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Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3. 红参多糖通过下调 AQP3 抑制 PI3K/Akt 通路,促进胃癌细胞的铁变态反应。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2023-12-05 DOI: 10.1080/15384047.2023.2284849
Yan Wang, Wen-Xian Guan, Yuan Zhou, Xiao-Yu Zhang, Hai-Jian Zhao

Objective: This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism.

Methods: GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 μg/mL). AGS cells treated with 200 μg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups (n = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded.

Results: RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosage-dependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects.

Conclusion: RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells.

研究目的本研究旨在探讨红参多糖(RGP)对胃癌(GC)发展的影响及其机制:方法:用不同浓度的 RGP(50、100 和 200 μg/mL)处理胃癌细胞株 AGS。用 200 μg/mL RGP 处理的 AGS 细胞转染水蒸蛋白 3(AQP3)过表达载体。细胞增殖、活力和凋亡分别通过 MTT、集落形成试验和流式细胞术进行评估。实时定量反转录 PCR(qRT-PCR)用于检测 AQP3 的表达。Fe2+、丙二醛和乳酸脱氢酶的水平用各自的检测试剂盒进行检测,活性氧水平用探针 2',7'-二氯二氢荧光素二乙酸酯进行检测。铁突变相关蛋白和 PI3K/Akt 通路相关蛋白的表达采用 Western 印迹法进行评估。裸鼠体内实验将小鼠分为四组(n = 5/组),分别灌胃 150 毫克/千克生理盐水和 75、150、300 毫克/千克 RGP。记录肿瘤重量和体积:结果:RGP 能有效抑制 AGS 细胞的增殖和存活,并诱导细胞凋亡,其抑制作用与剂量有关。它还能诱导 AGS 细胞的铁凋亡,并抑制 PI3K/Akt 相关蛋白的表达。AQP3 的过表达可以逆转 RGP 对铁细胞凋亡的影响。体内实验证实,RGP可减少植入肿瘤的生长,增加RGP浓度可产生更大的肿瘤抑制作用:结论:RGP 可有效抑制 AGS 细胞的增殖和活力,具有治疗 GC 的潜力。
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引用次数: 0
NRS2002 score as a prognostic factor in solid tumors treated with immune checkpoint inhibitor therapy: a real-world evidence analysis. NRS2002评分作为接受免疫检查点抑制剂治疗的实体瘤的预后因素:真实世界证据分析。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-30 DOI: 10.1080/15384047.2024.2358551
Wanfen Tang, Chenghui Li, Dong Huang, Shishi Zhou, Hongjuan Zheng, Qinghua Wang, Xia Zhang, Jianfei Fu

To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0-2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30-2.54, p value < .001; OS: HR = 2.49, 95% CI 1.73-3.59, p value < .001). Cox regression analysis revealed that the NRS2002 score was an independent prognostic factor for both PFS and OS. The objective response rate (ORR) in the group at nutritional risk was lower than that in the group without nutritional risk (8.33% and 19.71%, respectively, p value = .037). Patients at nutritional risk according to the NRS2002 score at initial treatment had a poorer prognosis than those without nutritional risk. The NRS2002 could be used as a preliminary index to predict the efficacy of immune checkpoint inhibitor therapy.

为了观察程序性死亡1(PD-1)抑制剂在现实世界中的抗肿瘤疗效,探索NRS2002评分或其他临床特征与免疫治疗疗效之间的关系,我们回顾性分析了在一个中心接受免疫检查点抑制剂(ICI)治疗的341例肿瘤患者。本研究回顾性纳入了2018年6月至2021年12月期间接受ICI治疗的共341例实体瘤患者。记录了患者特征、ICI反应和生存状态,并分析了临床因素与生存之间的关系。在所有患者中,中位无进展生存期(PFS)为5.8个月,中位总生存期(OS)为12.5个月。根据单变量分析,患者的表现状态(PS)、NRS2002评分、那不勒斯预后评分(NPS)、淋巴细胞与C反应蛋白比值(LCR)、治疗方案和营养支持与PFS或OS显著相关。无营养风险组(NRS2002 0-2)的中位 PFS 和 OS 明显优于有营养风险组(NRS2002 ≥ 3)(PFS:HR = 1.82,95% CI 1.30-2.54,p 值 p 值 p 值 = .037)。与无营养风险的患者相比,根据 NRS2002 评分在初始治疗时有营养风险的患者预后较差。NRS2002可作为预测免疫检查点抑制剂疗效的初步指标。
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引用次数: 0
Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma. 相互排斥的团队式基因调控模式是神经母细胞瘤去甲肾上腺素能-间充质轴表型异质性的特征。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-01-17 DOI: 10.1080/15384047.2024.2301802
Manas Sehgal, Sonali Priyadarshini Nayak, Sarthak Sahoo, Jason A Somarelli, Mohit Kumar Jolly

Neuroblastoma is the most frequent extracranial pediatric tumor and leads to 15% of all cancer-related deaths in children. Tumor relapse and therapy resistance in neuroblastoma are driven by phenotypic plasticity and heterogeneity between noradrenergic (NOR) and mesenchymal (MES) cell states. Despite the importance of this phenotypic plasticity, the dynamics and molecular patterns associated with these bidirectional cell-state transitions remain relatively poorly understood. Here, we analyze multiple RNA-seq datasets at both bulk and single-cell resolution, to understand the association between NOR- and MES-specific factors. We observed that NOR-specific and MES-specific expression patterns are largely mutually exclusive, exhibiting a "teams-like" behavior among the genes involved, reminiscent of our earlier observations in lung cancer and melanoma. This antagonism between NOR and MES phenotypes was also associated with metabolic reprogramming and with immunotherapy targets PD-L1 and GD2 as well as with experimental perturbations driving the NOR-MES and/or MES-NOR transition. Further, these "teams-like" patterns were seen only among the NOR- and MES-specific genes, but not in housekeeping genes, possibly highlighting a hallmark of network topology enabling cancer cell plasticity.

神经母细胞瘤是最常见的颅外儿科肿瘤,导致15%的儿童死于癌症。神经母细胞瘤的肿瘤复发和耐药性是由去甲肾上腺素能(NOR)细胞和间质(MES)细胞状态之间的表型可塑性和异质性驱动的。尽管这种表型可塑性非常重要,但与这些双向细胞状态转换相关的动力学和分子模式仍然知之甚少。在这里,我们分析了大体和单细胞分辨率的多个 RNA-seq 数据集,以了解 NOR 和 MES 特异性因子之间的关联。我们观察到,NOR 特异性和 MES 特异性表达模式在很大程度上是相互排斥的,在相关基因中表现出一种 "团队 "行为,这让人想起我们早先在肺癌和黑色素瘤中观察到的现象。NOR 和 MES 表型之间的这种拮抗作用还与代谢重编程、免疫疗法靶标 PD-L1 和 GD2 以及驱动 NOR-MES 和/或 MES-NOR 转化的实验扰动有关。此外,这些 "类似团队 "的模式只出现在NOR和MES特异性基因中,而不出现在保守基因中,这可能凸显了使癌细胞具有可塑性的网络拓扑特征。
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引用次数: 0
Salidroside inhibited the proliferation of gastric cancer cells through up-regulating tumor suppressor miR-1343-3p and down-regulating MAP3K6/MMP24 signal molecules. 水杨梅苷通过上调肿瘤抑制因子miR-1343-3p和下调MAP3K6/MMP24信号分子抑制胃癌细胞的增殖。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-04 DOI: 10.1080/15384047.2024.2322206
Xiaoping Wang, Zhendong Zhang, Xiaolan Cao

Salidroside inhibited the proliferation of cancer cell. Nevertheless, the mechanism has not been completely clarified. The purpose of the study is to explore the mechanisms of salidroside against gastric cancer. To analyze the changes of microRNA (miRNA) in gastric cancer cells under the treatment of salidroside, the miRNA expression was analyzed by using RNA-seq in cancer cells for 24 h after salidroside treatment. The differentially expressed miRNAs were clustered and their target genes were analyzed. Selected miRNA and target mRNA genes were further verified by q-PCR. The expressions of target genes in cancer cells were detected by immunohistochemistry. Cancer cell apoptotic index was significantly increased after salidroside treatment. The proliferation of gastric cancer cells were blocked at S-phase cell cycle. The expression of 44 miRNAs changed differentially after salidroside treatment in cancer cells. Bioinformatic analysis showed that there were 1384 target mRNAs corresponding to the differentially expressed miRNAs. Surprisingly, salidroside significantly up-regulated the expression of tumor suppressor miR-1343-3p, and down-regulated the expression of MAP3K6, STAT3 and MMP24-related genes. Salidroside suppressed the growth of gastric cancer by inducing the cancer cell apoptosis, arresting the cancer cell cycle and down-regulating the related signal transduction pathways. miRNAs are expressed differentially in gastric cancer cells after salidroside treatment, playing important roles in regulating proliferation and metastasis. Salidroside may suppress the growth of gastric cancer by up-regulating the expression of the tumor suppressor miR-1343-3p and down-regulating the expression of MAP3K6 and MMP24 signal molecules.

水杨甙能抑制癌细胞的增殖。然而,其机制尚未完全阐明。本研究的目的是探索柳氮磺吡啶对抗胃癌的机制。为了分析微RNA(miRNA)在柳氮磺胺吡啶治疗下在胃癌细胞中的变化,研究人员采用RNA-seq技术分析了柳氮磺胺吡啶治疗后24小时内癌细胞中miRNA的表达情况。对差异表达的 miRNA 进行聚类并分析其靶基因。选定的 miRNA 和靶 mRNA 基因通过 q-PCR 进一步验证。免疫组化法检测了靶基因在癌细胞中的表达。经柳氮磺胺吡啶处理后,癌细胞凋亡指数明显增加。在 S 期细胞周期,胃癌细胞的增殖被阻断。44个miRNAs的表达在经柳氮磺胺吡啶处理后发生了不同程度的变化。生物信息学分析表明,有1384个靶mRNA与表达不同的miRNA相对应。令人惊讶的是,水杨甙能显著上调抑癌基因miR-1343-3p的表达,下调MAP3K6、STAT3和MMP24相关基因的表达。通过诱导癌细胞凋亡、阻滞癌细胞周期和下调相关信号转导通路来抑制胃癌的生长。miRNAs在经柳氮苷治疗后的胃癌细胞中表达不同,在调控细胞增殖和转移中发挥重要作用。水杨甙可通过上调抑癌基因miR-1343-3p的表达,下调MAP3K6和MMP24信号分子的表达来抑制胃癌的生长。
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引用次数: 0
Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity. 谷氨酰胺酰肽环转酶在乳腺癌多柔比星敏感性中的作用
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-02-28 DOI: 10.1080/15384047.2024.2321767
Bin Xu, Liu Yang, Lixian Yang, Ahmed Al-Maamari, Jingyu Zhang, Heng Song, Meiqi Wang, Suwen Su, Zhenchuan Song

Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.

多柔比星(DOX)是最有效、应用最广泛的化疗药物之一。然而,DOX 耐药性是乳腺癌治疗中的一个关键风险问题。以往的研究表明,偏粘连蛋白(MTDH)参与了乳腺癌的 DOX 耐药性,但其确切机制仍不清楚。本研究发现,谷氨酰肽环转酶(QPCT)是乳腺癌中 MTDH DOX 抗性相关的下游基因。在 GEPIA 数据库、乳腺癌组织和乳腺癌细胞中都发现了 QPCT 的高表达。临床数据显示,QPCT的表达与DOX治疗患者的不良预后呈正相关。QPCT 的过表达可促进 MCF-7 和 MDA-MB-231 细胞的增殖、侵袭和迁移,并降低 DOX 的敏感性。从机理上讲,MTDH正向调控NF-κB(p65)和QPCT的表达,而NF-κB(p65)直接调控QPCT的表达。因此,我们提出了 MTDH/NF-κB (p65)/QPCT 信号轴。总之,我们的研究结果阐明了 MTDH/NF-κB (p65) 轴调控 QPCT 信号转导的机制,并提示该复合物可能在乳腺癌进展中发挥重要作用,并影响 DOX 的敏感性。
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引用次数: 0
M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma. 鼻咽癌中 M6A 介导的分子模式和肿瘤微环境浸润特征。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-26 DOI: 10.1080/15384047.2024.2333590
Yong Wang, Lisha Peng, Feng Wang

N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan-Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity.

N6-甲基腺苷(m6A)是真核细胞中最主要的 RNA 表观遗传调控。大量证据表明,m6A修饰在多种肿瘤的肿瘤微环境(TME)细胞浸润调控中发挥着至关重要的作用。研究人员利用从基因表达总库(Gene Expression Omnibus,GEO)获得的 GSE102349 和 GSE53819 数据集的 mRNA 表达数据和临床信息进行差异基因表达和后续分析。利用单变量 Cox 分析法,基于预后 m6A 调节因子对 88 个鼻咽癌样本进行共识聚类,以确定与 m6A 相关的分子模式。利用单样本基因组富集(ssGSEA)算法和 CIBERSORT 算法探讨了每个 m6A 相关亚类的 TME 细胞浸润特征。使用 edgeR 软件包筛选两个 m6A 相关亚类之间的 DEGs。根据 m6A 相关 DEGs 构建了预后特征和预测提名图。通过免疫组化(IHC)分析确定了鼻咽癌的细胞浸润和预后特征的表达。采用卡方检验分析分类变量差异的显著性。采用卡普兰-梅耶图和对数秩检验进行生存分析。鼻咽癌样本被分为两个与m6A相关的亚类。TME细胞浸润特征分析表明,群组1的特征是免疫相关和代谢通路被激活,对anit-PD1和抗CTLA4治疗和化疗反应较好。而群组2的特点是基质激活、HLA家族和免疫检查点低表达,以及对抗PD1和抗CTLA4治疗和化疗的反应较差。此外,我们还鉴定了两个m6A相关亚类之间的1558个DEGs,并构建了预测鼻咽癌患者无进展生存期(PFS)的预后特征。与非肿瘤样本相比,REEP2、TMSB15A、DSEL和ID4在鼻咽癌样本中上调。REEP2和TMSB15A的高表达表明鼻咽癌患者的生存率较低。研究发现了REEP2、TMSB15A、DSEL、ID4和m6A调节因子之间的相互作用。我们的发现表明,m6A修饰在调控TME异质性和复杂性方面发挥着重要作用。
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引用次数: 0
T-Cell redirecting bispecific antibodies: a review of a novel class of immuno-oncology for advanced prostate cancer. T细胞重定向双特异性抗体:一类治疗晚期前列腺癌的新型免疫肿瘤学综述。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-27 DOI: 10.1080/15384047.2024.2356820
Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick J Mille, William J Tester, Wm Kevin Kelly, Kevin K Zarrabi

Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor activity, but challenges related to drug delivery, immunogenicity, and treatment-associated adverse effects limited their success. The ongoing development of novel BiTE constructs continues to address these barriers and to yield promising results in terms of efficacy and safety. This review will highlight some of most recent developments of BiTE therapies for patients with advanced prostate cancer and the evolving data surrounding BiTE constructs undergoing clinical evaluation.

新型 T 细胞免疫疗法,如双特异性 T 细胞吞噬体(BiTEs),正逐渐成为治疗前列腺癌的有效策略。BiTEs 是一种工程化的双特异性抗体,含有两个不同的结合域,可同时与肿瘤相关抗原(TAAs)和免疫效应细胞结合,从而促进针对癌细胞的免疫反应。前列腺癌富含肿瘤相关抗原,如但不限于 PSMA、PSCA、hK2 和 STEAP1,因此在前列腺癌疾病领域使用 T 细胞重定向 BiTE 具有很强的生物学依据。临床研究中使用的第一代 BiTE 构建物已显示出有意义的抗肿瘤活性,但与给药、免疫原性和治疗相关的不良反应有关的挑战限制了它们的成功。目前,新型生物TE 构建物的开发工作正在继续解决这些障碍,并在疗效和安全性方面取得了可喜的成果。本综述将重点介绍针对晚期前列腺癌患者的生物TE疗法的一些最新进展,以及围绕正在接受临床评估的生物TE构建物不断变化的数据。
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引用次数: 0
Roles of TRPM channels in glioma. TRPM 通道在胶质瘤中的作用。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-04-29 DOI: 10.1080/15384047.2024.2338955
Zhigang Chen, Han Xie, Jun Liu, JiaJia Zhao, Ruixiang Huang, Yufei Xiang, Haoyuan Wu, Dasheng Tian, Erbao Bian, Zhang Xiong

Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.

胶质瘤是最常见的原发性脑肿瘤。尽管治疗手段不断进步,但它仍然是中枢神经系统(CNS)中侵袭性最强、最致命的肿瘤之一。胶质瘤的特点是高度恶性、异质性、侵袭性以及对放疗和化疗的高度耐受性。寻找潜在的胶质瘤新分子靶点迫在眉睫。TRPM通道由TRPM1-TPRM8组成,在细胞增殖、迁移、侵袭、血管生成等多种细胞功能中发挥作用。越来越多的研究表明,TRPM 通道可作为胶质瘤的新治疗靶点。在这篇综述中,我们首先介绍了 TRPM 通道的结构、激活模式和生理功能。此外,还介绍了由 TRPM2、3、7 和 8 介导的胶质瘤病理机制及相关信号通路。最后,我们讨论了靶向 TRPM 治疗神经胶质瘤的潜力。
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引用次数: 0
Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival. 根据人乳头瘤病毒状态比较分析头颈部粘膜癌的肿瘤微生物组、分子特征和免疫细胞丰度及其对生存的影响。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-09 DOI: 10.1080/15384047.2024.2350249
Rituraj Upadhyay, Aastha Dhakal, Caroline Wheeler, Rebecca Hoyd, Malvenderjit Jagjit Singh, Vidhya Karivedu, Priyanka Bhateja, Marcelo Bonomi, Sasha Valentin, Mauricio E Gamez, David J Konieczkowski, Sujith Baliga, John C Grecula, Dukagjin M Blakaj, Emile Gogineni, Darrion L Mitchell, Nicholas C Denko, Daniel Spakowicz, Sachin R Jhawar

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.

头颈部鳞状细胞癌(HNSCC)是一种类型多样的肿瘤,其治疗反应和预后各不相同。包括微生物组和免疫细胞在内的肿瘤微环境(TME)会影响预后。在此,我们试图利用癌症基因组图谱(TCGA)中的肿瘤转录组学研究特定微生物的存在、基因表达和肿瘤免疫浸润,并将其与总生存期(OS)联系起来。TCGA中HNSCC肿瘤的RNA测序(RNAseq)通过肿瘤和免疫细胞外源序列(exotic)管道进行处理,以识别和量化低丰度微生物。乳头瘤病毒科病毒的检测评估了 HPV 状态。所有统计分析均使用 R 进行。共分析了来自 TCGA 的 499 份 RNAseq 样本。在111个样本(22%)中检测到了HPV,最常见的是Alphapapillomavirus 9(90.1%)。Alphapapillomavirus 9的存在与OS改善相关[HR = 0.60 (95%CI: 0.40-0.89, p = .01)]。在其他微生物中,耶尔森氏菌假结核与最差的存活率相关(HR = 3.88;p = .008),而病毒假单胞菌的存活率最高(HR = 0.05;p = .036)。在HPV-肿瘤中发现较多的微生物种类包括几种革兰氏阴性厌氧菌。HPV-肿瘤中的M0含量明显更高(p p = .035),而HPV+肿瘤中的T调节细胞含量更高(p p = .035)。
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引用次数: 0
The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response. 肿瘤微环境与肿瘤衍生小细胞外囊泡在癌症发展和治疗反应中的相互作用。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-20 DOI: 10.1080/15384047.2024.2356831
Xuanyu Guo, Jiajun Song, Miao Liu, Xinyi Ou, Yongcan Guo

The tumor microenvironment (TME) plays an essential role in tumor cell survival by profoundly influencing their proliferation, metastasis, immune evasion, and resistance to treatment. Extracellular vesicles (EVs) are small particles released by all cell types and often reflect the state of their parental cells and modulate other cells' functions through the various cargo they transport. Tumor-derived small EVs (TDSEVs) can transport specific proteins, nucleic acids and lipids tailored to propagate tumor signals and establish a favorable TME. Thus, the TME's biological characteristics can affect TDSEV heterogeneity, and this interplay can amplify tumor growth, dissemination, and resistance to therapy. This review discusses the interplay between TME and TDSEVs based on their biological characteristics and summarizes strategies for targeting cancer cells. Additionally, it reviews the current issues and challenges in this field to offer fresh insights into comprehending tumor development mechanisms and exploring innovative clinical applications.

肿瘤微环境(TME)对肿瘤细胞的增殖、转移、免疫逃避和抗药性有着深远的影响,在肿瘤细胞的生存过程中扮演着至关重要的角色。细胞外囊泡(EVs)是所有类型细胞释放的小颗粒,通常反映其母细胞的状态,并通过其运输的各种货物调节其他细胞的功能。肿瘤源性小囊泡(TDSEVs)可以运输特定的蛋白质、核酸和脂质,以传播肿瘤信号并建立有利的肿瘤组织生长环境。因此,TME 的生物特性会影响 TDSEV 的异质性,这种相互作用会扩大肿瘤的生长、扩散和抗药性。本综述根据 TME 和 TDSEV 的生物特性讨论了它们之间的相互作用,并总结了针对癌细胞的策略。此外,它还回顾了这一领域目前存在的问题和挑战,为理解肿瘤发生机制和探索创新性临床应用提供新的见解。
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引用次数: 0
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Cancer Biology & Therapy
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