检索结果-内蒙古大学图书馆

Immune and Metabolic Reprogramming Induced by Paclitaxel, Capecitabine and Eribulin in Breast Cancer: Insights into Therapeutic Targets

引用

Breast Cancer: Targets and Therapy 2025年 17卷 359-372页

作者： Hsiao, Hua-Hsin Patel, Riya Kalinski, Pawel Takabe, Kazuaki Gandhi, Shipra Rosario, Spencer R. Ernstoff, Marc S. Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center Buffalo 14263 NY United States Department of Medicine Roswell Park Comprehensive Cancer Center Buffalo 14263 NY United States Department of Immunology Roswell Park Comprehensive Cancer Center Buffalo 14263 NY United States Department of Surgical Oncology Roswell Park Comprehensive Cancer Center Buffalo 14263 NY United States Department of Medical Oncology Roswell Park Comprehensive Cancer Center Buffalo 14263 NY United States Department of Pharmacology and Therapeutics Roswell Park Comprehensive Cancer Center Buffalo 14263 NY United States ImmunoOncology NCI Division of Cancer Treatment and Diagnosis Bethesda 20892 MD United States

Purpose: Chemotherapeutic agents are known to exert anti-tumor effects by not only invoking cytotoxic effects, but also by altering both the immune profile and metabolic milieu. These alterations to both the immune milieu and circulating metabolome may be leveraged for designing rationale drug combinations with immunotherapeutic agents, once chemotherapy fails. Patients and Methods: Using publicly available transcriptomic data for breast cancer (BC) patients treated with neoadjuvant chemotherapy (GSE162187), we assessed transcriptional alterations that coincide with response to chemotherapy. To further study the metabolic and immune alterations associated with chemotherapeutic resistance, plasma samples from BC patients treated with eribulin, paclitaxel and capecitabine were obtained and assessed via Metabolomics and Luminex, at time of progression as compared to baseline. Results: Transcriptomics analysis revealed enrichment of amino acid and lipid metabolic pathways, as well as immune pathways including B cells, complement cascade and T cells, in patients resistant to chemotherapy. To validate these findings and assess the differences among different chemotherapies, plasma samples were obtained at baseline and disease progression. Increases in IL-18;IL-22, amylin and IL-6 were observed at the time of disease progression on eribulin, capecitabine and paclitaxel, respectively. Metabolically, increases in docosahexaenoic acid and decreases in sphingomyelins;increases in triacylglycerides and decreases in fatty acids, and decreases in glutamic acid, lipids and phosphatidylcholines were observed on disease progression on eribulin, capecitabine and paclitaxel, respectively. Conclusion: Distinct patterns of metabolic and immune dysregulation were associated with resistance to eribulin, capecitabine and paclitaxel. Varied immune and metabolic profiles were specific to each of the three chemotherapies, representing potential novel, and individualized, points of therapeutic

关键词： chemoresistance immune regulation metabolism metastatic breast cancer

来源：评论

学校读者我要写书评

暂无评论

Congestion Enriches Intra-hepatic Macrophages Through Reverse Zonation of CXCL9 in Liver Sinusoidal Endothelial Cells

引用

Cellular and Molecular Gastroenterology and Hepatology 2025年第7期19卷 101475-101475页

作者： Ma, Siyuan Habash, Nawras W. Dehankar, Mrunal K. Jalan-Sakrikar, Nidhi Cooper, Shawna A. Anwar, Abid A. Jerez, Sofia Sutthirat, Papawee Gao, Jinhang Diamond, Tamir Jiao, Jing Qiu, Caixin Yang, Jingchun Ilyas, Sumera I. Lee, Markcus Yaqoob, Usman Cao, Sheng Wells, Rebecca G. Shah, Vijay H. Hilscher, Moira B. Department of Biostatistics Vanderbilt University Medical Center Nashville TN United States Division of Gastroenterology and Hepatology Children's Hospital of Philadelphia Philadelphia Pennsylvania United States Department of Bioinformatics Mayo Clinic Rochester Minnesota United States Division of Gastroenterology and Hepatology Department of Medicine Mayo Clinic Rochester Minnesota United States Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic Rochester Minnesota United States Laboratory of Gastroenterology and Hepatology West China Hospital Sichuan University Chengdu China Division of Gastroenterology and Hepatology Department of Medicine University of Pennsylvania Philadelphia Pennsylvania United States Department of Pediatrics University of Pennsylvania Philadelphia Pennsylvania United States Department of Radiology Mayo Clinic Rochester Minnesota United States

Background & Aims: Congestion alters the microenvironment of the liver sinusoid along the portal-central axis. We studied spatial changes in immune cells in the sinusoid that contribute to congestive fibrosis and portal hypertension (PHTN). Methods: To visualize the distribution of immune cells in congestive hepatopathy (CH), we performed imaging mass cytometry (IMC) on liver tissue from patients with CH, Fontan-associated liver disease (FALD), and controls. We performed partial ligation of the inferior vena cava (pIVCL) to simulate CH in mice and isolated primary liver cells for single-cell RNA-sequencing (scRNA-seq) to study zonation of liver sinusoidal endothelial cells (LSECs). After pIVCL, mice were treated with intraperitoneal injections of AMG487, an inhibitor of the CXCL9 receptor, or a neutralizing antibody to CXCL9. Results: Intra-hepatic macrophages are enriched in CH and FALD. Given the role of CXCL9 in macrophage patterning in the liver, we performed RNA in situ hybridization (RNAish) in CH and determined that CXCL9 was highly expressed in LSECs in FALD, suggesting that LSECs recruit macrophages in CH. After pIVCL, treatment with AMG487 or an antibody to CXCL9 attenuated portal pressures, fibrosis, and intra-hepatic macrophages. To study changes in LSECs that promote macrophage chemotaxis, we performed scRNA-seq after pIVCL and sham procedures. Analysis revealed 3 LSEC subpopulations according to sinusoidal location. RNAish identified peri-central LSECs as the predominant source of CXCL9 in FALD. In vitro analyses revealed that β-catenin and hypoxia inducible factor-1 α regulate CXCL9 transcription in peri-central LSECs. Conclusions: CXCL9 derived from peri-central LSECs enriches intra-hepatic macrophages in CH and FALD, contributing to congestive fibrosis and PHTN. Strategies to target LSEC-derived CXCL9 may prevent the progression of CH and FALD. © 2025 The Authors

关键词： Fibrosis Fontan-associated Liver Disease Hypoxia Imaging Mass Cytometry Portal Hypertension

来源：评论

学校读者我要写书评

暂无评论

Effects of sickle trait on maternal and perinatal outcomes among pregnant women

Blood Vessels, Thrombosis & Hemostasis

引用

Blood Vessels, Thrombosis & Hemostasis 2025年第2期2卷 100049-100049页

作者： Sarah Sewaralthahab Jiling Chou Stephen Fernandez Nawar Shara Hedy P. Smith Department of Medicine College of Medicine King Saud University Riyadh Saudi Arabia Division of Hematology Oncology Center King Saud University Medical City Riyadh Saudi Arabia Department of Biostatistics Bioinformatics and Biomathematics Center of Biostatistics Informatics and Data Science Medstar Research Institute Hyattsville MD Depatment of Internal Medicine Medstar Washington Hospital Center Washington DC

Abstract The risk of multiple adverse pregnancy outcomes and perinatal outcomes among pregnant women with sickle cell trait (SCT) is not known. Our objective was to compare differences in adverse outcomes, specifically pregnancy-related hypertensive disease (PRHD), pyelonephritis/urinary tract infection (UTI), and low birth weight (LBW), between pregnant women with SCT and healthy controls. This was a retrospective cohort study of women who delivered between 2015 and 2020. We included all women with SCT, that is, hemoglobin electrophoresis AS. Women with SCT were matched in a 1:2 to women without SCT, controlling for age, gravidity, and parity. Our primary outcomes were PRHD, pyelonephritis/UTI, and LBW baby. Multivariable logistic regression modeling examined the associations between patients’ characteristics and the primary *** were 162 women with SCT, and 324 healthy control women were enrolled. Bivariate analysis revealed that women with SCT had a higher proportion of PRHD (38.9% vs 34.9%; P = .39), pyelonephritis/UTI (11.7% vs 7.1%; P = .09), but a lower proportion of LBW (10.5% vs 16.0%; P = .1). In multivariable analysis, after controlling for confounders, SCT was not an independent predictor of PRHD. However, SCT was an independent predictor of pyelonephritis/UTI (adjusted odds ratio [aOR], 1.98; 95% confidence interval [CI], 1.02-3.85) and of a lower risk of having a LBW baby (aOR, 0.48; 95% CI, 0.25-0.94). SCT is not associated with an increased risk of PRHD. However, SCT is associated with pregnancy outcomes, including higher risk of pyelonephritis/UTI but a lower risk of LBW babies.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Pre-Treatment Higher Eosinophil Count Is Associated with Improved Survival after Autologous CAR-T Therapy for Hematologic Malignancies

引用

Transplantation and Cellular Therapy 2025年第2期31卷 S334-S334页

作者： Kagalwalla, Sana, MD Sumransub, Nuttavut, MD Cao, Qing, MS Hu, Marie, MD Tracy, Sean, MD, PhD O'Leary, Daniel, MD Maakaron, Joseph E., MD Juckett, Mark Bachanova, Veronika Department of Medicine University of Minnesota Minneapolis MN Division of Hematology Oncology and Transplantation University of Minnesota Minneapolis MN Biostatistics and Bioinformatics Masonic Cancer Center University of Minnesota Minneapolis MN Bone and Marrow Transplant Program University of Minnesota Medical Center Minneapolis MN Division of Hematology Oncology and Transplantation University of Minnesota Minneapolis MN

IntroductionEosinophils (Eo) play an important role in recruiting T-cells to tumors, and recently were associated with an improved response to immune checkpoint inhibitor therapy. Preclinical studies showed that combining stem cell-derived eosinophil therapy with CAR-T leads to improved treatment efficacy. Limited clinical observations reported that patients greater eosinophil counts after CAR-T had superior CR rate and survival. We therefore examined associations between eosinophil count and immunologic recovery pre and post CAR-T cell therapy and treatment outcomes. MethodsWe included consecutive patients (>18 yrs) with leukemia, lymphoma or myeloma treated between January 2018 and June 2023 on the observational phase 2 study using commercial CAR-T products targeting CD19 and BCMA (NCT03642626). We collected CAR-T related toxicities, history of autoimmune diseases, peak absolute and percentage eosinophil counts and lymphocyte subset before aphaeresis, CAR-T cell therapy and at ∼30, 60, and 100 days after CAR-T infusion. Analysis of categorical variables was performed by Chi-square and of continuous variables by Wilcoxon rank-sum tests. Recursive partitioning methods were used to find the optimal eosinophil count cutoff based on two-year overall survival (OS) and progression-free survival (PFS). ResultsWe included 106 patients with a median age of 62.3 years (range 19-86), 61% were male, 66% had DLBCL. Peak eosinophil count varied widely among patients at baseline (0-2400 cells/μl), median was 200 cells/μl. Using recursive partitioning, pre-apheresis Eo count 150 determined the high eosinophil group (n=56, 53%; median eo count of 300 (range 100-2400) and low eo group (n=50, 47%, median 100; range 0 - 100 cells/μl). Baseline characteristics of the two groups were similar except in the low eo group, more patients had pre-existing autoimmune condition (34% vs 11%; P<0.01), and high ferritin levels. Eo levels (hi vs low) were not associated with CR rate (76% vs 66%) no

关键词：

来源：评论

学校读者我要写书评

暂无评论

Split-plot microarray experiments: Issues of design, power and sample size

引用

Applied bioinformatics 2005年第3期4卷 187-194页

作者： Tsai, Pi-Wen Lee, Mei-Ling Ting Division of Biostatistics and Bioinformatics National Health Research Institutes Taipei Taiwan Division of Biostatistics School of Public Health Ohio State University Columbus OH United States Division of Biostatistics School of Public Health Ohio State University Columbus OH 43210-1240 320 W. 10th Avenue United States

This article focuses on microarray experiments with two or more factors in which treatment combinations of the factors corresponding to the samples paired together onto arrays are not completely random. A main effect of one (or more) factor(s) is confounded with arrays (the experimental blocks). This is called a split-plot microarray experiment. We utilise an analysis of variance (ANOVA) model to assess differentially expressed genes for between-array and within-array comparisons that are generic under a split-plot microarray experiment. Instead of standard t- or F-test statistics that rely on mean square errors of the ANOVA model, we use a robust method, referred to as 'a pooled percentile estimator', to identify genes that are differentially expressed across different treatment conditions. We illustrate the design and analysis of split-plot microarray experiments based on a case application described by Jin et al. A brief discussion of power and sample size for split-plot microarray experiments is also presented. © 2005 Adis Data Information BV. All rights reserved.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Classifying normal, nevus, and primary melanoma skin samples using penalized ordinal regression 1

引用

Seminar on Science, Technology, Engineering, Agriculture, Mathematics, and Health, STEAM-H 2014

作者： Archer, Kellie J Hou, Jiayi Williams, André A.A Department of Biostatistics Virginia Commonwealth University RichmondVA23298-0032 United States Division of Biostatistics and Bioinformatics National Jewish Health DenverCO80206 United States

ISBN: (数字)9783319077550

ISBN: (纸本)9783319077543

Many investigators conducting translational research are developing multigenic classifiers using data from high-throughput genomic experiments. While often the class to be predicted is nominal, sometimes it may be inherently ordinal. For example, tissue samples may be collected with the goal of classifying them as normal © Springer International Publishing Switzerland 2014.

关键词： Gene expression

来源：评论

学校读者我要写书评

暂无评论

Inconsistency between overall and subgroup analyses

引用

General Psychiatry 2022年第3期35卷 201-204页

作者： Hongyue Wang Bokai Wang Xin M Tu Changyong Feng Departments of Biostatistics&Computational Biology University of RochesterRochesterNew YorkUSA Division of Biostatistics and Bioinformatics Herbert Wertheim School of Public Health and Human Longevity ScienceUC San DiegoLa JollaCaliforniaUSA

Suppose we have a sample of subjects in two treatment *** study the difference of the treatment effects,we can analyse the data using all subjects(overall analysis).We may also divide the subjects into several subgroups based on some covariates of interest(eg,gender),and study the treatment effects within each *** results of these two analyses may be different or even in opposite *** this paper,we give a general sufficient condition of consistency between the overall and subgroup analyses.

关键词： subgroup consistency groups.

来源：评论

学校读者我要写书评

暂无评论

Colonoscopy surveillance for high risk polyps does not always prevent colorectal cancer

引用

World Journal of Gastroenterology 2018年第8期24卷 905-916页

作者： Mohamad A Mouchli Lidia Ouk Marianne R Scheitel Alisha P Chaudhry Donna Felmlee-Devine Diane E Grill Shahrooz Rashtak Panwen Wang Junwen Wang Rajeev Chaudhry Thomas C Smyrk Ann L Oberg Brooke R Druliner Lisa A Boardman Division of Gastroenterology and Hepatology Mayo Clinic Knowledge and Delivery Center Mayo Clinic Biostatistics and Bioinformatics Health Sciences Research Mayo Clinic Division of Biomedical Statistics and Informatics Health Sciences Research Mayo Clinic Biostatistics and Bioinformatics Health Science Research Center for Individualized Medicine Mayo Clinic Department of Biomedical Informatics Arizona State University Primary Care Internal Medicine Mayo Clinic Center for Innovation Mayo Clinic Department of Laboratory Medicine and Pathology Mayo Clinic

AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.

关键词： Colon cancer Rectal Cancer Advanced adenoma Sessile serrated adenoma High risk polyps Post-polypectomy colorectal cancer

来源：评论

学校读者我要写书评

暂无评论

Genome Wide Association Study: Searching for Genes Underlying Body Mass Index in the Chinese

引用

Biomedical and Environmental Sciences 2014年第5期27卷 360-370页

作者： YANG Fang CHEN Xiang Ding TAN Li Jun SHEN Jie LI Ding You ZHANG Fang SHA Bao Yong DENG Hong Wen Department of Epidemiology and Biostatistics School of Public Health Central South University Laboratory of Molecular and Statistical Genetics College of Life Sciences Hunan Normal University Department of Endocrinology The Third Affiliated Hospital of Southern Medical University Department of Pediatrics University of Missouri Kansas City School of Medicine Division of Gastroenterology Children's Mercy Hospital Systematic Biomedicine Research Center University of Shanghai for Science and Technology Center for Bioinformatics and Genomics Department of Biostatistics and Bioinformatics Tulane University

Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.

关键词： Body mass index Genome wide association EIF2AK4 Replication

来源：评论

学校读者我要写书评

暂无评论

Profiling Long Noncoding RNA in Psoriatic Skin Using Single-Cell RNA Sequencing

引用

Journal of Investigative Dermatology 2025年第5期145卷 1060-1069.e7页

作者： Bogle, Rachael Patrick, Matthew T. Sreeskandarajan, Sutharzan Gharaee-Kermani, Mehrnaz Zhang, Haihan Li, Qinmengge Zhou, Ruiwen Ma, Feiyang Kahlenberg, J. Michelle Plazyo, Olesya Elder, James T. Billi, Allison C. Gudjonsson, Johann E. Tsoi, Lam C. Department of Dermatology University of Michigan Medical School Ann Arbor MI United States Cincinnati Children's Hospital Medical Center Cincinnati OH United States Center for Statistical Genetics Department of Biostatistics University of Michigan Ann Arbor MI United States Division of Rheumatology Department of Internal Medicine University of Michigan Medical School Ann Arbor MI United States Ann Arbor Veterans Affairs Hospital Ann Arbor MI United States Department of Computational Medicine & Bioinformatics University of Michigan Ann Arbor MI United States

The expressions of long noncoding RNAs (lncRNAs) and their roles in epidermal differentiation have been previously defined using bulk RNA sequencing. Despite their tissue-specific expression profiles, most lncRNAs are not well-annotated at the single-cell level. In this study, we evaluated the use of single-cell RNA sequencing to profile and characterize lncRNAs using data from 6 patients with psoriasis with paired uninvolved and lesional psoriatic skin. Despite their overall lower expression, we were able to detect >7000 skin-expressing lncRNAs and their cellular sources. Differential gene expression analysis revealed 137 differentially expressed lncRNAs in lesional psoriasis skin and identified 169 cell-type–specific lncRNAs. Keratinocytes had the highest number of differentially expressed lncRNA in psoriatic skin, which we validated using spatial transcriptomic data. We further showed that expression of the keratinocyte-specific lncRNA, AC020916.1, upregulated in lesional skin, is significantly correlated with expressions of genes participating in cell proliferation/epidermal differentiation, including SPRR2E and transcription factor ZFP36, particularly in the psoriatic skin. Our study highlights the potential for using single-cell RNA sequencing to profile skin-expressing lncRNA transcripts and to infer their cellular origins, providing a crucial approach that can be applied to the study of other inflammatory skin conditions. © 2025

关键词： bioinformatics Keratinocytes LncRNA Psoriasis Single-cell RNA-seq

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：