Journal of Chemotherapy最新文献

Rosuvastatin (RSV) is widely used to treat hyperlipidemia and hypercholesterolemia and is recommended for the primary and secondary prevention of cardiovascular diseases (CVD). In this study, we aimed to explore its action and mechanism in lung adenocarcinoma (LUAD) therapy. Lewis and CMT64 cell-based murine subcutaneous LUAD models were employed to explore the effects of RSV monotherapy combined with cisplatin and gemcitabine. Human lung fibroblasts and human LUAD cell lines were used to assess the effects of RSV on normal and LUAD cells. Bioinformatics and RNA interference were used to observe the contribution of cyclin A2 (CCNA2) knockdown to RSV inhibition and to improve chemosensitivity in LUAD. RSV significantly suppressed grafted tumor growth in a murine subcutaneous LUAD model and exhibited synergistic anti-tumor activity with cisplatin and gemcitabine. In vitro and in vivo experiments demonstrated that RSV impaired the proliferation and migration of cancer cells while showing little inhibition of normal lung cells. RNA interference and CCK8 detection preliminarily indicated that RSV inhibited tumor growth and enhanced the chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2. RSV suppressed LUAD progression and enhanced chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2, which should be prior consideration for the treatment of LUAD, especially for patients co-diagnosed with hyperlipidemia and hypercholesterolemia.

Lung cancer is one of the most frequently diagnosed cancers worldwide, associated with a poor survival rate. Taxol (Paclitaxel) is commonly used as a chemotherapeutic treatment for advanced lung cancers. While Taxol has improved clinical outcomes for lung cancer patients, a significant number of them develop resistance to Taxol, resulting in treatment failure. The role of the long noncoding RNA HCG18 in lung cancer and Taxol resistance has not yet been fully understood. To investigate this, we examined the expression of HCG18 and miR-34a-5p in lung tumors and normal lung tissues using qRT-PCR. We also assessed Taxol resistance through cell viability and apoptosis assays. Through the starBase online service, we analyzed the interactions between lncRNA and mRNA as well as miRNA and mRNA. We further validated the association between lncRNA and miRNA through luciferase and RNA pull-down assays. Our findings demonstrated that HCG18 was significantly upregulated in lung cancer tissues compared to normal lung tissues. Silencing HCG18 increased the sensitivity of lung cancer cells to Taxol. Additionally, our study established a Taxol-resistant cell line and observed a substantial upregulation of HCG18 in Taxol-resistant lung cancer cells. Bioinformatic analysis predicted that HCG18 could bind to miR-34a-5p, forming a competing endogenous RNA network, which was confirmed through luciferase assay. We found that miR-34a-5p was downregulated in lung cancer tissues and negatively correlated with Taxol resistance, as it directly bound to the 3'UTR region of HDAC1. Further results showed that inhibition of HCG18 significantly increased miR-34a-5p expression and sensitized lung cancer cells to Taxol. This sensitization could be reversed by inhibiting miR-34a-5p. Finally, we demonstrated in a xenograft mouse model that inhibition of HCG18 sensitized Taxol-resistant lung cancer cells to Taxol treatment by modulating the miR-34a-5p-HDAC1 axis. In conclusion, our in vitro and in vivo results uncover a novel molecular mechanism by which HCG18 promotes Taxol resistance through modulation of the miR-34a-5p/HDAC1 axis. These findings contribute to the diagnosis and treatment of chemo-resistant lung cancer.

This study aimed to identify the potential factors associated with immune thyroid dysfunction caused by programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in cancer patients. We conducted a retrospective study of thyroid immune-related adverse events (irAEs) in cancer patients treated with PD-1/PD-L1 inhibitors at Tianjin First Central Hospital from January 2020 to March 2023. Thyroid irAEs were characterized as hypothyroidism, hyperthyroidism and thyrotoxicosis followed by hypothyroidism. A total of 175 patients were screened in the study, of whom 48 patients (27%) developed thyroid irAEs (including 24 hypothyroidism, 11 hyperthyroidism and 13 thyrotoxicosis followed by hypothyroidism) following PD-1/PD-L1 inhibitors treatment. Multivariate logistic regression analysis showed that combination therapy with PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (lenvatinib/regorafenib) and high baseline anti-TPO level were associated with the development of thyroid irAEs caused by PD-1/PD-L1 inhibitors. The nomogram models showed good discriminant ability and could bring net benefits for more patients according to the decision curve analysis. However, the model needs to be further validated in other large cohorts.

Dalbavancin is a relatively new long-acting anti-Gram positive antimicrobial approved for the treatment of acute bacterial skin and skin structures infections. An increasing number of observational studies and case series were published on its off-label uses. Great interest is emerging about complicated cases where antibiotic treatment cannot be discontinued, and a chronic suppressive therapy is needed. We described a case series of 6 patients treated or ongoing on treatment with dalbavancin as chronic suppressive therapy (CAST) administered with the following regimen: dalbavancin 1500 mg on day 1 and 8 and then every 4 weeks. CAST median duration was 27 weeks. Five out of 6 patients reached a good clinical control of the infection (one of them completely resolved) while in one case we observed a recurrence of the infection. No adverse events were detected. Larger studies are needed to better clarify dalbavancin off-label uses and the most appropriate dose regimen.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer represents the most prevalent subtype of breast cancer. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, in combination with endocrine therapy (ET), have shown substantial benefits in improving progression-free survival and, for ribociclib, an overall survival advantage. Despite clinical benefits, ribociclib is associated with elevated liver enzymes and severe liver dysfunction. We present a 44-year-old Caucasian woman with HR-positive, HER2-negative metastatic breast cancer who developed drug-induced autoimmune-like hepatitis (DI-ALH) after ribociclib therapy. Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Treatment was complicated by grade 3 hepatotoxicity, confirmed as DI-ALH by liver biopsy. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.

Managing locally advanced, or metastatic radioactive iodine-refractory differentiated thyroid cancers (RAIR-DTC) poses substantial challenges, with few available treatment options. The aim of this study was to evaluate clinical outcomes of patients receiving sorafenib as first line treatment. In addition, prognostic markers affecting progression-free survival (PFS) were identified. This retrospective, 6 centers study included 62 patients with locally advanced or RAIR-DTC treated 2008-2023. The median PFS was 16.5 months. The presence of liver metastases was strongly associated with a lower PFS (3.1 months (p < 0.001)). The use of sorafenib as initial treatment resulted longer PFS compared to chemotherapy, with a median of 25.5 vs 4.7 months respectively (p = 0.01). Increased neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with worse outcomes (p = 0.01; p = 0.009, respectively). In conclusion, sorafenib has demonstrated significant PFS benefits when used as first-line treatment. It has been shown that the presence of liver metastases and higher levels of NLR and PLR are associated with a more unfavorable prognosis.

The emergence of resistance to 5-Fluorouracil (5-FU) is a staple in breast cancer chemotherapy. This paper delves into the role of PTEN in breast cancer resistance to 5-FU and examines the underlying molecular pathways. PTEN expression was detected in bioinformatics databases and upstream transcription factors (TFs) were identified. PTEN mRNA and protein levels, aerobic glycolysis proteins, lactate production, glucose consumption, and cell viability were measured. Binding interactions were confirmed, and cell proliferation assessed. In breast cancer cells, PTEN expression was downregulated. PTEN overexpression counteracted 5-FU resistance through the suppression of aerobic glycolysis. KLF9, as a TF upstream of PTEN, enhanced the levels of PTEN. In conclusion, the TF KLF9 inhibits the aerobic glycolysis level of breast cancer cells by up-regulating PTEN expression, thereby reducing their resistance to 5-FU. The discovery of this mechanism provides a new theoretical basis for the treatment of breast cancer.

This study explores the relationship between m6A modification and ferroptosis in intrahepatic cholangiocarcinoma (ICC) and its impact on cisplatin resistance. We established cisplatin-resistant cells. CCK-8 and Transwell assays were conducted to evaluate the effects of METTL3 on drug resistance, migration, and invasion. RT-qPCR and Western blotting were used to measure target gene expression and the effects of overexpression and suppression. RIP, luciferase reporter assay, and other experiments were utilized to investigate the interaction between METTL3 and NRF2. Additionally, rescue experiments were performed to confirm the role of the METTL3/NRF2 axis in tumor drug resistance. METTL3 was found to be highly expressed in cisplatin-resistant cells, enhancing m6A modification levels, stabilizing NRF2 mRNA, and increasing NRF2 protein expression to inhibit ferroptosis. These findings indicate that the METTL3/NRF2 axis inhibits ferroptosis in cisplatin-resistant cells, thereby promoting chemotherapy resistance in ICC. This provides a potential direction for future research and treatment of ICC.

Glioma coined as 'butterfly tumor' exhibits intense heterogeneity at the molecular and cellular levels. Although, Temozolomide exerted a long-ranging and prevailing therapeutic effect against glioma, albeit it has provided modest survival outcome. Fucoidan, (marine brown algal derivative) has demonstrated potent anti-tumor effects including glioma. Nevertheless, there is paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. The present study aimed to explore the plausible synergistic anti-glioma efficacy of Fucoidan in combination with Temozolomide in an in vivo experimental model. The dual-drug combination significantly inhibited tumor growth in in vivo and prolonged the survival rate when compared with the other treatment and tumor-control groups, via down-regulation of inflammatory cascade- IL-6/T LR4 and JAK/STAT3 as per the immunohistochemistry findings. Furthermore, the ultrastructural analysis indicated that the combinatorial treatment had restored the normal neuronal architecture of glioma-induced rats. Overall, the dual-drug cocktail might enhance the therapeutic outcome in glioma patients.