MedComm – Oncology最新文献

{"title":"Nanoparticle-encapsuled celastrol-Fe(III): “Single-edged sword” for tumor therapy featuring microenvironment-dependent toxicity","authors":"Yu Liu, Zhiyong Qian","doi":"10.1002/mog2.70001","DOIUrl":"https://doi.org/10.1002/mog2.70001","url":null,"abstract":"<p>Recently, Li et al. published a study in <i>Science Advances</i> on the use of dual-responsive celastrol (CEL) materials for cancer treatment. The study took advantage of the high adenosine triphosphate (ATP) levels in the tumor microenvironment to modify the interior and surface of CEL, reducing its toxicity to normal tissues and maximizing the efficacy of its cancer treatment which contributed significantly to drug delivery for tumor therapy.<span><sup>1</sup></span></p><p>CEL is a drug with anticancer activity isolated from traditional Chinese medicinal herbs.<span><sup>2</sup></span> It inhibits cancer cell growth and survival signaling by binding to Cdc37 and Hsp90 reaction sites, causing disruption of the Hsp90-Cdc37 binding and folding of some of the client proteins.<span><sup>3</sup></span> However, its water stability, bioavailability, and targeting are undesirable, which limited its clinical application. There are currently two main approaches to promote CEL's therapeutic potential in clinic: 1. synthesizing derivatives by surface modification which mainly focuses on C-20 carboxylic acid functionality, alteration at the A ring, and C-6-modification at the B ring, and 2. adopting nanomedicine delivery systems, where liposomes, polymeric micelles, and nanoparticles (NPs) are commonly used. The second approach, however, requires strictly selected materials. Liposomes, with its ease of aggregation and instability and leakage when packaging drugs, and polymeric micelles, with potential toxicity, unclear drug delivery mechanisms, and poor quality/specification control, demand extra considerations in application. In this study an ATP/ROS dual-responsive CEL derivative was designed for tumor therapy by mainly taking advantage of the environment in which ATP levels inside and outside tumor cells are 10<sup>3</sup> to 10<sup>4</sup> times higher than that around normal tissues.<span><sup>4</sup></span> Surface modification of CEL using metal chelation was performed to address the toxicity to normal tissues, and NPs were selected for packaging to promote the release of CEL when it reaches the tumor site. Compared with liposomes and polymeric micelles, CEL-Fe with ATP/ROS dual-response has a well-defined structural study, low drug toxicity, high stability, and ultimately the ability to respond to the specificity of the tumor microenvironment for effective drug release and treatment which improves the biosafety and biocompatibility of the therapeutic drugs. Fe(III) was chosen to coordinately bond with oxygens on C-2 and C-3 in CEL to produce the less toxic CEL-Fe, which is then coated with polymer membrane consisting of thioketal-containing polyethylene glycol-grafted polymer and polyethylene enamine-modified F127 polymer to elevate its permeability and retention effects.<span><sup>5</sup></span> The high concentration of ATP in tumor tissues disrupts the coordination of Fe(III), restoring the pharmacological toxicity of CEL. In response to high ","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in cancer drug resistance: Mechanistic insights and therapeutic implications","authors":"Jing Zuo,&nbsp;Han Yan,&nbsp;Siyuan Qin,&nbsp;Yonghao Yan,&nbsp;Shiqi Wang,&nbsp;Li Yang,&nbsp;Jinlin Yang,&nbsp;Jun Yang","doi":"10.1002/mog2.94","DOIUrl":"https://doi.org/10.1002/mog2.94","url":null,"abstract":"<p>Despite significant advancements in the treatment of cancer, therapeutic resistance remains a major hurdle for the achievement of full cures. Besides being typically driven by intratumoral heterogeneity, such acquired resistance also relies heavily on cell-cell communication whereby extracellular vesicles (EVs) carrying resistance-related components can be transferred from drug-resistant cells or nontumorigenic members within tumor microenvironment (TME) to their sensitive neighbors. The cargo and membrane surface proteins of EVs derived from drug-resistant cells and TME cells carry abundant biological information, transferring therapy-resistant capacity to sensitive cancer cells. Hence, a deep understanding of the roles of EVs in cancer therapy resistance will facilitate identifying biomarkers and developing new approaches to restore therapy sensitivity. In this review, we summarize our current understanding regarding the causes and effects of EV-mediated cell–cell communication in drug resistance, with a particular notice on how various kinds of cargoes derived from different cells within TME are linked to the resistant phenotype. We also discuss how this knowledge can contribute to improvements in clinical practice, that is, the opportunities and challenges of EVs in functioning as potential biomarkers in predicting therapeutic resistance and, by extension, EV-based therapy in achieving deeper and longer-lasting clinical responses.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.94","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA interplay: Mechanisms and therapeutic interventions in cancer","authors":"Zehua Wang,&nbsp;Hangxuan Wang,&nbsp;Shuhan Zhou,&nbsp;Jiasheng Mao,&nbsp;Zhiqing Zhan,&nbsp;Shiwei Duan","doi":"10.1002/mog2.93","DOIUrl":"https://doi.org/10.1002/mog2.93","url":null,"abstract":"<p>MicroRNAs (miRNAs) are key molecules that regulate gene expression. miRNAs regulate protein synthesis by binding to mRNA, influencing processes such as cell proliferation, metastasis, and apoptosis. They play a pivotal role in cancer development. Current research mainly explores miRNA mechanisms and applications, and the techniques underpinning this research are foundational to both basic science and clinical translation. However, no review has comprehensively examined miRNA mechanisms and applications from a technical perspective, creating a need for this work. Advances in RNA sequencing technology, CRISPR/Cas9 technology, and bioinformatics tools have deepened our understanding of miRNA interactions. miRNA can serve as a biomarker for cancer diagnosis and prognosis, with significant clinical potential. The development of miRNA mimics and inhibitors has brought new hope for cancer treatment, especially in reversing cancer drug resistance. This article reviews the vital role of miRNA interactions in cancer occurrence, development, diagnosis, and treatment, providing new perspectives and strategies for personalized medicine and cancer therapy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.93","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KMT2C/D deficiency promotes breast cancer metastasis by regulating KDM6A-mediated epigenetic remodeling","authors":"Zhao Huang,&nbsp;Wei Zhao","doi":"10.1002/mog2.95","DOIUrl":"https://doi.org/10.1002/mog2.95","url":null,"abstract":"&lt;p&gt;On June 26, 2024, Kornelia Polyak's team published an article in Nature Cell Biology that revealed a new mechanism by which histone-lysine N-methyltransferase 2 C (&lt;i&gt;KMT2C)&lt;/i&gt; or &lt;i&gt;KMT2D&lt;/i&gt; deletion promotes metalloproteinase 3 (MMP3) expression in a lysine-specific demethylase 6 A (KDM6A)-dependent manner, thereby driving brain metastasis (BMs) of triple-negative breast cancer (TNBC). It provides a new perspective for the treatment of TNBC at the epigenetic level.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Breast cancer is the most common neoplasm and the leading cause of tumor-related death in women worldwide. Breast cancer subtypes can be classified according to the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; TNBC is characterized by a high level of cell invasiveness and visceral metastasis to organs, usually brain, lungs, and liver, with an average survival time of 18 months. Although TNBC accounts for only about 15%–20% of all breast cancers, it is the subtype with the worst prognosis of breast cancer. Before the advent of immunotherapy, systemic chemotherapies including taxanes, anthracyclines and/or platinum were the predominant first-line treatment options for TNBC. However, the median overall survival of metastatic TNBC is only 9–12 months, and the 5-year survival rate is approximately 12%, which is a serious unmet medical need.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The most commonly mutated gene in BMs of breast cancer has been reported to be &lt;i&gt;KMT2C/D&lt;/i&gt;, and the results of gene sequencing showed that &lt;i&gt;KMT2C&lt;/i&gt; and &lt;i&gt;KMT2D&lt;/i&gt; were significantly reduced in distal metastasis compared to the primary tumor, suggesting that functional loss of &lt;i&gt;KMT2C/D&lt;/i&gt; plays a role in BMs of breast cancer. &lt;i&gt;KMT2C&lt;/i&gt; and &lt;i&gt;KMT2D&lt;/i&gt; catalyze the methylation of unmethylated H3K4 sites to form H3K4me1, which can be enriched in active enhancer and promoter regions. This modification recruits other histone modifying enzymes, including histone H3K27 acetyltransferases (such as P300) and demethylases (such as KDM6A), which are essential for the regulation of gene expression. As the core components of the SET1-associated protein epigenetic regulatory complex (COMPASS), &lt;i&gt;KMT2C&lt;/i&gt; and &lt;i&gt;KMT2D&lt;/i&gt; profoundly regulate the epigenetic landscape.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; However, it is still unclear how &lt;i&gt;KMT2C&lt;/i&gt;/&lt;i&gt;D&lt;/i&gt; mutations affect the epigenetic and transcriptomic landscape to promote tumorigenesis.&lt;/p&gt;&lt;p&gt;Recently, Marco Seehawer and colleagues from Dana-Farber Cancer Institute in the United States found that the loss of &lt;i&gt;KMT2C&lt;/i&gt; or &lt;i&gt;KMT2D&lt;/i&gt; can lead to metastasis (especially BMs) in a nonmetastatic TNBC mouse model. Mechanistic studies revealed that the loss of &lt;i&gt;KMT2C&lt;/i&gt; or &lt;i&gt;KMT2D&lt;/i&gt; promotes the expression of matrix MMP3 in a KDM6A-dependent manner, thereby driving BMs of TNBC.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This study provides not only a new perspective for the tre","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.95","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The application of the combination between artificial intelligence and endoscopy in gastrointestinal tumors","authors":"Shen Li,&nbsp;Maosen Xu,&nbsp;Yuanling Meng,&nbsp;Haozhen Sun,&nbsp;Tao Zhang,&nbsp;Hanle Yang,&nbsp;Yueyi Li,&nbsp;Xuelei Ma","doi":"10.1002/mog2.91","DOIUrl":"https://doi.org/10.1002/mog2.91","url":null,"abstract":"<p>Gastrointestinal (GI) tumors have always been a major type of malignant tumor and a leading cause of tumor-related deaths worldwide. The main principles of modern medicine for GI tumors are early prevention, early diagnosis, and early treatment, with early diagnosis being the most effective measure. Endoscopy, due to its ability to visualize lesions, has been one of the primary modalities for screening, diagnosing, and treating GI tumors. However, a qualified endoscopist often requires long training and extensive experience, which to some extent limits the wider use of endoscopy. With advances in data science, artificial intelligence (AI) has brought a new development direction for the endoscopy of GI tumors. AI can quickly process large quantities of data and images and improve diagnostic accuracy with some training, greatly reducing the workload of endoscopists and assisting them in early diagnosis. Therefore, this review focuses on the combined application of endoscopy and AI in GI tumors in recent years, describing the latest research progress on the main types of tumors and their performance in clinical trials, the application of multimodal AI in endoscopy, the development of endoscopy, and the potential applications of AI within it, with the aim of providing a reference for subsequent research.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.91","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive infiltration of CD8+ T cells and M1 macrophages is beneficial for multiple cancer patients undergoing chemotherapy","authors":"Yuquan Bai,&nbsp;He Xu,&nbsp;Minzhang Guo,&nbsp;Liang Xia,&nbsp;Senyi Deng","doi":"10.1002/mog2.89","DOIUrl":"https://doi.org/10.1002/mog2.89","url":null,"abstract":"<p>Not all patients can benefit from chemotherapy due to the various of tumor type, stage, location, and the different distribution of immune cells in tumor immune microenvironment (TIME). Immune cells are widely involved in every step of cancer progression, including immune escape, metastasis, drug response, and prognosis. In this study, we explored the transcriptome data of 10 solid tumors treated with chemotherapy to identify the role of immune cells. We downloaded the transcriptome and mutation data of 10 cancers from TCGA databases, and used ESTIMATE and CIBERSORT algorithms to assess the proportion of immune cells in the TIME. According to the proportion of specific immune cell infiltration (SICI) of CD8⁺ T cells and M1 macrophages to group the patients, we found that compared with the SICI low and medium groups, the SICI high group had a larger tumor mutation burden, more gene mutations with targeted drugs, more activation of immune checkpoints (PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT), and immune molecules (CD8a, CD80, CD86, TLR2, HLA-A, HLA-B, and CD11a) (<i>p</i> &lt; 0.05). Therefore, we can select an appropriate treatment for patients by clarifying the proportion of immune infiltration of CD8⁺ T cells and M1 macrophages in the TIME.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PGE2-EP2/EP4 axis: A new perspective on cancer immunotherapy","authors":"Lin Chen,&nbsp;Yu-Xin Xu,&nbsp;Jian-Liang Zhou","doi":"10.1002/mog2.90","DOIUrl":"https://doi.org/10.1002/mog2.90","url":null,"abstract":"&lt;p&gt;Lacher et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; in a recent publication in &lt;i&gt;Nature&lt;/i&gt;, revealed a crucial mechanism that limits the responsiveness of TCF1&lt;sup&gt;+&lt;/sup&gt; tumor-infiltrating lymphocytes (TILs) to interleukin-2 (IL-2), thereby impeding the anti-cancer T cell response derived from these cells. They identified the prostaglandin E&lt;sub&gt;2&lt;/sub&gt; (PGE&lt;sub&gt;2&lt;/sub&gt;)-EP&lt;sub&gt;2&lt;/sub&gt;/EP&lt;sub&gt;4&lt;/sub&gt; axis as a molecular target to restore IL-2 responsiveness in anti-cancer TILs, leading to cancer immune control. This study provides critical insights into the molecular interactions that govern TIL functionality and IL-2 responsiveness, which are essential for effective immunotherapy. Moreover, it suggests that therapeutic strategies aimed at inhibiting the PGE&lt;sub&gt;2&lt;/sub&gt;-EP&lt;sub&gt;2&lt;/sub&gt;/EP&lt;sub&gt;4&lt;/sub&gt; axis could enhance the efficacy of IL-2 based immunotherapies, potentially offering a new avenue for cancer treatment, particularly in tumors where TILs are a significant component of the immune response (Figure 1).&lt;/p&gt;&lt;p&gt;Tumor immunotherapy marks a significant breakthrough in cancer treatment, with research into immune cells and the tumor microenvironment (TME) uncovering various regulatory factors that influence immune cell activity within tumors. Tumor-derived PGE&lt;sub&gt;2&lt;/sub&gt; plays a crucial role in tumor immune evasion and acts as a key inflammatory mediator. Previous studies have shown that PGE&lt;sub&gt;2&lt;/sub&gt; affects immune cell activity, function, and metabolism, impacting their ability to recognize and target tumors.&lt;span&gt;&lt;sup&gt;2-4&lt;/sup&gt;&lt;/span&gt; This regulatory role of PGE&lt;sub&gt;2&lt;/sub&gt; is particularly important for the efficacy of tumor immunotherapy, especially concerning CD8&lt;sup&gt;+&lt;/sup&gt; T cells. CD8&lt;sup&gt;+&lt;/sup&gt; T cells are vital components of the immune system, responsible for identifying and eliminating tumor cells by recognizing specific antigens on their surfaces. Upon recognition, they release perforins and granzymes to induce apoptosis in tumor cells, contributing to tumor clearance and the success of immunotherapy.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; However, the mechanisms by which PGE&lt;sub&gt;2&lt;/sub&gt; limits the effector expansion of CD8&lt;sup&gt;+&lt;/sup&gt; T cells, particularly in the TME, remain unclear. This study investigates the interaction between PGE&lt;sub&gt;2&lt;/sub&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T cells, revealing how PGE&lt;sub&gt;2&lt;/sub&gt; restricts the effector expansion of tumor-infiltrating stem-like CD8&lt;sup&gt;+&lt;/sup&gt; T cells and its significance in tumor immunotherapy. The findings provide a theoretical basis and clinical guidance for optimizing immunotherapy strategies.&lt;/p&gt;&lt;p&gt;This study has revealed that tumor-derived PGE&lt;sub&gt;2&lt;/sub&gt; significantly inhibits the expansion and effector differentiation of TCF1&lt;sup&gt;+&lt;/sup&gt; CD8&lt;sup&gt;+&lt;/sup&gt; TILs, which are crucial for sustaining a long-term anti-tumor response. The expansion of these T cells ensures a sufficient quantity of effector cells, while their differentiation into effector cells is essential for directly attacking and eliminatin","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.90","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering transcriptional bursts and enhancer dynamics: Advancing cancer therapeutics through single-cell global run-on sequencing","authors":"Xiangyu Pan,&nbsp;Feifei Na,&nbsp;Xuelan Chen","doi":"10.1002/mog2.88","DOIUrl":"https://doi.org/10.1002/mog2.88","url":null,"abstract":"&lt;p&gt;The pioneering work of Phillip A. Sharp's research group has led to the development of a cutting-edge single-cell nascent RNA sequencing assay, revolutionizing our understanding of transcription dynamics. The study, published in Nature, incorporates click chemistry into global run-on and sequencing (GRO-seq) to create a single-cell GRO-seq (scGRO-seq) technique.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This method allows for the precise capture of the episodic and coordinated nature of transcription at high resolution, revealing critical dynamics such as burst size and enhancer-gene interactions. Such insights are particularly vital for unraveling the complexities of transcription regulation and cell cycle dynamics across various developmental stages and in the pathological context of diseases like cancer.&lt;/p&gt;&lt;p&gt;Transcription in development and cancer biology involves short bursts of activity and lengthy silent periods, essential for gene regulation. Core regulatory elements like promoters, transcription factors, and enhancers play key roles in these bursts. Enhancers, specific to cell types and states, regulate genes over long distances and are often linked to disease regions, making them potential targets for cancer therapies.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Current genomic tools provide insights into gene activation precursors but lack real-time transcription event capture. scGRO-seq addresses this gap, offering a dynamic view of regulatory mechanisms for targeted cancer treatment.&lt;/p&gt;&lt;p&gt;The scGRO-seq technique offers a novel and advanced method for analyzing genome-wide transcription dynamics at a single-cell resolution, filling critical gaps in understanding transcriptional regulation. This method involves labeling nascent RNAs with modified nucleotide triphosphates that contain alkyne groups during a nuclear run-on reaction (Figure 1A). These RNAs are subsequently linked to azide-tagged, single-cell barcode DNA molecules through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), known for its efficiency and robustness.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This process not only preserves the integrity of the nuclear membrane but also selectively enriches nascent RNA. Postreaction, these barcoded RNAs are pooled, reverse-transcribed, and PCR amplified to construct a sequencing library, which is then used to detail transcriptional activity within individual cells (Figure 1A).&lt;/p&gt;&lt;p&gt;The scGRO-seq method has revolutionized the understanding of transcriptional dynamics by refining the approach to detect transcription bursts. Focusing on a 10 kb central gene region and excluding the ends with paused polymerases, it utilizes an RNA Polymerase II elongation rate of 2.5 kb/min, limiting the burst detection window to just 4 min. This setup enables precise measurement of burst sizes, which range from 1 to 4 RNA polymerases, with an average of 1.23, and a mean interval between bursts that aligns with the previously reported 2-h global nascent transcription cycle by intron seqFISH","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.88","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CoCl2-induced glioma hypoxia environment enhances CD47-SIRPα to promote tumor immune evasion","authors":"Xiangfei Ding,&nbsp;Jianbing Hou,&nbsp;Xiaosong Hu,&nbsp;Wen Peng,&nbsp;Yongsen Li,&nbsp;Gaichao Zhao,&nbsp;Hongjuan Cui,&nbsp;Zonghui Wu,&nbsp;Ping Liang","doi":"10.1002/mog2.87","DOIUrl":"https://doi.org/10.1002/mog2.87","url":null,"abstract":"<p>Elevated levels of tumor-associated macrophages and microglia in the immune microenvironment of malignant gliomas promote tumor growth and progression. Although immune evasion has been implicated in these processes, the mechanisms underlying the regulation of CD47-SIRPα-mediated immune evasion under hypoxic conditions remain unclear. Therefore, this study aimed to explore the mechanisms through which CD47-SIRPα modulates immune evasion in a cobalt chloride (CoCl₂)-induced hypoxic microenvironment of malignant gliomas. Human and mouse glioma cell lines were used to investigate immune evasion in vitro. After membrane protein extraction and nucleoplasmic isolation, we downregulated the expression levels of transport receptors to elucidate the regulation of CD47-SIRPα transport. The CoCl₂-induced hypoxic microenvironment attenuated microglial phagocytosis in glioma cells. Enhanced CD47-SIRPα interaction promoted immune evasion, which negatively affected tumor clearance. In addition, the intracellular transport of CD47 was promoted in the CoCl₂-induced hypoxic state. This process was regulated by regulator of chromosome condensation 1 (RCC1) and sortilin in the nuclear cytoplasm and cytoplasmic membrane, respectively. These results demonstrate the CD47-SIRPα-mediated immune escape mechanism of the CoCl₂-induced glioma hypoxic environment, which is associated with enhanced intracellular transport of CD47. Our findings provide a theoretical basis for the potential development of novel therapies targeting CD47-SIRPα.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.87","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic value of microRNA-200 family expression in digestive system tumors: A meta-analysis and validation","authors":"Xiaoshuang Wu,&nbsp;Jinghua Heng,&nbsp;Mengxiang Li,&nbsp;Danxia Deng,&nbsp;Bingli Wu,&nbsp;Muting Wang,&nbsp;Sanqiang Li,&nbsp;Shegan Gao,&nbsp;Yijun Qi,&nbsp;Enmin Li","doi":"10.1002/mog2.86","DOIUrl":"https://doi.org/10.1002/mog2.86","url":null,"abstract":"<p>The relevance of miR-200 family in the prognosis of digestive system tumors remains controversial. Through a systematic review of the pertinent literature using online databases including PubMed, EMBASE, The Cochrane Library, and Web of Science, our pooled-analysis revealed that miR-200 family downregulation was significantly correlated with poor overall survival (OS, hazard ratio [HR] &gt; 1) and disease-free survival (HR &gt; 1) in digestive malignancies. Consistently, subgroup analyzes of various organ tissues, univariate analysis, gastric cancer, pancreatic cancer, and patients of American descent revealed the hazardous effects of miR-200 family downregulation. In contrast, low miR-200 family expression in blood samples predicted favorable OS (HR &lt; 1). Moreover, lower expression levels of miR-200c-5p and miR-429 were validated in esophageal squamous cell carcinoma (ESCC) tissues. Both the protein and messenger RNA expression levels of Paralemmin-2 (PALM2) and Mitotic Arrest Deficient 2-Like Protein (MAD2L1), regulated by miR-200c-5p, were notably higher in ESCC, and increased protein levels of PALM2 and MAD2L1 were correlated with adverse OS. PALM2 overexpression significantly enhanced ESCC cell migration. In conclusion, our study highlights the prognostic value of miR-200 family in digestive system tumors, and the decrease of miR-200c-5p may promote ESCC invasion through upregulation of PALM2 and MAD2L1.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.86","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}