Результаты поиска

Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recog

Совпадение в полном тексте источника
… Between prophase and metaphase, Aurora B is localized to the kinetochores and then migrates during cytokinesis to the cell midbody and cleavage furrow. It provides catalytic activity to the chromosome passenger complex (CPC) consisting of survivin, borealin, and INCENP. … Aurora B is necessary for effective cytokinesis at the end of mitosis; without it, the two daughter cells remain joined by cytoplasmic bridges, and the chromosomes misalign, determining the development of binucleate daughter cells [ 40 , 43 ]. …

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

Совпадение в полном тексте источника
… It may be present in the nucleus, in the centrosome during metaphase and anaphase, and in the midbody in cytokinesis [ 11 ]. The expression and activity of NEK6 increase during mitosis, wherein the activity of NEK6 is dependent on its phosphorylation at serine 206 by NEK9. … NEK7 shares some redundant functions with NEK6, such as participation in mitosis, the establishment of the mitotic spindle, and cytokinesis [ 11 ]. …

Ущерб от белой материи при нарушении центральной нервной системы.

По мере ускорения процесса старения и улучшения условий жизни болезни центральной нервной системы (СНС) стали одной из основных проблем здравоохранения. Болезни CNS вызывают не только повреждения серых веществ, которые в первую очередь характеризуются потерей нейронов, но и повреждения белых веществ. Однако в большинстве предыдущих исследований основное внимание уделялось травматизму серого вещества (ГМИ), при этом было проведено меньше исследований травматизма белого вещества (ВМИ). В этой статье мы кратко опишем структуру и функцию белого вещества, подытожим патологические изменения ВМИ и со

Совпадение в полном тексте источника
… Glutamate Excitotoxicity Glutamate excitotoxicity is one of the major factors in CNS ischemic injury. 15 In the mature healthy brain, glutamate is released from presynaptic neuronal endings into synapses via cytokinesis and binds to postsynaptic ionotropic (NMDA, AMPA, and erythrocyanine receptors) …

A Route for Investigating Psoriasis: From the Perspective of the Pathological Mechanisms and Therapeutic Strategies of Cancer.

Psoriasis is an incurable skin disease that develops in about two-thirds of patients before the age of 40 and requires lifelong treatment; its pathological mechanisms have not been fully elucidated. The core pathological process of psoriasis is epidermal thickening caused by the excessive proliferation of epidermal keratinocytes, which is similar to the key feature of cancer; the malignant proliferation of cancer cells causes tumor enlargement, suggesting that there is a certain degree of commonality between psoriasis and cancer. This article reviews the pathological mechanisms that are common

Совпадение в полном тексте источника
… The TOPK inhibitor OTS514 induces the cytokinesis defect of cancer cells, suggesting that the inhibition of TOPK may be a viable therapeutic option for the treatment of various cancers [ 91 ]. … TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci. Transl. Med. 2014;6:259ra145. doi: 10.1126/scitranslmed.3010277. 92. Zeng F., Lu H., Wu M., Dai C., Li J., Wang J., Hu G. …

Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.

Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JA

Совпадение в полном тексте источника
… receptor family member + + CD83 CD83 molecule Immune response/antigen presentation + + + JAM2 Junctional adhesion molecule, CD322 Adhesion/migration + + + ICAM1 Intercellular adhesion molecule 1 Adhesion/migration + + FAS CD95, Fas cell surface death receptor Apoptosis, pro + + DOCK10 Dedicator of cytokinesis … molecule | Immune response/antigen presentation | + | + | + JAM2 | Junctional adhesion molecule, CD322 | Adhesion/migration | + | + | + ICAM1 | Intercellular adhesion molecule 1 | Adhesion/migration | | + | + FAS | CD95, Fas cell surface death receptor | Apoptosis, pro | + | | + DOCK10 | Dedicator of cytokinesis …

Targeting Casein Kinase 1 (CK1) in Hematological Cancers.

The casein kinase 1 enzymes (CK1) form a family of serine/threonine kinases with seven CK1 isoforms identified in humans. The most important substrates of CK1 kinases are proteins that act in the regulatory nodes essential for tumorigenesis of hematological malignancies. Among those, the most important are the functions of CK1s in the regulation of Wnt pathways, cell proliferation, apoptosis and autophagy. In this review we summarize the recent developments in the understanding of biology and therapeutic potential of the inhibition of CK1 isoforms in the pathogenesis of chronic lymphocytic leu

Совпадение в полном тексте источника
… Lenalidomide has been shown to be able to eradicate del(5q) MDS clones, to inhibit growth of CD34+ cells carrying this aberration [ 130 , 131 ] and to induce cytokinesis defects in the treated del(5q) MDS-L cells [ 128 ]. … Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis. Leukemia. 2010 doi: 10.1038/leu.2009.296. 129. Chen Y., Borthakur G. Lenalidomide as a novel treatment of acute myeloid leukemia. Expert Opin. Investig. …

Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases.

Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone

Совпадение в полном тексте источника
… Proteomic comparison of the bone homing cell line to the parental MDA-MB-231 cells has identified several proteins with potential to be markers of bone metastasis risk including macrophage actin-capping protein-1 (CAPG) and PDZ domain-containing protein-1 (GIPC1) [ 21 ] as well as dedicator of cytokinesis … Dedicator of Cytokinesis 4: A Potential Prognostic and Predictive Biomarker Within the Metastatic Spread of Breast Cancer to Bone Cancer Inform. 2019 18 1176935119866842 10.1177/1176935119866842 31488945 PMC6712742 21. Westbrook J.A. Cairns D.A. Peng J. Speirs V. Hanby A.M. Holen I. Wood S.L. …

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma.

PURPOSE: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma. PATIENTS AND METHODS: Seventy-six adults with Karnofsky Performance Status ≥ 60 were enrolled. Patients undergoing cytoreductive surgery received up to three selinexor doses (twice weekly) preoperatively (Arm A; n = 8 patients). Patients not undergoing surgery received 50 mg/m2 (Arm B, n = 24), or 60 mg (Arm C, n = 14) twice weekly, or 80 mg once weekly (Arm

Совпадение в полном тексте источника
… Among the identified recurrently mutated genes, patients whose tumors harbored mutations in pancreatic and duodenal homeobox 1 ( PDX1 , n = 5), E1A Binding Protein P400 ( EP400 , n = 13), or Dedicator of Cytokinesis 8 ( DOCK8 , n = 7) survived longer than patients with wild-type tumors (Supplementary …

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA-mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viabi

Совпадение в полном тексте источника
… The bipartite rac1 guanine nucleotide exchange factor engulfment and cell motility 1/dedicator of cytokinesis 180 (elmo1/dock180) protects endothelial cells from apoptosis in blood vessel development J. Biol. Chem. 2015 290 6408 6418 10.1074/jbc.M114.633701 25586182 PMC4358276 25. Sharma K.R. …

Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas.

T-cell lymphomas are a heterogeneous group of cancers with different pathogenesis and poor prognosis. Histone deacetylases (HDACs) are epigenetic modifiers that modulate many key biological processes. In recent years, HDACs have been fully investigated for their roles and potential as drug targets in T-cell lymphomas. In this review, we have deciphered the modes of action of HDACs, HDAC inhibitors as single agents, and HDACs guided combination therapies in T-cell lymphomas. The overview of HDACs on the stage of T-cell lymphomas, and HDACs guided therapies both as single agents and combination

Совпадение в полном тексте источника
… HDAC inhibitors have been shown to induce the acetylation of histone and non-histone proteins (nuclear transcription factors mediating anti-cancer activity), cause DNA damage, promote the re-expression of repressed genes during oncogenesis, mediate lethality through cytokinesis failure, facilitate a … The combination of Romidepsin and alisertib has shown highly synergistic effect in TCL cell lines through modulation of cytokinesis 155 . A phase I clinical trial of this combination is currently ongoing in relapsed/refractory aggressive B/T-cell lymphomas ( NCT01897012 ) 156 . …

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

Совпадение в полном тексте источника
… Thirdly, we found a SNP in SEPTIN9, a gene that encodes for a protein involved in cytokinesis and cell cycle control via the microtubules [ 56 , 57 ]. The gene has been implicated with hereditary neuralgic amyotrophy [ 56 , 57 ]. …

Molecular Inhibitors of Growth Signals

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

метрики соотношений на основе пропорциональности при подсчете данных о составе.

Составные данные включают векторы, описывающие составные части целого. Данные, полученные с помощью различных -омикических платформ, таких, как 16S и RNA, носят составный характер. В таких данных корреляции между характеристиками первичных счетов не имеют сколько-нибудь значимого толкования. Для решения этой проблемы были сформулированы критерии пропорциональности. Однако имманентная погрешность возникает тогда, когда эти метрики рассчитываются эмпирически на основе показателей, основанных на подсчете, из-за изменчивости глубин считываемого материала. Мы подсчитали погрешность, введенная путем

Совпадение в полном тексте источника
… KIF20B is involved in cellular proliferation and regulation of cytokinesis. Silencing KFI20B has also been shown to increase cell arrest in G1 phase[ 30 ]. Table 1. …

A Comprehensive Analysis Revealing BUB1B as a Potential Prognostic and Immunological Biomarker in Lung Adenocarcinoma.

BUB1B, a member of the spindle assembly checkpoint family known as BUB1 mitotic checkpoint serine/threonine kinase B, has been associated with the promotion of tumor progression. Nevertheless, its specific contributions to tumorigenesis remain largely unexplored. This study seeks to offer a systematic and comprehensive analysis of the role of BUB1B in the progression of various cancers, with a particular focus on lung adenocarcinoma, utilizing a range of databases. We investigated BUB1B's role in pan-cancer using TCGA data, analyzing it with platforms like HPA, TIMER, TISIDB, GEPIA, cBioPortal

Совпадение в полном тексте источника
… Moreover, GO analysis (biological function) demonstrated that BUB1B mainly joined in spindle organization, DNA replication, cell cycle checkpoint, double-strand break repair, DNA recombination, cytokinesis, acute inflammatory response, etc. ( Figure 5 D). …

Antiphospholipid Antibodies and Lipids in Hematological Malignancies.

One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-β2 glycoprotein I (anti-β2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL.

Совпадение в полном тексте источника
… In addition, this protein is involved in cytokinesis, exocytosis, endocytosis, intracellular trafficking cell junctions, and the regulation of mitotic cell division, giving crucial importance to the signaling for cell survival and proliferation as well as to neoangiogenesis, tumor growth, and metastasis …

Telomere length and survival in primary cutaneous melanoma patients.

Telomere repeats at chromosomal ends, critical to genomic integrity, undergo age-dependent attrition. Telomere length, a polygenic trait, has been associated with risk of several disorders including cancers. In contrast to association of long telomeres with increased risk of several cancers, including melanoma, emerging reports suggest that short telomeres predict poor survival in patients with different cancers. In this study based on 1019 stage I and II cutaneous melanoma patients, we show an association between the patients with short telomeres and poor melanoma-specific survival (HR 2.05,

Совпадение в полном тексте источника
… Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 2005;437:1043–1047. doi: 10.1038/nature04217. 52. Davoli, T., Uno, H., Wooten, E. C. & Elledge, S. J. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. …

Combined Immune Defect in B-Cell Lymphoproliferative Disorders Is Associated with Severe Infection and Cancer Progression.

B cell chronic lymphoproliferative diseases (B-CLPD) are associated with secondary antibody deficiency and other innate and adaptive immune defects, whose impact on infectious risk has not been systematically addressed. We performed an immunological analysis of a cohort of 83 B-CLPD patients with recurrent and/or severe infections to ascertain the clinical relevance of the immune deficiency expression. B-cell defects were present in all patients. Patients with combined immune defect had a 3.69-fold higher risk for severe infection (p = 0.001) than those with predominantly antibody defect. Inte

Совпадение в полном тексте источника
… bacterial infections are more frequent in the setting of PID, but intrinsic complex oncogenic mechanisms may play a major pathogenic role, for instance: stem cell developmental defects; lymphocyte differentiation and apoptosis defects; co-stimulation, cytoskeleton and signalling defects; cell cycle and cytokinesis …

Identification and validation of CKAP2 as a novel biomarker in the development and progression of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic joint disease. However, many patients exhibit inadequate responses to treatment due to disease heterogeneity. Identifying novel biomarkers for RA is crucial for advancing molecular diagnosis and identifying potential therapeutic targets. METHODS: Synovial tissue transcriptome data from RA patients and healthy controls were obtained from the GEO database. Differentially expressed gene (DEG) analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) identified key gene modules in RA. Machine learni

Совпадение в полном тексте источника
… Cytoskeleton-associated protein 2 (CKAP2) encodes a protein that stabilizes microtubules and plays a crucial role in the regulation of cytokinesis, which is closely linked to cellular proliferative activity, migration, and invasion ( 17 – 19 ). …

Sacubitril/Valsartan Ameliorates Crizotinib-Induced Cardiotoxicity in Mice.

BackgroundLung cancer is one of the major cause of death globally. Crizotinib is a first-line drug used in treating non-small-cell lung cancer (NSCLC). However, the pathophysiological mechanisms underlying its cardiotoxicity are unknown. This study investigated the mechanisms of crizotinib-induced cardiotoxicity and explored whether this toxicity can be prevented by the angiotensin receptor/neprilysin inhibitor sacubitril/valsartan.MethodsMale C57BL/6 mice were randomly divided into three groups: control, crizotinib (40 mg ⋅ kg - 1 ⋅ d - 1 for four weeks), and crizotinib + sacubitril/valsartan

Совпадение в полном тексте источника
… adenosine-triphosphate; Fos , FBJ osteosarcoma oncogene; Uhrf1 , ubiquitin-like, containing PHD and RING finger domains, 1; Racgap1 , Rac GTPase-activating protein 1; Mki67 , antigen identified by monoclonal antibody Ki 67; Ube2c , ubiquitin-conjugating enzyme E2C; Pbk , PDZ binding kinase; Prc1 , protein regulator of cytokinesis …

The Potential Role of Sildenafil in Cancer Management through EPR Augmentation.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for the treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 has been reported in lung, colon, metastatic breast cancers, and bladder squamous carcinoma. Moreover, sildenafil has been reported to increase the sensitivity of

Совпадение в полном тексте источника
… Nevertheless, a nonsignificant decrease in the level of cytokinesis was observed when cells responsive to vincristine were treated with sildenafil. …