Neoplasma最新文献

{"title":"Elevation of cardiac biomarkers after allogeneic transplantation: the impact of hematopoietic stem cell cryopreservation.","authors":"Vladimíra Lábska, Beáta Mladosievičová, Michaela Martišová, Barbora Žiaková, Eva Bojtárová, Ladislav Sopko, Jozef Lukáš, Ľubica Harvanová","doi":"10.4149/neo_2026_251203N506","DOIUrl":"10.4149/neo_2026_251203N506","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation (HSCT) represents a curative treatment modality for numerous hematologic malignancies. Advances in treatment protocols and supportive care have markedly enhanced post-transplant survival rates. Consequently, the number of long-term survivors has increased. However, HSCT may induce organ and tissue injury of varying severity, ranging from subclinical alterations to severe, potentially fatal complications. The aim of this study was to quantify plasma levels of the cardiac biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin T (hs-cTnT), and to evaluate cardiovascular (CV) complications in patients undergoing HSCT with and without cryopreservation of stem cells. During the COVID-19 pandemic, the use of cryopreserved allografts increased. Dimethyl sulfoxide (DMSO) is a cryoprotectant added to cell media to prevent ice formation and subsequent cell death during the freezing process of cryopreserved grafts. This study included 106 consecutive hematologic patients who underwent allogeneic HSCT. Serial measurements of plasma NT-proBNP and hs-cTnT concentrations were performed on the day before the conditioning regimen (baseline), on the day after HSCT (D+1), and subsequently on days D+2, D+7, D+14, and D+30, or at the onset of clinical symptoms. Newly diagnosed cardiac events post-HSCT were evaluated. NT-proBNP concentrations increased in all patients on D+1 after HSCT, reaching their peak at that time. Thereafter, NT-proBNP levels showed a gradual decline, but they did not return to baseline. A statistically significant increase in NT-proBNP values was observed in the group of patients who received cryopreserved grafts compared to those who received non-cryopreserved grafts. Hs-cTnT values during the early post-transplant period were comparable to pre-transplant levels in both groups - in patients who received cryopreserved grafts and also in patients who received non-cryopreserved grafts. After transplantation, we observed persistent hs-cTnT levels above the cut-off value in 28% of patients. Clinically significant CV complications were identified in 10 (9.4%) patients. Patients with manifest CV complications had significantly higher concentrations of both cardiomarkers compared with those without CV complications. In conclusion, persistent elevation in cardiac biomarkers may indicate a reduced functional myocardial reserve or diminished cardiac tolerance to cardiac stressors. Potential cardiac toxicity related to DMSO exposure in cryopreserved grafts should be considered in the differential diagnosis of cardiac events following HSCT involving cryopreserved stem cells.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"310-317"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391476","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}

{"title":"Real-world clinical outcomes of newly diagnosed AML unfit for intensive chemotherapy treated with venetoclax and azacitidine: does it depend on the number of days of venetoclax administration?","authors":"Jozef Lukáš, Balázs Gálffy, Stanislava Fliegová, Zuzana Sninská, Ľubica Harvanová, Katarína Slezáková, Ladislav Sopko","doi":"10.4149/neo_2026_260404N105","DOIUrl":"10.4149/neo_2026_260404N105","url":null,"abstract":"<p><p>Until 2020, patients with acute myeloid leukemia (AML) who were not suitable for intensive treatment were mostly limited to symptomatic and palliative care, or to low-intensity regimens including low-dose cytosine-arabinoside (ARA-C) and azacitidine (AZA) monotherapy, which didn't bring much benefit. The situation changed with the arrival of venetoclax, a Bcl-2 inhibitor that causes leukemic cells to rapidly undergo apoptosis. The aim of our retrospective study was to summarize the treatment outcomes of all newly diagnosed patients with AML, unsuitable for intensive chemotherapy, treated with a combination of venetoclax and AZA at the Department of Hematology and Transfusion Medicine, University Hospital in Bratislava from January 1, 2021, to December 31, 2025. A total of 108 patients underwent treatment with a median follow-up of 35.9 months; median age was 69.5 years (47-84 years), and median number of cycles was 3 (1-34). Induction mortality rate was 7.4%, and tumor lysis syndrome occurred in 4.5%. The overall response rate, which included the number of complete remissions, complete remissions with incomplete hematopoietic recovery, and morphologically leukemia-free status (CR/CRi/MLFS), was 64%, the median overall survival was 9 months, and disease-free survival was 8 months. As of December 31, 2025, 23 patients are alive, and 85 have died. The main cause of death was the progression of the disease. The main contribution of our study is the finding that shortening the duration of venetoclax treatment maintains efficacy. There was no significant difference in remission rate achieved or in overall survival based on the number of days of venetoclax administration (<14 vs. 14 vs. 21 vs. 28 days). The combination of AZA and venetoclax in AML has proven to be highly effective in inducing complete remission, usually immediately after the first cycle. Unfortunately, remission is not long-lasting, relapses are frequent, and the median overall survival in real-world data is 7.9 to 13.6 months.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"295-300"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549945","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}

{"title":"A splice odyssey: periostin's journey through the sea of crabs.","authors":"Radka Macova, Michal Selc, Andrea Babelova","doi":"10.4149/neo_2026_260403N103","DOIUrl":"10.4149/neo_2026_260403N103","url":null,"abstract":"<p><p>Periostin is an extracellular matrix protein involved in processes ranging from early embryonic development to life-threatening cancer progression. Instead of acting as a single entity, it exists in numerous alternatively spliced isoforms, primarily differing in their C-terminal region, which drives diversification and context-dependence in its biological functions. Despite growing interest, inconsistencies in nomenclature and fragmented data still complicate the interpretation of isoform-specific roles. Therefore, the aim of this review is to provide a structured overview of periostin isoforms, focusing on their roles in development and carcinogenesis, while addressing challenges in their nomenclature. During embryogenesis, expression of periostin is dynamically regulated across developmental stages and tissues. Distinct isoforms exhibit specific patterns, both spatially and temporally, that reflect specialized functions during organogenesis (particularly in the cardiac, neural, and skeletal systems), and as experimental evidence points out, certain exons play critical roles in morphogenesis. Regulatory mechanisms influencing these patterns persist beyond development and are often changed in pathological conditions. In oncological diseases, expression of periostin isoforms varies widely between tumor types and microenvironments. Many isoforms are present in malignant as well as in adjacent non-malignant tissues, with differences in their relative abundance. Functionally, exon 17-containing variants tend to influence tumor cell-intrinsic properties, while variants with exon 21 are more closely linked to stromal interactions and modulation of the tumor microenvironment. Interesting is also the fact that periostin can exert both tumor-promoting and tumor-limiting effects, depending on the isoform and biological context. Taken together, periostin isoforms represent a complex regulatory system whose better understanding and standardized classification may enhance their potential in diagnostics and therapy.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"251-260"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605733","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}

{"title":"Postoperative clinical prognosis in 160 cases of glioblastoma and efficacy of vascular targeted therapy for recurrence.","authors":"Jiayuan Li, Liubing Hou, Huandi Zhou, Zizhou Zhang, Yu Wang, Xiang Zhan, Wenyan Wang, Lei Tian, Xiaoying Xue","doi":"10.4149/neo_2026_260306N56","DOIUrl":"10.4149/neo_2026_260306N56","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common primary malignant brain tumor. Concurrent chemoradiotherapy and adjuvant chemotherapy have become the standard treatment modalities after surgery. However, despite such aggressive treatment, the overall survival (OS) rate remains low, and the disease is highly prone to recurrence with an extremely poor prognosis after recurrence. Currently, there is no standard salvage treatment regimen. This study conducted a clinical prognostic analysis of 160 patients with GBM after surgery and evaluated the clinical efficacy of anti-angiogenic drugs (apatinib/bevacizumab) as salvage treatment after recurrence, providing a strong direction for future treatment. Among the 160 patients with GBM included in the study, univariate analysis showed that age, use of apatinib, adjuvant chemotherapy, and radiotherapy were significantly associated with OS, while gender, CD34 expression, Ki-67 expression, bevacizumab, and P53 expression were not significantly associated with OS. Multivariate analysis revealed that adjuvant chemotherapy, age, and radiotherapy were independent prognostic factors for OS in patients with GBM. The median OS of the entire cohort was 20.0 months, with 1-year, 3-year, and 5-year survival rates of 74.6%, 28.7%, and 12.4%, respectively. Analysis of the clinical efficacy of salvage chemotherapy in 65 patients with recurrent GBM showed that the combined anti-angiogenic drug group had a significant survival advantage compared to the chemotherapy-only group (33 months vs. 19 months). Among patients in the combined anti-angiogenic drug group, 36 patients achieved clinical control, with a disease control rate (DCR) of 73.47%, significantly higher than the 43.75% DCR in the control group. The chemotherapy combined with apatinib group had a significant survival advantage in OS (p=0.012) and also benefited in DCR (66.67% vs. 43.75%); however, the chemotherapy combined with the bevacizumab group did not show a survival benefit in OS (p=0.078).</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"301-309"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422970","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}

{"title":"The interplay between cancer and follicular fluid: molecular changes and tumor-promoting properties.","authors":"Dominika Melegová, Monika Šramková, Katarina Kozics","doi":"10.4149/neo_2026_260415N118","DOIUrl":"10.4149/neo_2026_260415N118","url":null,"abstract":"<p><p>Follicular fluid is a complex biological microenvironment essential for oocyte maturation and folliculogenesis. Alterations in follicular fluid composition have been associated with reproductive disorders reflecting compromised oocyte quality. Emerging evidence suggests that malignancies also significantly alter the composition of follicular fluid, potentially compromising the follicular microenvironment and impacting fertility preservation outcomes. Interestingly, the follicular fluid itself exhibits tumor-initiating and tumor-promoting properties, inducing DNA damage, pro-inflammatory signaling, mild proliferation, and suppressing apoptosis. Understanding cancer-associated follicular fluid alterations may improve fertility care, identify early biomarkers, and inform strategies for ovarian cancer prevention and therapy. This review aims to summarize current knowledge on how cancer can alter follicular fluid composition and its role in ovarian malignancies.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"261-268"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265691","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}

{"title":"Targeting the MDM2/Caspase-3/GSDME axis: apatinib and cinobufagin synergistically induce pyroptosis to suppress gastric cancer progression.","authors":"Lei Cao, Lijuan Meng, Yueyao Lu, Lixin Yang, Weiyou Zhu","doi":"10.4149/neo_2026_250923N408","DOIUrl":"10.4149/neo_2026_250923N408","url":null,"abstract":"<p><p>Gastric cancer (GC) is a highly heterogeneous and aggressive malignancy with a poor prognosis, especially in advanced stages. Apatinib and cinobufagin (CS-1) have shown promising antitumor potential. However, the therapeutic efficacy and underlying mechanisms of their combined use in GC remain unclear. GC cell lines (AGS and GPM-1) were treated with apatinib, CS-1, or both. Cell viability, proliferation, migration, apoptosis, stemness, and pyroptosis-related protein expression were evaluated using cell counting kit-8 (CCK-8), colony formation, wound healing assays, flow cytometry, tumorsphere assays, and western blotting. The role of mouse double minute 2 homolog (MDM2) in modulating treatment response was investigated via overexpression experiments. Antitumor efficacy in vivo was assessed using a subcutaneous xenograft mouse model, and tumor apoptosis and proliferation were analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemistry. Combined treatment with apatinib and CS-1 significantly inhibited GC cell viability, proliferation, migration, and stemness, while inducing apoptosis and pyroptosis more effectively than either agent alone. Mechanistically, the combination therapy downregulated MDM2 expression and upregulated cleaved caspase-3 (C-caspase-3) and gasdermin E-N (GSDME-N). Overexpression of MDM2 partially reversed these effects both in vitro and in vivo, leading to reduced apoptosis, pyroptosis, and antitumor efficacy. Apatinib combined with CS-1 synergistically suppresses GC progression by inducing MDM2/C-caspase-3/GSDME-regulated pyroptosis. These findings highlight MDM2 as a critical therapeutic target and provide novel insights into the molecular mechanisms underlying the combined use of targeted agents and natural compounds in GC therapy.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"283-294"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422922","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}

{"title":"SMAP1 promotes hepatoblastoma cell proliferation by modulating the C-Kit-activated ERK/MAPK pathway.","authors":"Jie Liu, Ke Xu, Hongyue Wang, Yan Cheng, Zihui Cheng, Wenjie Bu, Feifei Wang, Xiaoxuan Zuo, Xiaojian Li, Nan Xia, Qian Dong, Wenli Xiu, Aiqin Lin","doi":"10.4149/neo_2026_251105N462","DOIUrl":"https://doi.org/10.4149/neo_2026_251105N462","url":null,"abstract":"<p><p>Hepatoblastoma (HB) is the most common pediatric liver malignancy. We investigated the role of SMAP1 in HB proliferation and its mechanism. Sixty-seven HB tissues were analyzed for SMAP1 expression via immunohistochemistry and correlated with clinical outcomes. qRT-PCR quantified SMAP1 mRNA in HB cell lines versus normal hepatocytes. SMAP1 was knocked down (siRNA/lentivirus) or overexpressed (plasmid) in HB cells; proliferation was assessed by CCK-8 and colony formation. A nude-mouse xenograft model was used to evaluate tumorigenicity. Western blotting determined C-Kit and ERK/MAPK pathway activity after SMAP1 modulation. Rescue experiments used ERK activator C16-PAF, inhibitor U0126, or C-Kit inhibitor ISCK03. SMAP1 was upregulated in HB and predicted poor prognosis. Knockdown reduced C-Kit, p-C-Kit, and p-ERK1/2, inhibited proliferation and colony formation, and suppressed xenograft growth. Overexpression produced opposite effects. U0126 reversed ERK1/2 phosphorylation and p-Rb in SMAP1-overexpressing cells, whereas C16-PAF restored ERK signaling and c-Myc/p-Rb in knockdown cells. ISCK03 blocked C-Kit/ERK activation prompted by SMAP1 overexpression. SMAP1 drives HB progression by activating C-Kit-ERK/MAPK signaling, representing a potential therapeutic target.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605806","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}

{"title":"Baseline circulating tumor plasma cells are associated with progression-free survival in newly diagnosed multiple myeloma: a single-center real-world NGF study.","authors":"Ján Sýkora, Dominik Kľoc, Bianca Dubiková, Slavomír Kurhajec, Tomáš Guman, Marek Sarissky","doi":"10.4149/neo_2026_260427N133","DOIUrl":"10.4149/neo_2026_260427N133","url":null,"abstract":"<p><p>Circulating tumor plasma cells (CTPCs) in peripheral blood provide a direct readout of myeloma dissemination. While CTPCs are increasingly recognized as prognostically relevant in newly diagnosed multiple myeloma (NDMM), practical cutoffs vary across cohorts and detection methods. Here, we evaluated baseline CTPCs quantified by a single-tube 10-color next-generation flow cytometry (NGF) approach in 55 consecutive patients with symptomatic treatment-indicated NDMM. Progression-free survival (PFS) from diagnosis was analyzed using Kaplan-Meier method and compared across pragmatic CTPCs cutoffs (0.02%, 0.05%, and 0.07%) and the cohort median (0.0159%). The median follow-up by reverse Kaplan-Meier analysis was 27.9 months (interquartile range IR 20.2-31.9). The recently proposed 0.02% CTPCs threshold showed a non-significant PFS separation (median PFS 27.3 vs. 40.3 months for >0.02% vs. ≤0.02%; log-rank p=0.068; hazard ratio HR 2.23, 95% confidence interval CI 0.92-5.42). CTPCs dichotomized at 0.05% significantly stratified PFS (log-rank p=0.007), whereas 0.07% and the median cutoff yielded borderline separation. Patients with >0.05% CTPCs at diagnosis showed a significantly shorter PFS compared to those with ≤0.05% CTPCs (median PFS 14.3 vs. 40.3 months). Patients with >0.05% CTPCs were at a significantly higher risk of event (HR 3.07, 95% CI 1.29-7.31, p=0.011). Peripheral blood normal plasma cells and bone marrow tumor plasma cells showed additional associations with PFS, while bone marrow normal plasma cells did not. R2-ISS stage and high-risk cytogenetics did not stratify PFS in this cohort. To conclude, these findings support the clinical relevance of baseline CTPCs quantification in real-world NDMM, but this small single-center cohort does not formally validate any specific cutoff or establish a new clinical cutoff.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549958","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}

{"title":"Value of PD-1 and CD28 expression on T lymphocytes in predicting radiation-induced lung injury: a prospective observational study.","authors":"Liang Dong, Chunyang Li, Jiarui Yu, Wei Wang, Zhiwu Wang","doi":"10.4149/neo_2026_251208N511","DOIUrl":"10.4149/neo_2026_251208N511","url":null,"abstract":"<p><p>Radiation-induced lung injury (RILI) remains a major dose-limiting toxicity in thoracic radiotherapy, with risk prediction relying primarily on dosimetric parameters, which show significant individual heterogeneity. This study aimed to evaluate dynamic changes in peripheral blood T-cell immune checkpoints as predictive biomarkers for ≥ Grade 2 RILI. In this prospective observational study, 274 lung cancer patients receiving thoracic radiotherapy were enrolled. Peripheral blood T-cell subsets (PD-1/CD28 expression on CD4+ and CD8+ cells) were analyzed by flow cytometry before radiotherapy (W0) and at week 2 (W2). The primary endpoint was ≥ Grade 2 RILI, assessed using CTCAE v4.0. With a median follow-up of 19 months, 87 patients (31.8%) developed ≥ Grade 2 RILI. Multivariate Cox analysis identified immunotherapy (HR=1.61, p=0.044), high mean lung dose (HR=2.33, p=0.002), and elevated levels of CD8+PD-1+ (W2, HR=2.18, p=0.030) and CD8+CD28+ (W2, HR=1.73, p=0.025) T cells as independent risk factors. Dynamic monitoring of CD8+PD-1+ and CD8+CD28+ T cells early during radiotherapy provides a novel and independent biological indicator for predicting RILI risk, complementing traditional dosimetric assessment.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"73 3","pages":"242-249"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376533","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}

{"title":"V9302, an inhibitor of glutamine transport, suppresses proliferation and migration, and induces apoptosis in non-small cell lung cancer cells through ROS-mediated mTOR/p70S6K pathway.","authors":"Shuo Li, Xingyu Zhang, Teng Chen, Xiaofan Cong, Wenjing Feng, Xiaojin Sun, Cheng Zha, Surong Zhao, Pei Zhang","doi":"10.4149/neo_2026_251028N451","DOIUrl":"10.4149/neo_2026_251028N451","url":null,"abstract":"<p><p>This study aimed to investigate the effects and underlying mechanisms of V9302, an inhibitor of glutamine transport, on non-small cell lung cancer (NSCLC) cells. Proliferation was assessed using the cell counting kit-8, colony formation, and EdU assays. Mitochondrial membrane potential was evaluated through JC-1 staining. Cell cycle distribution, apoptosis, and reactive oxygen species (ROS) levels were analyzed by flow cytometry, while migration was assessed using wound healing and Transwell assays. Western blotting was performed to determine protein expression levels. The antitumor efficacy of V9302 in vivo was evaluated using a xenograft mouse model with PC-9 cells. The results demonstrated that V9302 inhibited cell proliferation and induced G1-phase arrest in human lung adenocarcinoma PC-9 and A549 cells. Western blotting showed that V9302 significantly inhibited the ASCT2 protein expression in both PC-9 and A549 cells. Additionally, V9302 promoted apoptosis through a mitochondrial-dependent pathway, as evidenced by elevated levels of cleaved PARP, cleaved Caspase 3, cleaved Caspase 9, and Bax. V9302 also suppressed cell migration by downregulating N-cadherin and vimentin expression. Notably, V9302 triggered significant ROS accumulation and inhibited mTOR/p70S6K pathway activation, an effect that was partially restored by N-acetylcysteine, a ROS scavenger. Pretreatment with mTOR activator MHY1485 mitigated the inhibitory effects of V9302 on cell proliferation and migration, as well as its induction of apoptosis. Furthermore, V9302 inhibited tumor growth and induced apoptosis in a xenograft mouse model, without inducing detectable visceral toxicity. In conclusion, these findings demonstrate that V9302 reduces cell proliferation and migration, and causes apoptosis through the ROS-mediated mTOR/p70S6K pathway in NSCLC cells. These findings provide a novel theoretical foundation for advancing both academic and clinical research on NSCLC treatment.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"210-225"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691336","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}