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Unveiling the shared etiology between gastrointestinal disorders and valvular heart diseases through a genome-wide pleiotropy study.

This study explores the genetic link between gastrointestinal disorders and valvular heart disease (VHD), aiming to clarify shared mechanisms through a genome-wide pleiotropy analysis. We assessed the genetic correlation between six gastrointestinal disorders-including GERD, IBS, PUD, IBD, Crohn's disease, and ulcerative colitis-and VHD, employing methods like linkage disequilibrium score regression and pleiotropic analysis under a composite null hypothesis. Our results show significant genetic correlations, particularly with GERD (rg = 0.211), IBS (rg = 0.23), and PUD (rg = 0.21). Fifteen var

Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review.

Gastric adenocarcinoma is one of the most common types of cancer worldwide, with an incidence of a million new cases annually. In addition to having a high mortality rate due to often delayed detection and its poor response to cancer therapy, it also spreads aggressively. Inflammation has been shown to play a role in carcinogenesis. Consequently, macrophages are important in phagocytosis, antigen presenting and producing cytokines and growth factors. As a response to microenvironmental signals, they may polarize into tumor resisting M1 or tumor promoting M2 macrophages. Recently, studies have

Вирус Эпштейн-Барр BALF0/1 подрывает пути кавеолина и ERAD, чтобы охватить комплексы рецепторов клеток B для разложения.

Вирус Эпштейн-Барр (ЭБВ) устанавливает стойкую инфекцию, вызывает инфекционный мононуклеоз, является одним из основных пусковых факторов множественного склероза и способствует возникновению множественных раковых заболеваний. Тем не менее, знания о том, как вирус реконструирует клетки В для поддержки литического воспроизведения, остаются неполными. Ранее мы обнаружили, что EBV литическое воспроизведение приводит к избирательному истощению комплексов рецепторов клеток В (КРВ), состоящих из иммуноглобулина, а также цепочек сигнализации CD79A и CD79B. Здесь мы использовали протеомные и биохимическ

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… Whereas activated BCR complexes are typically delivered to lysosomes to support presentation of peptide antigens to CD4+ T cells by major histocompatibility complex (MHC) class II molecules ( 21 ), EBV instead routes BCR to cytosolic proteasomes by an unidentified pathway ( 20 ). …

New Directions in the Study and Treatment of Metastatic Cancer.

Traditional cancer therapy has relied on a strictly cytotoxic approach that views non-metastatic and metastatic tumor cells as identical in terms of molecular biology and sensitivity to therapeutic intervention. Mounting evidence suggests that, in fact, non-metastatic and metastatic tumor cells differ in key characteristics that could explain the capacity of the metastatic cells to not only escape the primary organ but also to survive while in the circulation and to colonize a distant organ. Here, we lay out a framework for a new multi-pronged therapeutic approach. This approach involves modif

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… Specifically, when the T cell receptor (TCR) of a T cell recognizes foreign antigens in the context of the major histocompatibility complex, additional binding events modulate the ensuing response through co-stimulatory factors, such as CD28 (serving to amplify the signal by binding to CD80/CD86 on antigen-presenting …

The role of noble bumblebee (Bombus terrestris) queen glycosaminoglycan in aged rat and gene expression profile based on DNA microarray.

IL-1 induces a significant number of metabolic and hematological changes. In experimental animals, IL-1 treatments cause hypotension due to rapid reduction of systemic blood pressure, reduced vascular resistance, increased heart rate and leukocyte aggregations. IL-1 causes endothelial dysfunction, the triggering factor of which may be of a different nature including pathogen infection. This dysfunction, which includes macrophage intervention and increased protein permeability, can be mediated by several factors including cytokines and arachidonic acid products. These effects are caused by the

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… Tumor antigens can be processed and presented with the major histocompatibility complex (MHC) on the cell membrane and recognized by receptors on the cell surface of T-cells to elicit an antitumor immune response ( 36 ). …

CD70-targeted CAR-T/NK therapy: Rationale, advances, and future directions.

Chimeric antigen receptor T and natural killer (CAR-T/NK) cells is a rapidly evolving cellular immunotherapy technology that has made great achievements in the treatment of hematologic diseases. CD70, as a surface antigen expressed on tumor cells in a variety of hematologic malignancies, including acute myeloid leukemia, non-Hodgkin lymphoma, multiple myeloma, etc., and solid tumors such as renal cell carcinoma, osteosarcoma, and glioma, is a potential target for CAR-T/NK cells. Several preclinical studies and clinical trials on CAR-T/NK cells targeting CD70 are currently underway, bringing ne

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… histocompatibility complex MM multiple myeloma MM multiple myeloma NHL non-Hodgkin lymphoma NIK NF-κB-inducing kinase NK cell natural killer cell NKp30 natural killer protein 30 NSCLC non-small cell lung cancer OVs Oncolytic viruses PARP Polyadenosine diphosphate-ribose polymerase PDAC pancreatic ductal … Antigen recognition by CAR-T cells does not depend on the major histocompatibility complex (MHC). These cells can recognize specific antigens on the surface of tumor cells without the need for antigen processing and presentation. …

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of

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… Several factors are thought to contribute to ICI resistance in SCLC, including downregulation of major histocompatibility complex (MHC) molecules, failure of antigen presentation, and high intratumoral heterogeneity [ 15 , 16 ]. … histocompatibility complex Neuroendocrine carcinoma Neuroendocrine prostate cancer Neuroendocrine tumor Nonhuman primate Natural killer Nonobesediabetic/severe combined immunodeficiency Objective response rate Overall survival Pyrrolobenzodiazepine Programmed cell death protein-1 Programmed …

Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential.

Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects t

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… Most vaccines that use these TERT-derived peptides were found to have major histocompatibility complex (MHC) I and MHC II epitopes specific to the tumor [ 229 , 230 ]. GV1001 and GRNVAC1 are two well-studied vaccines against human malignancies ( Figure 3 ). … These antigenic peptides are recognized by CD8+ and CD4+ T cells via the major histocompatibility complex class I and class II, respectively. This results in the amplification of telomerase-mediated cytotoxic T lymphocytes response in cancer patients. …

A Novel Approach to Prognostic Factors and Risk Stratification in Pediatric AML: Case Report and Literature Review.

Acute myeloid leukemia (AML), the second most common type of leukemia in children, is a heterogeneous disease known to be caused by genetic, epigenetic, and transcriptional changes, predominantly somatic and germline abnormalities. Despite significant improvement of overall survival rates, the prognosis of pediatric AML remains unfavorable in comparison with acute lymphoblastic leukemia (ALL), especially in relapsed or refractory settings. The current status and future directions are focused on establishing an accurate diagnosis and treatment strategies based on the genomic background. Next-ge

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… AML cells express both major histocompatibility complex (MHC) class I and II molecules, which is related to being recognized by T cells and vulnerable to T-cell-mediated cytotoxicity. … Histocompatibility Complex NK Natural Killer CAR-T Chimeric Antigen Receptor T cell ADCs Antibody–Drug Conjugates BiTE Bispecific T-cell Engager DART Dual-Affinity Retargeting MNs Modal Numbers ctDNA Circulating Tumor DNA cfDNA Circulating Free Cell DNA miRNA-29a microRNA-29a miRNA-100 microRNA-100 …

Провоспалительные молекулы, имплицитно связанные с множественным склерозом Divert Development of Human Oligodendrocyte Lineage Cells.

ИСТОРИЯ И ЗАДАЧИ: Олигодендроциты (ОИ) и их процессы формирования миелина теряются во время заболевания, вызванного множественным склерозом (МС), цель которого заключается в проникновении лейкоцитов и их эффектных цитокинов. Считается, что ремонт миелин зависит от набора и дифференциации ячеек потомков олигодендроцитов. До сих пор не определены основания для отказа от воспоминаний во время болезни MS. Цель этого исследования состояла в том, чтобы определить влияние на дифференциацию опухолей человека факторов некроза (ОКП) и интерферона (ИФН).Мы создали человека OPC из индуцированных плюрипоте

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… In addition to their motility, it has been noted that OPCs have phagocytic capacity, 12 release proinflammatory cytokines, 13 and express major histocompatibility complex (MHC) molecules, 14,15 which are involved with leukocyte activation and recruitment. …

Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management.

BackgroundVarious types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment.ResultsClinical presentation

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… They target neoantigens presented by the major histocompatibility complex (MHC) molecules on the surface of cancer cells. …

Patterns of CMV infection after letermovir withdrawal in recipients of posttransplant cyclophosphamide-based transplant.

Reactivation of latent cytomegalovirus (CMV) is increased in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with seropositive CMV using posttransplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis. Letermovir, a novel DNA terminase complex inhibitor, reduces the incidence of clinically significant CMV infection (csCMVi) in this population; however, parameters that predict csCMVi after letermovir withdrawal are not well described. Here, we examined clinical and immunological parameters in 294 recipients of PT-Cy-based allo-HCT, including 157

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… Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant. 2002;8(3):131–138. doi: 10.1053/bbmt.2002.v8.pm11939602. 14. …

Induction of maturation and activation of human dendritic cells: a mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer.

BackgroundViscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.MethodsFour day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 microg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyze

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… Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J Exp Med. 1998;188:2163–2173. doi: 10.1084/jem.188.11.2163. Rabinovich GA, Gabrilovich D, Sotomayor EM. …

CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial.

BackgroundPatients with microsatellite stable (MSS) colorectal carcinoma (CRC) do not respond to immune checkpoint inhibitors. Preclinical models suggested synergistic anti-tumour activity combining CXD101 and anti-programmed cell death protein 1 treatment; therefore, we assessed the clinical combination of CXD101 and nivolumab in heavily pre-treated patients with MSS metastatic CRC (mCRC).Patients and methodsThis single-arm, open-label study enrolled patients aged 18 years or older with biopsy-confirmed MSS CRC; at least two lines of systemic anticancer therapies (including oxaliplatin and ir

Current Landscape of Genome-Wide Association Studies in Acute Myeloid Leukemia: A Review.

Acute myeloid leukemia (AML) is a clonal hematopoietic disease that arises from chromosomal and genetic aberrations in myeloid precursor cells. AML is one of the most common types of acute leukemia in adults; however, it is relatively rare overall, comprising about 1% of all cancers. In the last decade or so, numerous genome-wide association studies (GWAS) have been conducted to screen between hundreds of thousands and millions of variants across many human genomes to discover genetic polymorphisms associated with a particular disease or phenotype. In oncology, GWAS has been performed in almos

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… Within the discovery cohort, genome-wide significant ( p < 5 × 10 −8 ) susceptibility loci were observed in CN-AML and included SNP rs3997854 located in Major Histocompatibility Complex, Class II, DQ Alpha 2 ( HLA-DQA2 ) gene (Chr 6p21.32) and rs75391980 (Chr 4q22.3). …

Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen rece

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… Eshhar et al. designed structures that specifically recognise and respond to the antigen without signalisation of major histocompatibility complex (MHC) [ 39 ]. … histocompatibility complex MMPs | matrix metalloproteinases MSLN | mesothelin MUC16 | mucin 16 NK | natural killer OC | ovarian cancer OCSCs | ovarian cancer stem cells OSE | ovarian surface epithelium PARP1 | poly [ADP-ribose] polymerase 1 PCR | polymerase chain reaction PD-1 | Programmed cell death …

Review of Adoptive Cellular Therapies for the Treatment of Sarcoma.

Sarcomas are a heterogeneous group of malignancies with limited therapeutic options, particularly in the metastatic setting. Adoptive cellular therapies (ACTs), including tumor-infiltrating lymphocyte (TIL) therapy, chimeric antigen receptor (CAR) T-cell therapy, and T-cell receptor (TCR) gene-modified T-cell therapy, offer promising novel approaches for these refractory tumors. TIL-based therapy has demonstrated early efficacy in melanoma and myeloma, with ongoing trials exploring its role in sarcoma. CAR T-cell strategies targeting HER2, GD2, and B7-H3 antigens are in development, though cha

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… The potential benefit of engineered TCRs is that they allow for the recognition of intracellularly processed peptides presented via major histocompatibility complexes (MHCs). … Histocompatibility Complex MRCLS | Myxoid/Round Cell Liposarcoma NY-ESO-1 | New York Esophageal Squamous Cell Carcinoma-1 ORR | Overall Response Rate OS | Overall Survival OTOT | On-Target/Off-Tumor Toxicity PD | Progressive Disease PFS | Progression-Free Survival PR | Partial Response SD | Stable Disease …

Mucin1 as a potential molecule for cancer immunotherapy and targeted therapy.

Mucin1 is a highly glycosylated type 1 transmembrane mucin that ranks second among 75 tumor-related antigens published by the National Cancer Institute, and has been identified as a possible therapeutic target over the past 30 years. MUC1 plays an important role in malignant transformation and disease evolution, including cell proliferation, survival, self-renewal, and metastatic invasion. MUC1 has been shown to interact with diverse effectors such as β-catenin, receptor tyrosine kinases, and cellular-abelsongene, which are of importance in the pathogenesis of various malignant tumors. Targeti

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… histocompatibility complex tumor-associated MUC1 programmed death 1 prostate stem cell antigen natural killer peripheral blood mononuclear cells keyhole limpet hemocyanin bacillus Calmette-Guerin maltose binding protein Quillaja saponaria extract pathological complete response pathological … Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-MUC1 signal peptide vaccine, in multiple myeloma patients. Br J Haematol. 2015;169(1):44–56. doi: 10.1111/bjh.13245. 83. …

Cancer-Associated Thrombosis in Patients Treated with Immune Checkpoint Inhibitors.

The incidence of cancer-associated thrombosis has increased in recent years. While the association between venous thromboembolism (VTE) and chemotherapy is well established, there is no clear link between immune checkpoint inhibitors (ICIs) and VTE risk. Many risk assessment models (RAMs) have been developed to identify high-risk patients who need prophylaxis. However, these models are validated in patients undergoing chemotherapy, while they are scarce in those receiving immunotherapy. Moreover, the mechanisms linking ICIs to thrombosis are still a matter of debate. They include the upregulat

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… Interferon gamma (IFN-γ), another significant participant in the process enabling thrombosis, stimulates the immune system and increases the expression of major histocompatibility complex class 1 (MHC I) at the endothelial level, thereby increasing exposure to cytotoxic CD8+ T lymphocytes, promoting … Histocompatibility Complex Class I NETs Neutrophil Extracellular Traps NF-KB Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells NFAT Nuclear Factor of Activated T-cells NSCLC Non-Small Cell Lung Cancer OAC Oral Anticoagulant OR Odds Ratio PAI-1 Plasminogen Activator Inhibitor 1 PD-1 Programmed …

The Black Hole: CAR T Cell Therapy in AML.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed/refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen-targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything. One must consider the fact that only around 30% of

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… DARIC: dimerizing agent–regulated immunoreceptor complex; HSPC: hematopoietic stem and progenitor cells; IDO: indoleamine 2,3-dioxygenase (IDO); KO: knock-out; MHC-I: major histocompatibility complex-I; PD-1: programmed cell death-1; TCR: T cell receptor). …