Результаты поиска

An AXL/LRP-1/RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo.

The phagocytosis of apoptotic cells (ACs), or efferocytosis, by DCs is critical for self-tolerance and host defense. Although many efferocytosis-associated receptors have been described in vitro, the functionality of these receptors in vivo has not been explored in depth. Using a spleen efferocytosis assay and targeted genetic deletion in mice, we identified a multiprotein complex--composed of the receptor tyrosine kinase AXL, LDL receptor-related protein-1 (LRP-1), and RAN-binding protein 9 (RANBP9)--that mediates DC efferocytosis and antigen cross-presentation. We found that AXL bound ACs, b

Differential activation of MAP kinase family members triggered by CD99 engagement.

The molecular basis for the modulatory properties of CD99 is not well understood. Treatment of human Jurkat T lymphocytes with anti-CD99 antibody led to activation of three mitogen-activated protein kinase (MAPK) members, ERK, JNK, and p38 MAPK, along with homotypic aggregation. While phosphorylation of ERK and JNK was inhibited by the pretreatment of a PKC inhibitor, bisindolylmaleimide I, activation of p38 MAPK was upregulated by the same pretreatment. The signaling pathways to MAPKs by CD99 engagement were independent of PI-3 kinase, distinguishing from those by CD3 engagement. Among MAPKs,

Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex.

Caspase-8 activation can be triggered by death receptor-mediated formation of the death-inducing signaling complex (DISC) and by the inflammasome adaptor ASC. Caspase-8 assembles with FADD at the DISC and with ASC at the inflammasome through its tandem death effector domain (tDED), which is regulated by the tDED-containing cellular inhibitor cFLIP and the viral inhibitor MC159. Here we present the caspase-8 tDED filament structure determined by cryoelectron microscopy. Extensive assembly interfaces not predicted by the previously proposed linear DED chain model were uncovered, and were further

XPO1 inhibitor selinexor enhances the apoptotic effect of azacitidine in T-cell lymphoma with TET2/RHOA mutations via JAK3/STAT3 axis.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous group of lymphoid malignancies with diverse pathological and molecular features. Patients harboring TET2 and RHOA double mutations exhibit poor response to anthracycline-based chemotherapy and unfavorable prognosis. Azacitidine, a hypomethylating agent, is frequently used in combination with anthracycline-based regimens in PTCL. However, resistance remains a significant challenge. This study aims to explore novel targeted therapies to overcome therapeutic resistance in TET2/RHOA-mutated PTCL patients. METHODS: A systemati

Совпадение в полном тексте источника
… A Venn diagram showing differentially expressed genes across various drug combinations in TET2 MUT / RHOA MUT Jurkat cells. B Pathways enriched in AZA and SEL treated TET2 MUT / RHOA MUT Jurkat cells identified by GSEA analysis. … A Venn diagram showing differentially expressed genes across various drug combinations in TET2 MUT / RHOA MUT Jurkat cells. B Pathways enriched in AZA and SEL treated TET2 MUT / RHOA MUT Jurkat cells identified by GSEA analysis. …

Polyphenols enhance the activity of alkylating agents in leukaemia cell lines.

Polyphenols have been shown to sensitize solid tumours to alkylating agents such as cisplatin, and induce apoptosis and/or cell-cycle arrest. Here, we assess the effects of five polyphenols alone and in combination with three alkylating agents: cisplatin, cyclophosphamide and chlorambucil in lymphoid and myeloid leukaemia cells lines, and non-tumour control cells. In lymphoid leukaemia cell lines there was a synergistic reduction in ATP and glutathione levels, an induction of cell cycle arrest, DNA damage and apoptosis when quercetin, apigenin, emodin and rhein were combined with cisplatin and

Совпадение в полном тексте источника
… Following apigenin combination treatment with cisplatin or cyclophosphamide a synergistic increase in γH2AX foci was seen in all leukaemia cell lines ( P ≤ 0.05), shown here in Jurkat cells ( Figure 6B ). …

Quantification of cell-free DNAfor the analysis of CD19-CAR-T cells during lymphoma treatment.

Chimeric antigen receptor (CAR)-T cells are increasingly used for the treatment of hematologic malignancies. Treatment success relies highly upon sufficient expansion of CAR-T effector cells. Accordingly, longitudinal quantification of CAR-T cells during therapy is clinically important. Techniques to quantify CAR-T cells in patient blood samples are based on flow cytometry and PCR. However, cellular kinetics of CAR-T cells are very complex and under current investigation. In this study, feasibility of CAR-T cell quantification by cell-free DNA (cfDNA) was analyzed. cfDNA isolated from 74 blood

Совпадение в полном тексте источника
… However, without specific killing of CD19 − Jurkat cells by CD19-directed CAR-T cells, no additional reference cfDNA was released by Jurkat cells, and, by consequence the ratio of cfCAR-DNA and reference cfDNA remained constant ( Figure 5 ; red columns). … In co-cultures with CD19 − Jurkat cells, the ratio was constant (red columns). …

Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies.

Targeting cancer cells that are highly dependent on the nicotinamide adenine dinucleotide (NAD+) metabolite is a promising therapeutic strategy. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme catalyzing NAD+ production. Despite the high efficacy of several developed NAMPT inhibitors (i.e., FK866 (APO866)) in preclinical studies, their clinical activity was proven to be limited. Here, we report the synthesis of new NAMPT Inhibitors, JJ08, FEI191 and FEI199, which exhibit a broad anticancer activity in vitro. Results show that these compounds are potent NAMPT inhibito

Совпадение в полном тексте источника
… Accordingly, we monitored necrotic cell death in time-dependent analyses, as well as the drug effect on cell proliferation in ML2 and Jurkat cells cultured with or without the new NAMPT inhibitors. … ML2 and Jurkat cells were treated with APO866 , JJ08, FEI191 and FEI199 for 72 h. Mitochondrial ( A ) and cytosolic ( B ) superoxide anions and hydrogen peroxide ( C ) were detected by flow cytometry using MitoSOX, DHE and H2DCFDA fluorescent probes, respectively. …

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

Совпадение в полном тексте источника
… For instance, CBD (5 μM, serum-free medium) produced multiple cytotoxic effects in Jurkat cells at 24 h, which were CB2-dependent [ 31 ]. …

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms

Proteasomal adaptations to FDA-approved proteasome inhibitors: a potential mechanism for drug resistance?

With proteasome inhibitors (PIs) becoming clinically available since 2003, outcomes for patients with multiple myeloma (MM) have dramatically changed, improving quality of life and survival. Despite the impressive treatment success, however, almost all MM patients who initially respond to these PIs eventually develop resistance. Furthermore, a portion of MM patients is inherently unresponsive to the PIs. Extensive mechanistic investigations identified several non-proteasomal signaling pathways suspected to be linked to the PI resistance, for which several excellent reviews are currently availa

Совпадение в полном тексте источника
… When Jurkat cells were repeatedly exposed to bortezomib over 6 months, researchers found increased expression of PSMB5 mRNA, which was also coincident with increased CT-L activity [ Table 2 ] [ 44 ] . … In the same Jurkat cells, a considerable decrease in IκB-α levels was observed, indicating that the bortezomib-mediated upregulation of NF-κB activity may contribute to survival and proliferation of bortezomib-resistant cells. …

Является ли DEXI множественным склерозом удобочитаемым геном?

Генетический ландшафт множественного склероза (MS) был тщательно просчитан, что позволило глубже понять молекулярные механизмы расстройства. В ходе первых исследований были выявлены ключевые гены, связанные с иммунной системой, в частности с Т клетками, которые имеют решающее значение для MS-чувствительности. В ходе последующих широкомасштабных исследований, проведенных в рамках всей ассоциации генома (GWAS), было выявлено более 200 генетических вариантов, связанных с MS, что выявило сложную взаимосвязь между риском, связанным с MS, и генами, вовлеченными в различные процессы в рамках адаптивн

Ранняя реакция на рост Gene 1 Выгоды Аутоиммунная болезнь путем поощрения дифференциации ячеек в качестве регулятора Foxp3.

Foxp3+ Регулирующие T (Treg) клетки, как один из подтипов CD4+T клеток, являются важнейшим сторожем в патогенезе самоантигенных реактивных заболеваний. В этом контексте мы продемонстрировали, что выборочная абляция гена раннего реагирования роста 1 (Egr-1) в CD4+T клеток усугубила экспериментальный аутоиммунный энцефаломиелит (EAE) в мюриновых моделях. Отсутствие Egr-1 в клетках CD4+T, полученное из мышей EAE и наивных клеток CD4+T, препятствовало дифференциации и влиянию Treg. Важно то, что в CD4+T клеток нескольких склерозных пациентов как Egr-1, так и Foxp3 было обнаружено снижение. Дальней

Совпадение в полном тексте источника
… As depicted in Fig. 6 A, CAL and formononetin (FN) substantially enhanced the ERE reporter luciferase activity in Jurkat cells ( P < 0.001). … Western blotting analysis Jurkat cells were stimulated with TGF-β (10 ng/ml) for 9 h to investigate the agonistic impact of TGF-β on Egr-1 through the Raf/Mek/Erk route. …

Exploring the Therapeutic Potential of Ganoderma lucidum in Cancer.

Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types

Совпадение в полном тексте источника
… Jurkat cells and the immortalized human epidermal HaCat cell line were used for the experiments; the cells were exposed to different concentrations of GLP (0 to 1000 mg/L) for 48 h. … Then, apoptosis in HaCat and Jurkat cells after exposure to 25 and 50 mg/l GLP5 was assessed using flow cytometry. …

Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induc

Совпадение в полном тексте источника
… In one study, researchers identified a truncated Tat variant that effectively reactivated HIV-1 in both latently-infected Jurkat cells and in CD4+ T cells from cART-treated individuals [ 304 ]. …

Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in spontaneous canine cancer: results of a phase I study.

BackgroundThe purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE) compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1) against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability.Methods and findingsCanine tumor cell lines derived from non-Hodgkin lymphoma (NHL), mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations o

Совпадение в полном тексте источника
… KPT185-trans isomer (which has ∼100 fold less XPO1 inhibition activity as the cis-isomer), showed much less toxicity when it was tested using Jurkat cells and one of primary canine DLBCL samples (IC 50 were >1000 nM in both tumor cells). … (A) Jurkat cells and primary canine DLBCL cells (sample #1–5, #5 was independently tested twice) were cultured in 96-well plates for 72 hours with log serial dilutions of KPT-185 and the cell viability was analyzed using the MTS assay. …

An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications.

Arsenic trioxide is a first-line treatment drug for acute promyelocytic leukemia, which is also effective for other kinds of leukemia. Its side effects, however, limit its clinical application, especially for patients with complex leukemia symptoms. Combination therapy can effectively alleviate these problems. This review summarizes the research progress on the combination of arsenic trioxide with anticancer drugs, vitamin and vitamin analogs, plant products, and other kinds of drugs in the treatment of leukemia. Additionally, the new progress in arsenic trioxide-induced cardiotoxicity was sum

Совпадение в полном тексте источника
… Arsenic trioxide (1 μM) and buthionine sulfoximine (10 μM) synergistically induced apoptosis in NB4, U-937, NAMALWA, and Jurkat cells primarily through the activation of c-Jun NH2-terminal kinase (JNK) and upregulation of death receptor 5 and cleaved Caspase-8. … cells | – | [ 102 , 103 ] Thalidomide | U-937 and KG-1 cells | – | [ 99 ] Venetoclax | KG-1 and KG-1a cells | – | [ 113 ] Author contributions YJ, BY, and YB contributed to conception of the review. …

Ferroptosis: a new dawn in the treatment of acute lymphoblastic leukemia.

Acute lymphoblastic leukemia poses substantial challenges in therapeutic management. As a novel form of programmed cell death, ferroptosis has emerged as a promising research direction in cancer therapy. Studies have emphasized the pivotal role of ferroptosis in ALL, indicating that targeting this pathway could provide a novel therapeutic strategy. This article systematically reviews the molecular regulatory mechanisms of ferroptosis in ALL and explores its potential clinical applications in the treatment and prognostic evaluation of the disease.

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies.

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic dr

Совпадение в полном тексте источника
… PEG-modified AuNPs (AuNPs-PEG) were uptaken by leukemic HL-60 II (p53 null) and Jurkat cells to a similar extent, although there was no targeting moiety. … Interestingly, AuNPs-PEG (15 nm) with 5 Gy external radiation showed a higher sensitivity enhancement ratio against HL-60 II (1.33) compared to Jurkat cells (1.18). …

Medicinal Plants with Anti-Leukemic Effects: A Review.

Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient's survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half

Совпадение в полном тексте источника
… . | U937 cell line and Jurkat cell lines | Anti-leukemic, and Growth Inhibition | [ 67 ] Berberis amurensis | Berberidaceae | Alkaloids Bisbenzylisoquinoline group Berbamine,4-Chlorobenzoyl Berbamine and Berberine. | Leukemic NB4 cells, Leukemic cell line K562, Chronic myeloid Leukemia cell line KU812 … An investigation on the cytotoxicity of O. europaea ethanol extract against Jurkat leukemic cells indicated that the extract inhibits the growth of Jurkat cells and causes apoptosis at non-cytotoxic concentrations [ 95 ]. …

The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy.

Cancer is a challenging problem for the global health community, and its increasing burden necessitates seeking novel and alternative therapies. Most cancers share six basic characteristics known as "cancer hallmarks", including uncontrolled proliferation, refractoriness to proliferation blockers, escaping apoptosis, unlimited proliferation, enhanced angiogenesis, and metastatic spread. Apoptosis, as one of the best-known programmed cell death processes, is generally promoted through two signaling pathways, including the intrinsic and extrinsic cascades. These pathways comprise several compone

Совпадение в полном тексте источника
… Hemanthamine and hemanthidine, alkaloid compounds from Amaryllidaceae family, treatment of Jurkat cells lead to the decreased MMP, strong activation of caspase-9 and caspase-3/7, and weaker activation of caspase-8 [ 129 ]. …