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Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE.

IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is present on all IgE-producing cells, serves as an excellent molecular target for ACT that

Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients.

Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occas

A brief clinical genetics review: stepwise diagnostic processes of a monogenic disorder-hypertriglyceridemia.

The completion of the Human Genome Project and tremendous advances in automated high-throughput genetic analysis technologies have enabled explosive progress in the field of genetics, which resulted in countless discoveries of novel genes and pathways. Many phenotype- or disease-associated single nucleotide polymorphisms (SNPs) with a high statistical significance have been identified through numerous genome-wide association studies (GWAS), and various polygenic risk scoring (PRS) schemes have been proposed to identify individuals with a high risk for a certain trait or disorder. Meanwhile, me

Нацеливание микроглиа-Тх17 на петлю питания вперёд для подавления аутоиммунной нейроинфламмации.

Microglia и TH17 являются основными иммунопатогенными клетками в множестве склероза и его животной модели иммунных аспектов, экспериментального аутоиммунного энцефаломиелита (EAE). Хотя исследования выявили различные роли микроглий и TH17 клеток в EAE, остается неясным, может ли микроглия как потенциальные профессиональные антигенопредставляющие клетки активировать и стабилизировать программу воздействия EAE-патогенных клеток TH17 в vivo; и если да, то может ли TH17, в свою очередь, усилить активное состояние микроглии. Наши данные показывают в целом ряде моделей мыши, включая активные/пассивн

Эпигенетические достижения в педиатрическом многоразовом склерозе: ДНК-метилирование примечательно участие Эпштейна-Барра заражённых вирусом и принимающих иммунных сетей.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛИ: Педиатрический множественный склероз (PedMS) предоставляет уникальную возможность для изучения патогенеза MS с учетом короткого интервала между воздействием на окружающую среду и возникновением заболеваний. Цель этого исследования состояла в том, чтобы выявить различные метилированные регионы (ДМР), которые способствуют взаимодействию между экологическими факторами и геномными факторами на ранних этапах заболевания. В этом многоцентровом исследовании мы проанализировали периферическую ДНК крови. 175 Итальянские предметы122 Пациенты педиатрии, 53 - здоровый контрол

Targeting HDACs with dacinostat amplifies radiation-induced DNA damage via sustained phosphorylated p53 and repair inhibition in aggressive meningioma.

The lack of standard systemic treatments in meningioma presents a therapeutic challenge, making radiotherapy a crucial intervention for recurrent, high-grade, or inoperable tumours. Nonetheless, the efficacy of radiotherapy is constrained by the inherent radioresistance of meningiomas, attributed to their proficient DNA damage repair and robust cell cycle checkpoint regulation. These biological barriers, along with anatomical constraints of avoiding damage to adjacent neural tissues, restrict dose escalation and therapeutic gains. Histone deacetylases (HDACs) are mediators of radioresistance i

Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.

BackgroundMultiple myeloma is a hematologic malignancy characterized by complex interactions within the tumor microenvironment, where mesenchymal stem cells (MSCs) contribute significantly to disease progression, immune suppression, and drug resistance.MethodsThis study investigated the heterogeneity of MSCs in multiple myeloma using single-cell RNA sequencing (10X) and bulk transcriptomic data. Further analysis was performed by Seurat, SCENIC, CellChat. GSE4581 and GSE136337 were used as training set and validation set to construct a newly described prognostic model through COX and LASSO.Resu

Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances.

Introduction: Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool to guide therapeutic choices. The most standardized methods to study MRD in ALL are multi-parametric flow cytometry (MFC) and polymerase chain reaction (PCR) amplification-based methods. Emerging technologies hold the promise to improve MRD detection in ALL patients. Moreover, novel therapies, such as monoclonal antibodies, bispecific T-cell engagers, and chimeric antigen receptor T cells (CART)

Regulatory Convergence in Cell and Gene Therapy: Harmonizing Quality, CMC, and Approval Pathways Across the FDA, EMA, PMDA, and Emerging Markets.

Cell and gene therapies (CGTs) have progressed from proof of concept to an established commercial pipeline, yet global translation remains constrained by fragmented regulatory frameworks; heterogeneous Chemistry, Manufacturing, and Controls (CMC) requirements; and divergent approval pathways. This narrative review compares CGT quality, CMC, and approval-pathway regulation across the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), together with five emerging-market agencies: Brazil, Russia, India, China, and

Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions.

TP53 aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with TP53 aberrations. We observed no significant differences between MDS and AML regarding TP53 genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus TP53 varian

Construction of a Prognostic Risk Prediction Model for Obesity Combined With Breast Cancer.

The improvement in the quality of life is accompanied by an accelerated pace of living and increased work-related pressures. Recent decades has seen an increase in the proportion of obese patients, as well as an increase in the prevalence of breast cancer. More and more evidences prove that obesity may be one of a prognostic impact factor in patients with breast cancer. Obesity presents unique diagnostic and therapeutic challenges in the population of breast cancer patients. Therefore, it is essential to have a better understanding of the relationship between obesity and breast cancer. This st

Перенос Митохондрии для ремонта миелина.

Обезвоживание является общей характеристикой нейро-воспалительных и дегенеративных заболеваний центральной нервной системы (КНС), таких, как множественный склероз (МС). Часто это связано с нарушениями межклеточной связи, биоэнергетики и метаболического баланса в сочетании с митохондриальной дисфункцией в таких клетках, как олигодендроциты, нейроны, астроциты и микроглиа. Несмотря на то, что нынешние методы лечения MS сосредоточены на иммуномодуляции, они не могут остановить или обратить вспять прогресс демиэлизации. Последние достижения подчеркивают межклеточный митохондриальный обмен в качест

Резюме книги: ISEV2017.

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Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients.

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3,

Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats.

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-w

NETs: organ-related epigenetic derangements and potential clinical applications.

High-throughput next-generation sequencing methods have recently provided a detailed picture of the genetic landscape of neuroendocrine tumors (NETs), revealing recurrent mutations of chromatin-remodeling genes and little-to-no pathogenetic role for oncogenes commonly mutated in cancer. Concurrently, multiple epigenetic modifications have been described across the whole spectrum of NETs, and their putative function as tumorigenic drivers has been envisaged. As result, it is still unclear whether or not NETs are epigenetically-driven, rather than genetically-induced malignancies. Although the N

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… However, whether the observed modifications of DNA packaging are driver or passenger events, and their position and role in the evolutionary tree of NETs still remains to be clarified. …

NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma.

Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels.

Computational approaches in rheumatic diseases - Deciphering complex spatio-temporal cell interactions.

Inflammatory arthritis, including rheumatoid (RA), and psoriatic (PsA) arthritis, are clinically and immunologically heterogeneous diseases with no identified cure. Chronic inflammation of the synovial tissue ushers loss of function of the joint that severely impacts the patient's quality of life, eventually leading to disability and life-threatening comorbidities. The pathogenesis of synovial inflammation is the consequence of compounded immune and stromal cell interactions influenced by genetic and environmental factors. Deciphering the complexity of the synovial cellular landscape has accel

Collateral Victim or Rescue Worker?-The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer.

Disrupted DNA damage signaling greatly threatens cell integrity and plays significant roles in cancer. With recent advances in understanding the human genome and gene regulation in the context of DNA damage, chromatin biology, specifically biology of histone post-translational modifications (PTMs), has emerged as a popular field of study with great promise for cancer therapeutics. Here, we discuss how key histone methylation pathways contribute to DNA damage repair and impact tumorigenesis within this context, as well as the potential for their targeting as part of therapeutic strategies in ca

Абстрактный сборник ISEV2022.

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