Medical Oncology最新文献

The cGAS-STING signaling pathway is indeed a pivotal component of the immune system and serve as a crucial link between innate and adaptive immune responses. STING is involved in the cellular response to pathogen invasion and DNA damage, and which has important consequences for host defense mechanisms and cancer regulation. Ongoing research aiming to modulate the cGAS-STING pathway for improved clinical outcomes in cancer and autoimmune diseases is underway. Indeed, the interaction between the cGAS-STING pathway and immune evasion mechanisms is a complex and critical aspect of cancer biology. Pathogens and various host factors can exploit this pathway to reduce the effectiveness of cancer therapies, particularly immunotherapies. Thus, immunotherapies or combination therapies may assist in overcoming the immune suppression and improving clinical outcomes. This review explores recent advancements in understanding the cGAS-STING signaling pathway, with particular emphasis on its activation mechanisms and role in tumor immune evasion. The dual role of the pathway in boosting immune responses while simultaneously enabling tumors to evade the immune system makes it a crucial target for innovative cancer treatment approaches.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 2 Given name: [Md Mazedul] Last name [Islam], Author 3 Given name: [Mst Rubaiat Nazneen] Last name [Akhand] and Author 5 Given name: [Md Rashedunnabi] Last name [Akanda]. Also, kindly confirm the details in the metadata are correct.AQ1: Here Author 4 given name: [Byung-Yong] Last name [Park] is missing. Metadata are correct.

Risk management and self-management strategies for breast cancer-related lymphedema (BCRL) must balance best-evidence guidelines and associated risk factor knowledge. There is an evidence-based practice gap in the understanding of whether a change in education about risk factors and whether behavioral changes actually influence BCRL manifestation or progression. The purpose of this study was to (1) review if current evidence supports or refutes patient precautions to prevent the manifestation and/or progression of BCRL, (2) review if behavioral changes result in the prevention or reduction of BCRL, and (3) identify related gaps of knowledge for future research. Evidence map methodology was used to systematically review literature related to reducing the risk of BCRL. Literature searches were conducted in Medline, CINAHL, and Cochrane for the categories of trauma, blood pressure, temperature, air travel, and behavior change. One hundred and forty-eight articles were included for full-text review, of which 37 articles were included in this study. Within the confines of limb and trunk circumferential and/or volume enlargement, a 'just in case' approach to patient education on risk factors may not be appropriate for breast cancer survivors at risk of manifesting lymphedema. Patient education about precautionary risks for the onset of BCRL needs to align with research evidence. There is scant evidence about the risks of BCRL progression suggesting a need for future research.

Complex decongestive therapy is the current gold standard for non-surgical clinical lymphedema management and consists of manual therapy, compression exercise, skincare, and education. Complex decongestive therapy involves an intensive volume reduction phase (Phase I) followed by a maintenance phase (Phase II). The aim of the maintenance phase is to promote life-long control of lymphedema through use of self-management strategies and the provision of ongoing reduction therapies as needed. Compression therapies are the mainstay of lymphedema self-management. Poor adherence to self-management practices has been associated with increased volume and progression of lymphedema to more advanced stages, supporting the importance of education and regular monitoring to promote adherence to the Phase II maintenance recommendations. In this editorial, we provide consensus recommendations on the essential components of the maintenance phase, including education, skin care practices, managing infection/cellulitis, compression therapies, health and weight management, exercise, and ongoing follow-up care.

The identification of effective therapeutic modalities to manage lymphedema secondary to cancer is a high priority among patients and clinicians. Complex decongestive therapy (CDT) remains a fundamental intervention for individuals with lymphedema; however, interventions involving modalities such as low level laser therapy, specially designed compression systems, and compression pumps may be helpful to improve outcomes and reduce costs of care. We conducted a rapid review of the literature examining compression therapies and therapeutic modalities in the treatment of lymphedema secondary to cancer. A search of the electronic databases from June 2018 to October 2023 was performed including MEDLINE, EMBASE, and CINAHL. The electronic search yielded 438 potentially relevant citations with 40 randomized controlled trials included in the review, and 30 in the mapping process. Ninety-three percent (n = 37) of the trials included participants with a diagnosis of breast cancer. Across all categories and domains, all but two trials were rated as having 'some concerns' or a 'high risk of bias'. Intervention effects ranged from clinically insignificant to large effects on lymphedema volume. Evidence mapping suggests potential for benefit from (1) compression garments for the prevention of lymphedema, (2) interventions added to CDT in the intensive reduction phase, and (3) nighttime compression and compression pump treatments in the maintenance phase. A multi-centre collaborative research approach is needed to support the conduct of high-quality large-scale trials to inform the optimal type, timing, and combination of compression therapies and therapeutic modalities in the treatment of lymphedema secondary to cancer.

Pheochromocytomas and paragangliomas (PCCs/PGLs) are uncommon neuroendocrine tumors with a significant genetic tendency. Approximately 35-40% of these tumors are associated with genetic factors. The present study performed a thorough analysis using publicly accessible genetic and clinical data from the Cancer Genome Atlas (TCGA) to examine the involvement of six genes, namely GBP1, KIF13B, GPT, CSDE1, CEP164, and CLCA1, in the development of PCCs/PGLs. By employing multi-omics data, this study investigates the relationship between mutational patterns and the prognosis of tumors, focusing on the possibility of tailoring treatment methods to individual patients. The study utilizes Mutect2 to detect somatic mutations with high confidence in whole-exome sequencing data from PCCG samples. The study uncovers mild effects on protein function caused by particular mutations, including GBP1 (p.Cys12Tyr), KIF13B (p.Arg847Gly), and GPT (p.Gln50Arg). A random forest classifier uses mutational profiles to predict potential drug recommendations, proposing a focused therapy strategy. This study thoroughly analyzes the genetic mutations found in PCCs/PGLs, highlighting the significance of precision medicine in developing specific treatments for these uncommon types of cancer. This study aims to improve the understanding of the development of tumors and identify personalized treatment approaches by combining genetic data with machine learning analyses.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8⁺ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

DNA Fragmentation Factor (DFF) is a heterodimer protein involved in DNA fragmentation during apoptosis, which acts as a trigger downstream of caspase-3 activation. DFF40 catalytically active homo-oligomers break down chromosomal DNA. Previous scientific investigations have revealed a link between DFF40 expression changes and various cancers. DFF40 deletion or down-regulation has been observed in some cancers. Consequently, therapeutic strategies involving the DFF40 molecule compensating led to an increased rate of cancer cell apoptosis. In this review article, we aimed to introduce cancers with low expression of this protein first. The second part of this paper focuses on studies that utilized exogenous DFF40 protein produced by recombinant DNA technology and surveyed during in vitro and in vivo tests. Finally, compensation for diminished expression of the mentioned protein via gene therapy-based techniques to make up for this apoptotic molecule's low expression is the topic of the last part of this review article.

Colorectal cancer (CRC) continues to be one of the leading causes of cancer-related death worldwide. Exosomes have been established to play an important role in intercellular communication and that long non-coding RNA (lncRNA) CASC19 is enriched within M1 macrophage-derived exosomes (M1-exo). However, the biological functions and underlying molecular mechanisms of exosomal CASC19 from macrophages on CRC remain unknown. Cell proliferation and migration were evaluated by MTS and transwell assays. The exosomes were characterized by western blot, nanoparticle tracking analysis (NTA) and electron microscope imaging. The expression levels of CASC19 and its putative target miR-410-3p were quantified by reverse-transcription polymerase chain reaction (RT-qPCR). The interaction between CASC19 and miR-410-3p was detected by the pull-down assay. We found that the non-contact inhibition of M1 macrophages on the proliferation of colon cancer cells is largely dependent on the CASC19 released from M1 exosomes. M1 exosomes successfully delivered CASC19 to colon cancer cells, exerting an inhibitory effect on cell proliferation and migration. The exosomes secreted by M1 cells with CASC19 knockdown showed less inhibition effect on cell proliferation and migration. Mechanically, CASC19 exerted an inhibitory effect on colon cancer cells by sponging miR-410-3p via tube morphogenesis and TGF-β signaling pathway. We first proved that CASC19 in M1 macrophages is delivered into colon cancer cells via exosomes, exerting an inhibitory effect on their proliferation and migration by sponging miR-410-3p. The study may provide mechanistic insights into the roles of lncRNAs in CRC progression and a potential therapeutic target for the treatment of CRC.

Cancer is a leading cause of fatality worldwide. Due to the heterogeneity of cancer cells the effectiveness of various conventional cancer treatment techniques is constrained. Thus, researchers are diligently investigating therapeutic approaches like immunotherapy for effective tumor managements. Immunotherapy harnesses the inherent potential of patient's immune system to achieve desired outcomes. Within the realm of immunotherapy, CAR-T (Chimeric Antigen Receptor T) cells, emerges as a revolutionary innovation for cancer therapy. The process of CAR-T cell therapy entails extracting the patient's T cells, altering them with customized receptors designed to specifically recognize and eradicate the tumor cells, and then reinfusing the altered cells into the patient's body. Although there has been significant progress with CAR-T cell therapy in certain cases of specific B-cell leukemia and lymphoma, its effectiveness is hindered in hematological and solid tumors due to the challenges such as severe toxicities, restricted tumor infiltration, cytokine release syndrome and antigen escape. Overcoming these obstacles requires innovative approaches to design more effective CAR-T cells, which require a competent and diverse team to develop and implement. This comprehensive review addresses numerous therapeutic issues and provides a strategic solution while providing a deep understanding of the structural intricacies and production processes of CAR-T cells. In addition, this review explores the practical aspects of CAR-T cell therapy in clinical settings.

The purpose of this study is to enhance the effectiveness of known anticancer medications using natural compounds. The study investigated the impact of combining AVE with PAX on non-small cell lung cancer (A549) and breast cancer (MCF7). In this study, A549 and MCF7 cells were treated with PAX (5 μM), AVE (24 μg/mL), and a combination of PAX and AVE (5 μM + 24 μg/mL). The glucose consumption rates of the cells were determined by extracellular acidification rate (ECAR) thanks to the SeaHorse XFe24 instrument. In addition, gene expression profiles were determined by performing Total RNA sequencing with the Novaseq 6000 instrument. Finally, the expressions of GAPDH, BAX, and BCL-2 genes involved in the apoptotic pathway were detected by RT-qPCR. The combined application of PAX and AVE reduced the ECAR value in both cell lines. According to the RT-qPCR results, the expression level of the apoptotic gene BAX increased in both cell lines (p < 0.05). Total RNA sequencing revealed that the combination effects of PAX and AVE play a role in the ribosome mechanism, thereby affecting the protein translation system in MCF7 while apoptosis and cell cycle have come to the forefront in A549.