Pub Date : 2024-08-13DOI: 10.1007/s12032-024-02466-7
Wardah Ashfaq, Khurram Rehman, Abubaker Shahid, Muhammad Numair Younis
Prostate cancer is one of the most common cancers and leading cause of death due to cancer across the globe. This persuaded researchers to devise innovative treatment modalities that may prove effective, safe, and demonstrate better outcomes in terms of patient morbidity and survival. The advancement in theranostics such as lutetium-177 (177Lu)-PSMA-617 radioligand therapies can target prostate cancer cells causing negligible or no damage to most of the normal tissues in patients. It has been proven to effectively improve the quality of life and progression-free survival. In this study, stage IV metastatic castration-resistant prostate cancer patients were treated with 177Lu-PSMA-617, and the therapeutic response and safety of 177Lu-PSMA-617 radioligand therapy were evaluated six months after the treatment. Additionally, molecular docking studies were also conducted to find the possible mechanism at the molecular level that causes the effectiveness of 177Lu-PSMA-617 in prostate cancer.
{"title":"Therapeutic response and safety of radioligand therapy with <sup>177</sup>Lu-PSMA-617 in metastatic castration-resistant prostate cancer patients.","authors":"Wardah Ashfaq, Khurram Rehman, Abubaker Shahid, Muhammad Numair Younis","doi":"10.1007/s12032-024-02466-7","DOIUrl":"10.1007/s12032-024-02466-7","url":null,"abstract":"<p><p>Prostate cancer is one of the most common cancers and leading cause of death due to cancer across the globe. This persuaded researchers to devise innovative treatment modalities that may prove effective, safe, and demonstrate better outcomes in terms of patient morbidity and survival. The advancement in theranostics such as lutetium-177 (<sup>177</sup>Lu)-PSMA-617 radioligand therapies can target prostate cancer cells causing negligible or no damage to most of the normal tissues in patients. It has been proven to effectively improve the quality of life and progression-free survival. In this study, stage IV metastatic castration-resistant prostate cancer patients were treated with <sup>177</sup>Lu-PSMA-617, and the therapeutic response and safety of <sup>177</sup>Lu-PSMA-617 radioligand therapy were evaluated six months after the treatment. Additionally, molecular docking studies were also conducted to find the possible mechanism at the molecular level that causes the effectiveness of <sup>177</sup>Lu-PSMA-617 in prostate cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1007/s12032-024-02470-x
Fan Tang, Qingyang Cui
Aldolase enzymes, particularly ALDOA, ALDOB, and ALDOC, play a crucial role in the development and progression of cancer. While the aldolase family is mainly known for its involvement in the glycolysis pathway, these enzymes also have various pathological and physiological functions through distinct signaling pathways such as Wnt/β-catenin, EGFR/MAPK, Akt, and HIF-1α. This has garnered increased attention in recent years and shed light on other sides of this enzyme. Potential therapeutic strategies targeting aldolases include using siRNA, inhibitors like naphthol AS-E phosphate and TX-2098, and natural compounds such as HDPS-4II and L-carnosine. Additionally, anticancer peptides derived from ALDOA, like P04, can potentially increase cancer cells' sensitivity to chemotherapy. Aldolases also affect cancer drug resistance by different approaches, making them good therapeutic targets. In this review, we extensively explore the role of aldolase enzymes in various types of cancers in proliferation, invasion, migration, and drug resistance; we also significantly explore the possible treatment considering aldolase function.
{"title":"Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.","authors":"Fan Tang, Qingyang Cui","doi":"10.1007/s12032-024-02470-x","DOIUrl":"10.1007/s12032-024-02470-x","url":null,"abstract":"<p><p>Aldolase enzymes, particularly ALDOA, ALDOB, and ALDOC, play a crucial role in the development and progression of cancer. While the aldolase family is mainly known for its involvement in the glycolysis pathway, these enzymes also have various pathological and physiological functions through distinct signaling pathways such as Wnt/β-catenin, EGFR/MAPK, Akt, and HIF-1α. This has garnered increased attention in recent years and shed light on other sides of this enzyme. Potential therapeutic strategies targeting aldolases include using siRNA, inhibitors like naphthol AS-E phosphate and TX-2098, and natural compounds such as HDPS-4II and L-carnosine. Additionally, anticancer peptides derived from ALDOA, like P04, can potentially increase cancer cells' sensitivity to chemotherapy. Aldolases also affect cancer drug resistance by different approaches, making them good therapeutic targets. In this review, we extensively explore the role of aldolase enzymes in various types of cancers in proliferation, invasion, migration, and drug resistance; we also significantly explore the possible treatment considering aldolase function.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer (BC) is a significant cause of cancer-related mortality, and triple-negative breast cancer (TNBC) is a particularly aggressive subtype associated with high mortality rates, especially among younger females. TNBC poses a considerable clinical challenge due to its aggressive tumor behavior and limited therapeutic options. Aberrations within the PI3K/AKT pathway are prevalent in TNBC and correlate with increased therapeutic intervention resistance and poor outcomes. MicroRNAs (miRs) have emerged as crucial PI3K/AKT pathway regulators influencing various cellular processes involved in TNBC pathogenesis. The levels of miRs, including miR-193, miR-4649-5p, and miR-449a, undergo notable changes in TNBC tumor tissues, emphasizing their significance in cancer biology. This review explored the intricate interplay between miR variants and PI3K/AKT signaling in TNBC. The review focused on the molecular mechanisms underlying miR-mediated dysregulation of this pathway and highlighted specific miRs and their targets. In addition, we explore the clinical implications of miR dysregulation in TNBC, particularly its correlation with TNBC prognosis and therapeutic resistance. Elucidating the roles of miRs in modulating the PI3K/AKT signaling pathway will enhance our understanding of TNBC biology and unveil potential therapeutic targets. This comprehensive review aims to discuss current knowledge and open promising avenues for future research, ultimately facilitating the development of precise and effective treatments for patients with TNBC.
乳腺癌(BC)是导致癌症相关死亡的重要原因,而三阴性乳腺癌(TNBC)是一种侵袭性特别强的亚型,死亡率很高,尤其是在年轻女性中。TNBC 因其侵袭性肿瘤行为和有限的治疗方案而构成了相当大的临床挑战。PI3K/AKT通路的畸变在TNBC中很普遍,并与治疗干预耐药性的增加和不良预后相关。微RNA(miRs)已成为PI3K/AKT通路的重要调节因子,影响着TNBC发病机制中的各种细胞过程。包括miR-193、miR-4649-5p和miR-449a在内的miRs水平在TNBC肿瘤组织中发生了显著变化,强调了它们在癌症生物学中的重要性。本综述探讨了 TNBC 中 miR 变异与 PI3K/AKT 信号转导之间错综复杂的相互作用。综述重点探讨了 miR 介导的该通路失调的分子机制,并强调了特定的 miR 及其靶点。此外,我们还探讨了 miR 失调在 TNBC 中的临床意义,特别是它与 TNBC 预后和治疗耐药性的相关性。阐明 miRs 在调节 PI3K/AKT 信号通路中的作用将加深我们对 TNBC 生物学的理解,并揭示潜在的治疗靶点。本综述旨在讨论现有知识,为未来研究开辟前景广阔的途径,最终促进 TNBC 患者精确有效治疗方法的开发。
{"title":"Impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer: comprehensive review.","authors":"Ehsan Mehrtabar, Amirreza Khalaji, Mojtaba Pandeh, Aram Farhoudian, Nadia Shafiee, Atefe Shafiee, Fatemeh Ojaghlou, Parinaz Mahdavi, Mehdi Soleymani-Goloujeh","doi":"10.1007/s12032-024-02469-4","DOIUrl":"10.1007/s12032-024-02469-4","url":null,"abstract":"<p><p>Breast cancer (BC) is a significant cause of cancer-related mortality, and triple-negative breast cancer (TNBC) is a particularly aggressive subtype associated with high mortality rates, especially among younger females. TNBC poses a considerable clinical challenge due to its aggressive tumor behavior and limited therapeutic options. Aberrations within the PI3K/AKT pathway are prevalent in TNBC and correlate with increased therapeutic intervention resistance and poor outcomes. MicroRNAs (miRs) have emerged as crucial PI3K/AKT pathway regulators influencing various cellular processes involved in TNBC pathogenesis. The levels of miRs, including miR-193, miR-4649-5p, and miR-449a, undergo notable changes in TNBC tumor tissues, emphasizing their significance in cancer biology. This review explored the intricate interplay between miR variants and PI3K/AKT signaling in TNBC. The review focused on the molecular mechanisms underlying miR-mediated dysregulation of this pathway and highlighted specific miRs and their targets. In addition, we explore the clinical implications of miR dysregulation in TNBC, particularly its correlation with TNBC prognosis and therapeutic resistance. Elucidating the roles of miRs in modulating the PI3K/AKT signaling pathway will enhance our understanding of TNBC biology and unveil potential therapeutic targets. This comprehensive review aims to discuss current knowledge and open promising avenues for future research, ultimately facilitating the development of precise and effective treatments for patients with TNBC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1007/s12032-024-02462-x
Nawal Helmi, Abdullah Hamadi, Osama M Al-Amer, Hassan A Madkhali, Atif Abdulwahab A Oyouni, Amany I Alqosaibi, Jawaher Almulhim, Rashed Mohammed Alghamdi, Israa J Hakeem, Misbahuddin M Rafeeq
Cervical Cancer remains a women's health concern worldwide and ranks among the most prevalent cancers, particularly in developing countries. Many women are diagnosed with cervical cancer, with a substantial number succumbing to the disease even after the availability of vaccines and drugs. The tumour microenvironment often exhibits immune evasion, including suppression of T-cell activity and altered cytokine, impacting the efficacy of therapeutic interventions and highlighting the need for treatments to modulate the immune response. Despite efforts to promote HPV vaccination and regular screenings, it causes many deaths, underscoring the urgent need for continued research, healthcare access, and rapid drug development or repurposing. In this study, we identified various proteins involved in cervical cancer cell cycle regulation and DNA replication proteins, performed the multitargeted docking with an FDA-approved library, and identified Oxidopamine HBr as a multitargeted drug. Studies extended with pharmacokinetics and compared with the standard values followed by DFT, which supported the compound as a multitargeted inhibitor. Further, the docked complexes were taken for the interaction fingerprints, and it was identified that there are many 9 polar, 5 hydrophobic, 2 aromatic, and 2 basic residues. We extended our studies for 100ns MD Simulation in water, and the computations explored the deviation and fluctuations under 2Å and many intermolecular interactions; the same trajectory files were used for the MMGBSA studies. All the studies have supported the Oxidopamine HBr as a cervical cancer multitargeted inhibitor-however, experimental studies are needed before human use.
{"title":"Unveiling the potency of FDA-approved oxidopamine HBr for cervical cancer regulation and replication proteins.","authors":"Nawal Helmi, Abdullah Hamadi, Osama M Al-Amer, Hassan A Madkhali, Atif Abdulwahab A Oyouni, Amany I Alqosaibi, Jawaher Almulhim, Rashed Mohammed Alghamdi, Israa J Hakeem, Misbahuddin M Rafeeq","doi":"10.1007/s12032-024-02462-x","DOIUrl":"10.1007/s12032-024-02462-x","url":null,"abstract":"<p><p>Cervical Cancer remains a women's health concern worldwide and ranks among the most prevalent cancers, particularly in developing countries. Many women are diagnosed with cervical cancer, with a substantial number succumbing to the disease even after the availability of vaccines and drugs. The tumour microenvironment often exhibits immune evasion, including suppression of T-cell activity and altered cytokine, impacting the efficacy of therapeutic interventions and highlighting the need for treatments to modulate the immune response. Despite efforts to promote HPV vaccination and regular screenings, it causes many deaths, underscoring the urgent need for continued research, healthcare access, and rapid drug development or repurposing. In this study, we identified various proteins involved in cervical cancer cell cycle regulation and DNA replication proteins, performed the multitargeted docking with an FDA-approved library, and identified Oxidopamine HBr as a multitargeted drug. Studies extended with pharmacokinetics and compared with the standard values followed by DFT, which supported the compound as a multitargeted inhibitor. Further, the docked complexes were taken for the interaction fingerprints, and it was identified that there are many 9 polar, 5 hydrophobic, 2 aromatic, and 2 basic residues. We extended our studies for 100ns MD Simulation in water, and the computations explored the deviation and fluctuations under 2Å and many intermolecular interactions; the same trajectory files were used for the MMGBSA studies. All the studies have supported the Oxidopamine HBr as a cervical cancer multitargeted inhibitor-however, experimental studies are needed before human use.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1007/s12032-024-02464-9
Bibhukalyan Mohapatra, Suresh B Pakala
Cancer is characterized by metabolic reprogramming in cancer cells, which is crucial for tumorigenesis. The highly deregulated chromatin remodeler MORC2 contributes to cell proliferation, invasion, migration, DNA repair, and chemoresistance. MORC2 also plays a key role in metabolic reprogramming, including lipogenesis, glucose, and glutamine metabolism. A recent study showed that MORC2-regulated glucose metabolism affects the expression of E-cadherin, a crucial protein in the epithelial-to-mesenchymal transition. This review discusses recent developments in MORC2 regulated cancer cell metabolism and its role in cancer progression.
{"title":"Emerging roles of the chromatin remodeler MORC2 in cancer metabolism.","authors":"Bibhukalyan Mohapatra, Suresh B Pakala","doi":"10.1007/s12032-024-02464-9","DOIUrl":"10.1007/s12032-024-02464-9","url":null,"abstract":"<p><p>Cancer is characterized by metabolic reprogramming in cancer cells, which is crucial for tumorigenesis. The highly deregulated chromatin remodeler MORC2 contributes to cell proliferation, invasion, migration, DNA repair, and chemoresistance. MORC2 also plays a key role in metabolic reprogramming, including lipogenesis, glucose, and glutamine metabolism. A recent study showed that MORC2-regulated glucose metabolism affects the expression of E-cadherin, a crucial protein in the epithelial-to-mesenchymal transition. This review discusses recent developments in MORC2 regulated cancer cell metabolism and its role in cancer progression.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1007/s12032-024-02468-5
Mano Chitra Karthikeyan, Chandhru Srinivasan, Kowsika Prabhakar, Priyadharshini Manogar, Abirami Jayaprakash, Antony Joseph Velanganni Arockiam
Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC.
乳腺癌(BC)是世界上最常见的癌症,其发病机制复杂。目前迫切需要揭示作为潜在治疗靶点的关键基因,这对推进乳腺癌的治疗至关重要。本研究试图调查多柔比星(DOX)对通过生物信息学分析获得的众多乳腺癌数据集中已确定的关键基因的影响。迄今为止,已对基因表达总库(GEO)中公开可用的阵列表达谱编码数据集进行了荟萃分析。使用 GEO2R 鉴定的差异表达基因(DEGs)显示,在三个平台(GPL570、GPL6244 和 GPL17586)的数据集中,共有 23 个常见的 DEGs,包括 9 个上调基因和 14 个下调基因,而且在 KEGG 分析中,常见的上调 DEGs 在细胞周期中表现出显著的富集。在细胞视图程序中,NUSAP1、CENPF、TPX2、PRC1、ANLN、BUB1B、AURKA、CCNB2和CDK-1这九个基因的度值和MCODE得分较高,被认为是枢纽基因。经 GEPIA 和 UALCAN 数据库验证,这些枢纽基因在 BC 所有亚类的疾病状态中普遍被激活,并与 BC 患者的总生存期相关。qRT-PCR 证实,DOX 治疗会导致 BC 细胞系中这些基因的表达减少,这进一步证明 DOX 仍是治疗 BC 的有效药物,并表明开发多柔比星的改良配方以减少毒性和耐药性,可提高其作为 BC 有效疗法的疗效。
{"title":"Doxorubicin downregulates cell cycle regulatory hub genes in breast cancer cells.","authors":"Mano Chitra Karthikeyan, Chandhru Srinivasan, Kowsika Prabhakar, Priyadharshini Manogar, Abirami Jayaprakash, Antony Joseph Velanganni Arockiam","doi":"10.1007/s12032-024-02468-5","DOIUrl":"10.1007/s12032-024-02468-5","url":null,"abstract":"<p><p>Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder cancer is a common malignancy worldwide, posing a substantial healthcare challenge. Current standard treatment regimens are primarily based on cisplatin, but their success is often limited by cisplatin resistance and associated toxicities. Therefore, there is an urgent need to develop effective and less toxic therapies as alternatives to cisplatin. We screened the activity of FDA-approved anti-cancer drugs on a panel of cisplatin-resistant bladder cancer cell lines. Based on initial responses, cabazitaxel was selected for further evaluation of its inhibitory effects on the phenotypic properties of these cells. Cabazitaxel, primarily used for metastatic castration-resistant prostate cancer, demonstrated remarkable efficacy in inhibiting colony formation, proliferation, and migration of cisplatin-resistant bladder cancer cells. This study highlights the potential of drug repurposing as a cost-effective and efficient strategy to overcome drug resistance in bladder cancer.
膀胱癌是全球常见的恶性肿瘤,给医疗保健带来了巨大挑战。目前的标准治疗方案主要以顺铂为基础,但其成功率往往受到顺铂耐药性和相关毒性的限制。因此,迫切需要开发有效且毒性较低的疗法来替代顺铂。我们在一组顺铂耐药的膀胱癌细胞系中筛选了美国 FDA 批准的抗癌药物。根据初步反应,我们选择了卡巴他赛,以进一步评估其对这些细胞表型特性的抑制作用。卡巴他赛主要用于治疗转移性耐阉割前列腺癌,在抑制顺铂耐药膀胱癌细胞的集落形成、增殖和迁移方面表现出显著疗效。这项研究强调了药物再利用的潜力,它是克服膀胱癌耐药性的一种经济有效的策略。
{"title":"Cabazitaxel as a promising therapy for cisplatin-resistant bladder cancer: a preliminary study.","authors":"Asim Joshi, Abantika Ghosh, Prashant Rai, Sarika Tilwani, Venkataramanan Ramachandran, Kumar Prabhash, Mahul Amin, Prashant Kumar","doi":"10.1007/s12032-024-02461-y","DOIUrl":"10.1007/s12032-024-02461-y","url":null,"abstract":"<p><p>Bladder cancer is a common malignancy worldwide, posing a substantial healthcare challenge. Current standard treatment regimens are primarily based on cisplatin, but their success is often limited by cisplatin resistance and associated toxicities. Therefore, there is an urgent need to develop effective and less toxic therapies as alternatives to cisplatin. We screened the activity of FDA-approved anti-cancer drugs on a panel of cisplatin-resistant bladder cancer cell lines. Based on initial responses, cabazitaxel was selected for further evaluation of its inhibitory effects on the phenotypic properties of these cells. Cabazitaxel, primarily used for metastatic castration-resistant prostate cancer, demonstrated remarkable efficacy in inhibiting colony formation, proliferation, and migration of cisplatin-resistant bladder cancer cells. This study highlights the potential of drug repurposing as a cost-effective and efficient strategy to overcome drug resistance in bladder cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1007/s12032-024-02460-z
YuHan Wang, YaLing Li, Jun Li
{"title":"Comment on \"Pharmacokinetic studies, molecular docking, and molecular dynamics simulations of phytochemicals from Morus alba: a multi-receptor approach for potential therapeutic agents in colorectal cancer\".","authors":"YuHan Wang, YaLing Li, Jun Li","doi":"10.1007/s12032-024-02460-z","DOIUrl":"10.1007/s12032-024-02460-z","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1007/s12032-024-02465-8
Ahmad Kooshari, Fahimeh Shahriyary, Minoo Shahidi, Mahshid Vafajoo, Mohammad Reza Amirzargar
Multiple myeloma (MM) is a neoplastic condition resulting from the uncontrolled expansion of B-cell-derived plasma cells. The importance of angiogenesis in MM development has also been demonstrated. Extracellular vesicles (EVs) have vital functions in interactions between neighboring cells, such as angiogenesis. The objective of this in vitro study was to examine the transfection and angiogenesis effects of MM-EVs on endothelial cells (ECs) upon treatment with Tetrahydroisoquinoline (THIQ) as a bioactive organic compound derivative from isoquinoline. Following treatment of multiple myeloma cells (U266) with THIQ, MM-EVs were harvested and transmigrated to human umbilical vein endothelial cells (HUVEC) in a co-culture model. EVs transmigration was traced by flow cytometry. Correspondingly, the expression of angiogenic genes and/or proteins in U266 cells and HUVECs was measured by RT-PCR and ELISA methods. Likewise, the proliferation and migration of HUVECs treated with THIQ-treated MM-EVs were visualized and estimated by performing both tube formation and scratch wound healing methods. Surprisingly, the anti-angiogenic effect of THIQ-treated MM-EVs was evident by the decreased expression of CD34, VEGFR2, and IL-6 at the mRNA and/or protein levels after internalization of MM-EVs in HUVEC. Finally, tube formation and scratch wound healing experiments showed inhibition of HUVEC cell proliferation and migration by THIQ-treated MM-EVs compared to control MM-EVs. MM-EVs derived from THIQ-treated myeloma cells (U266) inhibited angiogenesis in HUVECs. This phenomenon is coordinated by the internalized THIQ-treated MM-EVs in HUVECs, and ultimately the reduction of angiogenic factors and inhibition of tube formation and scratch wound healing.
{"title":"Tetrahydroisoquinoline reduces angiogenesis by interacting myeloma cells with HUVECs mediated by extracellular vesicles.","authors":"Ahmad Kooshari, Fahimeh Shahriyary, Minoo Shahidi, Mahshid Vafajoo, Mohammad Reza Amirzargar","doi":"10.1007/s12032-024-02465-8","DOIUrl":"10.1007/s12032-024-02465-8","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a neoplastic condition resulting from the uncontrolled expansion of B-cell-derived plasma cells. The importance of angiogenesis in MM development has also been demonstrated. Extracellular vesicles (EVs) have vital functions in interactions between neighboring cells, such as angiogenesis. The objective of this in vitro study was to examine the transfection and angiogenesis effects of MM-EVs on endothelial cells (ECs) upon treatment with Tetrahydroisoquinoline (THIQ) as a bioactive organic compound derivative from isoquinoline. Following treatment of multiple myeloma cells (U266) with THIQ, MM-EVs were harvested and transmigrated to human umbilical vein endothelial cells (HUVEC) in a co-culture model. EVs transmigration was traced by flow cytometry. Correspondingly, the expression of angiogenic genes and/or proteins in U266 cells and HUVECs was measured by RT-PCR and ELISA methods. Likewise, the proliferation and migration of HUVECs treated with THIQ-treated MM-EVs were visualized and estimated by performing both tube formation and scratch wound healing methods. Surprisingly, the anti-angiogenic effect of THIQ-treated MM-EVs was evident by the decreased expression of CD34, VEGFR2, and IL-6 at the mRNA and/or protein levels after internalization of MM-EVs in HUVEC. Finally, tube formation and scratch wound healing experiments showed inhibition of HUVEC cell proliferation and migration by THIQ-treated MM-EVs compared to control MM-EVs. MM-EVs derived from THIQ-treated myeloma cells (U266) inhibited angiogenesis in HUVECs. This phenomenon is coordinated by the internalized THIQ-treated MM-EVs in HUVECs, and ultimately the reduction of angiogenic factors and inhibition of tube formation and scratch wound healing.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1007/s12032-024-02455-w
Hanan Elimam, Sherif S Abdel Mageed, Abdulrahman Hatawsh, Rewan Moussa, Abdullah F Radwan, Nourhan Elfar, Nora A A Alhamshry, Mai A Abd-Elmawla, Osama A Mohammed, Mohamed Bakr Zaki, Ahmed S Doghish
Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.
{"title":"Unraveling the influence of LncRNA in gastric cancer pathogenesis: a comprehensive review focus on signaling pathways interplay.","authors":"Hanan Elimam, Sherif S Abdel Mageed, Abdulrahman Hatawsh, Rewan Moussa, Abdullah F Radwan, Nourhan Elfar, Nora A A Alhamshry, Mai A Abd-Elmawla, Osama A Mohammed, Mohamed Bakr Zaki, Ahmed S Doghish","doi":"10.1007/s12032-024-02455-w","DOIUrl":"10.1007/s12032-024-02455-w","url":null,"abstract":"<p><p>Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}