A. Overall, there was a slight decrease in LOE I (-2%) and an increase in the proportion of GOR A (+1%) in the current CPG compared to previous versions. The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials (LOE I-II) shows a decrease (71% <i>vs</i>. 63%, <i>p</i> = 0.009) while recommendations based on lower levels of evidence (LOE III-V) show an increase (29% <i>vs</i>. 37%, <i>p</i> = 0.01) between previous and current version. In the current versions, the highest proportion of LOE I (42%) was found in recommendations related to pharmacotherapy, while the highest proportion of GOR A recommendations was found in the areas of pathology (50%) and diagnostic (50%) recommendations. Significant variability in LOE I and GOR A recommendations and their changes over time was observed across different cancer types.</p><p><strong>Conclusion: </strong>One-third of the current ESMO CPG recommendations are supported by the highest level of evidence. More well-designed randomized clinical trials are needed to increase the proportion of LOE I and GOR A recommendations, ultimately leading to improved outcomes for cancer patients.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866300","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2024.048988
Shahid Karim, Alanoud Naher Alghanmi, Maha Jamal, Huda Alkreathy, Alam Jamal, Hind A Alkhatabi, Mohammed Bazuhair, Aftab Ahmad
Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using in vitro experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as well as reductions in intracellular ATP and lactate levels. Moreover, this effect was found to be dependent on the dosages of the drugs. In addition to effectively inhibiting the cell cycle, the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression. This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications, namely CAN, DAP, and EMP, on the responsiveness to the anticancer properties of DOX. The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.
{"title":"A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells.","authors":"Shahid Karim, Alanoud Naher Alghanmi, Maha Jamal, Huda Alkreathy, Alam Jamal, Hind A Alkhatabi, Mohammed Bazuhair, Aftab Ahmad","doi":"10.32604/or.2024.048988","DOIUrl":"10.32604/or.2024.048988","url":null,"abstract":"<p><p>Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using <i>in vitro</i> experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as well as reductions in intracellular ATP and lactate levels. Moreover, this effect was found to be dependent on the dosages of the drugs. In addition to effectively inhibiting the cell cycle, the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression. This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications, namely CAN, DAP, and EMP, on the responsiveness to the anticancer properties of DOX. The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862162","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2024.045972
Andi Zhao, Yue Wang, Zijin Wang, Qing Shao, Q I Gong, Hui Zhu, Shiya Shen, H U Liu, Xuejuan Chen
Numerous studies have characterized the critical role of circular RNAs (circRNAs) as regulatory factors in the progression of multiple cancers. However, the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma (UM) remain enigmatic. In this study, we identified a novel circRNA, circ_0053943, through re-analysis of UM microarray data and quantitative RT-PCR. Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings. Mechanistically, circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA. RNA sequencing assays identified epidermal growth factor receptor (EGFR) as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level. Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Collectively, circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex, thus providing a potential biomarker and therapeutic target for UM.
{"title":"<i>Circ_0053943</i> complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of <i>Epidermal growth factor receptor</i>.","authors":"Andi Zhao, Yue Wang, Zijin Wang, Qing Shao, Q I Gong, Hui Zhu, Shiya Shen, H U Liu, Xuejuan Chen","doi":"10.32604/or.2024.045972","DOIUrl":"https://doi.org/10.32604/or.2024.045972","url":null,"abstract":"<p><p>Numerous studies have characterized the critical role of circular RNAs (circRNAs) as regulatory factors in the progression of multiple cancers. However, the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma (UM) remain enigmatic. In this study, we identified a novel circRNA, <i>circ_0053943</i>, through re-analysis of UM microarray data and quantitative RT-PCR. <i>Circ_0053943</i> was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both <i>in vitro</i> and <i>in vivo</i> settings. Mechanistically, <i>circ_0053943</i> was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA. RNA sequencing assays identified <i>epidermal growth factor receptor</i> (<i>EGFR</i>) as a target gene of <i>circ_0053943</i> and IGF2BP3 at the transcriptional level. Rescue assays demonstrated that <i>circ_0053943</i> exerts its biological function by stabilizing <i>EGFR</i> mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Collectively, <i>circ_0053943</i> may promote UM progression by stabilizing <i>EGFR</i> mRNA and activating the MAPK/ERK signaling pathway through the formation of a <i>circ_0053943</i>/IGF2BP3/<i>EGFR</i> RNA-protein ternary complex, thus providing a potential biomarker and therapeutic target for UM.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852238","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2023.042604
Yiwen Zhu, Liu Yang, Ying Yu, Ying Xiong, Ping Xiao, Xiao Fu, Xin Luo
Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis. Since there is no permanent therapy for this condition, it is necessary to develop a cure. Therefore, this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A (HYSA) in osteosarcoma cell lines (MG63). In this investigational study, MG63 cells were utilized. Microarray experiments, quantitative polymerase chain reaction (qPCR), immunofluorescent staining, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption, lactate production, and ATP levels, proliferation assay, 5-Ethynyl-2'-deoxyuridine (EDU) staining, and Western blot were performed. In MG63 cells, HYSA lowered cell proliferation and metastasis rates, suppressed EDU cell number, and enhanced caspase-3/9 activity levels. HYSA reduced the Warburg effect and induced ferroptosis (FPT) in MG63 cells. Inhibiting ferroptosis diminished HYSA's anti-cancer activities in MG63 cells. The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA's anti-cancer activities in MG63 cells. HIF-1α is one target spot for HYSA in a model of osteosarcoma cancer (OC). HYSA altered HIF-1α's thermophoretic activity; following binding with HYSA, HIF-1α's melting point increased from ~55°C to ~60°C. HYSA significantly enhanced the thermal stability of exogenous WT HIF-1α while not affecting Mut HIF-1α, suggesting that ARG-311, GLY-312, GLN-347, and GLN-387 may be involved in the interaction between HIF-1α and HYSA. Conclusively, our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway. HYSA is a possible therapeutic option for OC or other cancers.
{"title":"Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway.","authors":"Yiwen Zhu, Liu Yang, Ying Yu, Ying Xiong, Ping Xiao, Xiao Fu, Xin Luo","doi":"10.32604/or.2023.042604","DOIUrl":"10.32604/or.2023.042604","url":null,"abstract":"<p><p>Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis. Since there is no permanent therapy for this condition, it is necessary to develop a cure. Therefore, this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A (HYSA) in osteosarcoma cell lines (MG63). In this investigational study, MG63 cells were utilized. Microarray experiments, quantitative polymerase chain reaction (qPCR), immunofluorescent staining, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption, lactate production, and ATP levels, proliferation assay, 5-Ethynyl-2'-deoxyuridine (EDU) staining, and Western blot were performed. In MG63 cells, HYSA lowered cell proliferation and metastasis rates, suppressed EDU cell number, and enhanced caspase-3/9 activity levels. HYSA reduced the Warburg effect and induced ferroptosis (FPT) in MG63 cells. Inhibiting ferroptosis diminished HYSA's anti-cancer activities in MG63 cells. The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA's anti-cancer activities in MG63 cells. HIF-1α is one target spot for HYSA in a model of osteosarcoma cancer (OC). HYSA altered HIF-1α's thermophoretic activity; following binding with HYSA, HIF-1α's melting point increased from ~55°C to ~60°C. HYSA significantly enhanced the thermal stability of exogenous WT HIF-1α while not affecting Mut HIF-1α, suggesting that ARG-311, GLY-312, GLN-347, and GLN-387 may be involved in the interaction between HIF-1α and HYSA. Conclusively, our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway. HYSA is a possible therapeutic option for OC or other cancers.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857677","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 : 2024-04-23eCollection Date: 2024-01-01DOI: 10.32604/or.2023.042384
Jingjing Chen, Dan Wang, Zequn Wang, Mengyuan Han, Houqing Yin, Wenting Zhou, Ribai Yan, Yan Pan
Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.
{"title":"Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome.","authors":"Jingjing Chen, Dan Wang, Zequn Wang, Mengyuan Han, Houqing Yin, Wenting Zhou, Ribai Yan, Yan Pan","doi":"10.32604/or.2023.042384","DOIUrl":"https://doi.org/10.32604/or.2023.042384","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that <i>cdk1</i> and <i>rps27a</i> ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857558","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}