Pub Date : 2024-11-12DOI: 10.1016/j.tranon.2024.102191
Xiping Shen, Ji Wu
{"title":"A conventional radiomics model for predicting disease-free survival in colorectal cancer patients with liver metastasis","authors":"Xiping Shen, Ji Wu","doi":"10.1016/j.tranon.2024.102191","DOIUrl":"10.1016/j.tranon.2024.102191","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102191"},"PeriodicalIF":5.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-11DOI: 10.1016/j.tranon.2024.102187
Agnieszka Rusak , Benita Wiatrak , Klaudia Krawczyńska , Tomasz Górnicki , Karol Zagórski , Łukasz Zadka , Wojciech Fortuna
Glioblastoma multiforme (GBM) is one of the most aggressive and lethal brain tumors, characterized by rapid growth, invasiveness, and resistance to standard therapies, including surgery, chemotherapy, and radiotherapy. Despite advances in treatment, GBM remains highly resistant due to its complex molecular mechanisms, including angiogenesis, invasion, immune modulation, and lipid metabolism dysregulation. This review explores recent breakthroughs in targeted therapies, focusing on innovative drug carriers such as nanoparticles and liposomes, and their potential to overcome GBM's chemo- and radioresistant phenotypes. We also discuss the molecular pathways involved in GBM progression and the latest therapeutic strategies, including immunotherapy and precision medicine approaches, which hold promise for improving clinical outcomes. The review highlights the importance of understanding GBM's genetic and molecular heterogeneity to develop more effective, personalized treatment protocols aimed at increasing survival rates and enhancing the quality of life for GBM patients.
{"title":"Starting points for the development of new targeted therapies for glioblastoma multiforme","authors":"Agnieszka Rusak , Benita Wiatrak , Klaudia Krawczyńska , Tomasz Górnicki , Karol Zagórski , Łukasz Zadka , Wojciech Fortuna","doi":"10.1016/j.tranon.2024.102187","DOIUrl":"10.1016/j.tranon.2024.102187","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is one of the most aggressive and lethal brain tumors, characterized by rapid growth, invasiveness, and resistance to standard therapies, including surgery, chemotherapy, and radiotherapy. Despite advances in treatment, GBM remains highly resistant due to its complex molecular mechanisms, including angiogenesis, invasion, immune modulation, and lipid metabolism dysregulation. This review explores recent breakthroughs in targeted therapies, focusing on innovative drug carriers such as nanoparticles and liposomes, and their potential to overcome GBM's chemo- and radioresistant phenotypes. We also discuss the molecular pathways involved in GBM progression and the latest therapeutic strategies, including immunotherapy and precision medicine approaches, which hold promise for improving clinical outcomes. The review highlights the importance of understanding GBM's genetic and molecular heterogeneity to develop more effective, personalized treatment protocols aimed at increasing survival rates and enhancing the quality of life for GBM patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102187"},"PeriodicalIF":5.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1016/j.tranon.2024.102185
Ruhua Zhang , Wanqi Chen , Xuelan Peng , Zhiguang Zhang , Shangjiu Yang , Li Zhong
Purpose
Procollagen C-proteinase enhancer 1 (PCPE-1) is associated with liver fibrosis, a major risk factor of hepatocellular carcinoma (HCC). However, its role in HCC remains unclear.
Materials and Methods
The mRNA and protein expression levels of PCPE-1 were analyzed using publicly available datasets of HCC tissues and matched normal tissues. Western blotting was performed to determine PCPE-1 levels in 7 paired HCC tumor and normal tissues. Immunohistochemistry was used to detect PCPE-1 levels in 155 HCC patients. The ROC curve was employed to determine the optimal cutoff value of PCPE-1. Univariate and multivariate analyses identified independent risk factors associated with overall survival (OS) of HCC patients. Kaplan-Meier analysis assessed the relationship between PCPE-1 expression and OS, and a prognostic model was constructed.
Results
PCPE-1 protein was upregulated in HCC tissues compared to normal tissues and positively correlated with the expression of several procollagens. 78 out of 155 HCC patients exhibited elevated PCPE-1 expression with cytoplasmic staining. High PCPE-1 expression significantly correlated with tumor necrosis (P = 0.045), poorer histologic grade (G3-G4, P = 0.008), and higher α-fetoprotein (AFP) level (>20 ng/ml, P = 0.043). Both univariate and multivariate analyses showed a significant association between elevated PCPE-1 and poorer overall survival (P < 0.001 in both analyses). Remarkably, combined prognostic model with PCPE-1 and AFP effectively stratified the risk for OS in HCC.
Conclusion
Our results demonstrate for the first time that PCPE-1 serves as an independent prognostic marker for HCC, and the combined prognostic model involving PCPE-1 and AFP emerges as a valuable tool for predicting patient outcomes.
{"title":"Prognostic significance of combined PCPE-1 and α-fetoprotein for hepatocellular carcinoma","authors":"Ruhua Zhang , Wanqi Chen , Xuelan Peng , Zhiguang Zhang , Shangjiu Yang , Li Zhong","doi":"10.1016/j.tranon.2024.102185","DOIUrl":"10.1016/j.tranon.2024.102185","url":null,"abstract":"<div><h3>Purpose</h3><div>Procollagen C-proteinase enhancer 1 (PCPE-1) is associated with liver fibrosis, a major risk factor of hepatocellular carcinoma (HCC). However, its role in HCC remains unclear.</div></div><div><h3>Materials and Methods</h3><div>The mRNA and protein expression levels of PCPE-1 were analyzed using publicly available datasets of HCC tissues and matched normal tissues. Western blotting was performed to determine PCPE-1 levels in 7 paired HCC tumor and normal tissues. Immunohistochemistry was used to detect PCPE-1 levels in 155 HCC patients. The ROC curve was employed to determine the optimal cutoff value of PCPE-1. Univariate and multivariate analyses identified independent risk factors associated with overall survival (OS) of HCC patients. Kaplan-Meier analysis assessed the relationship between PCPE-1 expression and OS, and a prognostic model was constructed.</div></div><div><h3>Results</h3><div>PCPE-1 protein was upregulated in HCC tissues compared to normal tissues and positively correlated with the expression of several procollagens. 78 out of 155 HCC patients exhibited elevated PCPE-1 expression with cytoplasmic staining. High PCPE-1 expression significantly correlated with tumor necrosis (<em>P</em> = 0.045), poorer histologic grade (G3-G4, <em>P</em> = 0.008), and higher α-fetoprotein (AFP) level (>20 ng/ml, <em>P</em> = 0.043). Both univariate and multivariate analyses showed a significant association between elevated PCPE-1 and poorer overall survival (<em>P</em> < 0.001 in both analyses). Remarkably, combined prognostic model with PCPE-1 and AFP effectively stratified the risk for OS in HCC.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate for the first time that PCPE-1 serves as an independent prognostic marker for HCC, and the combined prognostic model involving PCPE-1 and AFP emerges as a valuable tool for predicting patient outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102185"},"PeriodicalIF":5.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1016/j.tranon.2024.102166
Xianglong Tian , Guihua Liu , Linhua Ji , Yi Shen , Junjun Gu , Lili Wang , Jiali Ma , Zuguang Xia , Xinghua Li
TGF-β signaling pathway has been demonstrated to be closely related to chemoresistance, which is the major cause of recurrence and poor outcome in colorectal cancer (CRC), however, the comprehensive epigenetic landscape that functionally implicates in the regulation of TGF-β pathway-associated chemoresistance has not yet well established in CRC. In our study, chromatin immunoprecipitation sequencing (ChIP-seq) and Western blot were employed to investigate epigenetic modifications for histones in response to TGF-β1 intervene. We found that the activation of the TGF-β pathway was characterized by genome-wide high levels of H3K9ac and H3K18ac. Mechanistically, the activation of the TGF-β signaling pathway leads to the downregulation of the deacetylase HDAC4, resulting in the upregulation of H3K9ac and H3K18ac. Consequently, this cascade induces oxaliplatin chemoresistance in CRC by triggering the anti-apoptotic PI3K/AKT signaling pathway. Our in vivo experiment results confirmed that overexpression of HDAC4 significantly enhances the sensitivity of CRC to oxaliplatin chemotherapy. Moreover, the expression level of HDAC4 was positively correlated with patients’ prognosis in CRC. Our data suggest that histone-acetyl modification demonstrates a crucial role in modulating TGF-β pathway-associated chemoresistance in CRC, and HDAC4 would be a biomarker for prognostic prediction and potential therapeutic target for treatment in CRC.
{"title":"Histone-acetyl epigenome regulates TGF-β pathway-associated chemoresistance in colorectal cancer","authors":"Xianglong Tian , Guihua Liu , Linhua Ji , Yi Shen , Junjun Gu , Lili Wang , Jiali Ma , Zuguang Xia , Xinghua Li","doi":"10.1016/j.tranon.2024.102166","DOIUrl":"10.1016/j.tranon.2024.102166","url":null,"abstract":"<div><div>TGF-β signaling pathway has been demonstrated to be closely related to chemoresistance, which is the major cause of recurrence and poor outcome in colorectal cancer (CRC), however, the comprehensive epigenetic landscape that functionally implicates in the regulation of TGF-β pathway-associated chemoresistance has not yet well established in CRC. In our study, chromatin immunoprecipitation sequencing (ChIP-seq) and Western blot were employed to investigate epigenetic modifications for histones in response to TGF-β1 intervene. We found that the activation of the TGF-β pathway was characterized by genome-wide high levels of H3K9ac and H3K18ac. Mechanistically, the activation of the TGF-β signaling pathway leads to the downregulation of the deacetylase HDAC4, resulting in the upregulation of H3K9ac and H3K18ac. Consequently, this cascade induces oxaliplatin chemoresistance in CRC by triggering the anti-apoptotic PI3K/AKT signaling pathway. Our in vivo experiment results confirmed that overexpression of HDAC4 significantly enhances the sensitivity of CRC to oxaliplatin chemotherapy. Moreover, the expression level of HDAC4 was positively correlated with patients’ prognosis in CRC. Our data suggest that histone-acetyl modification demonstrates a crucial role in modulating TGF-β pathway-associated chemoresistance in CRC, and HDAC4 would be a biomarker for prognostic prediction and potential therapeutic target for treatment in CRC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102166"},"PeriodicalIF":5.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08DOI: 10.1016/j.tranon.2024.102182
Wei Liu , Wei Xu , Hui Hao , Lin Yang , Bo Zhang , Yan Zhang
Background
This study aims to explore the role of RIPK2 in lung cancer metastasis and its potential mechanisms.
Methods
The expression levels of RIPK2 in lung cancer patients and cell lines were detected by immunohistochemistry, qRT-PCR, and Western blot. RIPK2 expression was knocked down using siRNA technology, and its effects on the proliferation, migration, and invasion capabilities of lung cancer cells were assessed through CCK-8, EdU, colony formation, and Transwell assays. Furthermore, by overexpressing RIPK2 and LAMP2, the regulatory effect of RIPK2 on the lysosomal pathway and its mechanism of action in lung cancer metastasis were investigated.
Results
The results showed that the expression of RIPK2 was significantly increased in lung cancer patients and cell lines. Knockdown of RIPK2 significantly inhibited the migration, invasion, and proliferation capabilities of lung cancer cells, while overexpression of RIPK2 promoted these malignant behaviors. Further studies found that RIPK2 promoted lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. Additionally, overexpression of LAMP2 could reverse the promotive effects of RIPK2 overexpression on the malignant behaviors of lung cancer cells.
Conclusion
This study reveals for the first time that RIPK2 promotes lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. In the future, targeted therapy against RIPK2 and LAMP2 may become an effective means to inhibit lung cancer metastasis.
{"title":"RIPK2 and lysosomal pathway: Unveiling a new mechanism for lung cancer metastasis","authors":"Wei Liu , Wei Xu , Hui Hao , Lin Yang , Bo Zhang , Yan Zhang","doi":"10.1016/j.tranon.2024.102182","DOIUrl":"10.1016/j.tranon.2024.102182","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to explore the role of RIPK2 in lung cancer metastasis and its potential mechanisms.</div></div><div><h3>Methods</h3><div>The expression levels of RIPK2 in lung cancer patients and cell lines were detected by immunohistochemistry, qRT-PCR, and Western blot. RIPK2 expression was knocked down using siRNA technology, and its effects on the proliferation, migration, and invasion capabilities of lung cancer cells were assessed through CCK-8, EdU, colony formation, and Transwell assays. Furthermore, by overexpressing RIPK2 and LAMP2, the regulatory effect of RIPK2 on the lysosomal pathway and its mechanism of action in lung cancer metastasis were investigated.</div></div><div><h3>Results</h3><div>The results showed that the expression of RIPK2 was significantly increased in lung cancer patients and cell lines. Knockdown of RIPK2 significantly inhibited the migration, invasion, and proliferation capabilities of lung cancer cells, while overexpression of RIPK2 promoted these malignant behaviors. Further studies found that RIPK2 promoted lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. Additionally, overexpression of LAMP2 could reverse the promotive effects of RIPK2 overexpression on the malignant behaviors of lung cancer cells.</div></div><div><h3>Conclusion</h3><div>This study reveals for the first time that RIPK2 promotes lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. In the future, targeted therapy against RIPK2 and LAMP2 may become an effective means to inhibit lung cancer metastasis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102182"},"PeriodicalIF":5.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08DOI: 10.1016/j.tranon.2024.102165
Armen Parsyan , Vasudeva Bhat , Harjot Athwal , Emily A. Goebel , Alison L Allan
Artemis is a key nuclease involved in the non-homologous end joining repair pathway upon DNA double-stranded breaks and during V(D)J recombination. It participates in various cellular processes and cooperates with various proteins involved in tumorigenesis. Its hereditary mutations lead to several pathological conditions, such as severe combined immunodeficiency with radiation sensitivity. Recent studies suggest that Artemis deregulation plays an important role in cancer and is associated with poorer oncologic outcomes and resistance to treatment including radiotherapy, chemotherapy and targeted therapeutics. Artemis emerges as an attractive candidate for cancer prognosis and treatment. Its role in modulating sensitivity to ionizing radiation and DNA-damaging agents makes it an appealing target for drug development. Various existing drugs and novel compounds have been described to inhibit Artemis activity. This review synthesizes the up-to-date information regarding Artemis function, its role in different malignancies and its clinical utility as a potential biomarker and therapeutic target in Oncology.
Artemis 是一种关键的核酸酶，在 DNA 双链断裂和 V(D)J 重组过程中参与非同源末端连接修复途径。它参与多种细胞过程，并与多种参与肿瘤发生的蛋白质合作。它的遗传突变会导致多种病症，如对辐射敏感的严重联合免疫缺陷症。最近的研究表明，Artemis 的失调在癌症中发挥着重要作用，并与较差的肿瘤治疗效果以及对放疗、化疗和靶向治疗等疗法的耐药性有关。Artemis 成为癌症预后和治疗的一个有吸引力的候选对象。它在调节对电离辐射和 DNA 损伤剂的敏感性方面的作用，使其成为一个有吸引力的药物开发靶点。已有多种现有药物和新型化合物被描述为能抑制 Artemis 的活性。这篇综述综述了有关Artemis功能的最新信息、它在不同恶性肿瘤中的作用及其作为肿瘤学潜在生物标记物和治疗靶点的临床实用性。
{"title":"Artemis and its role in cancer","authors":"Armen Parsyan , Vasudeva Bhat , Harjot Athwal , Emily A. Goebel , Alison L Allan","doi":"10.1016/j.tranon.2024.102165","DOIUrl":"10.1016/j.tranon.2024.102165","url":null,"abstract":"<div><div>Artemis is a key nuclease involved in the non-homologous end joining repair pathway upon DNA double-stranded breaks and during V(D)J recombination. It participates in various cellular processes and cooperates with various proteins involved in tumorigenesis. Its hereditary mutations lead to several pathological conditions, such as severe combined immunodeficiency with radiation sensitivity. Recent studies suggest that Artemis deregulation plays an important role in cancer and is associated with poorer oncologic outcomes and resistance to treatment including radiotherapy, chemotherapy and targeted therapeutics. Artemis emerges as an attractive candidate for cancer prognosis and treatment. Its role in modulating sensitivity to ionizing radiation and DNA-damaging agents makes it an appealing target for drug development. Various existing drugs and novel compounds have been described to inhibit Artemis activity. This review synthesizes the up-to-date information regarding Artemis function, its role in different malignancies and its clinical utility as a potential biomarker and therapeutic target in Oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102165"},"PeriodicalIF":5.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.tranon.2024.102177
Wenqing Liu , Yan Liu , Haoyuan Li , Shixiong Wang , Pengfei Chen , Zhongtao Liu , Xianhao Huo , Jihui Tian
Glioblastoma (GBM) is a highly invasive and malignant central nervous system tumor with a median survival duration of 15 months despite multimodal therapy. The insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) has been implicated in various cancers and is known to regulate RNA metabolism and alternative splicing (AS). However, its role in GBM remains unclear. Overexpression of IGF2BP2 led to significant alterations in gene expression, with 472 genes upregulated and 99 downregulated. Gene ontology (GO) analysis indicated enrichment in immune-related biological processes. Notably, IGF2BP2 was found to regulate AS events, with 1372 regulated AS genes (RASGs) and 2096 significantly distinct ASEs identified. Furthermore, IGF2BP2 selectively bound to 3′ and 5′ untranslated regions (UTRs) via GG[AU]C motifs, and IFIH1 was identified as a direct binding partner and upregulated gene upon IGF2BP2 overexpression. Functional enrichment analysis suggested that IGF2BP2 influences pathways related to RNA splicing and immune responses. Our findings demonstrate that IGF2BP2 plays a crucial role in GBM by modulating the transcriptome and AS events. The upregulation of immune-related genes and the regulation of AS by IGF2BP2 highlight its potential as a therapeutic target in GBM, particularly for immunotherapy. The study provides a foundation for further investigation into the molecular mechanisms of IGF2BP2 in GBM and its implications for cancer treatment.
{"title":"IGF2BP2 orchestrates global expression and alternative splicing profiles associated with glioblastoma development in U251 cells","authors":"Wenqing Liu , Yan Liu , Haoyuan Li , Shixiong Wang , Pengfei Chen , Zhongtao Liu , Xianhao Huo , Jihui Tian","doi":"10.1016/j.tranon.2024.102177","DOIUrl":"10.1016/j.tranon.2024.102177","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly invasive and malignant central nervous system tumor with a median survival duration of 15 months despite multimodal therapy. The insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) has been implicated in various cancers and is known to regulate RNA metabolism and alternative splicing (AS). However, its role in GBM remains unclear. Overexpression of IGF2BP2 led to significant alterations in gene expression, with 472 genes upregulated and 99 downregulated. Gene ontology (GO) analysis indicated enrichment in immune-related biological processes. Notably, IGF2BP2 was found to regulate AS events, with 1372 regulated AS genes (RASGs) and 2096 significantly distinct ASEs identified. Furthermore, IGF2BP2 selectively bound to 3′ and 5′ untranslated regions (UTRs) via GG[AU]C motifs, and IFIH1 was identified as a direct binding partner and upregulated gene upon IGF2BP2 overexpression. Functional enrichment analysis suggested that IGF2BP2 influences pathways related to RNA splicing and immune responses. Our findings demonstrate that IGF2BP2 plays a crucial role in GBM by modulating the transcriptome and AS events. The upregulation of immune-related genes and the regulation of AS by IGF2BP2 highlight its potential as a therapeutic target in GBM, particularly for immunotherapy. The study provides a foundation for further investigation into the molecular mechanisms of IGF2BP2 in GBM and its implications for cancer treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102177"},"PeriodicalIF":5.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1016/j.tranon.2024.102179
Guanglin Qiu , Lindi Cai , Gan Li , Yiwei Ren , Enmeng Li , Kai Deng , Mengke Zhu , Shangning Han , Xiangming Che , Xuqi Li , Lin Fan
Background
Gastric cancer (GC) is still a serious threat to human health worldwide. As a natural compound, resveratrol has been proven to have anti-tumor activity, and the nano-delivery carrier has shown its excellent ability to retain and control drug release.
Methods
Res@ZIF-90 underwent synthesis via a one-pot method and subsequent characterization encompassing Dynamic Light Scattering, Scanning Electron Microscope, Transmission Electron Microscope, and UV–vis absorption spectroscope. The release of resveratrol from Res@ZIF-90 across varied pH environments were delineated employing High Performance Liquid Chromatography. The mitochondrial targeting of Res@ZIF-90 was scrutinized utilizing Fluorescent Inverted Microscopy. The cytotoxic impact of Res@ZIF-90 on HGC-27 cells was evaluated through CCK-8 assay, Live/Dead staining, scratch test, and JC-1 assay. Furthermore, the HGC-27 tumor-bearing mice model was established to explore the anti-tumor effect of Res@ZIF-90.
Results
ZIF-90 can effectively release resveratrol under acidic (pH = 5.5) conditions. In addition, Res@ZIF-90 could be taken up by cells and localized into mitochondria. ZIF-90 has no obvious cytotoxicity at the experimental concentration, while Res@ZIF-90 was more cytotoxic to HGC-27 cells than free resveratrol at the same concentration. Res@ZIF-90 significantly reduced the expressions of PGCS 1α, TFAM, PINK1, and COX IV, which together induced mitochondrial homeostasis disorders and inhibited the tumor growth of HGC-27 tumor-bearing mice in vivo.
Conclusions
Res@ZIF-90 can inhibit the progression of gastric cancer by targeting the mitochondria of gastric cancer cells and disrupting mitochondrial homeostasis to produce cytotoxic effects. Res@ZIF-90 may be a promising antitumor drug with potential application value.
{"title":"Res@ZIF-90 suppress gastric cancer progression by disturbing mitochondrial homeostasis","authors":"Guanglin Qiu , Lindi Cai , Gan Li , Yiwei Ren , Enmeng Li , Kai Deng , Mengke Zhu , Shangning Han , Xiangming Che , Xuqi Li , Lin Fan","doi":"10.1016/j.tranon.2024.102179","DOIUrl":"10.1016/j.tranon.2024.102179","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is still a serious threat to human health worldwide. As a natural compound, resveratrol has been proven to have anti-tumor activity, and the nano-delivery carrier has shown its excellent ability to retain and control drug release.</div></div><div><h3>Methods</h3><div>Res@ZIF-90 underwent synthesis via a one-pot method and subsequent characterization encompassing Dynamic Light Scattering, Scanning Electron Microscope, Transmission Electron Microscope, and UV–vis absorption spectroscope. The release of resveratrol from Res@ZIF-90 across varied pH environments were delineated employing High Performance Liquid Chromatography. The mitochondrial targeting of Res@ZIF-90 was scrutinized utilizing Fluorescent Inverted Microscopy. The cytotoxic impact of Res@ZIF-90 on HGC-27 cells was evaluated through CCK-8 assay, Live/Dead staining, scratch test, and JC-1 assay. Furthermore, the HGC-27 tumor-bearing mice model was established to explore the anti-tumor effect of Res@ZIF-90.</div></div><div><h3>Results</h3><div>ZIF-90 can effectively release resveratrol under acidic (pH = 5.5) conditions. In addition, Res@ZIF-90 could be taken up by cells and localized into mitochondria. ZIF-90 has no obvious cytotoxicity at the experimental concentration, while Res@ZIF-90 was more cytotoxic to HGC-27 cells than free resveratrol at the same concentration. Res@ZIF-90 significantly reduced the expressions of PGCS 1α, TFAM, PINK1, and COX IV, which together induced mitochondrial homeostasis disorders and inhibited the tumor growth of HGC-27 tumor-bearing mice in vivo.</div></div><div><h3>Conclusions</h3><div>Res@ZIF-90 can inhibit the progression of gastric cancer by targeting the mitochondria of gastric cancer cells and disrupting mitochondrial homeostasis to produce cytotoxic effects. Res@ZIF-90 may be a promising antitumor drug with potential application value.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102179"},"PeriodicalIF":5.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.tranon.2024.102173
Shan Wang , Zining Jin , Zhaohui Li , Guolian Zhu , Bin Liu , Dianlong Zhang , Shuhong Tang , Fan Yao , Jian Wen , Yi Zhao , Xiaolan Wang , Feng Jin , Jia Wang
Background
The combination of pyrotinib (Py) with cytotoxic agents proved to be effective in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, the optimal chemotherapy regimen is unknown. This study attempts to explore it from real-world research data.
Methods
Information was collected from patients with early-stage HER2-positive BC from 23 centers across the country. They were categorized into the anthracycline group (A group) and non-anthracycline group (non-A group). Patients in the non-A group were further categorized into the platinum group and non-platinum group and the short-cycle (≤4 cycles) taxane group and long-cycle (>4 cycles) taxane group. Total pathological complete response (tpCR, ypT0/is ypN0) and breast pathological complete response (bpCR, ypT0/is) rates were assessed.
Results
A total of 107 patients were enrolled. Postoperative pathology indicated a tpCR rate of 36.8 %, a bpCR rate of 42.1 % in the A group, the non-A group had a tpCR rate of 47.8 %, and a bpCR rate of 53.6 %, with P-values of 0.273 and 0.254, respectively. In the long-cycle taxane group, the tpCR and bpCR rates were 60.8 % and 66.7 %, respectively. In the short-cycle taxane group, the tpCR and bpCR rates were 11.1 % and 16.7 %, respectively (both P<0.001). The platinum group had higher tpCR rate (62.9 % vs. 32.4 %, respectively; P = 0.011) and bpCR rate (65.7 % vs. 41.2 %, respectively; P = 0.041).
Conclusion
As for a neoadjuvant therapy regimen with Py, an anthracycline-free regimen is feasible. Besides, platinum-containing, long-cycle taxane regimens appear to achieve superior efficacy under anthracycline-removed conditions.
{"title":"An exploration of the optimal combination chemotherapy regimen based on neoadjuvant therapy containing pyrotinib for HER2-positive breast cancer: A multicenter real-world study","authors":"Shan Wang , Zining Jin , Zhaohui Li , Guolian Zhu , Bin Liu , Dianlong Zhang , Shuhong Tang , Fan Yao , Jian Wen , Yi Zhao , Xiaolan Wang , Feng Jin , Jia Wang","doi":"10.1016/j.tranon.2024.102173","DOIUrl":"10.1016/j.tranon.2024.102173","url":null,"abstract":"<div><h3>Background</h3><div>The combination of pyrotinib (Py) with cytotoxic agents proved to be effective in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, the optimal chemotherapy regimen is unknown. This study attempts to explore it from real-world research data.</div></div><div><h3>Methods</h3><div>Information was collected from patients with early-stage HER2-positive BC from 23 centers across the country. They were categorized into the anthracycline group (A group) and non-anthracycline group (non-A group). Patients in the non-A group were further categorized into the platinum group and non-platinum group and the short-cycle (≤4 cycles) taxane group and long-cycle (>4 cycles) taxane group. Total pathological complete response (tpCR, ypT0/is ypN0) and breast pathological complete response (bpCR, ypT0/is) rates were assessed.</div></div><div><h3>Results</h3><div>A total of 107 patients were enrolled. Postoperative pathology indicated a tpCR rate of 36.8 %, a bpCR rate of 42.1 % in the A group, the non-A group had a tpCR rate of 47.8 %, and a bpCR rate of 53.6 %, with <em>P</em>-values of 0.273 and 0.254, respectively. In the long-cycle taxane group, the tpCR and bpCR rates were 60.8 % and 66.7 %, respectively. In the short-cycle taxane group, the tpCR and bpCR rates were 11.1 % and 16.7 %, respectively (both <em>P</em><0.001). The platinum group had higher tpCR rate (62.9 % vs. 32.4 %, respectively; <em>P</em> = 0.011) and bpCR rate (65.7 % vs. 41.2 %, respectively; <em>P</em> = 0.041).</div></div><div><h3>Conclusion</h3><div>As for a neoadjuvant therapy regimen with Py, an anthracycline-free regimen is feasible. Besides, platinum-containing, long-cycle taxane regimens appear to achieve superior efficacy under anthracycline-removed conditions.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102173"},"PeriodicalIF":5.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.tranon.2024.102168
Olivia D. Lara , Elke Van Oudenhove , Luiza Pereira , Selim Misirlioglu , Douglas A. Levine , Kari E. Hacker
Background
Overcoming the heterogeneous mechanisms of metastasis and chemoresistance will improve outcomes for women with tubo-ovarian carcinomas (TOCs). CD44 expression has been shown to be associated with poor prognosis and advanced disease in TOCs. In addition, studies have shown a link between chemoresistance and CD44 pathways. Given the therapeutic implications of targeting CD44, this manuscript examines the biologic effects of a novel CD44 modulator, SPL-108, in TOCs.
Materials and Methods
We assessed the effects of SPL-108 on chemosensitivity and migration in a panel of ovarian cancer cell lines with varied CD44 and MDR1 expression. In vitro experiments (cell viability assay, Western blot analysis, Calcein AM fluorescence assay, and migration assay) were carried out to determine the functional effects of SPL-108 in TOCs.
Findings
Ovarian cancer cell lines OVCAR5 and OVCAR8 expressed higher protein levels of CD44 as demonstrated through Western Blot analysis. SPL-108 treatment significantly decreased the number of migrating cells in OVCAR8, OVCAR5 and OVCAR3 cell lines and migratory response was independent of CD44 expression. Treatment with SPL-108 led to significant accumulation of the MDR1 substrate Calcein in OVCAR5, OVCAR8 and OVCAR3 cells lines compared to verapamil treated positive control cells. Retention of Calcein after SPL-108 treatment was seen in cell lines with high MDR1 protein expression and no Calcein retention was seen in cells lacking MDR1 expression, suggesting SPL-108 inhibits MDR1.
Conclusions
SPL-108 treatment has anti-metastatic properties and may play a role in chemoresistance in preclinical models of TOCs independent of CD44 expression. Ongoing in vitro and in vivo studies will help guide further clinical development of SPL-108.
{"title":"SPL-108 mitigates metastasis and chemoresistance in tubo-ovarian carcinoma","authors":"Olivia D. Lara , Elke Van Oudenhove , Luiza Pereira , Selim Misirlioglu , Douglas A. Levine , Kari E. Hacker","doi":"10.1016/j.tranon.2024.102168","DOIUrl":"10.1016/j.tranon.2024.102168","url":null,"abstract":"<div><h3>Background</h3><div>Overcoming the heterogeneous mechanisms of metastasis and chemoresistance will improve outcomes for women with tubo-ovarian carcinomas (TOCs). CD44 expression has been shown to be associated with poor prognosis and advanced disease in TOCs. In addition, studies have shown a link between chemoresistance and CD44 pathways. Given the therapeutic implications of targeting CD44, this manuscript examines the biologic effects of a novel CD44 modulator, SPL-108, in TOCs.</div></div><div><h3>Materials and Methods</h3><div>We assessed the effects of SPL-108 on chemosensitivity and migration in a panel of ovarian cancer cell lines with varied CD44 and MDR1 expression. <em>In vitro</em> experiments (cell viability assay, Western blot analysis, Calcein AM fluorescence assay, and migration assay) were carried out to determine the functional effects of SPL-108 in TOCs.</div></div><div><h3>Findings</h3><div>Ovarian cancer cell lines OVCAR5 and OVCAR8 expressed higher protein levels of CD44 as demonstrated through Western Blot analysis. SPL-108 treatment significantly decreased the number of migrating cells in OVCAR8, OVCAR5 and OVCAR3 cell lines and migratory response was independent of CD44 expression. Treatment with SPL-108 led to significant accumulation of the MDR1 substrate Calcein in OVCAR5, OVCAR8 and OVCAR3 cells lines compared to verapamil treated positive control cells. Retention of Calcein after SPL-108 treatment was seen in cell lines with high MDR1 protein expression and no Calcein retention was seen in cells lacking MDR1 expression, suggesting SPL-108 inhibits MDR1.</div></div><div><h3>Conclusions</h3><div>SPL-108 treatment has anti-metastatic properties and may play a role in chemoresistance in preclinical models of TOCs independent of CD44 expression. Ongoing <em>in vitro</em> and <em>in vivo</em> studies will help guide further clinical development of SPL-108.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102168"},"PeriodicalIF":5.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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