[This retracts the article DOI: 10.3892/etm.2017.4393.].

As a vital form of post-transcriptional modification, RNA N6-methyladenosine methylation (m6A) dysregulation is usually associated with the pathogenesis of a range of diseases, including cancer, but the function and underlying mechanisms of m6A in regulating gastric cancer initiation and progression are still poorly understood. Here, we have found methytransferase like 3 (METTL3) and the level of RNA m6A modification were significantly upregulated in gastric cancerous tissues relative to their normal counterparts. In addition, higher METTL3 expression always predicted poorer outcomes for patients with gastric cancer. Methylated RNA sequencing revealed that METTL3 deposited m6A modification on FNTA (farnesyltransferase, subunit alpha) mRNA and accelerated its translation relying on YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) recognition. When METTL3 or FNTA expression was silenced in gastric cancer cells, the FNTA-mediated KRAS plasma membrane distribution was disrupted, resulting in downstream MEK/ERK signaling inactivation, which finally contributed to gastric cancer suppression in vitro and in vivo. In summary, our studies revealed a crosstalk between METTL3-mediated RNA methylation and FNTA-mediated protein modification which synergized to drive gastric cancer progression through orchestrating KRAS/ERK signaling activity. Implications: Targeting METTL3/FNTA pathway will provide an alternative to overcome the resistance of gastric cancer to canonical KRAS inhibitors.

HER2 exon 20 insertions exhibit relative resistance to chemotherapy and covalent HER2-targeted tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Furthermore, specific missense mutations in the extracellular domain of the HER2 protein have been identified as oncogenic drivers in NSCLC. However, their structural properties and clinical response to HER2-targeted inhibitors remain poorly understood, warranting further investigation. R456C represents a rare exon 12 missense mutation in the HER2 extracellular domain, with limited documentation in NSCLC. This study presents an atypical case of NSCLC with a HER2 R456C mutation, where the patient experienced a favorable response and substantial survival benefit from the HER2-targeted inhibitor pyrotinib. A patient, a 65-year-old man diagnosed with stage IIIB lung adenocarcinoma, initially underwent radical concurrent chemoradiotherapy. Upon disease recurrence, polymerase chain reaction assay detected no oncogenic alterations, and programmed cell death ligand 1 (PD-L1) expression was negative. Chemotherapy in combination with bevacizumab resulted in stable disease, providing a progression-free survival (PFS) benefit of 6 months. However, anlotinib proved ineffective against brain metastasis, necessitating brain radiotherapy. A subsequent lung biopsy confirmed adenocarcinoma and next-generation sequencing identified a somatic HER2 exon 12 missense mutation, p.R456C. Following pyrotinib administration, the patient's pulmonary metastases significantly diminished, and the brain metastasis regressed, resulting in a partial response and a PFS benefit of 13 months. To the best of our knowledge, this study represents the first reported case demonstrating the promising efficacy of pyrotinib in HER2-altered NSCLC harboring the ra-re exon 12 R456C mutation. Heterogeneous alterations in the HER2 extracellular segment, such as R456C, may be targetable and could confer survival benefits with HER2-targeted inhibitors.

The use of radiotherapy sensitizers has proven to be effective in overcoming tumor radiotherapy resistance and improving treatment efficacy. However, challenges such as poor biocompatibility and difficulty in accurately guiding tumor radiotherapy with high efficiency still persist. Herein, we propose a radiosensitizer with Janus nanostructure to address these issues by enabling dual-modal fluorescence (FL)/photoacoustic (PA) imaging in the second near-infrared region (NIR-II, 900-1700 nm) for precise and efficient tumor radiotherapy guidance. The Janus nanoprobes are fabricated by initially coating silica (SiO2) on one end of gold nanorod (AuNR) with a high aspect ratio, followed by in situ decoration of a lanthanide-doped down-conversion nanoparticle (DCNP) shell on SiO2, and finally modifying it with biocompatible polyethylene glycol (PEG), named as AuNR@DCNP@PEG. Guided by NIR-II FL/PA imaging, AuNR@DCNP@PEG was successfully irradiated at the optimal tumor enrichment time point, generating a significant amount of reactive oxygen species and exhibiting excellent sensitization effects in vitro and in vivo. This dual-modal NIR-II FL/PA imaging-guided radiotherapy sensitizer is anticipated to offer an approach for overcoming radiotherapy resistance and achieving precise and efficient radiotherapy.

The novel HLA-DPB1*1758:01 allele differs from HLA-DPB1*1273:01 by one nucleotide substitution in Exon 4.

Background: To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex® in Chinese patients with premenopausal breast cancer. Methods: From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex® every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results: A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex®. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex®. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex® group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion: LY01005 is as effective as Zoladex® in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

BackgroundFinancial Toxicity (FT) is prevalent among lung cancer patients. Identifying high-risk groups and implementing comprehensive, targeted interventions can alleviate FT and improve patients’ quality of life. Hence, the objective of this study was to analyze the status and potential profiles of FT in lung cancer patients and explore the related factors of FT levels in different categories of lung cancer patients.MethodsA cross-sectional design was used in this study. A total of 421 patients with lung cancer hospitalized in the oncology department of a Grade A general hospital and a provincial oncology hospital in Shandong Province from October to December 2023 were selected by convenience sampling. General data questionnaires, FT scale for reported outcomes of cancer patients, Chinese version of the Quality of Life Scale for lung cancer patients, Social Support Rating Scale and simplified version of the Mental Resilience Scale were used. Potential profile analysis of FT levels in lung cancer patients was performed, and multiple logistic regression was used to analyze the related factors of FT levels in different categories.ResultsAmong 421 lung cancer patients, the median FT (FT) score was 16 (IQR: 9–24). Latent profile analysis identified four distinct FT patterns: mild (19.5%), moderate resource-deficient (7.8%), moderate balanced (35.6%), and severe (37.1%). Multivariate analysis revealed significant associations between FT severity and hospitalization frequency, lifestyle modifications, employment status, insurance coverage, education level, social support, emotional distress, family resilience, problem-solving capacity, and social resource utilization.ConclusionFT demonstrates high prevalence and substantial heterogeneity in lung cancer patients, with over 70% experiencing moderate-to-severe levels. Clinical interventions should prioritize early screening and stratified management through psychological support, financial navigation programs, cost-containment strategies, and enhanced health literacy to alleviate economic burdens and optimize treatment outcomes.