Medical Oncology最新文献_第2页

Vitamin D3 and its active form calcitriol suppress erythroleukemia through upregulation of CHAC1 and downregulation of NOTCH1.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-27 DOI: 10.1007/s12032-025-02695-4

Jiankun Hong, Zhongyou Yang, Jian Gao, Kunlin Yu, Anling Hu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Xiao Xiao, Chunlin Wang, Wuling Liu, Yaacov Ben-David

{"title":"Vitamin D3 and its active form calcitriol suppress erythroleukemia through upregulation of CHAC1 and downregulation of NOTCH1.","authors":"Jiankun Hong, Zhongyou Yang, Jian Gao, Kunlin Yu, Anling Hu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Xiao Xiao, Chunlin Wang, Wuling Liu, Yaacov Ben-David","doi":"10.1007/s12032-025-02695-4","DOIUrl":"10.1007/s12032-025-02695-4","url":null,"abstract":"Vitamin D3 (VD3) and its active form calcitriol (Ca) exhibit anti-neoplastic activity against several types of cancer, although the underlying mechanism is not fully understood. Herein, we tested the effects of VD3 and Ca on erythro-leukemogenesis and investigated the underlying mechanism. VD3 and Ca treatment strongly inhibited cancer progression in a mouse model of erythroleukemia induced by the Friend virus. In tissue culture, VD3 and Ca inhibited proliferation of leukemic cell lines. Growth inhibition was associated with induction of G1 phase cell cycle arrest and apoptosis. Transcription of the VD3 receptor, VDR, is strongly induced by Ca, but not VDR. However, leukemia growth suppression by both VD3 and Ca is shown to be independent of VDR. In leukemic cells, both VD3 and Ca induced genes associated with metabolic pathways. Both VD3 and Ca induce the cytosolic glutathione degradase CHAC1 through activation of the ER stress response pathway ATF3/ATF4/CHOP genes. Higher expression of CHAC1 also suppressed the oncogene NOTCH1. Accordingly, knockdown of CHAC1 antagonized the inhibitory effect of VD3 and Ca on leukemic growth leading to higher NOTCH1 expression. Conversely, overexpression of CHAC1 suppressed leukemia cell growth and inhibited the expression of NOTCH1. Additionally, glutathione antagonized leukemia cell suppression induced by VD3 and Ca, demonstrating that this vitamin inhibits the proliferation of leukemic cells via CHAC1. Taken together, our results demonstrated that VD3 and Ca can prolong the survival of leukemia mice and inhibit the proliferation of erythroleukemia cell HEL through CHAC1 or CHAC1-mediated NOTCH1 inhibition.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"138"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720208","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

Identification of Isovitexin as a novel CYP17A1 inhibitor through virtual screening and evaluation of its anti-cancer effects in MCF-7 breast cancer cells.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-26 DOI: 10.1007/s12032-025-02637-0

Lathika Shanmugam, Priyadharshini Kaliyamoorthy, Vivia Yazhini Sashikumar, Sowmya Ravichandran, Kanishka Padmanaban, Nithya Elango

{"title":"Identification of Isovitexin as a novel CYP17A1 inhibitor through virtual screening and evaluation of its anti-cancer effects in MCF-7 breast cancer cells.","authors":"Lathika Shanmugam, Priyadharshini Kaliyamoorthy, Vivia Yazhini Sashikumar, Sowmya Ravichandran, Kanishka Padmanaban, Nithya Elango","doi":"10.1007/s12032-025-02637-0","DOIUrl":"https://doi.org/10.1007/s12032-025-02637-0","url":null,"abstract":"Over 75% of breast cancers are hormone receptor positive and are associated with better prognosis after treatment, when compared to other types of breast cancer. However, discontinuation of treatment due to side effects is common among one-third of the patients, leading to poor outcomes. On long-term treatment, development of resistance to the current therapeutics is common. CYP17A1, a key enzyme in androgen and estrogen synthesis, is associated in the development and progression of breast cancers. Phytochemicals, which are abundant in three traditional medicinal plants, Fenugreek, Ginger, and Basil, generally used in regulating hormonal disorders were screened for potential inhibition of CYP17A1, by molecular docking (Autodock Vina). The binding affinities were compared with standard CYP17A1 inhibitors Abiraterone and Ketoconazole. Docking analysis revealed that Isovitexin (- 9.5 kcal/mol) and Orientin (- 9.4 kcal/mol) showed comparable binding affinities to Abiraterone and Ketoconazole. Molecular Simulations and MM-GBSA were employed to explore the stability of ligand-protein complexes. Isovitexin had stable interactions with the CYP17A1 than Orientin evident from the RMSD, RMSF, Protein-Ligand contacts and MM-GBSA values. In silico ADMET profiles of the phytochemicals and standard breast cancer drugs (Letrozole, Tamoxifen, Paclitaxel, and Docetaxel) were evaluated using Swiss ADME and pkCSM and found to be similar. In in vitro assays, Isovitexin was found to be cytotoxic to MCF-7 cells, causing 46% apoptosis at < 10 nM levels. The study reveals that Isovitexin, with high cytotoxicity, may be effective in the treatment of both ER- and PR-positive (MCF-7) cancers. Overall, the findings have implications for the therapeutic development of hormone receptor-positive breast cancers.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"137"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730737","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

Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-25 DOI: 10.1007/s12032-025-02663-y

Shuaiyang Wang, Bei Xie, Haohua Deng, Xingyuan Ma, Baoyuan Tang, Lei Ma, Jinmei Zhu, Jing Li, Linjing Li

{"title":"Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.","authors":"Shuaiyang Wang, Bei Xie, Haohua Deng, Xingyuan Ma, Baoyuan Tang, Lei Ma, Jinmei Zhu, Jing Li, Linjing Li","doi":"10.1007/s12032-025-02663-y","DOIUrl":"https://doi.org/10.1007/s12032-025-02663-y","url":null,"abstract":"Protein kinase D3 (PRKD3), belonging to the protein kinase D family, significantly influences tumor development and progression. The role of PRKD3 in advancing gastric cancer (GC) and its effects on the cell cycle are not well understood, necessitating detailed investigation. Assessment of PRKD3 expression in both malignant and normal gastric tissues was performed using bioinformatics databases. The influence of PRKD3 on GC's malignant characteristics was evaluated through in vitro experiments utilizing cell line models of GC. Additionally, proteomic analyses were conducted to investigate the potential mechanisms of PRKD3 in GC progression. PRKD3 was notably overexpressed in GC tissues, correlating with adverse outcomes for patients. PRKD3 knockdown impaired GC cell malignancy, manifesting as a 2.12-fold decline in proliferation(p < 0.01), 2.64-fold suppression of migration(p < 0.01), 2.16-fold inhibition of invasion(p < 0.01), and G2/M phase arrest. Proteomic and Western blot analyses had revealed a substantial enrichment in differentially expressed proteins (DEPs) associated with tumor-related signaling pathways, including FoxO and p53, which was paralleled by significant alterations in the levels of key cell cycle proteins such as CDK1, CyclinB1, CHK1 and PLK1, with a 6.8-fold elevation in CHK1 levels(p < 0.05). The overexpression of PRKD3 was intricately linked with the aggressive behaviors of GC. Targeting PRKD3 activity offers potential for effective treatments of GC.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"135"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710548","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

Gastrointestinal perforation in general oncology, metastatic colorectal cancer, and metastatic melanoma population.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-25 DOI: 10.1007/s12032-025-02691-8

Arun Parashar, Vineet Mehta, Varsha Sharma, Muskan Thakur

{"title":"Gastrointestinal perforation in general oncology, metastatic colorectal cancer, and metastatic melanoma population.","authors":"Arun Parashar, Vineet Mehta, Varsha Sharma, Muskan Thakur","doi":"10.1007/s12032-025-02691-8","DOIUrl":"https://doi.org/10.1007/s12032-025-02691-8","url":null,"abstract":"Gastrointestinal perforation (GIP) is a rare and potentially fatal adverse event of antineoplastic therapy. GIP is a rare but serious complication in oncology patients, often leading to significant morbidity and mortality. In general oncology patients, the incidence of GIP ranged from 0.5 to 1.9%. A meta-analysis of six clinical trials with 4579 patients reported an incidence of 1.0%. Among mCRC patients, the incidence varied between 0.5 and 2.4%, with geographic differences-1.5% in the USA and 2.4% in Australia. For metastatic melanoma patients, the incidence of GIP ranged from 0.4 to 0.67%, with U.S. rates of 0.57% and 0.67% and a lower rate of 0.40% reported in Germany. The findings suggest that the risk of GIP varies significantly across oncology populations and treatment regimens, with higher risks noted in metastatic cancer patients undergoing therapies such as VEGF inhibitors or immune checkpoint inhibitors. These data highlight the need for careful monitoring and early intervention in high-risk populations to reduce the impact of GIP on patient outcomes. This systematic review aims to summarize the incidence of GIP in general oncology, metastatic colorectal cancer (mCRC), and metastatic melanoma (MM) populations. A literature search was conducted in Embase and Medline databases from January 1, 2011 to August 30, 2017, identifying relevant studies on GIP incidence.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"133"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710553","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

Fatty acid synthase inhibitor cerulenin attenuates glioblastoma progression by reducing EMT and stemness phenotypes, inducing oxidative and ER stress response, and targeting PI3K/AKT/NF-κB axis.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-25 DOI: 10.1007/s12032-025-02697-2

Murat Pekmez, Şefika Beyza Mete, Yunus Aksüt, İrem Öğütcü, Fatma Nur Baştürk, Yusuf Can Gerçek, Aslıhan Şengelen

{"title":"Fatty acid synthase inhibitor cerulenin attenuates glioblastoma progression by reducing EMT and stemness phenotypes, inducing oxidative and ER stress response, and targeting PI3K/AKT/NF-κB axis.","authors":"Murat Pekmez, Şefika Beyza Mete, Yunus Aksüt, İrem Öğütcü, Fatma Nur Baştürk, Yusuf Can Gerçek, Aslıhan Şengelen","doi":"10.1007/s12032-025-02697-2","DOIUrl":"10.1007/s12032-025-02697-2","url":null,"abstract":"Targeting cellular metabolism is becoming a critical approach for stopping cancer progression. Limited information is available regarding the effects of inhibiting the lipogenic enzyme fatty acid synthase (FASN) in glioblastoma (GB) cells (grade-IV-astrocytoma), which have high invasion and low response to standard treatments. Herein, we used cerulenin (CER) to inhibit FASN. CER treatments (3.6 μg/mL/48 h and 5.55 μg/mL/48 h indicate IC20 and IC50 values, respectively) led to a dose- and time-dependent decrease in the viability of the U-87MG human GB cells. A significant decrease was detected in the levels of fatty acids, including palmitic acid, determined by GS-MS analysis. FASN inhibition attenuated cell motility, 2D and 3D-clonogenic survival, and cell differentiation characteristics (related markers of epithelial-mesenchymal transition/EMT and stemness). Moreover, treatments caused mitochondrial membrane potential (MMP) collapse and increased intracellular reactive oxygen species (ROS) levels. Protein aggregates and ER stress in the cells also increased. Remarkably, despite increased Hsp70 and p-HSF1 levels against induced cellular stress, CER promoted markedly autophagy and apoptosis. The network pharmacology approach revealed that protein and lipid kinases are crucial targets in cell signaling, and PI3K, AKT, and NF-κB levels were confirmed by immunoblotting. The results demonstrated for the first time that inhibiting FA production and FASN function induces cell death through ROS generation and ER stress while simultaneously reducing the motility and aggressiveness of U-87MG human glioblastoma cells by attenuating EMT and stemness phenotypes. Therefore, blocking lipid metabolism using CER may be considered as a good candidate for GB therapeutic option.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"136"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710550","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

Smart nanomedicines powered by artificial intelligence: a breakthrough in lung cancer diagnosis and treatment.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-25 DOI: 10.1007/s12032-025-02680-x

Moloudosadat Alavinejad, Maryam Shirzad, Mohammad Javad Javid-Naderi, Abbas Rahdar, Sonia Fathi-Karkan, Sadanand Pandey

{"title":"Smart nanomedicines powered by artificial intelligence: a breakthrough in lung cancer diagnosis and treatment.","authors":"Moloudosadat Alavinejad, Maryam Shirzad, Mohammad Javad Javid-Naderi, Abbas Rahdar, Sonia Fathi-Karkan, Sadanand Pandey","doi":"10.1007/s12032-025-02680-x","DOIUrl":"https://doi.org/10.1007/s12032-025-02680-x","url":null,"abstract":"Lung cancer remains one of the leading causes of cancer-related mortality worldwide, primarily due to challenges in early detection, suboptimal therapeutic efficacy, and severe adverse effects associated with conventional treatments. The convergence of nanotechnology and artificial intelligence (AI) offers transformative potential in precision oncology, enabling innovative solutions for lung cancer diagnosis and therapy. Intelligent nanomedicines facilitate targeted drug delivery, enhanced imaging, and theranostic applications, while AI-driven models harness big biomedical data to optimize nanomedicine design, functionality, and clinical application. This review explores the synergistic integration of AI and nanotechnology in lung cancer care, highlighting recent advancements, key challenges, and future directions for clinical translation. Ethical considerations, including data standardization and privacy concerns, are also addressed, providing a comprehensive roadmap to overcome current barriers and advance the adoption of AI-driven intelligent nanomedicines in precision oncology. This synthesis underscores the critical role of emerging technologies in revolutionizing lung cancer management.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"134"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710556","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

Retraction Note: Molecular and therapeutic effect of CRISPR in treating cancer.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-24 DOI: 10.1007/s12032-025-02692-7

Sawani Rodrigo, Kaveesha Senasinghe, Sameer Quazi

引用次数: 0

Molecular crosstalk between GPCR and receptor tyrosine-protein kinase in neuroblastoma: molecular mechanism and therapeutic implications.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-23 DOI: 10.1007/s12032-025-02685-6

Kousik Maparu, Dhrita Chatterjee, Romanpreet Kaur, Nileshwar Kalia, Omkar Kumar Kuwar, Mayank Attri, Shamsher Singh

{"title":"Molecular crosstalk between GPCR and receptor tyrosine-protein kinase in neuroblastoma: molecular mechanism and therapeutic implications.","authors":"Kousik Maparu, Dhrita Chatterjee, Romanpreet Kaur, Nileshwar Kalia, Omkar Kumar Kuwar, Mayank Attri, Shamsher Singh","doi":"10.1007/s12032-025-02685-6","DOIUrl":"https://doi.org/10.1007/s12032-025-02685-6","url":null,"abstract":"Neuroblastoma is an aggressive pediatric tumor condition derived from neural crest cells that typically affect infants and children under the age of five. It can often originate in the adrenal glands but can also develop in the sympathetic nervous system. G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases have been shown in recent research to have a vital role in the progression of neuroblastoma. GPCR-RTK crosstalk stimulates signaling pathways such as MAP kinase, and the activation of the GPCR-AKT signaling pathway plays a critical role in neuroblastoma progression by promoting cell growth, survival, and resistance to apoptosis through complex interactions with insulin signaling pathways. ALK (Anaplastic lymphoma kinase), a member of the RTK family, and any mutations can lead to oncogenic signaling and resistance to targeted therapy in neuroblastoma. By interfering with cellular signaling via novel therapeutic strategies by selective RET inhibitors, ALK inhibitors, and Trk-specific inhibitors may be able to reduce the prevalence of neuroblastoma. Understanding the complicated signaling relationships between GPCRs, RTKs, and the insulin pathway is critical when developing new cancer treatments. The integration of these signaling networks offers promising avenues for enhancing the effectiveness of existing treatments and improving patient outcomes in neuroblastoma.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"131"},"PeriodicalIF":2.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692376","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

Retraction Note: Niosomes: a novel targeted drug delivery system for cancer. 撤稿说明：Niosomes：一种新型癌症靶向给药系统。

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-22 DOI: 10.1007/s12032-025-02693-6

Maryam Moghtaderi, Kamand Sedaghatnia, Mahsa Bourbour, Mahdi Fatemizadeh, Zahra Salehi Moghaddam, Faranak Hejabi, Fatemeh Heidari, Sameer Quazi, Bahareh Farasati Far

引用次数: 0

Retraction Note: In vitro cytotoxicity and anti-cancer drug release behavior of methionine-coated magnetite nanoparticles as carriers.

IF 2.8 4区医学

Medical Oncology Pub Date : 2025-03-22 DOI: 10.1007/s12032-025-02688-3

Faten Eshrati Yeganeh, Amir Eshrati Yeganeh, Mahdi Fatemizadeh, Bahareh Farasati Far, Sameer Quazi, Muhammad Safdar

引用次数: 0