Journal of Molecular Pathology最新文献

Exploring the Molecular Pathology of Iatrogenic Amyloidosis 探索先天性淀粉样变性的分子病理学

Journal of Molecular Pathology Pub Date : 2024-06-05 DOI: 10.3390/jmp5020016

Bernardo Bonilauri

引用次数: 0

How Molecular and Ancillary Tests Can Help in Challenging Cytopathology Cases: Insights from the International Molecular Cytopathology Meeting 分子和辅助检验如何帮助处理棘手的细胞病理学病例：国际分子细胞病理学会议的启示

Journal of Molecular Pathology Pub Date : 2024-06-04 DOI: 10.3390/jmp5020015

E. Vigliar, Claudio Bellevicine, Gennaro Acanfora, Allan Argueta Morales, Anna Maria Carillo, Domenico Cozzolino, Mariantonia Nacchio, C. Luca, P. Pisapia, María D Lozano, S. Roy-Chowdhuri, G. Troncone

引用次数: 0

Impact of Gut–Brain Axis on Hepatobiliary Diseases in Fetal Programming 肠脑轴对胎儿肝胆疾病的影响

Journal of Molecular Pathology Pub Date : 2024-05-16 DOI: 10.3390/jmp5020014

Mukesh Kumar Yadav, Zeeshan Ahmed Khan, Jing-Hua Wang, AbuZar Ansari

{"title":"Impact of Gut–Brain Axis on Hepatobiliary Diseases in Fetal Programming","authors":"Mukesh Kumar Yadav, Zeeshan Ahmed Khan, Jing-Hua Wang, AbuZar Ansari","doi":"10.3390/jmp5020014","DOIUrl":"https://doi.org/10.3390/jmp5020014","url":null,"abstract":"The hepatobiliary system is vital for the biotransformation and disposition of endogenous molecules. Any impairment in the normal functioning of the hepatobiliary system leads to a spectrum of hepatobiliary diseases (HBDs), such as liver cirrhosis, fatty liver, biliary dyskinesia, gallbladder cancer, etc. Especially in pregnancy, HBD may result in increased maternal and fetal morbidity and mortality. Maternal HBD is a burden to the fetus’s growth, complicates fetal development, and risks the mother’s life. In fetal programming, the maternal mechanism is significantly disturbed by multiple factors (especially diet) that influence the development of the fetus and increase the frequency of metabolic diseases later in life. Additionally, maternal under-nutrition or over-nutrition (especially in high-fat, high-carbohydrate, or protein-rich diets) lead to dysregulation in gut hormones (CCK, GLP-1, etc.), microbiota metabolite production (SCFA, LPS, TMA, etc.), neurotransmitters (POMC, NPY, etc.), and hepatobiliary signaling (insulin resistance, TNF-a, SREBPs, etc.), which significantly impact fetal programming. Recently, biotherapeutics have provided a new horizon for treating HBD during fetal programming to save the lives of the mother and fetus. This review focuses on how maternal impaired hepatobiliary metabolic signaling leads to disease transmission to the fetus mediated through the gut–brain axis.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":"23 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140967267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liquid Biopsy Profiling with Multiple Tests in Patients with Metastatic Breast Cancer 用多种检测方法对转移性乳腺癌患者进行液体活检分析

Journal of Molecular Pathology Pub Date : 2024-05-09 DOI: 10.3390/jmp5020013

Nikki Higa, L. Welter, Liya Xu, A. Kolatkar, K. Bramlett, Ole V. Gjoerup, Ryon P Graf, Richard S P Huang, Rebecca J. Leary, Young Lee, Jeremy Perkins, Adam Riker, Angad P Singh, Lorraine Tafra, Carol Kaplan Tweed, C. Shriver, James B. Hicks, Peter Kuhn

{"title":"Liquid Biopsy Profiling with Multiple Tests in Patients with Metastatic Breast Cancer","authors":"Nikki Higa, L. Welter, Liya Xu, A. Kolatkar, K. Bramlett, Ole V. Gjoerup, Ryon P Graf, Richard S P Huang, Rebecca J. Leary, Young Lee, Jeremy Perkins, Adam Riker, Angad P Singh, Lorraine Tafra, Carol Kaplan Tweed, C. Shriver, James B. Hicks, Peter Kuhn","doi":"10.3390/jmp5020013","DOIUrl":"https://doi.org/10.3390/jmp5020013","url":null,"abstract":"The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxidative Stress and ROS Link Diabetes and Cancer 氧化应激和 ROS 将糖尿病与癌症联系在一起

Journal of Molecular Pathology Pub Date : 2024-03-01 DOI: 10.3390/jmp5010007

Homer S. Black

{"title":"Oxidative Stress and ROS Link Diabetes and Cancer","authors":"Homer S. Black","doi":"10.3390/jmp5010007","DOIUrl":"https://doi.org/10.3390/jmp5010007","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. Reactive oxygen species (ROS)-altered metabolic and signaling pathways link T2DM to cancer. These reprogrammed metabolic and signaling pathways contribute to diabetic complications, impact the redox balance (oxidative stress), and have differential roles in the early and late stages of cancer. A respiratory chain that is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevations. The amplification of ROS results in the activation of PKC, an overarching signaling pathway that activates MAPK with a subsequent regulation in several factors that result in pathophysiological manifestations of T2DM and cancer. An upregulation in PKC leads to a deregulation in NF-kß, which regulates the PKB/P13/Akt pathway and orchestrates the cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin-stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines, and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in the early and late stages of cancer makes antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting the formation of ROS early during the pre-diabetic stage, whereas antioxidant therapy must be halted in later stages to retard metastasis.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":"114 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140089393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing Classifications from Multiple Variant Annotation Software Solutions Using Real-World Next Generation Sequencing Data from Oncology Testing 利用肿瘤检测的真实下一代测序数据，比较多种变异注释软件解决方案的分类方法

Journal of Molecular Pathology Pub Date : 2024-03-01 DOI: 10.3390/jmp5010006

Roy Khalife, Tara M. Love, Lara Sucheston-Campbell, Michael J. Clark, Helle Sorensen, Shuba Krishna, Anthony Magliocco

引用次数: 0

Delving into the Role of Receptor-like Tyrosine Kinase (RYK) in Cancer: In Silico Insights into Its Diagnostic and Prognostic Utility 探究受体样酪氨酸激酶 (RYK) 在癌症中的作用：对其诊断和预后作用的硅学见解

Journal of Molecular Pathology Pub Date : 2024-02-06 DOI: 10.3390/jmp5010005

Jessica Alejandra Zapata-García, L. Jave-Suárez, A. Aguilar-Lemarroy

{"title":"Delving into the Role of Receptor-like Tyrosine Kinase (RYK) in Cancer: In Silico Insights into Its Diagnostic and Prognostic Utility","authors":"Jessica Alejandra Zapata-García, L. Jave-Suárez, A. Aguilar-Lemarroy","doi":"10.3390/jmp5010005","DOIUrl":"https://doi.org/10.3390/jmp5010005","url":null,"abstract":"The RYK gene encodes a receptor-like tyrosine kinase crucial for several biological processes, including development, tissue homeostasis, and cancer. This study utilized data from the Cancer Genome Atlas Project (TCGA) to evaluate RYK expression at both mRNA and protein levels in various cancers, determine its prognostic significance, and explore its involvement in cancer-related signaling pathways. Elevated levels of RYK mRNA were identified in cholangiocarcinoma (CHOL), pancreatic adenocarcinoma (PAAD), glioblastoma multiforme (GBM), lung squamous cell carcinoma (LUSC), brain lower grade glioma (LGG), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LICH), esophageal carcinoma (ESCA), and colon adenocarcinoma (COAD), while RYK protein levels were observed to be increased in colon adenocarcinoma (COAD), GBM, LICH, cervical and endocervical adenocarcinoma (CESC), and breast invasive carcinoma (BRCA). Additionally, RYK overexpression correlated with poorer prognosis in several cancers, including PAAD, LICH, BRCA, ESCA, COAD, and CESC. Furthermore, RYK showed a positive correlation with the upregulation of multiple receptors and coreceptors in the WNT signaling pathway in various types of cancer. In terms of cancer-related signaling pathways, RYK was found to potentially interact with DNA damage, TSC/mTOR, PI3K/AKT, EMT, RTK, RAS/MAPK, ER hormone, AR hormone, and the cell cycle. This study provides new and previously unreported insights into the role of RYK in cancer biology.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":"54 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139860460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Delving into the Role of Receptor-like Tyrosine Kinase (RYK) in Cancer: In Silico Insights into Its Diagnostic and Prognostic Utility 探究受体样酪氨酸激酶 (RYK) 在癌症中的作用：对其诊断和预后作用的硅学见解

Journal of Molecular Pathology Pub Date : 2024-02-06 DOI: 10.3390/jmp5010005

Jessica Alejandra Zapata-García, L. Jave-Suárez, A. Aguilar-Lemarroy

{"title":"Delving into the Role of Receptor-like Tyrosine Kinase (RYK) in Cancer: In Silico Insights into Its Diagnostic and Prognostic Utility","authors":"Jessica Alejandra Zapata-García, L. Jave-Suárez, A. Aguilar-Lemarroy","doi":"10.3390/jmp5010005","DOIUrl":"https://doi.org/10.3390/jmp5010005","url":null,"abstract":"The RYK gene encodes a receptor-like tyrosine kinase crucial for several biological processes, including development, tissue homeostasis, and cancer. This study utilized data from the Cancer Genome Atlas Project (TCGA) to evaluate RYK expression at both mRNA and protein levels in various cancers, determine its prognostic significance, and explore its involvement in cancer-related signaling pathways. Elevated levels of RYK mRNA were identified in cholangiocarcinoma (CHOL), pancreatic adenocarcinoma (PAAD), glioblastoma multiforme (GBM), lung squamous cell carcinoma (LUSC), brain lower grade glioma (LGG), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LICH), esophageal carcinoma (ESCA), and colon adenocarcinoma (COAD), while RYK protein levels were observed to be increased in colon adenocarcinoma (COAD), GBM, LICH, cervical and endocervical adenocarcinoma (CESC), and breast invasive carcinoma (BRCA). Additionally, RYK overexpression correlated with poorer prognosis in several cancers, including PAAD, LICH, BRCA, ESCA, COAD, and CESC. Furthermore, RYK showed a positive correlation with the upregulation of multiple receptors and coreceptors in the WNT signaling pathway in various types of cancer. In terms of cancer-related signaling pathways, RYK was found to potentially interact with DNA damage, TSC/mTOR, PI3K/AKT, EMT, RTK, RAS/MAPK, ER hormone, AR hormone, and the cell cycle. This study provides new and previously unreported insights into the role of RYK in cancer biology.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":"181 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139800792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Single-Tube Next Generation Sequencing Assay for B-Cell Receptor Clonality Testing 用于 B 细胞受体克隆性检测的新型单管下一代测序分析法

Journal of Molecular Pathology Pub Date : 2024-02-02 DOI: 10.3390/jmp5010004

Landon Pastushok, S. Sarda, K. Mochoruk, Wayne Hill, Loni Pickle, Michelle A. Toro, Carolina Gonzalez, Stephanie Ostresh, T. Looney, Chenchen Yang, Julie Stakiw, Mark J. Bosch, Hadi Goubran, C. Geyer, G. Lowman, J. Decoteau

{"title":"A Novel Single-Tube Next Generation Sequencing Assay for B-Cell Receptor Clonality Testing","authors":"Landon Pastushok, S. Sarda, K. Mochoruk, Wayne Hill, Loni Pickle, Michelle A. Toro, Carolina Gonzalez, Stephanie Ostresh, T. Looney, Chenchen Yang, Julie Stakiw, Mark J. Bosch, Hadi Goubran, C. Geyer, G. Lowman, J. Decoteau","doi":"10.3390/jmp5010004","DOIUrl":"https://doi.org/10.3390/jmp5010004","url":null,"abstract":"B-cell neoplasms possess clonal B-cell receptor rearrangements (BCR clonotype lineages) that can be identified by sequencing the B-cell repertoire for use in diagnostics, risk stratification, and high-sensitivity monitoring. BCR somatic hypermutation (SHM) can result in clonality detection failure from point mutations in PCR primer binding regions, often necessitating splitting samples into multiple reactions which increases test costs, turnaround times, and sample requirements. We evaluated the Oncomine BCR Pan-Clonality Assay, a novel single-tube PCR reaction that simultaneously amplifies all BCR loci for next-generation DNA sequencing, using neoplastic B-cell lines and clinical research samples from multiple myeloma (MM) patients, a plasma cell neoplasm associated with high SHM levels. The assay showed a linear detection range down to 1 ng of clonal DNA input, sensitivity to 10−6 in a polyclonal background, and high reproducibility. Clonotype lineages were identified in 42/45 (93%) MM samples. Ion Reporter software packaged with the assay permitted straightforward identification of MM subgroups. As expected, SHM was identified in 94% of MM cases, but several unexpected subgroups were identified including biased IGHV3-11 or IGHV4-34 usage in 20% of MM samples, and two cases with very low levels of SHM. Evidence of intraclonal diversity/ongoing SHM was identified in 18% of samples, suggesting a possible germinal center origin for some MM cases. The single-tube Oncomine BCR Pan-Clonality assay efficiently detects BCR clonotype lineages at rates comparable to existing multiple reaction assays and permits their characterization for cell of origin studies and lymphoma classification.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":"7 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139809472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Single-Tube Next Generation Sequencing Assay for B-Cell Receptor Clonality Testing 用于 B 细胞受体克隆性检测的新型单管下一代测序分析法

Journal of Molecular Pathology Pub Date : 2024-02-02 DOI: 10.3390/jmp5010004

Landon Pastushok, S. Sarda, K. Mochoruk, Wayne Hill, Loni Pickle, Michelle A. Toro, Carolina Gonzalez, Stephanie Ostresh, T. Looney, Chenchen Yang, Julie Stakiw, Mark J. Bosch, Hadi Goubran, C. Geyer, G. Lowman, J. Decoteau

{"title":"A Novel Single-Tube Next Generation Sequencing Assay for B-Cell Receptor Clonality Testing","authors":"Landon Pastushok, S. Sarda, K. Mochoruk, Wayne Hill, Loni Pickle, Michelle A. Toro, Carolina Gonzalez, Stephanie Ostresh, T. Looney, Chenchen Yang, Julie Stakiw, Mark J. Bosch, Hadi Goubran, C. Geyer, G. Lowman, J. Decoteau","doi":"10.3390/jmp5010004","DOIUrl":"https://doi.org/10.3390/jmp5010004","url":null,"abstract":"B-cell neoplasms possess clonal B-cell receptor rearrangements (BCR clonotype lineages) that can be identified by sequencing the B-cell repertoire for use in diagnostics, risk stratification, and high-sensitivity monitoring. BCR somatic hypermutation (SHM) can result in clonality detection failure from point mutations in PCR primer binding regions, often necessitating splitting samples into multiple reactions which increases test costs, turnaround times, and sample requirements. We evaluated the Oncomine BCR Pan-Clonality Assay, a novel single-tube PCR reaction that simultaneously amplifies all BCR loci for next-generation DNA sequencing, using neoplastic B-cell lines and clinical research samples from multiple myeloma (MM) patients, a plasma cell neoplasm associated with high SHM levels. The assay showed a linear detection range down to 1 ng of clonal DNA input, sensitivity to 10−6 in a polyclonal background, and high reproducibility. Clonotype lineages were identified in 42/45 (93%) MM samples. Ion Reporter software packaged with the assay permitted straightforward identification of MM subgroups. As expected, SHM was identified in 94% of MM cases, but several unexpected subgroups were identified including biased IGHV3-11 or IGHV4-34 usage in 20% of MM samples, and two cases with very low levels of SHM. Evidence of intraclonal diversity/ongoing SHM was identified in 18% of samples, suggesting a possible germinal center origin for some MM cases. The single-tube Oncomine BCR Pan-Clonality assay efficiently detects BCR clonotype lineages at rates comparable to existing multiple reaction assays and permits their characterization for cell of origin studies and lymphoma classification.","PeriodicalId":506404,"journal":{"name":"Journal of Molecular Pathology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139869517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0