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Амиотропический латеральный склероз и лобовое дегенерация: сходства в генетическом фоне

Амиотрофический боковой склероз (ALS) — это разрушительное, равномерно смертоносное прогрессивное дегенеративное расстройство моторных нейронов, которое перекликается с клиническим, морфологическим и генетическим дегенерацией лобар (FTLD). Хотя известно, что многие различные мутации в различных генах вызывают амиотрофный боковой склероз, по-прежнему мало что известно о том, как они избирательно влияют на биологию моторных нейронов и сходятся ли они на общих путях, чтобы вызвать нейронное дегенерацию. Многие генные мутации содержатся в белках, которые имеют схожие функции. Их можно сгруппироват

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… Overal TDP % TBK1 | 12q14.2 | AD | 3 | <1 | 1.3 | 2 | 1 | <1 | autophagy CHCHD10 | 22q11.23 | AD | 2 | <1 | <1 | <1 | <1 | <1 | mitochondrial dysfunction, synaptic integrity TIA1 | 2p13.3 | AD | 2 | | <1 | | | | RNA metabolism ANXA11 | 10q22.3 | AD | 1.2 | <1 | 1.1 | | | | apoptosis, exocytosis, cytokinesis …

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, mi

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… With low levels of BRD4, mitosis may become abnormal leading to increased incidence of lagging chromosomes, micronuclei and bridging chromosomes, eventually resulting in failed cytokinesis and multilobulated nuclei ( 16 ). …

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc

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… Tumour-treating fields (TTFields): investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis. Sci. Rep. 9, 7362. Bobkova I.V., Bobkov A.M., Silaev M.A. (2021). …

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

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… Further, another pool of phospho-BCL-xL Ser49 occurs through telophase where it seems to play a role in cytokinesis. … In telophase Ser49 phosphorylation is implicated in cytokinesis | [ 137 ] Asp52 | ? | Deamidation | Decreases BCL-xL affinity for pro-apoptotic BH3 domains. …

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin w

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… Antioxidative stress effects Lipid peroxidation is one of the characteristic features of secondary SCI, which is caused by significantly increased levels of ROS and RNS and eventually leads to cytokinesis, the destruction of proteins and nucleic acids, and apoptosis or necrosis [ 170 , 171 ]. …

B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy that arises from the clonal expansion of transformed B-cell precursors and predominately affects childhood. Even though significant progresses have been made in the treatment of B-ALL, pediatric patients' outcome has to be furtherly increased and alternative targeted treatment strategies are required for younger patients. Over the last decade, novel approaches have been used to understand the genomic landscape and the complexity of the molecular biology of pediatric B-ALL, mainly next generation sequencing, offering import

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… AkB is involved in centrosome function, mitotic spindle assembly and cytokinesis. Its overexpression is often reported in different cancers, where it correlates with higher malignancy, higher proliferation, and worse outcome [ 159 ]. …

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

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… A number of proteins associated with cell-cycle progression in the SARS-CoV-2 interactome has been identified, including proteins associated with the centrosome, mitotic spindle, and cytokinesis control [ 168 ]. …

The Proliferative and Apoptotic Landscape of Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is an aggressive molecular subtype that represents up to 15% of breast cancers. It occurs in younger patients, and typically shows rapid development of locoregional and distant metastasis, resulting in a relatively high mortality rate. Its defining features are that it is positive for basal cytokeratins and, epidermal growth factor receptor and/or c-Kit. Problematically, it is typically negative for the estrogen receptor and human epidermal growth factor receptor 2 (HER2), which means that it is unsuitable for either hormone therapy or targeted HER2 therapy. As

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… I ( n = 7) | Various advanced solid tumors PLK1 inhibitor | Volasertib [ 130 , 131 , 132 ] (BI 6727; Boehringer Ingekheim) | Cell cycle kinase inhibitor targeting PLK1, PLK2 and PLK3 Induces pro-metaphase arrest by interfering with mitosis (e.g., entry, spindle formation, chromosome separation and cytokinesis …

Proceedings of the CIMAGO Meeting - Challenges in Oncobiology Coimbra, 31st january 2020.

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… Chromosomal damage was analyzed using the cytokinesis-block micronucleus cytome assay. Two hours after H 2 O 2 treatment, DNA repair was accessed with the alkaline comet assay. …

Esid 2014 oral presentations.

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Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

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… They can lead to selective reduction of tumor metastases, impairment of angiogenesis, differentiation of tumor cells, impediment of cytokinesis, cell cycle halt, immune stimulation and intensification of immune reactions against tumors ( Van Blitterswijk and Verheij, 2008 ; Kostadinova et al., 2015 ; …

RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.

In the last decades, colorectal cancer (CRC) has emerged as a global problem, representing approximately 10% of all malignant tumors and the second leading cause of cancer-related death. Colitis-associated cancer (CAC) arises from chronic unresolved inflammation and is typically characterised by poor prognosis. Among key cellular regulators, the small GTPase RHOA controls cytoskeleton dynamics in various cell types and, thereby, key biological processes. Although it has been linked to various diseases, the role of RHOA in cancer remains controversial. RHOA has been proposed as a biomarker in c

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… In physiological situations, RHOA activity is particularly important during the last steps of mitosis, anaphase, and telophase; GTP-RHOA localizes at the plasma membrane and cleavage furrow, and promotes the contractile ring, permitting cytokinesis and the division of the cytoplasm for the two daughter …

Autophagy in tumor immune escape and immunotherapy.

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of immune resistance remains significant. Autophagy, a cellular response to various stressors, involves the degradation of damaged proteins and organelles via lysosomal pathways, maintaining cellular homeostasis. This process not only supports tumor cell survival but also profoundly impacts the efficacy of cancer immunotherapies. The modulation of autophagy in tumor cells or immune cells exerts dual effects on tumor immune escape and immunotherapy. However,

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… Complex II, on the other hand, is a complex that contains UVRAG mainly involved in promoting autophagosome maturation, endocytosis, and cytokinesis [ 25 ]. …

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellul

Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications.

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides a comprehensive analysis of the complex interactions between tumor cells and the bone microenvironment, emphasizing the relevance of the "seed and soil" hypothesis, the RANK/RANKL/OPG signaling axis, and Wnt signaling pathways that collectively drive metastatic progression. The molecular and cellular mechanisms underlying the formation of osteolytic and osteoblastic lesions are examined in detail, with a particular foc

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… A significant example is DOCK4 (Dedicator of Cytokinesis 4), identified as a biomarker for assessing the risk of bone metastasis in early-stage breast cancer. Heightened DOCK4 expression is associated with increased invasiveness and a higher risk of metastatic recurrence in the bone. …

Classical Hodgkin Lymphoma: From Past to Future-A Comprehensive Review of Pathophysiology and Therapeutic Advances.

Hodgkin lymphoma, a hematological malignancy of lymphoid origin that typically arises from germinal-center B cells, has an excellent overall prognosis. However, the treatment of patients who relapse or develop resistant disease still poses a substantial clinical and research challenge, even though current risk-adapted and response-based treatment techniques produce overall survival rates of over 95%. The appearance of late malignancies after the successful cure of primary or relapsed disease continues to be a major concern, mostly because of high survival rates. Particularly in pediatric HL pa

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… RS cells continually develop from the Hodgkin cells as a result of incomplete cytokinesis and re-fusion [ 39 ]. …

Cell therapies in the clinic.

Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes. As such, cell therapies are currently one of the most investigated

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… immunodeficiency syndrome; AML, acute myeloid leukemia; ADA, adenosine deaminase; ARDS, acute respiratory distress syndrome; aGvHD, acute graft versus host disease; CNS, central nervous system; COVID‐19, coronavirus disease 2019; COPD, chronic obstructive pulmonary disease; DOCK8 deficiency, dedicator of cytokinesis …

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

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… During the late stages of mitosis, tumour cells often fail to undergo cytokinesis, potentially leading to endoreplication and whole‐genome doubling (WGD), resulting in polyploidy formation. …

Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibito

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… Misaponin B Induces G2/M Arrest, Cytokinesis Failure and Impairs Autophagy BioMed Res. Int. 2020 2020 5925094 10.1155/2020/5925094 32090100 PMC7029305 131. Bilir A. Erguven M. Yazihan N. Aktas E. Oktem G. Sabanci A. …

Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkp

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… Moreover, ‘Aurora B kinase’ (AURKB) as a part of the chromosomal passenger complex influences chromosome alignment in the metaphase and during the cytokinesis [ 154 ]. Helfrich et al. investigated the AURKB inhibitor, barasertib, in c-MYC, MYCL1 and MYCN-amplified SCLC cell lines. …