Medical Oncology最新文献_第5页

Exosomes derived from natural killer cells: transforming immunotherapy for aggressive breast cancer. 来自自然杀伤细胞的外泌体：侵袭性乳腺癌的转化免疫疗法。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-18 DOI: 10.1007/s12032-025-02647-y

Abdulmalik Saleh Alfawaz Altamimi, M Arockia Babu, Muhammad Afzal, Ashok Kumar Bishoyi, R Roopashree, Suman Saini, R S K Sharma, Piyus Kumar Pathak, Ashish Singh Chauhan, Kavita Goyal, Haider Ali, Nawaid Hussain Khan, Ashok Kumar Balaraman

{"title":"Exosomes derived from natural killer cells: transforming immunotherapy for aggressive breast cancer.","authors":"Abdulmalik Saleh Alfawaz Altamimi, M Arockia Babu, Muhammad Afzal, Ashok Kumar Bishoyi, R Roopashree, Suman Saini, R S K Sharma, Piyus Kumar Pathak, Ashish Singh Chauhan, Kavita Goyal, Haider Ali, Nawaid Hussain Khan, Ashok Kumar Balaraman","doi":"10.1007/s12032-025-02647-y","DOIUrl":"10.1007/s12032-025-02647-y","url":null,"abstract":"Natural killer cell-derived exosomes (NK-Exos) hold great promise as immune modulators and immunotherapeutics against cancer due to their intrinsically latent anti-tumor effects. They use these nanosized vesicles to deliver cytotoxic molecules, such as perforin, granzymes, and miRNAs, directly to cancer cells to kill them, avoiding immune suppression. NK-Exos has particular efficacy for treating aggressive breast cancer by modulating the TME to activate the immune response and suppress immunosuppressive factors. Bioengineering advances have extended the therapeutic potential of NK-Exos, which permits precise tumor cell targeting and efficient delivery of therapeutic payloads, including small RNAs and chemotherapeutic agents. In engineered NK-Exos, sensitization of cancer cells to apoptosis, reduction of tumor growth, and resistance to drugs have been demonstrated to be highly effective. When combined, NK-Exos synergizes with radiotherapy, chemotherapy, or checkpoint inhibitors, enhancing therapeutic efficacy, and minimizing systemic toxicity. This review emphasizes the critical role of NK-Exos in breast cancer treatment, their integration into combination therapies, and the need for further research to overcome existing limitations and fully realize their clinical potential.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"114"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657598","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}

引用次数: 0

Diagnosis and treatment of cardiac tumors. 心脏肿瘤的诊断与治疗。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-17 DOI: 10.1007/s12032-025-02661-0

Toru Imai, Tatsunori Shimoi, Akira Kawai, Kan Yonemori

{"title":"Diagnosis and treatment of cardiac tumors.","authors":"Toru Imai, Tatsunori Shimoi, Akira Kawai, Kan Yonemori","doi":"10.1007/s12032-025-02661-0","DOIUrl":"10.1007/s12032-025-02661-0","url":null,"abstract":"Cardiac tumors, though rare, present significant diagnostic and therapeutic challenges due to their diverse nature and potential severity. These tumors, which can be primary or metastatic, are often detected incidentally through imaging modalities such as echocardiography or CT scans. Differentiating between benign and malignant forms is crucial for guiding appropriate management strategies. This review synthesizes current diagnostic approaches and treatment modalities for cardiac tumors, with a focus on the role of imaging techniques like UCG, CT, MRI, and PET in tumor characterization. Multidisciplinary treatment plans are necessary, including surgical resection for benign tumors, chemotherapy, and radiotherapy for malignant tumors, and novel targeted therapies such as MDM2 inhibitors for selected cases. While primary malignant tumors like sarcomas and mesotheliomas exhibit rapid progression and poor prognosis, recent advances in multimodal therapy offer potential improvements in survival. The incidence of primary cardiac tumors is low, with an autopsy-reported occurrence rate of 0.02%. Benign cardiac tumors, such as myxomas and fibromas, generally have favorable outcomes with surgical resection. In contrast, primary malignant tumors like sarcomas and mesotheliomas exhibit rapid progression and poor prognosis, necessitating aggressive treatment including surgery, chemotherapy, and radiotherapy. Metastatic cardiac tumors occur in approximately 10% of cancer patients at autopsy and are managed according to the treatment plan for the primary malignancy. The management of cardiac tumors requires a multidisciplinary approach tailored to tumor type, location, and systemic effects. While benign tumors often respond well to surgical management, malignant and metastatic tumors demand more complex strategies to optimize patient outcomes.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"110"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649427","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}

引用次数: 0

Cost-effective isolation of Viburnum opulus-derived nanovesicles and evaluation of their cytotoxic, anticancer, and antioxidant properties on human glioblastoma cell line U87MG. 豆荚源性纳米囊泡的经济高效分离及其对人胶质母细胞瘤细胞系U87MG的细胞毒、抗癌和抗氧化性能的评价

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-17 DOI: 10.1007/s12032-025-02669-6

Nazli Irmak Giritlioglu, Fatma Sayan Poyraz, Banu Mansuroglu, Semiha Erisen

{"title":"Cost-effective isolation of Viburnum opulus-derived nanovesicles and evaluation of their cytotoxic, anticancer, and antioxidant properties on human glioblastoma cell line U87MG.","authors":"Nazli Irmak Giritlioglu, Fatma Sayan Poyraz, Banu Mansuroglu, Semiha Erisen","doi":"10.1007/s12032-025-02669-6","DOIUrl":"10.1007/s12032-025-02669-6","url":null,"abstract":"Glioblastoma is the most common and highly invasive glial tumor, significantly reducing patient survival. Current therapeutic approaches have limited success rates. Plant-derived nanovesicles are a rapidly developing area, recognized for their exceptional biofunctional properties, and are emerging as a promising approach in cancer treatment. The present study focuses on the isolation of nanovesicles from Viburnum opulus fruits using a cost-effective method that includes a polymer-based exosome precipitation buffer and size exclusion chromatography, followed by their characterization. Morphological analysis via Field Emission Scanning Electron Microscopy and Transmission Electron Microscopy revealed nanovesicles ranging from oval to elliptical shapes, with average diameters of 54.23 nm and 41.21 nm, respectively. Dynamic light scattering analysis determined the average size of 45.36 nm indicating the presence of nanovesicles, and the zeta potential was - 2.87 mV. Biochemical characterization showed total protein and phenolic concentrations of 1534 ± 97.78 µg/ml and 4.270 ± 0.66 mg gallic acid equivalents/L, respectively, with total antioxidant status values of 3.83 ± 0.37 mmol Trolox equivalents/L. Based on IC50 values, these nanovesicles were 7.5 times more toxic to U87MG human glioblastoma cells compared to healthy human dermal fibroblasts. Analyses including clonogenic cell survival, wound healing, apoptosis, total antioxidant status, and total oxidant status were continued on only U87MG cells, as human dermal fibroblasts showed a low response to nanovesicle treatment. Qualitative and quantitative assessments demonstrated that Viburnum opulus-derived nanovesicles effectively inhibited cancer cell proliferation and migration. Due to their non-toxic, anticancer, and antioxidant properties, these nanovesicles hold significant potential in glioblastoma management.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"112"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649425","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}

引用次数: 0

Nanomedicine innovations in colon and rectal cancer: advances in targeted drug and gene delivery systems. 结肠癌和直肠癌的纳米医学创新：靶向药物和基因传递系统的进展。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-17 DOI: 10.1007/s12032-025-02670-z

Sobia Razzaq, Iqra Fatima, Zeinab Moafian, Abbas Rahdar, Sonia Fathi-Karkan, Zelal Kharaba, Maryam Shirzad, Ahmad Khan, Sadanand Pandey

{"title":"Nanomedicine innovations in colon and rectal cancer: advances in targeted drug and gene delivery systems.","authors":"Sobia Razzaq, Iqra Fatima, Zeinab Moafian, Abbas Rahdar, Sonia Fathi-Karkan, Zelal Kharaba, Maryam Shirzad, Ahmad Khan, Sadanand Pandey","doi":"10.1007/s12032-025-02670-z","DOIUrl":"10.1007/s12032-025-02670-z","url":null,"abstract":"Nanotechnology has revolutionized cancer diagnostics and therapy, offering unprecedented possibilities to overcome the constraints of conventional treatments. This study provides a detailed overview of the current progress and difficulties in the creation of nanostructured materials, with a specific emphasis on their use in drug and gene delivery systems. The study examines tactics that attempt to improve the effectiveness and safety of chemotherapeutic drugs such as doxorubicin (Dox) by focusing on the potential of antibody-drug conjugates and functionalized nanoparticles. Moreover, it clarifies the challenges encountered in administering nanoparticles orally for gastrointestinal treatments, emphasizing the crucial physicochemical properties that affect their behavior in the gastrointestinal system. This study highlights the transformational potential of nanostructured materials in precision oncology by examining advanced breakthroughs such cell membrane-camouflaged nanoparticles and inorganic nanoparticles designed for gastrointestinal disorders. The text investigates the processes involved in the absorption of nanoparticles and their destruction in lysosomes, revealing the many methods in which enterocytes take up these particles. This study strongly supports the use of advanced nanoparticle-based methods to reduce the harmful effects on the whole body and improve the effectiveness of therapy, based on a thorough examination of current experiments on animals and humans. The main objective of this paper is to provide a fundamental comprehension that will stimulate more investigation and practical use in the field of cancer nanomedicine, advancing its boundaries.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"113"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649429","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}

引用次数: 0

Role of hepatotropic viruses in promoting hepatocellular carcinoma-current knowledge and recent advances. 嗜肝病毒在促进肝细胞癌中的作用——目前的知识和最新进展。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-17 DOI: 10.1007/s12032-025-02674-9

Piotr Starnawski, Klaudia Nowak, Zuzanna Augustyn, Dominik Malicki, Aleksandra Piąta, Dominika Lorek, Jakub Janczura

{"title":"Role of hepatotropic viruses in promoting hepatocellular carcinoma-current knowledge and recent advances.","authors":"Piotr Starnawski, Klaudia Nowak, Zuzanna Augustyn, Dominik Malicki, Aleksandra Piąta, Dominika Lorek, Jakub Janczura","doi":"10.1007/s12032-025-02674-9","DOIUrl":"10.1007/s12032-025-02674-9","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with chronic infections by hepatotropic viruses such as hepatitis B virus (HBV), and hepatitis C virus (HCV), being major risk factors. Chronic infections with these viruses are the leading cause of HCC worldwide, with HBV alone responsible for over 50% of cases. Despite advances in direct-acting antivirals (DAAs) for HCV and nucleos(t)ide analogues (NAs) for HBV, challenges remain in HCC prevention, early detection, and treatment. Recent research highlights the role of viral-induced metabolic alterations, such as the Warburg effect, mitochondrial dysfunction, and lipid dysregulation, in promoting HCC. Moreover, immune checkpoint inhibitors have emerged as effective treatments for advanced HCC, though responses vary between HBV- and HCV-related cancers. Additionally, novel therapeutic approaches and metabolic-targeted therapies offer promising avenues for virus-associated HCC treatment. Advancements in liquid biopsy biomarkers and artificial intelligence-driven diagnostics are improving HCC surveillance and risk stratification, potentially enabling earlier interventions. While HBV vaccination has significantly reduced HCC incidence, disparities in global vaccination coverage persist. Furthermore, antiviral therapies combined with structured surveillance programs have proven effective in reducing HCC incidence and mortality. This review highlights the complex connection between viral, genetic, and environmental factors in HCC development and underscores the importance of integrated prevention strategies to reduce its burden globally.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"111"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649430","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}

引用次数: 0

LncRNA CCAT1 decreases the sensitivity to doxorubicin in lung cancer cells by regulating miR-181a/CPEB2 axis. LncRNA CCAT1通过调控miR-181a/CPEB2轴降低肺癌细胞对阿霉素的敏感性。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-16 DOI: 10.1007/s12032-025-02668-7

Qi Muge, Yu Qing, Wenshan Bao, Xiangrong Bao, Arong Gaowa, Lanying Chen

{"title":"LncRNA CCAT1 decreases the sensitivity to doxorubicin in lung cancer cells by regulating miR-181a/CPEB2 axis.","authors":"Qi Muge, Yu Qing, Wenshan Bao, Xiangrong Bao, Arong Gaowa, Lanying Chen","doi":"10.1007/s12032-025-02668-7","DOIUrl":"10.1007/s12032-025-02668-7","url":null,"abstract":"Recently, long non-coding RNAs have gained an increasing amount of attention in treating lung cancer. However, a full understanding of how CCAT1 lncRNA works against proliferation is not yet available. Therefore, we assess the impact of CCAT1 on the lung cancer cell proliferation, apoptosis, and doxorubicin (DOX) sensitivity, and the involvement of miR-181a/CPEB2 pathway. For this purpose, lung cancer A549 cells were exposed to siRNA against CCAT1 and DOX and cell viability were measured by MTT assay. ELISA was used to evaluate cell apoptosis. The protein and mRNA expression levels of apoptotic markers, miR-181a and CPEB2 were measured by western blot and qRT-PCR. Knock-downing CCAT1 inhibited the cell viability of A549 cells. In addition, si-CCAT1 treatment increased apoptosis in both cell lines via modulating the anti- and pro-apoptotic markers. Si-CCAT1 increased the levels miR-181a and decreased CPEB2 in A549 cells. In conclusion, our study has provided strong evidence that lncRNA CCAT1 decreased the sensitivity to doxorubicin in lung cancer cells by regulating the miR-181a/CPEB2 axis.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"109"},"PeriodicalIF":2.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639703","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}

引用次数: 0

Contribution of tumor microenvironment (TME) to tumor apoptosis, angiogenesis, metastasis, and drug resistance. 肿瘤微环境（TME）在肿瘤凋亡、血管生成、转移和耐药中的作用。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-14 DOI: 10.1007/s12032-025-02675-8

Yanhong Xiao, Mahan Hassani, Melina Barahouei Moghaddam, Ahmad Fazilat, Masoud Ojarudi, Mohammad Valilo

{"title":"Contribution of tumor microenvironment (TME) to tumor apoptosis, angiogenesis, metastasis, and drug resistance.","authors":"Yanhong Xiao, Mahan Hassani, Melina Barahouei Moghaddam, Ahmad Fazilat, Masoud Ojarudi, Mohammad Valilo","doi":"10.1007/s12032-025-02675-8","DOIUrl":"10.1007/s12032-025-02675-8","url":null,"abstract":"The tumor microenvironment (TME) contains tumor cells, surrounding cells, and secreted factors. It provides a favorable environment for the maintenance of cancer stem cells (CSCs), the spread of cancer cells to metastatic sites, angiogenesis, and apoptosis, as well as the growth, proliferation, invasion, and drug resistance of cancer cells. Cancer cells rely on the activation of oncogenes, inactivation of tumor suppressors, and the support of a normal stroma for their growth, proliferation, and survival, all of which are provided by the TME. The TME is characterized by the presence of various cells, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), CD8 + cytotoxic T cells (CTLs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs), endothelial cells, adipocytes, and neuroendocrine (NE) cells. The high expression of inflammatory cytokines, angiogenic factors, and anti-apoptotic factors, as well as drug resistance mechanisms in the TME, contributes to the poor therapeutic efficacy of anticancer drugs and tumor progression. Hence, this review describes the mechanisms through which the TME is involved in apoptosis, angiogenesis, metastasis, and drug resistance in tumor cells.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"108"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634264","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}

引用次数: 0

αKG-induced oxidative stress and mTOR inhibition as a therapeutic strategy for liver cancer. α kg诱导的氧化应激和mTOR抑制作为肝癌的治疗策略

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-13 DOI: 10.1007/s12032-025-02653-0

Sung Kyung Choi, Myoung Jun Kim, Jueng Soo You

{"title":"αKG-induced oxidative stress and mTOR inhibition as a therapeutic strategy for liver cancer.","authors":"Sung Kyung Choi, Myoung Jun Kim, Jueng Soo You","doi":"10.1007/s12032-025-02653-0","DOIUrl":"10.1007/s12032-025-02653-0","url":null,"abstract":"Despite the availability of targeted therapies, liver cancer remains a severe health burden. The need for adjuvant therapy to improve treatment efficacy and prevent recurrence is emerging. Alpha-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle and a cofactor for various oxygenases. A critical role of this multifunctional metabolite has started to be revealed in physiological and pathological conditions. We found that αKG exerts various anti-tumor effects in liver cancer cells. Our kinetic transcriptome study suggested that increasing reactive oxygen species and inhibiting mTORC1 signaling underlies. Indeed, αKG treatment elevated oxidative stress and induced DNA damage, presumably caused by early downregulation of the antioxidant gene SLC7A11. Further, we validated impaired mTOR signaling and decreased cellular energy production. This unique mechanism underscores αKG's potential as a liver cancer therapy by harnessing oxidative stress and disrupting metabolic signaling. These findings could provide valuable insights into further exploration of αKG as a promising therapeutic agent in liver cancer.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"105"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625374","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}

引用次数: 0

Evaluation of the antiangiogenic effect of AMG232 in multiple myeloma coculture systems. AMG232在多发性骨髓瘤共培养系统中抗血管生成作用的评价。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-13 DOI: 10.1007/s12032-025-02659-8

Zahra Pooraskari, Hossein Barri Ghazani, Reyhane Piri, Sina Habibi, Minoo Shahidi

{"title":"Evaluation of the antiangiogenic effect of AMG232 in multiple myeloma coculture systems.","authors":"Zahra Pooraskari, Hossein Barri Ghazani, Reyhane Piri, Sina Habibi, Minoo Shahidi","doi":"10.1007/s12032-025-02659-8","DOIUrl":"10.1007/s12032-025-02659-8","url":null,"abstract":"This study explored the efficacy of AMG232, a potent and selective MDM2 inhibitor, as an antiangiogenic agent in a multiple myeloma (MM) cell line (AMO-1) cocultured with endothelial cells (HUVECs) in vitro. HUVECs and AMO-1 cells were cocultured in transwell systems. Cell viability was assessed through an MTT assay after exposure to various concentrations of AMG232. Following treatment, gene expression changes were analyzed via quantitative real-time PCR. Wound healing and tube formation assays were also conducted to quantify the effects on cell migration and angiogenesis. AMG232 showed dose-dependent cytotoxicity in AMO-1 cells (IC50 = 386.1 nM), whereas HUVECs were moderately sensitive (IC50= 942.1 nM). In coculture, both cell types displayed increased resistance to AMG232, indicating a protective cell-cell interaction. Treatment with 250-nM AMG232 significantly downregulated the mRNA expression of angiogenic factors-including VEGF-A, VEGFR-2, MMP-2, IL-6, and HIF-1α-in both AMO-1 cells and HUVECs (P < 0.05). Wound healing assays revealed that AMG232 markedly inhibited HUVEC migration, with significantly reduced wound closure rates at 24 and 48 h compared with the controls (P < 0.01). Tube formation assays further revealed that AMG232 substantially decreased angiogenesis in HUVECs, as evidenced by reductions in junction number, mesh number, and total tube length (P < 0.01). Our research revealed that AMG232 effectively inhibited angiogenesis and exhibited cytotoxic effects on MM cells by downregulating key angiogenic factors and impairing endothelial cell functions. These results suggest that AMG232 has significant potential as a therapeutic agent for targeting angiogenesis in MM treatment.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"107"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625357","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}

引用次数: 0

Dual targeting of CXC chemokine receptor 4 and multidrug resistance protein 1 by ZIN056 effectively combat daunorubicin resistance in acute myeloid leukemia cells. ZIN056 对 CXC 趋化因子受体 4 和多药耐药蛋白 1 的双重靶向作用可有效抑制急性髓性白血病细胞对多柔比星的耐药性。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-13 DOI: 10.1007/s12032-025-02656-x

Mohammad Abohassan, Mesfer Mohammad Al Shahrani, Sarah Khaled AlOuda, Prasanna Rajagopalan

{"title":"Dual targeting of CXC chemokine receptor 4 and multidrug resistance protein 1 by ZIN056 effectively combat daunorubicin resistance in acute myeloid leukemia cells.","authors":"Mohammad Abohassan, Mesfer Mohammad Al Shahrani, Sarah Khaled AlOuda, Prasanna Rajagopalan","doi":"10.1007/s12032-025-02656-x","DOIUrl":"10.1007/s12032-025-02656-x","url":null,"abstract":"Drug resistance, associated with the overexpression of CXC chemokine receptor CXCR4 and multidrug resistance protein 1 (MDR1) remains a significant barrier to effective therapy in Acute Myeloid Leukemia (AML). Targeting both CXCR4 and MDR1 could potentially enhance treatment efficacy in resistance. In silico computational screening of the Zinc natural product library using Discovery Studio Visualizer, Protein-Ligand Interaction Profiler, GROMACS, and GMX_MMPBSA techniques were used. THP-1, and SKM-1 cells were used for in vitro analysis. Flow cytometry was employed for target analysis and apoptosis enumerations. The virtual screening identified ZIN056 with favorable binding affinities of - 10.6 kcal/mol and - 9.1 kcal/mol for CXCR4 and MDR1, respectively. MD simulations demonstrated stable binding interactions, with Root Mean Square Deviation values around 0.2 nm for both proteins. The ΔG binding calculations further confirmed values of - 30.09 kcal/mol for CXCR4 and - 34.47 kcal/mol for MDR1, indicating energetically favorable binding. The compound inhibited the THP-1 and SKM-1 cell proliferation with GI50 values of 250.6 nM, and 346.7 nM, respectively. ZIN056 decreased CXCR-4 expression and MDR1-induced positive population (MDR1+) in THP-1 and SKM-1 cells. ZIN056 inhibited the proliferation of the regular and MDR1+ AML cells, while Daunorubicin exhibited a tenfold resistance in controlling MDR1+ AML cell proliferation. ZIN056-induced apoptosis in MDR1 + AML cells, whereas Daunorubicin failed to promote apoptosis in these cells. The findings suggest that dual targeting of CXCR4 and MDR1 using ZIN056 may offer a promising strategy to overcome drug resistance in AML and provide a foundation for further development of dual inhibitors for AML patients.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"106"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625355","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}

引用次数: 0