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Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis.

Osteonecrosis is a frequent complication after treatment for childhood leukemia and other steroid-based therapies. The success rate of core decompression surgery is limited. Therefore, we evaluated relevant biological characteristics of human multipotent mesenchymal stromal cells (MSCs) in vitro. MSCs cultured under low-oxygen tensions showed decreased proliferation and differentiation into bone. However, these MSCs secreted significant amounts of vascular endothelial-derived factor in the presence of interferon-gamma. These in vitro results with potential effects on neovascularization and bon

Perspective: Does personalized medicine hold the future for medicine?

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… The human genome sequencing was completed in 2000[ 4 ] and by 2003 the Human Genome Project was completed by the Unites States department of Energy and the National Institutes of Health by identifying 22,000–23,000 genes in the human genome.[ 6 ] The human genome is the total genetic makeup which is … The gathered genetic information is aimed at individualizing disease risk factors, biological characteristics, and personal ancestries.[ 19 ] Furthermore, the increasing approach toward Genome-Wide Association Studies (GWAS) since the completion of the human genome project has successfully found genetic …

Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis.

BACKGROUND: The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. RESULTS: To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentia

Патогенная адаптация HLA Alleles и его корреляция с аутоиммунными заболеваниями на китайском языке.

Гены антигена лейкоцита человека (HLA) играют решающую роль в адаптации населения к динамичной патогенной среде. Несмотря на их важное значение, изучение патогенной эволюции ВПП и ее последствий для аутоиммунных заболеваний сопряжено с серьезными проблемами. Вот, мы генотипировали 20 Гены HLA 3-field разрешение 8278 лиц, принадлежащих к различным этническим группам, включая 4013 Не связанные с Ханом китайские личности. Мы сосредоточили внимание на адаптации ХЛА среди населения Китая, анализируя их связь с различными патогенами, и изучили потенциальную корреляцию между патогенной адаптацией и а

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification.

Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers

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… Meanwhile, the Human Genome Project, which was launched in 1990, required 13 years and billions of euros in order to sequence the complete human genome. With NGS, the today promise of today is that a complete genome can be sequenced in a few days for less than $1000 per genome. …

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and

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… The ability to practice precision medicine is largely due to the completion of the Human Genome Project (HGP), and the development of proteomics, metabolomics, genomics, and transcriptomics approaches to study biology and disease [ 1 , 6 ]. … Abbreviations Amyotrophic Lateral Sclerosis Castleman disease Castleman Disease Collaborative Network cystic fibrosis contract research organizations Human Genome Project Human Herpes Virus-8 Interleukin-6 idiopathic MCD International Research Agenda multicentric Castleman disease pseudoxanthoma …

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expre

Ancient genes establish stress-induced mutation as a hallmark of cancer.

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cance

Мультиэнштейная геномная ассоциация и мультиомикальный анализ позволяют выявить специфичные особенности многоклерозной генетики.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы, характеризующееся обезвоживанием, распространяющимся в пространстве и во времени. Здесь мы провели исследование ассоциации генома (GWAS) с использованием 688 Количество дел, связанных с НР и 205,199 :: контроль со стороны японского населения и выявление важных связей в основном сложном регионе, связанном с гистокомпьютерностью, и в 11q24 году вариант риска, учитывающий специфику населения. С помощью межнаселенных метаанализов GWAS с использованием всего 29,374 случаи и случаи 1,843,563 контроля с 4

Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume I-conceptual challenges.

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societ

CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma.

Clinical development of chimeric antigen receptor (CAR)-T-cell therapy has been enabled by advances in synthetic biology, genetic engineering, clinical-grade manufacturing, and complex logistics to distribute the drug product to treatment sites. A key ambition of the CARAMBA project is to provide clinical proof-of-concept for virus-free CAR gene transfer using advanced Sleeping Beauty (SB) transposon technology. SB transposition in CAR-T engineering is attractive due to the high rate of stable CAR gene transfer enabled by optimized hyperactive SB100X transposase and transposon combinations, en

GMrepo v3: кустарная база данных о кишечном микробиоме человека с расширенным охватом заболеваний и усовершенствованным биомаркером с перекрестными данными.

GMrepo (Gut Microbiome Data Repository) представляет собой кустарную и последовательно аннотированную базу данных по метагеномам человеческого кишечника, предназначенную для повышения возможности повторного использования данных и создания возможностей для межпроектных и перекрестных сопоставлений. В этом последнем выпуске GMrepo v3 был расширен до 890 проектов и 118 965 пробегов/выборок, включая 87 048 16S rRNA и 31 917 метагеномических наборов данных. Количество аннотированных заболеваний возросло со 133 до 302, что позволило провести более комплексный микробиомический анализ, связанный с заб

Pharmacogenomics and Big Data in medical oncology: developments and challenges.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient's response to various drugs with the aim to minimize tria

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… Since the birth of the field in the 1950s, pharmacogenomics has seen substantial growth owing to the completion of the Human Genome Project. …

Proceedings of the CIMAGO Congress - Environment, Genetics and Oncobiology in the 21st Century - Challenges and Opportunities.

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Mapping oncogenic protein interactions for precision medicine.

Normal protein-protein interactions (normPPIs) occur with high fidelity to regulate almost every physiological process. In cancer, this highly organised and precisely regulated network is disrupted, hijacked or reprogrammed resulting in oncogenic protein-protein interactions (oncoPPIs). OncoPPIs, which can result from genomic alterations, are a hallmark of many types of cancers. Recent technological advances in the field of mass spectrometry (MS)-based interactomics, structural biology and drug discovery have prompted scientists to identify and characterise oncoPPIs. Disruption of oncoPPI inte

Тип 1 Диабет и многоразовый склероз делятся общей генной переменой автономного иммунитета.

Справочная информация/цели: тип 1 диабет (T1D) и множественный склероз (MS) являются аутоиммунными, многофакторными, специфическими для органов расстройствами, обусловленными иммунными клетками. Их соучастие отчасти объясняется общими генетическими и экологическими факторами. Мы стремились расчленить общую генетическую архитектуру между T1D и MS с использованием крупномасштабных исследований по общегеномной ассоциации (GWAS) и анализа совместной локализации. Методы: Мы применили Байесовскую систему совместной локализации к two Крупномасштабные наборы данных GWAS: исследование T1D, включающее 1

Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis.

The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (nCase = 3,418, nControl = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (P BH = 3.28e-5, 0.05/1,5

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

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… The Human Genome Project ( HGP ), GWAS and ENCODE : their impact on translational medicine There have been three great landmarks in genomics: the first was the completion, in 2003, of the HGP and the discovery of 20 000–25 000 protein coding human genes (Clinton and Blair, 2000 ), later the search for …

Liquid biopsy and PCR-free ultrasensitive detection systems in oncology (Review).

In oncology, liquid biopsy is used in the detection of next-generation analytes, such as tumor cells, cell-free nucleic acids and exosomes in peripheral blood and other body fluids from cancer patients. It is considered one of the most advanced non-invasive diagnostic systems to enable clinically relevant actions and implement precision medicine. Medical actions include, but are not limited to, early diagnosis, staging, prognosis, anticipation (lead time) and the prediction of therapy responses, as well as follow-up. Historically, the applications of liquid biopsy in cancer have focused on cir