Anticancer research最新文献

Background/aim: There is increasing evidence for recognition of nutraceuticals as anti-tumour agents in various cancers. Over the years, anecdotal reports and our laboratory-based research have indicated their promising therapeutic potential for the management of glioblastoma. The aim of this study was to assess the effect of a combination of 7 micronutrients on overall survival of these patients.

Patients and methods: A Nutraceutical study was conducted at King's College and St Thomas' Hospitals, London. Fifty-three newly diagnosed patients (37 males and 16 females) with glioblastoma were recruited consecutively in this randomised entry, double blind Phase II trial. The treatment (containing chokeberry extract, red grape seed extract, red clover extract, curcumin, selenium, tangeretin and lycopene) was given to two-thirds of the patients for 1 year after neurosurgery. This was consistent with the start date of their concomitant Stupp Protocol chemoradiation therapy. The patients in the placebo group had identical capsules which contained lactose only.

Results: Although the Kaplan - Meier analysis showed that the overall survival for the active and placebo groups was 14 and 13 months respectively, the results were not statistically significant (p=0.752).

Conclusion: This study has limitations but it acts as a proof of principle towards larger studies, as clearly sufficiently powered trials are crucial in determining the nature and size of the treatment effect. Future trials should consider subgroup analysis, with respect to such factors as patient's age at diagnosis, gender, extent of surgery, MGMT mutation and IDH status to identify the optimal responders.

Background/aim: Survivors of early-stage breast cancer (BC) are at an increased risk of secondary breast angiosarcoma (AS), a rare cancer predominantly involving the superficial breast. The role of radiotherapy (RT) in the pathogenesis of this secondary malignancy is not completely understood. This study set out to assess the absorbed RT dose in secondary breast AS in a retrospective cohort.

Patients and methods: A retrospective search for patients with BC diagnosed with secondary breast AS from 2008 to 2017 in the Helsinki University Hospital was performed. Based on available patient records, imaging, and pathology review, the AS volume was contoured in the treatment planning system. After recalculation of all RT plans, the absorbed RT dose at the skin surface and the maximum absorbed dose inside AS volume were calculated.

Results: Ten patients with previous RT for BC were diagnosed with secondary breast AS. All ASs arose in the planning target volume of BC. Calculated RT dose at depths of 1 mm and 2 mm from the skin surface ranged from 67% to 90% and from 69% to 104 % of the prescribed dose, respectively. The maximum RT dose at the AS location varied from 86% to 117% of the prescribed dose.

Conclusion: The calculated RT dose at the location of the secondary breast AS was not distinctively lower than the prescribed dose. Therefore, this secondary malignancy does not seem to develop at sites of low RT dose.

Background/aim: Resistance to targeted therapy limits its efficacy in non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although concurrent administration of pemetrexed (PEM) and EGFR-tyrosine kinase inhibitors (TKIs) has yielded clinical benefits, it remains unclear whether concurrent PEM influences de novo mutations in the EGFR-TKI therapy. To address this gap, we aimed to compare the time to acquired resistance and accumulation of de novo tumor mutational burden (TMB) during in vitro exposure to osimertinib (OSI) and gefitinib (GEF), as well as their respective combinations with PEM.

Materials and methods: EGFR-mutated PC-9 cells were continuously exposed to EGFR-TKIs, alone or in combination with PEM, at equimolar concentrations. The drug concentration gradually increased to 1 and 3 μM for OSI and GEF, respectively. Whole-exome sequencing and quantitative PCR were performed to measure TMB and gene expression, respectively.

Results: Concurrent PEM with either OSI or GEF extended the treatment duration compared to single EGFR-TKIs, decreased the de novo accumulated TMB per treatment time, and increased the expression of POLE2, POLQ, MLH1, BRCA1, BRCA2, RAD51, and FEN1 compared to that of single EGFR-TKIs.

Conclusion: Concurrent PEM with EGFR-TKI treatment slowed TMB accumulation rate and resistance acquisition in EGFR-mutated NSCLC compared to single EGFR-TKIs in vitro.

Background/aim: Adjuvant radiotherapy is a key component in breast cancer treatment, improving local control. Three-dimensional conformal radiotherapy (3D-CRT) remains widely used owing to its robustness; however, treatment planning for whole-breast (WB) irradiation including regional lymph nodes (RLN) and internal mammary nodes (IMN) is challenging. Planner-dependent variability may affect plan quality and organ-at-risk (OAR) sparing. The aim of this study was to evaluate intra-institutional variability in 3D-CRT plan quality for locoregional breast radiotherapy.

Patients and methods: Seven anonymized copies of the planning computed tomography (CT) of a representative patient with left-sided breast cancer treated with WB, RLN, and IMN were created. The clinical target volume (CTV) for the WB, RNL and IMN and OARs were delineated according to institutional guidelines. The planning target volumes (PTVs) were generated using a 5-mm isotropic margin and cropped 5 mm from the skin. Seven treatment planners with varying experience independently generated 3D-CRT plans following institutional guidelines. Plan quality was evaluated using target coverage and dose-volume metrics for OARs according to Swedish national guidelines and compared with the clinically delivered plan.

Results: All plans fulfilled dose objectives for the PTVs (D98% >93%, V105% <20%) and CTVs (D98%>95%), for WB and RLN. Two plans failed to meet coverage criteria for the IMN CTV (D98% >90%). Mean heart dose was consistent across plans (1.3-1.5 Gy). In contrast, substantial variability was observed for the ipsilateral lung, with mean dose ranging from 11.5 to 13.2 Gy and V16Gy from 29.8% to 34.8%.

Conclusion: Although acceptable target coverage was generally achieved, clinically relevant variability in lung dose metrics was observed. These findings highlight the need for further standardization of 3D-CRT planning to improve consistency and optimize plan quality in WB radiotherapy with nodal involvement.

Background/aim: Although patients with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) can expect long-term survival, some patients develop leptomeningeal metastasis (LM). The study aimed to clarify whether patients with EGFR-positive NSCLC have a higher incidence of LM than patients with EGFR-negative NSCLC using propensity matching, and to clarify the clinical characteristics of patients with EGFR-positive NSCLC who develop LM.

Patients and methods: This retrospective study reviewed the medical records of consecutive patients diagnosed with NSCLC from 2009 to 2025. In addition to common non-parametric tests, we performed propensity matching.

Results: We evaluated 895 patients with NSCLC, including 185 EGFR-positive patients. The incidence of LM was higher in EGFR-positive patients than in EGFR-negative patients (2.7% vs. 1.4%; p=0.01). Using propensity matching for age, sex, pathological type, and clinical stage, we confirmed the incidence of LM in EGFR-positive patients was higher than in EGFR-negative patients (9.1% vs. 1.2%; p=0.01). In EGFR-positive patients, LM was more likely to develop in younger women, and in those with brain or bone metastases, or pleural or peritoneal dissemination during their clinical courses. Among patients with LM, EGFR-positive patients had a longer time from LM onset to death. Among EGFR-positive patients who developed LM, those who received osimertinib tended to have a longer time to onset of LM and a longer overall survival.

Conclusion: LM has been attracting attention, possibly due to the long-term survival achieved by EGFR-tyrosine kinase inhibitors. Additional information is required to clarify the risk of LM.

Background/aim: Pterygium is a chronic, fibrovascular ocular surface disorder with tumor-like biological behavior. Although inflammatory mediators such as interleukin-17 (IL17) are increasingly implicated in its pathogenesis, the genetic contribution of IL17 remain unclear. To our knowledge, this study is the first to investigate whether IL17A rs2275913 and IL17F rs763780 polymorphisms influence pterygium susceptibility in a Taiwanese population.

Materials and methods: This case-control study evaluated the association between promoter IL17A rs2275913 and exonic IL17F rs763780 polymorphisms with pterygium susceptibility in 160 patients and 320 age- and sex-matched controls by polymerase chain reaction-restriction fragment length polymorphism methods. The potential interactions between IL17A genotype and age or sex were tested by stratified analysis.

Results: IL17A rs2275913 genotype distribution showed borderline overall significance (p for trend=0.0522). Compared with GG carriers, individuals with AG and AA genotypes exhibited odds ratios (ORs) 1.39 [95% confidence interval (CI)=0.91-2.13, p=0.1546] and 1.92 (95%CI=1.11-3.30, p=0.0263), respectively. Under the dominant model (AG+AA vs. GG), risk of pterygium was increased significantly (OR=1.53, 95% CI=1.03-2.27, p=0.0449). The A allele conferred elevated susceptibility (OR=1.42, 95% CI=1.08-1.87, p=0.0136). No significant associations were observed for IL17F rs763780 (all p>0.05). Stratified analyses indicated significant increased effects of IL17A rs2275913 genotype by older age (≥60 years), and female sex.

Conclusion: Our findings demonstrate, for the first time, that IL17A rs2275913, particularly the A allele and AA genotype, is associated with increased pterygium risk among Taiwanese individuals, with stronger effects among older adults and females. These results suggest a potential genetic basis for IL17-mediated inflammation in pterygium and highlight IL17A rs2275913 as a promising biomarker for pterygium susceptibility.

Background/aim: Plasma-activated medium (PAM), which generates reactive oxygen and nitrogen species (RONS), has emerged as a promising anti-cancer approach. However, although PAM effectively eliminates bulk tumor cells, surviving populations often acquire enhanced stem cell-like properties, suggesting selective resistance in cancer stem cells (CSCs). This study aimed to elucidate the molecular mechanisms underlying CSC resistance to PAM-induced oxidative stress in non-small cell lung cancer (NSCLC).

Materials and methods: CD133⁺ and CD133^- subpopulations were isolated from A549 lung cancer cells to evaluate their sensitivity to PAM-induced cytotoxicity. Intracellular reactive oxygen species (ROS) levels, apoptosis, and antioxidant defense mechanisms were assessed in vitro, while therapeutic efficacy was examined using xenograft mouse models.

Results: CD133⁺ A549 cells exhibited marked resistance to PAM-induced apoptosis compared with CD133^- cells, accompanied by significantly reduced intracellular ROS accumulation. Peroxiredoxin 5 (PRDX5) was identified as a key antioxidant enzyme that was highly up-regulated in CD133⁺ cells and essential for maintaining redox homeostasis. Genetic silencing of PRDX5 in CD133⁺ cells significantly enhanced PAM-mediated cytotoxicity both in vitro and in vivo, restoring sensitivity to oxidative damage. Furthermore, combining PRDX5 knockdown with PAM treatment or co-administering PAM with paclitaxel substantially suppresses tumor growth in xenograft models, reducing tumor burden and inflammatory responses. These findings reveal PRDX5 as a key survival factor enabling CSCs to evade plasma therapy and suggest that targeting PRDX5 alongside PAM or conventional chemotherapy could improve treatment outcomes in NSCLC.

Conclusion: PRDX5 plays a central role in mediating oxidative stress resistance in CD133⁺ lung cancer stem-like cells, enabling their survival following PAM treatment. Targeting PRDX5, either alone or in combination with PAM or conventional chemotherapy, represents a promising strategy to overcome cancer stem cell-mediated resistance and improve therapeutic outcomes in non-small cell lung cancer.

Background/aim: Colon and gastric cancers are among the most prevalent gastrointestinal malignancies, often exhibiting poor prognosis due to resistance and recurrence. Polo-like kinase 1 (PLK1), a key regulator of mitosis, is frequently overexpressed in these cancers. BI-2536, a selective PLK1 inhibitor, has shown promising anticancer activity. β-Glucan, a natural immunomodulator, has also demonstrated anticancer potential. This study aimed to evaluate the antiproliferative, apoptotic, and cell cycle effects of BI-2536 alone and in combination with β-glucan on HT-29 colon and AGS gastric cancer cell lines.

Materials and methods: Cell viability was assessed using the XTT assay. Apoptosis and cell cycle profiles were evaluated using flow cytometry. The combination index (CI) was calculated using the Chou-Talalay method via CompuSyn software.

Results: BI-2536 significantly inhibited proliferation and induced G₂/M arrest and apoptosis in both cell lines. β-Glucan showed moderate cytotoxicity and enhanced BI-2536's effects. Synergistic antiproliferative activity was observed at lower drug concentrations, such as 2-16 nM BI-2536 combined with 31.25-250 μg/ml β-glucan (CI<1). The combination induced greater apoptosis and more pronounced G₂/M arrest compared with either agent alone, demonstrating a clear synergistic effect.

Conclusion: BI-2536 in combination with β-glucan exhibits synergistic anticancer effects in vitro, suggesting a promising strategy for treating colon and gastric cancers.

Background/aim: Chemotherapy-induced nausea and vomiting (CINV) remain major challenges during concurrent chemoradiotherapy (CCRT) for cervical cancer. Mannitol and furosemide are agents widely used to prevent cisplatin-induced nephrotoxicity; however, the differences in their effect on CINV have not been characterized. This study aimed to evaluate the impact of concomitant diuretic administration (mannitol versus furosemide) on the incidence and timing of vomiting in patients with cervical cancer undergoing CCRT.

Patients and methods: This multicenter, retrospective study evaluated the impact of concomitant diuretic administration on CINV in 485 patients receiving weekly, cisplatin-based CCRT between 2016 and 2024, including 206 who received mannitol and 279 who received furosemide.

Results: Vomiting occurred more frequently in the mannitol group than in the furosemide group (18.4% vs. 10.4%). Time-to-event analysis found that vomiting occurred earlier with mannitol during the entire CCRT course.

Conclusion: These findings may reflect mannitol's osmotic properties and the increased, intestinal permeability associated with CCRT-related mucosal injury. To the best of our knowledge, this study is the largest investigation to date comparing diuretic agents in this setting. The results suggested that furosemide may be a more appropriate option for patients with a high risk of CINV.

Background/aim: 3D culture models have become essential in cancer research, as they reflect tumor biology more accurately and predict in vivo responses more reliably. Numerous studies have proven that cells cultured in 3D systems exhibit greater resistance to anticancer agents than those grown in 2D monolayers. In this study, the anticancer activity and underlying mechanisms of salicylaldehyde benzoylhydrazone (SBH) were investigated in A549 lung cancer cells cultured under 2D and 3D spheroid (SP) conditions.

Materials and methods: Cell viability was assessed using the MTT and ATPlite 3D assays. Apoptosis and cell cycle distribution were analyzed with a Muse Cell Analyzer. Mitochondrial membrane potential and the activities of caspase-9 and caspase-3/7 were determined using the JC-10 assay kit, Caspase-Glo^® 9, and Caspase-Glo^® 3/7 assays, respectively. Cell migration and invasion were examined by Transwell assays. Effects on cell survival, motility, cell cycle regulators, and apoptotic signaling were elucidated by immunoblotting. Molecular docking and molecular dynamics simulations were conducted to model and evaluate the interactions of SBH with JAK2, STAT3, and FAK.

Results: Dissociated SP-culture cells displayed increased responsiveness to SBH treatment compared with corresponding 2D cultures. SBH primarily exerted cytostatic effects in both 2D and SP cells and reduced their migratory and invasive capabilities. Mechanistic analyses revealed that SBH treatment significantly decreased the phosphorylation levels of key oncogenic kinases, including JAK2, STAT3, and FAK. Molecular docking analysis and molecular dynamics simulations further supported these findings by confirming the interactions of SBH with JAK2 and FAK.

Conclusion: SBH may mediate the cytostatic and anti-metastatic effects by targeting the JAK2/STAT3 and FAK/MYLK signaling axes.