Integrated multi-omic analysis to reveal comprehensive tumor heterogeneity and novel immunophenotypic classification in primary liver cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15662-e15662
Author(s):  
Qi Zhang ◽  
Yu Lou ◽  
Xueli Bai ◽  
Tingbo Liang
Keyword(s):  
Tumor Heterogeneity ◽  
Single Cell Analysis ◽  
Primary Liver Cancer ◽  
Treatment Strategies ◽  
Local Immunity ◽  
Expression Levels ◽  
Chain Reactions ◽  
Prognostic Prediction ◽  
Practice Methods

e15662 Background: Hepatocellular carcinoma (HCC) is heterogeneous,especially in multifocal tumors, which decreases the efficacy of clinical treatments. Understanding tumor heterogeneity is critical when developingnovel treatment strategies. However, a comprehensive investigation of tumor heterogeneity in HCC is lacking, and the available evidence regarding tumor heterogeneity has not ledto improvements inclinical practice. Methods: We harvested 42 samples from eight HCC patients and evaluatedtumor heterogeneity using whole-exome sequencing, RNA sequencing, mass spectrometry-based proteomics and metabolomics, cytometry by time-of-flight, and single-cell analysis. Immunohistochemistry and quantitative polymerase chain reactions (qPCRs) were performed to confirm the expression levels of genes. Results: Tumor heterogeneity is considerable with regard to the genomes, transcriptomes, proteomes, and metabolomes of lesions and tumors. The immune status oftheHCC microenvironment had a relatively low level of heterogeneity. Targeting local immunity could be a suitable intervention with balanced precision and practicability. By clustering immune cells in the HCC microenvironment, we identified three distinctive HCC subtypes with immunocompetent, immunodeficient, and immunosuppressive features. We further revealed the specific metabolic features and cytokine/chemokine expression levels of the different subtypes. Determiningthe expression levels of PTPRCand FOXP3using qPCR and immunohistochemistry in two independent HCC cohorts facilitated the correct classification of HCC patients and the prediction of their prognosis. Conclusions: There is comprehensive intratumoral and intertumoral heterogeneity inall dimensions ofHCC. Based on the results, we propose a novel immunophenotypic classification of HCCs that facilitates prognostic prediction and may support decision making with regard to the choice of therapy.

scholarly journals Integrated multiomic analysis reveals comprehensive tumour heterogeneity and novel immunophenotypic classification in hepatocellular carcinomas

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 2019-2031 ◽  
Author(s):  
Qi Zhang ◽  
Yu Lou ◽  
Jiaqi Yang ◽  
Junli Wang ◽  
Jie Feng ◽  
...  
Keyword(s):  
Single Cell Analysis ◽  
Treatment Strategies ◽  
Tumour Heterogeneity ◽  
Local Immunity ◽  
Expression Levels ◽  
Chain Reactions ◽  
Polymerase Chain Reactions ◽  
Novel Treatment Strategies ◽  
Prognostic Prediction

ObjectiveHepatocellular carcinoma (HCC) is heterogeneous, especially in multifocal tumours, which decreases the efficacy of clinical treatments. Understanding tumour heterogeneity is critical when developing novel treatment strategies. However, a comprehensive investigation of tumour heterogeneity in HCC is lacking, and the available evidence regarding tumour heterogeneity has not led to improvements in clinical practice.DesignWe harvested 42 samples from eight HCC patients and evaluated tumour heterogeneity using whole-exome sequencing, RNA sequencing, mass spectrometry-based proteomics and metabolomics, cytometry by time-of-flight, and single-cell analysis. Immunohistochemistry and quantitative polymerase chain reactions were performed to confirm the expression levels of genes. Three independent cohorts were further used to validate the findings.ResultsTumour heterogeneity is considerable with regard to the genomes, transcriptomes, proteomes, and metabolomes of lesions and tumours. The immune status of the HCC microenvironment was relatively less heterogenous. Targeting local immunity could be a suitable intervention with balanced precision and practicability. By clustering immune cells in the HCC microenvironment, we identified three distinctive HCC subtypes with immunocompetent, immunodeficient, and immunosuppressive features. We further revealed the specific metabolic features and cytokine/chemokine expression levels of the different subtypes. Determining the expression levels of CD45 and Foxp3 using immunohistochemistry facilitated the correct classification of HCC patients and the prediction of their prognosis.ConclusionThere is comprehensive intratumoral and intertumoral heterogeneity in all dimensions of HCC. Based on the results, we propose a novel immunophenotypic classification of HCCs that facilitates prognostic prediction and may support decision making with regard to the choice of therapy.

scholarly journals Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

2021 ◽  
Author(s):  
Hanbing Song ◽  
Simon Bucher ◽  
Katherine Rosenberg ◽  
Margaret Tsui ◽  
Deviana Burhan ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Tumor Heterogeneity ◽  
Single Cell Analysis ◽  
Primary Liver Cancer ◽  
Patient Specific ◽  
Precision Oncology ◽  
Cell Of Origin ◽  
Specific Tumor ◽  
Transcriptomic Signature

Pediatric hepatoblastoma (HB) is the most common primary liver cancer in infants and children. Studies of HB that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, HB tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we used single- cell genomic techniques to analyze resected human pediatric HB specimens. This study establishes that tumor heterogeneity can be defined by the relative proportions of five distinct subtypes of tumor cells. Notably, patient-derived HB spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. Collectively, these results define HB tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

scholarly journals Circadian Regulation Patterns With Distinct Immune Landscapes in Gliomas Aid in the Development of a Risk Model to Predict Prognosis and Therapeutic Response

2022 ◽  
Vol 12 ◽  
Author(s):  
Ruotong Tian ◽  
Yimin Li ◽  
Minfeng Shu
Keyword(s):  
Circadian Rhythm ◽  
Tumor Heterogeneity ◽  
Risk Model ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Principal Component ◽  
Immune Checkpoint Blockade ◽  
Glioma Patient ◽  
Suitable Treatment ◽  
Prognostic Prediction

Circadian disruption in tumorigenesis has been extensively studied, but how circadian rhythm (CR) affects the formation of tumor microenvironment (TME) and the crosstalk between TME and cancer cells is largely unknown, especially in gliomas. Herein, we retrospectively analyzed transcriptome data and clinical parameters of glioma patients from public databases to explore circadian rhythm-controlled tumor heterogeneity and characteristics of TME in gliomas. Firstly, we pioneered the construction of a CR gene set collated from five datasets and review literatures. Unsupervised clustering was used to identify two CR clusters with different CR patterns on the basis of the expression of CR genes. Remarkably, the CR cluster-B was characterized by enriched myeloid cells and activated immune-related pathways. Next, we applied principal component analysis to construct a CRscore to quantify CR patterns of individual tumors, and the function of the CRscore in prognostic prediction was further verified by univariate and multivariate regression analyses in combination with a nomogram. The CRscore could not only be an independent factor to predict prognosis of glioma patients but also guide patients to choose suitable treatment strategies: immunotherapy or chemotherapy. A glioma patient with a high CRscore might respond to immune checkpoint blockade, whereas one with a low CRscore could benefit from chemotherapy. In this study, we revealed that circadian rhythms modulated tumor heterogeneity, TME diversity, and complexity in gliomas. Evaluating the CRscore of an individual tumor would contribute to gaining a greater understanding of the tumor immune status of each patient, enhancing the accuracy of prognostic prediction, and suggesting more effective treatment options.

Diverse Dimensions of the Cotard’s Syndrome - an Approach Towards a Clear Classification of the Phenomenon

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
A. Nagy ◽  
V. Voros ◽  
T. Tenyi
Keyword(s):  
Clinical Practice ◽  
Diagnostic Category ◽  
Treatment Strategies ◽  
Differential Diagnostics ◽  
Dimensional System ◽  
Central Feature ◽  
Scientific Databases ◽  
Search Terms ◽  
The One

Aim:The authors present the Cotard's syndrome, a rare psychiatric condition, pointing out the latest results in terms of psychoneurology and classification of the phenomenon. The central feature of the syndrome is a nihilistic delusion, in which the patient denies his or her own existence and that of the external world.Method:We searched electronic scientific databases using the appropriate search terms; relevant articles were carefully reviewed. We also present three cases from our clinical practice.Results:After the overview of the latest biological and neuropsychological findings, the terminology, the nosology, the classification and the differential diagnostics are discussed. To sum up with useful information for the clinical practice, the possible treatment strategies, the course and the prognosis of the disease are also presented.Conclusions:The reported cases together with the reviewed literature suggest that a dimensional system of classifying Cotard's syndrome is preferable. At the one end of the spectrum is the presence of the pure nihilistic delusions, appearing as a symptom of an underlying psychiatric or neurological condition. The full-blown, classical syndrome as a diagnostic category forms the other end of the spectrum. The presented theoretical and practical aspects give a lead on deeper understanding, easier recognition and more adequate therapy of the Cotard's syndrome.

scholarly journals Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (9) ◽  
pp. 1079-1109
Author(s):  
Patrick A. Brown ◽  
Bijal Shah ◽  
Anjali Advani ◽  
Patricia Aoun ◽  
Michael W. Boyer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Supportive Care ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Strategies ◽  
Adolescent And Young Adult ◽  
Cancer Center ◽  
Nccn Guidelines ◽  
Treatment Regimens

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

IHPBA concordant classification of primary liver cancer: working group report

2003 ◽  
Vol 10 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Masatoshi Makuuchi ◽  
Jacques Belghiti ◽  
Giulio Belli ◽  
Sheung-Tat Fan ◽  
Joseph Wan Yee Lau ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Working Group ◽  
Primary Liver Cancer ◽  
Group Report

Stress Testing as a Banking Risk Assessment Tool: A Review of International Practice, Methods and Methodology

2020 ◽  
pp. 99-117
Author(s):  
Davit S. Bidzhoyan
Keyword(s):  
Stress Testing ◽  
Assessment Tool ◽  
Research Area ◽  
Interest Rate Risk ◽  
Economic Science ◽  
Testing Methods ◽  
Financial Condition ◽  
Comprehensive Classification ◽  
Practice Methods

Stress testing is a broad research area, at the interference of many disciplines (finance, banking, econometrics, macroeconomics, microeconomics, mathematical analysis etc.), and is of interest to both theoretical scientists and practitioners. The usefulness of this approach became evident after the financial crisis of 2007–2009, which prompted many researchers to develop and constantly improve stress-testing methodologies, using which it is possible to accurately forecast the behavior of banks and the financial sector in crisis periods. It allows banks to assess the scale of losses and timely take the necessary measures to strengthen the financial condition. Today, economic science has the biggest arsenal of stress testing methods that allow us to assess potential losses in crisis periods that correspond to extreme but plausible events. The stress testing methodologies cover all-important types of risks (credit, interest rate risk, liquidity risk etc.), as well as specific risks. The presence of a huge number of stress testing methods guarantees its versatility and depth, which could be explained by the attempt using this methods to create a behavior model of banks, which are quite complex in structure and functionality. The purpose of this study is to provide a concise, but at the same time comprehensive classification of stress testing methods, as well as a review of the current approaches to stress testing or to solving its various aspects (for example, developing stress scenarios) presented by scientists, international organizations, central banks and other interested parties. This paper is an introduction to the vast field of analytics – stress testing, and is oriented to banking and financial analysts, macroeconomists who want either to familiarize themselves with stress testing as a tool for assessing banking risks, or to systematize all the accumulated knowledge in this area in order to better understand economic processes.

Psychiatry Board Review

2017 ◽  
Keyword(s):  
Clinical Practice ◽  
Treatment Strategies ◽  
The United States ◽  
Certification Examination ◽  
Board Examination ◽  
Diagnostic And Statistical Manual ◽  
Dsm 5 ◽  
Psychotherapeutic Techniques ◽  
Board Review

The field of psychiatry is rapidly evolving, specifically in the areas of psychopharmacology, psychotherapeutic strategies, and the classification of many major psychiatric disorders with the implementation of the Diagnostic and Statistical Manual of Mental Disorders: DSM-5 in 2013. A new board review textbook is imperative to address these changes in order to prepare board-eligible psychiatrists for the certification examination as well as for clinical practice in general. Additionally, the American Board of Psychiatry and Neurology is in the process of phasing in the DSM-5 criteria to the board examination, such that by 2017 the examination material will exclusively reflect the new manual. The book is aimed primarily at board-eligible psychiatrists preparing for their Initial certification in psychiatry. It will be a useful study tool for psychiatrists renewing certification as well, which in the United States is required every ten years. Furthermore the text will also be a useful reference for all psychiatrists in clinical practice to familiarize themselves with the new diagnostic classifications of DSM-5, the latest psychopharmacologic treatment strategies, and psychotherapeutic techniques.

scholarly journals Management of delayed-onset skin flap complications after pediatric cochlear implantation

2020 ◽  
Author(s):  
Qingling Bi ◽  
Zhongyan Chen ◽  
Yong Lv ◽  
Jie Luo ◽  
Naya Wang ◽  
...  
Keyword(s):  
Revision Surgery ◽  
Cochlear Implantation ◽  
Wound Closure ◽  
Wound Care ◽  
Skin Flap ◽  
Treatment Strategies ◽  
Clinical Situation ◽  
Delayed Onset ◽  
Reconstructive Option

Abstract Purpose To review delayed-onset skin flap complications associated with pediatric cochlear implantation (CI) in our institute, analyze the etiology, and explore effective treatment strategies. Methods Retrospective analyses of 811 children who had undergone cochlear implantation between January 2003 and March 2019 were performed. Twelve (1.48%) patients developed skin flap complications after CI. We present a classification of flap issues and wound histopathology following cochlear implantation. The interventions for flap problems included drug treatment, aspiration, local wound care, revision surgery, and explantation depending on the clinical situation. The temporalis myofascial reconstructive option is discussed. Results Seven subjects were cured with conservative treatment. Five cases with flap infection or necrosis underwent revision surgery, with wound closure in three cases (60%) and revision surgery with explantation in the remaining two cases (40%). Explantation ultimately led to wound healing in all cases. They all achieved excellent performance through re-implantation. Conclusion Flap complications after CI are rare but treatable. Comprehensive treatments should be developed to achieve a stable and healed wound for CI.

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