Precision Clinical Medicine最新文献

筛选
英文 中文
Health consequences of early-onset compared with late-onset type 2 diabetes mellitus. 早发性与晚发性2型糖尿病的健康后果比较
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-06-01 DOI: 10.1093/pcmedi/pbac015
Can Hou, Huazhen Yang, Yuanyuan Qu, Wenwen Chen, Yu Zeng, Yao Hu, K M Venkat Narayan, Huan Song, Dong Li
{"title":"Health consequences of early-onset compared with late-onset type 2 diabetes mellitus.","authors":"Can Hou,&nbsp;Huazhen Yang,&nbsp;Yuanyuan Qu,&nbsp;Wenwen Chen,&nbsp;Yu Zeng,&nbsp;Yao Hu,&nbsp;K M Venkat Narayan,&nbsp;Huan Song,&nbsp;Dong Li","doi":"10.1093/pcmedi/pbac015","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac015","url":null,"abstract":"<p><strong>Background: </strong>Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus (T2DM) conferred on patients a broader tendency for complications beyond vascular ones, a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.</p><p><strong>Method: </strong>We prospectively studied 1 777 early-onset (age at diagnosis ≤ 45 years) and 35 889 late-onset (>45 years) T2DM patients with matched unexposed individuals from the UK Biobank. Diabetes-specific and -related complications were examined using phenome-wide association analysis, with patterns identified by comorbidity network analysis. We also evaluated the effect of lifestyle modifications and glycemic control on complication development.</p><p><strong>Results: </strong>The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years, respectively. Compared to late-onset T2DM patients, patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs [hazard ratio (HR) 3.46 vs. 1.72], the endocrine/metabolic system (HR 3.08 vs. 2.01), and the neurological system (HR 2.70 vs. 1.81). Despite large similarities in comorbidity patterns, a more complex and well-connected network was observed for early-onset T2DM. Furthermore, while patients with early-onset T2DM got fewer benefits (12.67% reduction in pooled HR for all studied complications) through fair glycemic control (median HbA<sub>1c</sub> ≤ 53 mmol/mol) compared to late-onset T2DM patients (18.01% reduction), they seemed to benefit more from favorable lifestyles, including weight control, healthy diet, and adequate physical activity.</p><p><strong>Conclusions: </strong>Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM. Aggressive glucose-lowering intervention, complemented by lifestyle modifications, are feasible strategies for controlling early-onset T2DM-related complications.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/f1/pbac015.PMC9239845.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis 单细胞测序数据分析揭示细胞因子风暴促进重症COVID-19 T细胞衰竭
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-05-23 DOI: 10.1093/pcmedi/pbac014
Minglei Yang, Chenghao Lin, Yanni Wang, Kang Chen, Yutong Han, Haiyue Zhang, Weizhong Li
{"title":"Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis","authors":"Minglei Yang, Chenghao Lin, Yanni Wang, Kang Chen, Yutong Han, Haiyue Zhang, Weizhong Li","doi":"10.1093/pcmedi/pbac014","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac014","url":null,"abstract":"Abstract Background Evidence has suggested that cytokine storms may be associated with T cell exhaustion (TEX) in COVID-19. However, the interaction mechanism between cytokine storms and TEX remains unclear. Methods With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis, we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy people. We observed a novel subset of severely exhausted CD8 T cells (Exh T_CD8) that co-expressed multiple inhibitory receptors, and two macrophage subclasses that were the main source of cytokine storms in bronchoalveolar. Results Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe COVID-19. Cell–cell communication analysis indicated that cytokines (e.g. CXCL10, CXCL11, CXCL2, CCL2, and CCL3) released by macrophages acted as ligands and significantly interacted with inhibitory receptors (e.g. CXCR3, DPP4, CCR1, CCR2, and CCR5) expressed by Exh T_CD8. These interactions formed the cytokine–receptor axes, which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell carcinoma. Conclusions Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in COVID-19. Blocking cytokine-receptor axes may reverse TEX. Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76283422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Precision intervention for sarcopenia. 肌肉减少症的精确干预。
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-05-10 eCollection Date: 2022-06-01 DOI: 10.1093/pcmedi/pbac013
Xiaolei Liu, Jirong Yue
{"title":"Precision intervention for sarcopenia.","authors":"Xiaolei Liu,&nbsp;Jirong Yue","doi":"10.1093/pcmedi/pbac013","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac013","url":null,"abstract":"Sarcopenia is an aging-related disease characterized by progressive muscle mass loss, decreasing muscle strength, and physiological muscle function decline. It is associated with multiple adverse outcomes, including falls, fractures, physical disability, and death. The new code in ICD-10-CM (M62.84) in 2016 signifies its being recognized as a disease and drawing attention to the condition in this ever-aging society. The prevalence of sarcopenia in the elderly is ∼6.8%–25.7% for Asia1 and, in particular, 8.9%–38.8% for China.2 The mechanism of sarcopenia is complex and includes hormonal changes, nutritional deficiencies, chronic inflammation, neuromuscular function decline, and decreased physical activity. While no specific drugs have been approved to treat sarcopenia, ten pharmacological interventions have been identified to ameliorate the condition in the elderly, including growth hormone, growth hormone-releasing hormone, vitamin D, dehydroepiandrosterone, combined estrogen– progesterone, testosterone-growth hormone, pioglitazone, testosterone, insulin-like growth factor-1, and angiotensin-converting enzyme inhibitors.3 Possible drugs for sarcopenia are under development (Table 1).4 As a result, understanding the mechanisms of sarcopenia is critical for drug development. The treatment of sarcopenia currently focuses on nutrition and exercise interventions. However, the clinical evidence is very limited and many questions still remain unanswered. For example, how can the safety and compliance of exercise interventions be ensured according to stress adaptability? Besides, a large percentage of sarcopenic patients cannot live up to recommended degrees of both nutritional food intake and physical activity, resulting in numerous problems. Therefore, for elderly patients with sarcopenia with different conditions, individualized intervention and management strategies are urgently needed according to the patient’s metabolic and digestive functions. Food components with anti-inflammatory properties, such as probiotics and traditional Chinese medicine prescriptions, should be considered for intervention. Sarcopenia is associated with different genotypes. For example, in sarcopenia patients, the X allele of the alpha-actinin-3 (ACTN3) genotype was found to be more associated with decreased thigh muscle volume compared with the RR allele of the ACTN3 genotype.5 In addition, angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. Specifically, the I allele of ACE genotype is associated with endurance-orientated events, while the D allele is associated with strengthand power-orientated performance.6 Another gene associated with sarcopenia is vitamin D receptor (VDR), and FF carriers have double the risk of having sarcopenia compared with carriers of the f allele.7 Other genetic variations associated with sarcopenia include the tumo","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
A novel immunogenomic signature to predict prognosis and reveal immune infiltration characteristics in pancreatic ductal adenocarcinoma 一种新的免疫基因组特征预测胰腺导管腺癌的预后并揭示免疫浸润特征
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-04-25 DOI: 10.1093/pcmedi/pbac010
Ang Li, Bicheng Ye, Fangnan Lin, Yi-lin Wang, Xiaye Miao, Yanfang Jiang
{"title":"A novel immunogenomic signature to predict prognosis and reveal immune infiltration characteristics in pancreatic ductal adenocarcinoma","authors":"Ang Li, Bicheng Ye, Fangnan Lin, Yi-lin Wang, Xiaye Miao, Yanfang Jiang","doi":"10.1093/pcmedi/pbac010","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac010","url":null,"abstract":"Abstract Background The immune response in the tumor microenvironment (TME) plays a crucial role in cancer progression and recurrence. We aimed to develop an immune-related gene (IRG) signature to improve prognostic predictive power and reveal the immune infiltration characteristics of pancreatic ductal adenocarcinoma (PDAC). Methods The Cancer Genome Atlas (TCGA) PDAC was used to construct a prognostic model as a training cohort. The International Cancer Genome Consortium (ICGC) and the Gene Expression Omnibus (GEO) databases were set as validation datasets. Prognostic genes were screened by using univariate Cox regression. Then, a novel optimal prognostic model was developed by using least absolute shrinkage and selection operator (LASSO) Cox regression. Cell type identification by estimating the relative subsets of RNA transcripts (CIBERSORT) and estimation of stromal and immune cells in malignant tumors using expression data (ESTIMATE) algorithms were used to characterize tumor immune infiltrating patterns. The tumor immune dysfunction and exclusion (TIDE) algorithm was used to predict immunotherapy responsiveness. Results A prognostic signature based on five IRGs (MET, ERAP2, IL20RB, EREG, and SHC2) was constructed in TCGA-PDAC and comprehensively validated in ICGC and GEO cohorts. Multivariate Cox regression analysis demonstrated that this signature had an independent prognostic value. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve at 1, 3, and 5 years of survival were 0.724, 0.702, and 0.776, respectively. We further demonstrated that our signature has better prognostic performance than recently published ones and is superior to traditional clinical factors such as grade and tumor node metastasis classification (TNM) stage in predicting survival. Moreover, we found higher abundance of CD8+ T cells and lower M2-like macrophages in the low-risk group of TCGA-PDAC, and predicted a higher proportion of immunotherapeutic responders in the low-risk group. Conclusions We constructed an optimal prognostic model which had independent prognostic value and was comprehensively validated in external PDAC databases. Additionally, this five-genes signature could predict immune infiltration characteristics. Moreover, the signature helped stratify PDAC patients who might be more responsive to immunotherapy.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79301441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
A selective kernel-based cycle-consistent generative adversarial network for unpaired low-dose CT denoising 非配对低剂量CT去噪的基于选择性核的周期一致生成对抗网络
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-04-20 DOI: 10.1093/pcmedi/pbac011
C. Tan, Mingming Yang, Zhisheng You, Hu Chen, Yan Zhang
{"title":"A selective kernel-based cycle-consistent generative adversarial network for unpaired low-dose CT denoising","authors":"C. Tan, Mingming Yang, Zhisheng You, Hu Chen, Yan Zhang","doi":"10.1093/pcmedi/pbac011","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac011","url":null,"abstract":"Abstract Low-dose computed tomography (LDCT) denoising is an indispensable procedure in the medical imaging field, which not only improves image quality, but can mitigate the potential hazard to patients caused by routine doses. Despite the improvement in performance of the cycle-consistent generative adversarial network (CycleGAN) due to the well-paired CT images shortage, there is still a need to further reduce image noise while retaining detailed features. Inspired by the residual encoder–decoder convolutional neural network (RED-CNN) and U-Net, we propose a novel unsupervised model using CycleGAN for LDCT imaging, which injects a two-sided network into selective kernel networks (SK-NET) to adaptively select features, and uses the patchGAN discriminator to generate CT images with more detail maintenance, aided by added perceptual loss. Based on patch-based training, the experimental results demonstrated that the proposed SKFCycleGAN outperforms competing methods in both a clinical dataset and the Mayo dataset. The main advantages of our method lie in noise suppression and edge preservation.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82715383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Aminoflavone upregulates putative tumor suppressor miR-125b-2-3p to inhibit luminal A breast cancer stem cell-like properties. 氨基黄酮能上调假定的肿瘤抑制因子 miR-125b-2-3p,从而抑制管腔 A 型乳腺癌干细胞样特性。
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-03-28 eCollection Date: 2022-06-01 DOI: 10.1093/pcmedi/pbac008
Nicole Mavingire, Petreena Campbell, Tiantian Liu, Jonathan Wooten, Salma Khan, Xin Chen, Jason Matthews, Charles Wang, Eileen Brantley
{"title":"Aminoflavone upregulates putative tumor suppressor miR-125b-2-3p to inhibit luminal A breast cancer stem cell-like properties.","authors":"Nicole Mavingire, Petreena Campbell, Tiantian Liu, Jonathan Wooten, Salma Khan, Xin Chen, Jason Matthews, Charles Wang, Eileen Brantley","doi":"10.1093/pcmedi/pbac008","DOIUrl":"10.1093/pcmedi/pbac008","url":null,"abstract":"<p><p>Metastatic breast cancer is incurable and often due to breast cancer stem cell (CSC)-mediated self-renewal. We previously determined that the aryl hydrocarbon receptor (AhR) agonist aminoflavone (AF) inhibits the expression of the CSC biomarker α6-integrin (ITGA6) to disrupt the formation of luminal (hormone receptor-positive) mammospheres (3D breast cancer spheroids). In this study, we performed miRNA-sequencing analysis of luminal A MCF-7 mammospheres treated with AF to gain further insight into the mechanism of AF-mediated anti-cancer and anti-breast CSC activity. AF significantly induced the expression of >70 microRNAs (miRNAs) including miR125b-2-3p, a predicted stemness gene regulator. AF-mediated miR125b-2-3p induction was validated in MCF-7 mammospheres and cells. miR125b-2-3p levels were low in breast cancer tissues irrespective of subtype compared to normal breast tissues. While miR125b-2-3p levels were low in MCF-7 cells, they were much lower in AHR<sup>100</sup> cells (MCF-7 cells made unresponsive to AhR agonists). The miR125b-2-3p mimic decreased, while the antagomiR125b-2-3p increased the expression of stemness genes ITGA6 and SOX2 in MCF-7 cells. In MCF-7 mammospheres, the miR125b-2-3p mimic decreased only ITGA6 expression although the antagomiR125b-2-3p increased ITGA6, SOX2 and MYC expression. AntagomiR125b-2-3p reversed AF-mediated suppression of ITGA6. The miR125b-2-3p mimic decreased proliferation, migration, and mammosphere formation while the antagomiR125b-2-3p increased proliferation and mammosphere formation in MCF-7 cells. The miR125b-2-3p mimic also inhibited proliferation, mammosphere formation, and migration in AHR100 cells. AF induced AhR- and miR125b2-3p-dependent anti-proliferation, anti-migration, and mammosphere disruption in MCF-7 cells. Our findings suggest that miR125b-2-3p is a tumor suppressor and AF upregulates miR125b-2-3p to disrupt mammospheres via mechanisms that rely at least partially on AhR in luminal A breast cancer cells.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78233559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patient-directed vs. fixed-volume PEG for colonoscopy preparation: a randomized controlled trial 患者导向与固定体积PEG结肠镜准备:一项随机对照试验
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-03-26 DOI: 10.1093/pcmedi/pbac009
Jixiang Zhang, Xuemei Jia, Yuanmei Guo, Haotian Jiang, Jia-yuan Hu, Siwei Wang, Binglu Huang, Wenhao Su, Jun Liu, Xiaoli Wang, W. Dong
{"title":"Patient-directed vs. fixed-volume PEG for colonoscopy preparation: a randomized controlled trial","authors":"Jixiang Zhang, Xuemei Jia, Yuanmei Guo, Haotian Jiang, Jia-yuan Hu, Siwei Wang, Binglu Huang, Wenhao Su, Jun Liu, Xiaoli Wang, W. Dong","doi":"10.1093/pcmedi/pbac009","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac009","url":null,"abstract":"ABSTRACT Background Individualization using different volumes of polyethylene glycol is widely regarded as the optimal solution for bowel preparation, while the patient-directed regimen we propose may serve as a reliable individual solution. This study aimed to assess the efficacy, safety, and satisfaction of bowel preparation with a patient-directed regimen. Methods Patients in the fixed-volume group ingested the same amount of PEG, while those in patient-directed group ingested different amount according to stool consistency or stool water content. Results After filtering by exclusion criteria, 428 individuals in the fixed-volume group and 103 in the patient-directed group were successfully enrolled and analyzed. Eighty-three (80.6%) individuals in the patient-directed group had a reduced polyethylene glycol volume. There was no significant difference in the bowel preparation efficacy between the two groups (90.0% vs. 90.3%, χ² = 0.01; p = 0.918). Patients in the patient-directed group complained of fewer adverse effects (53.0% vs. 36.9%, χ² = 8.655; p = 0.003), especially vomiting (13.6% vs. 1.0%, χ² = 13.304; p < 0.001). Regarding comfort during bowel preparation, the degree of comfort was not significantly different between groups. Furthermore, the willingness rate for further colonoscopy in the patient-directed group was significantly higher than that in the fixed-volume group (90.3% vs. 77.1%, χ² = 8.912; p < 0.05). Multivariable logistic regression analysis showed that the body mass index served as an independent factor impacting quality of bowel preparation with the patient-directed regimen (OR 1.16, 95% CI 1.00–1.34; p = 0.043). Conclusions Without decreasing the bowel preparation efficacy, the patient-directed regimen increased the safety and satisfaction of bowel preparation and is expected to be a regular and individual solution for bowel preparation. Individuals with a lower body mass index are more likely to undertake this new regimen. Trial registration number ChiCTR1900022072 at ChiClinicalTrials.gov","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73240318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells 阻断整合素信号通路可减少化疗诱导的胶原培养膀胱癌细胞过早衰老
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-03-17 DOI: 10.1093/pcmedi/pbac007
L. Deng, K. Jin, Xianghong Zhou, Zilong Zhang, Liming Ge, X. Xiong, X. Su, Di Jin, Qiming Yuan, Chichen Zhang, Yifan Li, Haochen Zhao, Qiang Wei, L. Yang, S. Qiu
{"title":"Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells","authors":"L. Deng, K. Jin, Xianghong Zhou, Zilong Zhang, Liming Ge, X. Xiong, X. Su, Di Jin, Qiming Yuan, Chichen Zhang, Yifan Li, Haochen Zhao, Qiang Wei, L. Yang, S. Qiu","doi":"10.1093/pcmedi/pbac007","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac007","url":null,"abstract":"Abstract Background Diminished sensitivity towards chemotherapy remains the major impediment to the clinical treatment of bladder cancer. However, the critical elements in control of chemotherapy resistance remain obscure. Methods We adopted improved collagen gels and performed cytotoxicity analysis of doxorubicin (DOX) and mitomycin C (MMC) of bladder cancer cells in a 3D culture system. We then detected the expression of multidrug resistant gene ABCB1, dormancy-associated functional protein chicken ovalbumin upstream-transcription factor 1 (COUPTF1), cell proliferation marker Ki-67, and cellular senescence marker senescence-associated β-galactosidase (SA-β-Gal) in these cells. We further tested the effects of integrin blockade or protein kinase B (AKT) inhibitor on the senescent state of bladder cancer. Also, we examined the tumor growth and survival time of bladder cancer mouse models given the combination treatment of chemotherapeutic agents and integrin α2β1 ligand peptide TFA (TFA). Results Collagen gels played a repressive role in bladder cancer cell apoptosis induced by DOX and MMC. In mechanism, collagen activated the integrin β1/AKT cascade to drive bladder cancer cells into a premature senescence state via the p53/p21 pathway, thus attenuating chemotherapy-induced apoptosis. In addition, TFA had the ability to mediate the switch from senescence to apoptosis of bladder cancer cells in xenograft mice. Meanwhile, TFA combined with chemotherapeutic drugs produced a substantial suppression of tumor growth as well as an extension of survival time in vivo. Conclusions Based on our finding that integrin β1/AKT acted primarily to impart premature senescence to bladder cancer cells cultured in collagen gel, we suggest that integrin β1 might be a feasible target for bladder cancer eradication.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84023968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Precision medicine: a few thoughts from 2022 精准医疗:2022年的几点思考
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-02-12 DOI: 10.1093/pcmedi/pbac003
Sherman M. Weissman
{"title":"Precision medicine: a few thoughts from 2022","authors":"Sherman M. Weissman","doi":"10.1093/pcmedi/pbac003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac003","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90707884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Infantile hepatic hemangiomas: looking backwards and forwards 婴儿肝血管瘤:回顾和展望
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2022-02-11 DOI: 10.1093/pcmedi/pbac006
X. Gong, Yanan Li, Kaiying Yang, Siyuan Chen, Yi Ji
{"title":"Infantile hepatic hemangiomas: looking backwards and forwards","authors":"X. Gong, Yanan Li, Kaiying Yang, Siyuan Chen, Yi Ji","doi":"10.1093/pcmedi/pbac006","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac006","url":null,"abstract":"Abstract Infantile hepatic hemangiomas (IHHs) are common benign tumors seen in the liver of infants. IHHs are true infantile hemangiomas (IHs) and have phases of proliferation and involution parallel to those of cutaneous IHs. The definition and classification of IHH are still confusing in the literature. The mechanisms during the pathogenesis of IHH have yet to be discovered. The clinical manifestations of IHH are heterogeneous. Although most IHH lesions are asymptomatic, some lesions can lead to severe complications, such as hypothyroidism, consumptive coagulopathy, and high-output congestive cardiac failure. Consequently, some patients can possibly encounter a fatal clinical condition. The heterogeneity of the lesions and the occurrence of disease-related comorbidities can make the treatment of IHH challenging. Oral propranolol is emerging as an effective systemic approach to IHH with obvious responses in tumor remission and symptom regression. However, the precise clinical characteristics and treatment strategies for patients with severe IHH have not yet been well established. Here, we summarize the epidemiology, pathogenic mechanism, clinical manifestations, diagnosis, and treatment of IHH. Recent updates and future perspectives for IHH will also be elaborated.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85246610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信