Introduction: Pancreatic cancer is characterized by a poor prognosis and low survival rate, underscoring the urgent need for the development and optimization of novel therapeutic interventions. Morusin has been reported to have anticancer activity in a variety of cancers. Therefore, the present study aimed to elucidate the anticancer effects and potential mechanisms of Morusin in pancreatic cancer.
Methods: We evaluated the anticancer effect of Morusin in pancreatic cancer cells, including its impact on pancreatic cancer cell proliferation, colony formation potential, migration, invasion, cell cycle and apoptosis. RNA sequencing (RNA-seq) analysis was employed to identify potential genes involved in the anticancer activity of Morusin. Furthermore, RT-qPCR and Western blot analysis were utilized to verify the findings.
Results: Our results demonstrated that Morusin administration significantly impaired cell proliferation, migration and invasive activity of pancreatic cancer cells. Additionally, Morusin induced apoptosis and disrupted cell cycle progression. Importantly, Morusin was found to coregulate SLC6A12, HSPA2, P2RY6 and JPH2 in both cell lines by RNA-seq analysis, with the most significant decrease in mRNA levels of SLC6A12 following administration. Mechanistically, Morusin was found to regulate the expression of SLC6A12 and inhibit NF-κB and β- catenin signaling pathways, which may represent the underlying mechanisms of its antitumor activity.
Conclusion: Our findings suggest that Morusin holds potential as an anti-pancreatic cancer agent by targeting SLC6A12 and modulating its associated signaling pathways.
Background: Esophageal cancer is a common malignant tumor, making the search for effective treatments a critical research focus. L-methylselenocysteine (L-SeMC) has been reported to exert anticancer effects in various cancers; however, its role and underlying mechanisms in esophageal cancer remain unclear. This study aimed to investigate the anticancer effects of L-SeMC on esophageal cancer both in vitro and in vivo, and to explore its potential mechanisms of action.
Methods: For cellular studies, flow cytometry, colony formation assay, MTT assay, wound healing assay, and ROS measurement were employed. Western blotting was used to assess the expression levels of apoptotic proteins. A subcutaneous tumor xenograft model was established. The analysis included the evaluation of proteins related to the PI3K/AKT signaling pathway, TUNEL, and Ki-67 staining, as well as HE staining.
Results: L-SeMC caused cell death and, in a concentration-dependent manner, reduced the migration, invasion, and proliferation of esophageal cancer cells. Western blot analysis showed that L-SeMC was associated with a decrease in the anti-apoptotic protein Bcl-2 and an increase in the pro-apoptotic protein Bax. It also triggered the mitochondrial apoptosis pathway, promoting the activation of caspase-3 and subsequent cancer cell death induced by L-SeMC. In a dosedependent manner, L-SeMC decreased the phosphorylation of phosphatidylinositol 3-kinase (PI3K) downstream effector molecules. This suggests that L-SeMC inhibits the PI3K/AKT signaling pathway in esophageal cancer cells, contributing to its anticancer effects.
Conclusion: L-SeMC has a strong anticancer effect on human esophageal cancer cells and promotes apoptosis by inhibiting the PI3K/AKT signaling pathway, suggesting that L-SeMC may represent a novel strategy for the treatment of esophageal cancer.
Purpose: Metronomic chemotherapy (MC) represents a therapeutic approach characterized by the long-term administration of chemotherapeutic agents at relatively low doses, with minimal or no drug-free intervals (US20150283237, CN111110681A). This study aimed to evaluate the treatment characteristics, prognosis, and efficacy of S-1 MC as a compensatory strategy for nasopharyngeal carcinoma (NPC) patients who experienced radiotherapy interruption (RI) during the COVID-19 pandemic.
Methods: This study included NPC patients who experienced RI due to the COVID-19 pandemic. Patient characteristics, details of treatment after RI, compensatory treatment, and survival outcomes were analyzed.
Results: A total of 8 patients were identified, with a median RI duration of 19 days. All patients received an additional fraction of radiotherapy due to the interruption. Following RI, all patients completed the recommended radiotherapy regimen and underwent comprehensive locoregional and systemic assessment three months post-treatment. Complete remission of the nasopharyngeal tumor and cervical lymph nodes was achieved in 7 (87.5%) patients. These patients were administered oral tegafur, gimeracil, and oteracil potassium (S-1) MC. All patients completed one year of MC without experiencing grade 3-4 adverse reactions. With a median follow-up of 34.4 months, no instances of disease recurrence were observed. The 2-year disease-free survival and overall survival were both 100%.
Conclusion: MC may serve as an effective compensatory treatment strategy for NPC patients experiencing RI. These findings offer valuable insights for future clinical trials involving NPC patients with RI due to various reasons.
Background: Immunotherapy and targeted therapy have been shown to be notably effective in tumor treatment; however, the mechanism of PTEN function in tumorigenesis, development, and immune response of tumors remains unclear.
Methods: We show that PTEN expression varies significantly in many types of tumors and affects the prognosis of patients with cancer using pan-cancer analysis. Patents were reviewed using the World Intellectual Property Organisation database. We analyzed data from GTEx, CCLE, and TCGA to study the correlation between PTEN expression and prognosis, investigated the correlation between PTEN expression and tumor-infiltrating immune cells using TIMER, analyzed the mutation pattern of PTEN and its correlation with neoantigen expression, TMB, MSI, MMRs, and DNA methyltransferases in tumors, and conducted an enrichment analysis of PTEN in tumors using GSEA.
Results: PTEN expression is related to the levels of infiltrating immune cells, such as B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. PTEN expression is closely related to neoantigen expression, tumor mutational burden, microsatellite instability, and mismatch repair. The results of a functional enrichment analysis of PTEN showed that PTEN has the potential as a biomarker for precision immunotherapy of tumors.
Conclusion: This study suggests that PTEN may be involved in the recruitment and regulation of immune-infiltrating cells, tumor development, metastasis, prognosis, tumor immune escape, and immunotherapy, indicating its importance in tumor diagnosis and treatment.
Background: Multidrug resistance (MDR) in cancer is a major obstacle to achieving success in clinical chemotherapy. It has been observed that overexpression of ATP-Binding Cassette (ABC) transporters plays a crucial role in MDR.
Objective: This study aimed to find an effective resistance-reversed agent of ABC transporter. A series of new β-carboline derivatives have been synthesized and are being applied in various invention patents. One of these is B-9-8, a novel harman dimer, which was synthesized to conduct a series of experiments.
Methods: In this study, we investigated whether B-9-8 could reverse ABCG2-mediated drug resistance by using MTT assay, [3H]-mitoxantrone accumulation/efflux assay, western blot analysis, immunofluorescence analysis, ATPase assay, and molecular modeling assay.
Results: The results showed that B-9-8 could significantly increase the sensitivity of mitoxantrone, SN-38, and topotecan and effectively overcame drug resistance at non-toxic concentrations in ABCG2-overexpressing cells. Further studies showed that B-9-8 increased the intracellular accumulation of [3H]-mitoxantrone by suppressing the efflux function of ABCG2 in ABCG2-overexpressing cells. B-9-8 could down-regulate the ABCG2 protein expression but did not change the subcellular localization of ABCG2. ATPase analysis indicated that B-9-8 inhibited the ATPase activity of ABCG2 in a concentration-dependent manner. In the molecular docking analysis, B-9-8 demonstrated a strong interaction with the human ABCG2 transporter protein.
Conclusion: Our findings indicated that B-9-8 could reverse ABCG2-mediated MDR as a potential and reversible modulator in combination with conventional chemotherapeutic drugs.
Coumarins, a ubiquitous class of aromatic compounds present in a broad spectrum of organisms, including bacteria, fungi, and over 150 plant species, have been extensively studied over the years. Researchers have isolated and characterized more than 1,300 natural coumarins, many of which exhibit promising biomedical properties. Among these, daphnetin has emerged as a distinctive coumarin derivative that is characterized by its unique structural features to impart special physicochemical attributes. Daphnetin is renowned for its diverse range of biological activities, encompassing anticancer, anti-inflammatory, and antiallergic effects. These activities can be attributed to its ability to regulate specific molecular pathways within the body, making it a highly attractive compound for pharmacological research. Consequently, daphnetin has garnered considerable attention within the scientific community, specifically prompting an extensive investigation into its therapeutic potential across diverse clinical conditions. In this comprehensive review, we delved into the structure and sources of daphnetin, with a focus on its unique characteristics that underscore its potential as a therapeutic agent. We further explored the therapeutic potential of daphnetin, highlighting its multifaceted biological activities and the underlying molecular mechanisms. In addition, we scrutinized the potentially toxic effects of daphnetin in light of the current research status and prospects in this direction. By emphasizing the clinical significance of daphnetin, we aim to contribute to the ongoing endeavors toward the development of innovative and efficacious therapeutic strategies for an array of diseases.
Cancer drug resistance has emerged as a formidable challenge in the field of clinical oncology, significantly hampering the success of treatment strategies and leading to suboptimal outcomes for patients. In a broad array of therapeutic settings, the emergence of resistance has become a primary source of concern, ranging from conventional chemotherapy to modern immunotherapy and targeted therapies. The complexity of cancer drug resistance is further exacerbated by the involvement of oncoviruses, such as human papillomavirus (HPV), Epstein-Barr virus (EBV), and hepatitis B virus (HBV), which play pivotal roles in the initiation, progression, and response to treatment of various cancers. The intricate interactions between these oncoviruses and cancer cells have been found to significantly influence drug efficacy. These viruses can alter critical cellular pathways, including drug metabolism, DNA repair mechanisms, and the tumor microenvironment, thus promoting drug resistance. A profound understanding of these virus-cancer-drug interactions is crucial for the development of novel treatment approaches that can effectively overcome drug resistance. This review aimed to contribute to a broader awareness of the multifaceted nature of cancer drug resistance, particularly in the context of oncovirus involvement. By highlighting the critical role of oncoviruses in cancer development and treatment response, this review hopes to stimulate further research and the development of novel treatment strategies that can effectively overcome drug resistance and ultimately improve patient outcomes. As we advance toward precision oncology, a more holistic understanding of the complex interplay among cancer, its associated viruses, and therapeutic drugs is crucial for achieving optimal therapeutic responses.
Background: Diffuse Gastric Cancer (DGC) is a highly aggressive form of gastric cancer with a poor prognosis. Oxaliplatin (OX) is one of the first-line chemotherapeutic agents for the treatment of gastric cancer. However, some patients with DGC do not benefit from OX therapy. Resibufogenin (RBF), one of the main active components of the Chinese medicine Huachansu, has demonstrated significant anti-cancer effects. Nevertheless, the potential of RBF to enhance the sensitivity of OX treatment in DGC and its underlying mechanisms have not been reported.
Objective: The aim of this study is to investigate the sensitizing effect of RBF on OX therapy for DGC, as well as to elucidate the potential targets and mechanisms of action. This exploration is of significant importance for the development of sensitizers that can improve the therapeutic efficacy of OX and for the advancement of patentable innovations in this field.
Methods: MTT assay, flow cytometry, Western blotting, and immunofluorescence assays were employed to assess the inhibitory effects of Resibufogenin (RBF) in combination with OX on DGC in vitro. Human DGC cell xenografts were established in a mouse model to evaluate the efficacy and safety of RBF and OX for treating DGC in vivo.
Results: It was found that RBF inhibited the proliferation of DGC cells in a time- and dose-dependent manner. When RBF was used in combination with OX, the sensitivity of DGC cells to OX was improved. Significantly, the combination of OX and RBF acts synergistically to induce apoptosis and autophagy while inhibiting migration and invasion of DGC cells in vitro. In vivo, the combination of OX and RBF dramatically inhibited the progression of DGC in the subcutaneous xenograft model without observable toxicity. Mechanistically, RBF significantly inhibited the expression and activation of FAK. OX and RBF synergistically inhibited the phosphorylation of FAK, AKT, and GSK3β to abrogate the entry of β-catenin into the cell nucleus.
Conclusion: RBF exhibits a pronounced suppressive effect on FAK, and its combination with OX synergistically blocks the FAK/AKT/GSK3β/β-catenin signaling cascade, thereby inhibiting the growth and metastasis of DGC. This study provides a novel avenue for future research and patent development of FAK inhibitors, with the potential to enhance the therapeutic efficacy of DGC treatment and overcome drug resistance.
Introduction: Acute myeloid leukemia is characterized by high heterogeneity, and the current European Leukemia Net (ELN) risk stratification system is not universally applicable to all AML patients, requiring approximately three weeks for testing.
Aim: This study aimed to develop an applicable prognostic tool capable of addressing the limitations of current methods. We selected AML patients from the clinic and TCGA database to explore the role of ER stress in response to chemotherapy.
Methods: Patients from the TCGA database were employed as the training cohort, and two GEO datasets were used as external validation cohorts. Univariate/multivariate COX and LASSO regression were exemplified to establish the prognostic model. Kaplan-Meier and timedependent ROC were used to assess and compare the efficiency of the model with ELN stratification and other models. In the training cohort, we selected 5 ER stress-related genes to predict chemosensitivity and establish the ERS-5 prognostic model.
Results: The model successfully predicted the overall survival of patients (p < 0.0001, HR = 4.86 (2.79-8.44); AUC = 0.83). It was verified in validation cohorts and could further stratify the risk of various AML subgroups. It also enhanced the ability of ELN to predict the response of patients with AML to main chemotherapeutic drugs. Finally, an "ERS-5" risk score was constructed by the nomogram based on the ERS-5 model and age.
Conclusion: Consequently, in this study, the ERS-5 model was constructed, which allowed more rapid (about 3 hours) and accurate risk stratification and complemented the ability of ELN to assess chemosensitivity.
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