Objective: Assessing the therapeutic efficacy of methotrexate (MTX) -modified magnetic nanoparticles in thermo-chemotherapy for rat breast cancer and its impact on immune function.
Methods: Female Wistar rats were subcutaneously inoculated with breast cancer Walker-256 cells to establish a transplantation tumor model, and injected with polyethyleneimine (PEI)-modified Fe3O4 magnetic nanoparticles (47T group, 42T group and multiple 42T group) or MTX-modified Fe3O4 magnetic nanoparticles (47TC group, 42TC group and multiple 42TC group) for thermotherapy under the magnetic field at different temperatures (47 ℃ and 42 ℃). The rats injected with MTX-modified magnetic fluid only (MFC group) and the tumor-bearing rats without any treatment (blank control group), with irradiation treatment in an alternating magnetic field only for 30 minutes (M group), with injection of PEI-modified magnetic fluid only (MF group), with treatment of MTX-mono drug (MTX group) and not inoculated with tumor cells (normal group) were used as control groups. X-ray radiography was used to display the distribution of magnetic fluid in the tumor tissue 24 hours, 2 weeks and 2 months after intra-tumor injection. After 24 hours of treatment, three rats were selected from each of the 47T and 47TC groups, and the effect of magnetic fluid on tumor cells was observed under an electron microscope after execution. After 14 days of treatment, the tumor volume of rats was measured and statistically analyzed. At the same time, 4 rats were selected from each of the 47TC, 47T, 42TC, 42T, MFC, MTX, blank control and normal groups, and the levels of IL-2, IFN-γ and IL-4 in peripheral blood were detected by ELISA method. The remaining rats were observed for long-term survival.
Results: The magnetic nanoparticles were evenly distributed in the center of the tumor but unevenly distributed at the tumor’s edge; they primarily localize amomg tumor cells and can penertrate into tumor cells. Tumor growth was inhibited in rats in the 47TC, 47T, multiple 42TC and multiple 42T groups (all P<0.05), and the survival rates of the rats were high. As compared with the blank control group, the levels of IL-2 and IFN-γ were increased while the IL-4 level was decreased in the 47TC and 47T groups (all P<0.05).
Conclusion: Thermo-chemotherapy at 47 ℃ for 30 minutes and multiple sessions at 42 ℃ for 60 minutes can partially inhibit tumor growth and prolong rat survival. This effect maybe related to the thermo-chemotherapy at 47 ℃ for 30 minutes which can activate the body’s immune function.
Objective: To explore the effect of C1q like protein 4 (C1ql4) on migration and invasion of breast cancer and its mechanism.
Methods: Real-time fluorescence quantitative PCR was used to detect the expression level of C1ql4 mRNA in tumor tissues and paracancerous tissues from 50 cases of breast cancer, as well as the breast cells including T549 and MCF-7 breast cancer cells, and MCF-10A normal breast cells. The siRNA targeting C1ql4 gene (siC1ql4) was synthesized and transfected into BT549 breast cancer cells by liposome transfection, and the silencing efficiency was detected by Western blotting. MTT assay was used to detect the proliferative ability of the cells in each group, the invasive ability of the cells was detected by Transwell assay, and the migratory ability of the cells was detected by scratch healing assay. Western blotting was used to detect the proliferative ability of the cells in each group. The expression levels of Snail, Slug, nuclear factor-κB (NF-κB) and phospho-NF-κB (p-NF-κB) were detected. The immunofluorescence was used to localize the distribution of NF-κB. Real-time fluorescence PCR was used to detect the mRNA expression levels of the NF-κB target genes TNF-α and IL-1β.
Results: The expression level of C1ql4 mRNA in breast cancer tissues was significantly higher than that in paracancerous tissues, and the expression level of C1ql4 mRNA in BT549 and MCF-7 breast cancer cells was significantly higher than that in MCF-10A normal breast cells (P<0.05). After silencing C1ql4 expression, the proliferation, invasion and migration abilities of BT549 cells were significantly decreased (all P<0.001); the mRNA and prorein expression levels of Snail and Slug were significantly down-regulated (both P<0.001), and the mRNA expression levels of TNFα and IL-1β were significantly reduced (both P<0.001). The amount of NF-κB entering the nucleus was reduced, and the ratio of p-NF-κB to NF-κB was reduced (both P<0.05).
Conclusion: The C1ql4 gene may regulate migration and invasion of breast cancer cells and promote breast cancer progression through the NF-κB pathway.
Objective: To Evaluate the potential causal relationship between the levels of 179 lipids in peripheral blood and the risk of different subtypes of lung cancer by Mendelian randomization analysis.
Methods: A two-sample Mendelian randomization analysis was performed using data from the Genome-Wide Association Study (GWAS), and sensitivity analysis was performed to verify the reliability of the results. Single nucleotide polymorphisms (SNPs) were used as instrumental variables, and GWAS data for different subtypes of lung cancer were used as outcome variables. We analyze potential causal associations between the levels of 179 lipids and the risk of different subtypes of lung cancer.
Results: The causal relationship between phosphatidylcholine and lung adenocarcinoma was established as a protective factor, and Sphingomyelin and Triacylglycerol have been identified as being linked to lung adenocarcinoma and function as risk factors. Phosphatidylcholine were found to have a causal association with lung squamous cell carcinoma serving as a protective factor, and Phosphatidylethanolamine and Sphingomyelin were identified as risk factors for lung squamous cell carcinoma. However, the effects of different subtypes of Phosphatidylcholine on lung adenocarcinoma and lung squamous cell carcinoma were different. The study did not find evidence that lipids can influence small cell lung carcinoma.
Conclusion: This study provides evidence of a causal relationship between lipids level features and different subtypes of lung cancer.
Objective: To evaluate the efficacy of almonertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), as a first-line treatment for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) in the real-world clinical practise, and to systematically analyze the independent risk factors influencing their prognosis.
Methods: This retrospective cohort study enrolled 73 patients with EGFR-mutated advanced NSCLC who received first-line treatment with aumolertinib from April 1, 2020 to December 31, 2021. Survival curves were generated by using the Kaplan-Meier method, and intergroup comparisons were performed via log-rank test. Univariate and multivariate analyses of prognostic factors were conducted by using the COX proportional hazards regression model, with a focus on identifying prognostic factors in the subgroup of baseline brain metastases.
Results: Among 73 patients, the median progression-free survival (mPFS) was 19.4 months, and the disease control rate (DCR) was 93.2%. Multivariate COX regression analysis revealed that central nervous system (CNS) metastasis status, EGFR mutation subtype, ECOG performance status (PS) score, and gender might be independent risk factors for PFS. Among 33 patients with baseline brain metastases, combined almonertinib with radiotherapy or bevacizumab, maximum diameter of brain metastases(≥3 cm), and ECOG PS score might be independent risk factors of PFS.
Conclusion: This first real-world study confirms that aumolertinib demonstrates favorable efficacy as first-line treatment for EGFR-mutated locally advanced or metastatic NSCLC patients, aligning with findings from phase Ⅲ clinical trials. For patients in subgroup of baseline brain metastases, combining almonertinib with radiotherapy or bevacizumab is recommended to optimize outcomes.
Objective: To compare the efficacy differences between the combination therapy of Callicarpa nudiflora and dexamethasone versus dexamethasone monotherapy via retention enema in the treatment of acute radiation proctitis.
Methods: A total of 100 patients with pelvic malignancies who developed acute radiation proctitis during radiotherapy at Jiangxi Provincial People's Hospital from November 2021 to June 2023 were enrolled, and randomly divided into two groups: a control group (50 cases) vs a treatment group (50 cases). Based on the acute radiation injury scoring criteria established by the Radiation Therapy Oncology Group (RTOG), patients with injury severity scores ≤1 were excluded. Subsequently, the remaining patients received the following interventions: the control group (45 cases) underwent single-agent dexamethasone retention enema, while the treatment group (47 cases) received a combined regimen of Callicarpa nudiflora combined with dexamethasone retention enema. Clinical symptoms, defecation frequency, and routine fecal parameters (leukocyte and erythrocyte counts) were recorded before and at 2 weeks of retention enema, to compare the efficacy differences between the two regimens.
Results: A statistically significant difference in therapeutic efficacy was observed between the treatment and control groups (χ2 =11.37, P=0.003, P<0.05), with the regimen of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment group demonstrating a markedly higher efficacy rate compared to the regimen of single-agent dexamethasone retention enema in the control group (82.2% vs 62.2%).
Conclusion: Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis, can significantly alleviates clinical symptoms and improves life quality of patients with acute radiation proctitis. This approach provides novel insights for optimizing clinical treatment strategies for acute radiation proctitis.
Cervical esophageal cancer (CEC) is a relatively rare pathological subtype of esophageal cancer, accounting for 2%~10% of all esophageal cancer cases, 95% of which are esophageal squamous cell carcinoma. Due to nonspecific clinical symptoms, most CEC patients are diagnosed at advanced or locally advanced stages, resulting in a 5-year overall survival (OS) rate of approximately 30%. Although therapeutic outcomes for CEC patients remain suboptimal, current studies have demonstrated the clinical value of multiple treatment modalities, including endoscopic therapy, photodynamic therapy, selective or salvage surgery, radiotherapy, chemotherapy, concurrent chemoradiotherapy (CCRT), immunotherapy, and targeted therapy. This article systematically reviews recent advances in CEC management, focusing on the aforementioned approaches, and delves into the optimal treatment strategies, aiming to provide a scientific and reliable foundation for clinical practise.
Thyroid cancer is the most common malignant tumor in head and neck surgery. In recent years, the incidence rate of thyroid cancer has increased rapidly. The traditional treatment is mainly surgical resection, supplemented by 131I treatment, but for advanced or metastatic thyroid cancer, these methods have limited effect. With the deepening of research on the molecular pathogenesis of thyroid cancer, targeted therapy has become a new research hot spot and important treatment method. In recent years, targeted therapy drugs have emerged one after another, such as sorafenib, anlotinib, serpatinib, pratinib, etc., all of which have shown good efficacy and significantly improved the progression free survival and objective remission rate of patients. However, targeted therapy still faces many problems such as drug resistance, and further research and development of more effective new drugs are needed. This article summarized the research progress of targeted therapy, and aimed to provide reference for the treatment of advanced or iodine refractory thyroid cancer.
p21-activated kinase 5 (PAK5), a critical member of the PAK family, plays a significant regulatory role in cellular signaling transduction and cytoskeleton rearrangement. Accumulating researches have revealed that PAK5 is aberrantly expressed in various human malignancies, and its expression level is significantly correlated with tumor metastasis, invasiveness, and clinical prognosis of patients. At the molecular level, PAK5 promotes tumor cells migration and invasion by activating key signaling pathways (such as Wnt/β- catenin and MAPK) to induce epithelial-mesenchymal transition (EMT), modulating tumor-associated microRNA (miRNA) networks, and remodeling actin cytoskeleton to enhance cellular motility. This review systematically dissects the molecular structural features and phosphorylation-dependent activation mechanisms of PAK5, delves into molecular mechanisms of PAK5 in tumor cells migration and invasion, and evaluates the potential of PAK5 as a therapeutic target. This work aims to provide a new perspective for developing PAK5-targeted precision therapeutic strategies in malignant tumors.
Osteosarcoma is a primary bone tumor originating from mesenchymal tissues, highly aggressive and metastatic, and is one of the causes of orthopedic disorders in children and adolescents. The establishment of an osteosarcoma model is useful for studying the changes in the physiology and pathology of the organism after the occurrence of osteosarcoma. The establishment methods of osteosarcoma models not only differ in terms of difficulty, tumorigenicity, tumor-formation time, tumor survival time, tumor metastasis, and safety, but also in terms of simulating human osteosarcoma biological characteristics and histological features. In addition, the wide application of tissue engineering in tumor modeling is conducive to better study the role of the osteosarcoma microenvironment in osteosarcoma genesis and development. In this paper, we summarize the roles of different osteosarcoma animal models and their tissue engineering models in different experiments, in order to provide help for the study of osteosarcoma pathogenesis and drug intervention mechanism.
Gasdermin family proteins play critical roles in cell pyroptosis. Previous studies mainly focused on the function of Gasdermin D and Gasdermin E, less attention has been paid to Gasdermin C. Recently, accumulating studies revealed some distinctive characters of Gasdermin C different from other Gasdermin proteins and the impact of Gasdermin C on the prognosis of different types of tumor. This review summarized the recent study progresses in terms of molecular structure of Gasdermin C, the Gasdermin C mediated pyroptotic pathway as well as the prognostic significance of Gasdermin C in tumors, by which to provide informative references for corresponding researchers.
