Minglei Yang, Chenghao Lin, Yanni Wang, Kang Chen, Yutong Han, Haiyue Zhang, Weizhong Li
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.
{"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":"56 1","pages":""},"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}
Pub Date : 2022-05-10eCollection Date: 2022-06-01DOI: 10.1093/pcmedi/pbac013
Xiaolei Liu, Jirong Yue
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
{"title":"Precision intervention for sarcopenia.","authors":"Xiaolei Liu, 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":"5 2","pages":"pbac013"},"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}
Ang Li, Bicheng Ye, Fangnan Lin, Yi-lin Wang, Xiaye Miao, Yanfang Jiang
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.
{"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":"36 1","pages":""},"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}
C. Tan, Mingming Yang, Zhisheng You, Hu Chen, Yan Zhang
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.
{"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":"7 1","pages":""},"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}
Jixiang Zhang, Xuemei Jia, Yuanmei Guo, Haotian Jiang, Jia-yuan Hu, Siwei Wang, Binglu Huang, Wenhao Su, Jun Liu, Xiaoli Wang, W. Dong
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
背景:个体化使用不同体积的聚乙二醇被广泛认为是肠道准备的最佳解决方案，而我们提出的以患者为导向的方案可能是可靠的个体化解决方案。本研究旨在评估以患者为导向的肠准备方案的有效性、安全性和满意度。方法固定体积组患者摄入相同量的聚乙二醇，而患者定向组患者根据粪便稠度或粪便含水量摄入不同量的聚乙二醇。结果通过排除标准筛选后，固定容量组428例，患者导向组103例成功入组分析。在患者导向组中，83人(80.6%)的聚乙二醇体积减少。两组患者的肠道准备效果差异无统计学意义(90.0% vs 90.3%， χ²= 0.01;P = 0.918)。患者导向组患者抱怨不良反应较少(53.0% vs 36.9%， χ²= 8.655;P = 0.003)，尤其是呕吐(13.6% vs. 1.0%， χ²= 13.304;P < 0.001)。在肠准备过程中的舒适度方面，各组之间的舒适度无显著差异。此外，患者指导组进一步结肠镜检查的意愿率显著高于固定容积组(90.3% vs 77.1%， χ²= 8.912;P < 0.05)。多变量logistic回归分析显示，体重指数是影响患者指导方案肠道准备质量的独立因素(OR 1.16, 95% CI 1.00-1.34;P = 0.043)。结论患者导向方案在不降低肠准备效果的前提下，提高了肠准备的安全性和满意度，有望成为一种常规的个体化肠准备方案。身体质量指数较低的人更有可能采用这种新疗法。试验注册号ChiCTR1900022072，登录chicclinicaltrials .gov
{"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":"43 1","pages":""},"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}
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
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.
{"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":"1 1","pages":""},"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}
{"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":"133 1","pages":""},"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}
X. Gong, Yanan Li, Kaiying Yang, Siyuan Chen, Yi Ji
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.
{"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":"12 1","pages":""},"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}
Abstract In 2006, Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4, Sox2, Klf44, and c-Myc. Since then, the future clinical application of somatic cell reprogramming technology has become an attractive research topic in the field of regenerative medicine. Of note, considerable interest has been placed in circumventing ethical issues linked to embryonic stem cell research. However, tumorigenicity, immunogenicity, and heterogeneity may hamper attempts to deploy this technology therapeutically. This review highlights the progress aimed at reducing induced pluripotent stem cells tumorigenicity risk and how to assess the safety of induced pluripotent stem cells cell therapy products.
{"title":"Tumorigenicity risk of iPSCs in vivo: nip it in the bud","authors":"Chaoliang Zhong, Miao Liu, Xinghua Pan, Haiying Zhu","doi":"10.1093/pcmedi/pbac004","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac004","url":null,"abstract":"Abstract In 2006, Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4, Sox2, Klf44, and c-Myc. Since then, the future clinical application of somatic cell reprogramming technology has become an attractive research topic in the field of regenerative medicine. Of note, considerable interest has been placed in circumventing ethical issues linked to embryonic stem cell research. However, tumorigenicity, immunogenicity, and heterogeneity may hamper attempts to deploy this technology therapeutically. This review highlights the progress aimed at reducing induced pluripotent stem cells tumorigenicity risk and how to assess the safety of induced pluripotent stem cells cell therapy products.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2022-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76213327","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}
{"title":"Management of severe asthma: from stepwise approach to therapy to treatable traits?","authors":"Gang Wang, V. McDonald, P. Gibson","doi":"10.1093/pcmedi/pbab028","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab028","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"30 1","pages":"293-296"},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89285774","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}
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