Introduction: Transformed follicular lymphoma (tFL) presents a formidable challenge in clinical oncology due to its high tumor mutational burden and therapeutic resistance. While anlotinib has demonstrated efficacy in solid tumors, its potential in tFL remains largely unexplored. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of anlotinib in tFL, shedding light on its apoptotic impacts and molecular pathways.Study Design:
The research employed a comprehensive approach, encompassing both in vitro and in vivo evaluations. In vitro assessments involved exposing tFL cells to varying concentrations of anlotinib, measuring cell viability via the CCK-8 method, and evaluating apoptosis levels using Annexin V/PI staining kits. In vivo tumorigenicity tests utilized mouse xenograft models implanted with tFL cells and treated with anlotinib to observe its therapeutic effects firsthand. Molecular probing techniques, including western blotting and immunohistochemistry staining, were employed for protein expression analysis and visualizing cellular repercussions of anlotinib treatments.
Methods:
The methods employed in this study encompassed both in vitro and in vivo approaches to evaluate the therapeutic efficacy and underlying mechanisms of anlotinib in transformed follicular lymphoma (tFL). In vitro experiments involved the cultivation of tFL cells followed by exposure to various concentrations of anlotinib. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) method, while apoptosis levels were quantified utilizing Annexin V/PI staining kits. For in vivo evaluation, mouse xenograft models bearing tFL cell implants were treated with anlotinib to observe its therapeutic effects firsthand. Additionally, molecular probing techniques such as western blotting and immunohistochemistry staining were employed to analyze protein expression levels and visualize cellular responses to anlotinib treatment. These comprehensive methodologies provided insights into the inhibitory effects of anlotinib on tFL cell proliferation, its ability to induce apoptosis, and the underlying molecular pathways involved in its therapeutic action.
Results
Anlotinib exhibited a dose-dependent inhibition of tFL cell proliferation, with increasing concentrations correlating with greater suppression of cell growth. Cell viability assays utilizing the CCK-8 method revealed a significant reduction in cell viability following anlotinib treatment compared to control groups. Furthermore, flow cytometry analysis of Annexin V/PI stained cells demonstrated a marked increase in apoptotic cell populations with escalating doses of anlotinib, indicating its potent pro-apoptotic effects on tFL cells.
In vivo tumorigenicity tests conducted in mouse xenograft models further corroborated the therapeutic potential of anlotinib. Treatment with anlotinib led to a substantial decrease in tumor mass and weight compared to untreated control groups, highlighting its ability to impede tumor growth in a translational setting. These findings underscore the promising efficacy of anlotinib as a therapeutic agent for tFL, warranting further exploration of its clinical utility in treating this challenging malignancy.
Discussion
The results of this study provide compelling evidence supporting the therapeutic efficacy of anlotinib in tFL, a disease characterized by its high tumor mutational burden and treatment resistance. The observed dose-dependent inhibition of tFL cell proliferation and induction of apoptosis suggest that anlotinib exerts potent anti-tumor effects on this aggressive lymphoma subtype. Moreover, the significant reduction in tumor growth observed in mouse xenograft models underscores the translational relevance of these findings, suggesting that anlotinib holds promise as a viable treatment option for tFL patients.
Mechanistically, the disruption of SETD1A expression by anlotinib, leading to increased p-p53 levels and modulation of key apoptotic proteins, provides insights into the underlying molecular pathways mediating its therapeutic effects. By targeting histone methylation and amplifying p53-dependent apoptosis, anlotinib offers a novel therapeutic strategy for overcoming the treatment challenges posed by tFL. These findings align with emerging evidence suggesting that targeting DNA damage response elements, particularly through epigenetic modulation, could represent a promising approach for treating tFL and other aggressive lymphomas.
Overall, the results of this study highlight the potential of anlotinib as a promising therapeutic agent for tFL, offering new hope for patients facing this challenging disease. Further research is warranted to validate these findings in clinical settings and explore the optimal dosing regimens and combination therapies to maximize the therapeutic benefits of anlotinib in tFL management.
In conclusion, the findings of this study underscore the promising therapeutic potential of anlotinib in transformed follicular lymphoma (tFL). Through a comprehensive evaluation of its inhibitory effects on cell proliferation, induction of apoptosis, and underlying molecular mechanisms, anlotinib emerges as a compelling candidate for the treatment of this aggressive lymphoma subtype. The significant reduction in tumor growth observed in mouse xenograft models further supports its translational relevance and clinical utility. Mechanistically, anlotinib’s ability to disrupt SETD1A expression, enhance p53-dependent apoptosis, and modulate key apoptotic proteins provides valuable insights into its mode of action in tFL. These findings offer new avenues for therapeutic intervention in a disease characterized by its high tumor mutational burden and therapeutic resistance. Moving forward, continued research efforts are warranted to validate these findings in clinical trials, optimize treatment strategies, and explore potential combination therapies to further enhance the therapeutic efficacy of anlotinib in tFL management. Overall, anlotinib represents a promising addition to the armamentarium of therapies for tFL, offering hope for improved outcomes and quality of life for patients facing this challenging disease.
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First and Corresponding Authors and Their Affiliates
The research paper on the efficacy of anlotinib in treating transformed follicular lymphoma (tFL) highlights Dr. Xinguo Zhuang, Jingwei Yao, and Dr. Bing Xu as primary contributors with equivalent significance to the work. Dr. Bing Xu, M.D. & Ph.D., and Jie Zha, M.D. & Ph.D., serve as the corresponding authors, providing critical oversight and direction for the research. Both Dr. Bing Xu and Jie Zha are affiliated with the Department of Hematology at The First Affiliated Hospital of Xiamen University, as well as with the Institute of Hematology at the School of Medicine within the same university. Additionally, they are involved with the Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy. Several other team members from this study are also affiliated with these institutions, showcasing a collaborative effort from a dedicated research team in Xiamen, China.
Journal Publication and Impact Factor
The research was published in the International Journal of Medical Sciences in 2024, volume 21. While the specific impact factor for the journal in the year of publication (2024) is not detailed within the excerpts, the International Journal of Medical Sciences is a peer-reviewed open-access medical journal that has been widely recognized in the domain of medical research. To assess the current impact factor of the International Journal of Medical Sciences, one would need to consult a database that tracks and updates this metric, such as the Journal Citation Reports.
Dr. Bing Xu’s Contribution
Dr. Bing Xu played a pivotal role in this study, serving as a leading author, corresponding author, and significant contributor to the study’s conception, methodology design, resource provision, manuscript review, and editing. Additionally, Dr. Xu played a crucial role in obtaining funding for the study, highlighting his integral involvement in the research process. His multifaceted contributions underscore his leadership and expertise in advancing the understanding and treatment of transformed follicular lymphoma.
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