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Conditioning regimens prior to hematopoietic stem cell transplantation (HSCT) are highly intensive and associated with significant toxicity, which can influence survival and quality of life. This study aimed to analyze the incidence of gastrointestinal, hematological toxicity, changes in quality of life, and cognitive functions in lymphoma patients undergoing autologous HSCT with BEAM/BeEAM conditioning. A total of 27 lymphoma patients indicated for autologous HSCT were enrolled in this prospective observational study from January 2020 to August 2023. Data collection was performed at admission and at the end of hospitalization, prior to discharge. Monitored parameters included laboratory tests (hematology and biochemistry), patient-reported quality of life assessed using the QLQ-C30 questionnaire, and perceived cognitive function evaluated using the FACT-Cog questionnaire. Mucositis of any grade occurred in 25 patients (92.6%), with diarrhea being the most common gastrointestinal symptom (any grade 85.2%, grade 3-4 37.0%). Diarrhea severity was generally independent of age, baseline blood counts, engraftment, weight loss, or hospitalization, except for an association between severe diarrhea and lower pre-transplant TSH (p=0.03). All patients experienced grade 1-2 weight loss, and 81.5% developed febrile neutropenia. Quality of life declined during transplantation, notably in role functioning, social functioning, and cognitive performance, alongside worsening fatigue, nausea/vomiting, pain, appetite loss, and diarrhea (all p-values <0.05). FACT-Cog scores showed no significant cognitive decline. The 2-year overall survival was 92.1% (95% CI 81.6-100%), while patients with SII >520.81 had lower survival (82.5%, 95% CI 60.4-100%, p=0.04), with higher SII significantly associated with worse outcomes. Autologous transplantation and the BEAM/BeEAM conditioning regimen are associated with considerable mucosal and hematologic toxicity. Patients are at risk of infections, nutritional deficits due to reduced intake, and deterioration in quality of life.

Lung cancer, a leading cause of death, is challenging to treat due to gemcitabine resistance. Dysregulated autophagy is associated with chemoresistance. Here, we aimed to study the mechanism of how HERC1 modulates autophagy and gemcitabine sensitivity in lung cancer. Paired tumor and adjacent normal tissues were collected from 30 patients with lung cancer. The viability, proliferation, apoptosis, migratory, and invasive capacity of gemcitabine-resistant A549 and H1299 cells (A549/R and H1299/R) were evaluated using Cell Counting Kit-8 (CCK-8), EdU staining, flow cytometry, wound healing, and Transwell assays, respectively. The interactions among HECT and RLD domain-containing E3 ubiquitin protein ligase family member 1 (HERC1)-lysine acetyltransferase 2A (KAT2A)-phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were verified by co-immunoprecipitation. A mouse xenograft tumor model was established. Ki-67 expression was determined by immunohistochemistry. Our data showed that HERC1 expression was downregulated in gemcitabine-resistant tumor tissues and A549/R cells, correlating with poor prognosis. Overexpressing HERC1 suppressed proliferation and migration, enhanced apoptosis in A549/R or H1299/R cells, and simultaneously inhibited autophagy. Mechanistically, HERC1 promoted KAT2A ubiquitination and degradation, which enhanced gemcitabine sensitivity by inhibiting autophagy. Further investigation revealed that KAT2A depletion inhibited the lysine acetylation modification of PIK3CB, leading to inactivation of the PI3K/AKT axis. Additionally, HERC1 suppressed autophagy and gemcitabine resistance in A549/R cells by KAT2A-dependent inactivation of the PI3K/AKT axis. Furthermore, HERC1 overexpression enhanced the inhibition of gemcitabine on tumor growth by suppressing autophagy in vivo. In conclusion, HERC1 inhibited autophagy by inactivating PIK3CB-mediated PI3K/AKT signaling via promoting KAT2A degradation, thereby enhancing the gemcitabine sensitivity in lung cancer.

Osthole (OST) is a natural component of the traditional Chinese medicinal herb, Cnidium monnieri, that exhibits antipruritic properties and may exert effects on dermatitis. Numerous previous studies have focused on the effects of OST in tumors; however, the potential impact on cutaneous squamous cell carcinoma (CSCC) remains to be fully elucidated. Thus, the present study aimed to evaluate CSCC cell proliferation following treatment with OST, and further analyzed the underlying mechanisms using multi-omics analyses. Due to their cancerous characteristics, both A431 and SCL-1 cells are used in drug screening and testing for CSCC, particularly for therapies targeting growth pathways and markers associated with SCC. Results of the flow cytometry analysis demonstrated that OST impacted the CSCC cell cycle, causing arrest in the G2 phase. Notably, OST exerted a slight growth-promoting effect on healthy skin HaCaT cells. In addition, our omics results revealed that there were 1,720 differentially expressed genes and 227 differentially expressed proteins in the OST-treated group. Transcriptomics combined with proteomics analyses revealed that 5 of the top 20 screened pathways were associated with the cell cycle, and ATR, CENPJ, and RAD54B were highlighted as specific targets for OST-mediated regulation. Collectively, these results suggested that OST has a potential inhibition on human CSCC cells, and ATR, CENPJ, and RAD54B may be the key factors regulated by OST in A431's cell cycle progression inhibition.

Hepatic arterial infusion chemotherapy using a combination of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) has shown promise for patients with advanced-stage hepatocellular carcinoma (HCC). In this study, we aim to evaluate the efficacy and safety of combining adebrelimab (anti-PD-L1 antibody) and bevacizumab with HAIC-FOLFOX for HCC patients in BCLC stage C. This retrospective study included 32 untreated advanced-stage HCC patients receiving HAIC-FOLFOX combined with adebrelimab and bevacizumab as first-line therapy. The primary endpoint is overall response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. From January 14th, 2024, to December 5th, 2024, a total of 32 patients received the triplet combination of HAIC-FOLFOX, adebrelimab, and bevacizumab. Median follow-up time was 6.1 months. According to RECIST v1.1 criteria, the confirmed ORR was 71.8% (95% CI: 55.4-88.3 %), with a disease control rate (DCR) of 93.7% (95% CI: 84.9-99.9%). Only one case (3.1%) had a grade 3 treatment-related adverse event (rash), which could be alleviated after symptomatic management. The combination of adebrelimab, bevacizumab, and HAIC-FOLFOX demonstrated encouraging results and manageable safety concerns for patients with HCC at BCLC stage C.

Radiotherapy (RT) plays a central role in the management of glioblastoma, often in combination with other treatment modalities. While RT can enhance both local and systemic tumor control, especially when used alongside immunotherapy, it is also associated with lymphopenia - a reduction in lymphocyte count - which has been linked to poorer treatment outcomes and reduced survival. This retrospective study aimed to examine the relationship between radiation dose delivered to brain vessels and the severity of lymphopenia in patients with newly diagnosed glioblastoma treated at a tertiary cancer center in 2021. Brain vessels were manually contoured using MRI data, and dose-volume analysis was conducted. Lymphopenia severity was graded according to CTCAE v5.0, and statistical analyses were performed to identify any correlations. Among the 28 patients analyzed, 32% developed grade 1-3 lymphopenia. No significant correlation was found between the radiation dose to brain vessels and the degree of lymphopenia. The median volume of irradiated vessels did not differ significantly between patients with and without lymphopenia. In glioblastoma patients, multiple factors contribute to decreased lymphocyte count - e.g., chemotherapy and corticosteroid use. Although no definitive link was identified, the study underscores the importance of preserving lymphocyte counts during glioblastoma treatment and supports the need for further prospective research to explore strategies like lymphocyte-sparing RT and to better understand the mechanisms behind treatment-related lymphopenia.

WD Repeat Domain 4 (WDR4) is integral to the development and progression of various cancers; however, its specific role and underlying molecular mechanisms in glioma remain inadequately elucidated. This study undertook an analysis of WDR4 expression levels in glioma and normal brain tissues utilizing publicly accessible datasets from TCGA and GTEx project, with further validation conducted through the GEPIA and the HPA databases. Prognostic significance was assessed using Kaplan-Meier survival analysis and multivariate Cox regression models. Cellular functions were investigated through CCK-8 viability assays, colony formation assays, and cell cycle analysis, while the tumorigenic potential in vivo was corroborated using a nude mouse xenograft model. The findings revealed a significant upregulation of WDR4 in both glioma tissues and cell lines. Elevated WDR4 expression correlated with reduced overall survival and emerged as an independent prognostic factor. Functional assays indicated that WDR4 silencing markedly inhibited glioma cell proliferation, induced G1 phase cell cycle arrest, and resulted in the downregulation of CDK1 and CDK2 protein expression. Further co-expression analysis, GSEA, KEGG pathway enrichment, and western blotting suggested that WDR4 may exert its oncogenic effects through activation of the PI3K/Akt signaling pathway. In conclusion, WDR4 is highly expressed in glioma and promotes tumor progression via the PI3K/Akt-CDK1/2 signaling axis. These findings indicate that WDR4 may serve as a potential prognostic biomarker and therapeutic target in glioma.

Accumulating evidence highlights the critical roles of autophagy-dependent ferroptosis mediators in colorectal cancer (CRC) pathogenesis. To elucidate SIRT6's tumor-suppressive role, HT29 cells stably overexpressing SIRT6 (Oe-SIRT6) were generated via plasmid transfection. Functional assays were performed to evaluate autophagy and ferroptosis. Rescue experiments using the autophagy inhibitor 3-MA or the mTOR agonist MHY1485 were conducted. Quantitative analyses revealed marked downregulation of SIRT6 expression in CRC cell lines (SW620, SW480, and HT29) compared to normal colon epithelial cells. SIRT6 overexpression induced autophagy and activated ferroptosis. The autophagy inhibitor 3-MA blocked SIRT6-driven ferroptosis, which confirmed its dependency on autophagy. Moreover, SIRT6 was found to inactivate mTOR/STAT3 signaling, whereas the mTOR agonist MHY1485 reversed SIRT6 overexpression on autophagy-dependent ferroptosis of CRC cells. Our findings establish SIRT6 as a dual-phase regulator of CRC cell death, suppressing mTOR/STAT3 signaling to orchestrate autophagy-dependent ferroptosis.

Salinomycin (Sal), an ionophore antibiotic, has shown promising anti-cancer activity in multiple cancers. In this study, we aimed to investigate the effect of Sal on the ROS/NF-κB/NLRP3 pathway in cholangiocarcinoma (CCA) in vitro and in vivo. We observed that Sal inhibited cell proliferation, migration, and invasion. Sal promoted an increase of Annexin-V positive cells in Huh-28 and RBE cells in a dose-dependent manner, which was efficiently inhibited by VX-765 (Caspase-1 inhibitor), while Sal-induced increase of ROS levels was partially inhibited by exposure to N-acetyl-L-cysteine (ROS scavenger). Moreover, Sal inhibited tumor growth in RBE tumor-bearing mice. The activation of Sal on the ROS/NF-κB/NLRP3 pathway was also identified in CCA cells and tumor tissues. Collectively, these results suggested that Sal activated the ROS/NF-κB/NLRP3 pathway to promote pyroptosis-induced cell death in CCA and suggest it may be a promising treatment strategy for anti-CCA.

In this study, we investigated the development and application of patient-derived xenograft (PDX) models for metastatic breast carcinoma. Orthotopic PDX models were established from tumor tissue of invasive ductal breast carcinoma patients without prior neoadjuvant therapy. Following successful tumor engraftment in immunodeficient NOD SCID gamma (NSG) mice, primary tumors were surgically excised using a procedure simulating radical mastectomy, enabling extended post-operative survival for the development of eventual metastases. Tumor growth, the presence of lung metastases, along with their histopathological features and immunohistochemical profiles, were evaluated. Three stable and transplantable PDX models were successfully established. Spontaneous lung metastases developed in one model following surgical resection, and this metastatic capability was preserved across multiple in vivo passages. Despite the successful engraftment, significant discrepancies were observed between the immunohistochemical characteristics of the original patient tumors and their corresponding PDXs, particularly in hormone receptor status and Ki-67 proliferation marker expression. These findings highlight the challenges of maintaining molecular fidelity in traditional PDX models.

This corrects the article DOI:10.4149/neo_2025_250411N162.