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The role of the innate immune system in the development and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms - known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirr

Monocyte Involvement in the Pathogenesis of Myeloproliferative Neoplasms.

Classical BCR-ABL-negative myeloproliferative neoplasms are a heterogeneous group of hematologic malignancies, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Monocytes, immune cells derived from hematopoietic stem cells, exhibit significant heterogeneity and contribute to immune regulation through cytokine secretion and differentiation into dendritic cells and macrophages. Aberrant monocytes are associated with the prognosis of MPNs, particularly PMF. Furthermore, these altered monocytes play a critical role in the pathogenesis and progression of MPNs. This

Последние изменения в многократной склерозовой нейропатологии.

ЦЕЛЬ ОБЗОРА: Нетрофологические исследования тканей головного мозга человека необходимы для понимания нами механизмов заболеваний при множественном склерозе (МС). Они служат основой для концепций эволюции повреждений, регенерации тканей и развития болезней и в идеале позволяют выявить новые механизмы борьбы с заболеваниями и терапевтические цели. Здесь мы рассматриваем недавние нейропатологические исследования, которые помогли нам лучше узнать о патогенезе MS.ПОСЛЕДНИЕ ИССЛЕДОВАНИЯ: Недавние когортные исследования подтверждают идею о том, что различные клинические фенотипы MS имеют общие патоло

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… To better understand the mechanisms of oligodendrocyte demise and remyelination failure, two recent studies determined markers of cellular senescence in lesions and observed an upregulation in oligodendrocytes as well as astrocytes, neurons, endothelia, and myeloid cells [ 36 , 37 ]. … Cellular senescence correlated with lesion activity and associated with faster disability progression. Remyelination is a well orchestrated regenerative process by which denuded axons are re-installed with functional myelin sheaths [ 38 ]. …

NF-κB in Thyroid Cancer: An Update.

The dysregulated NF-κB basal activity is a common feature of human thyroid carcinomas, especially in poorly differentiated or undifferentiated forms that, even if rare, are often resistant to standard therapies, and, therefore, are uncurable. Despite the molecular mechanisms leading to NF-κB activation in thyroid cancer being only partially understood, during the last few years, it has become clear that NF-κB contributes in different ways to the oncogenic potential of thyroid neoplastic cells. Indeed, it enhances their proliferation and viability, promotes their migration to and colonization o

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… Finally, NF-κB also plays a prominent role in cancer-associated cellular senescence induced by intrinsic or therapeutic stresses. …

Program-Abstracts

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The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

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… Complement Factor B Regulates Cellular Senescence and Is Associated with Poor Prognosis in Pancreatic Cancer. Cell. Oncol. 2021;44:937–950. doi: 10.1007/s13402-021-00614-z. 113. Mohebnasab M., Eriksson O., Persson B., Sandholm K., Mohlin C., Huber-Lang M., Keating B.J., Ekdahl K.N., Nilsson B. …

Mesenchymal stem cells lineage and their role in disease development.

BackgroundMesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for differen

Иммунные маркеры, чувствительные к возрасту периферальной крови, в множестве склерозов: отношение к сексу, статус цитомегаловируса и лечение.

КОЛИЧЕСТВО: Иммунонесенсекция ускоряется хроническими инфекционными и аутоиммунными заболеваниями и может способствовать патобиологии множественного склероза (МС). О том, как MS и корректирующие болезни методы лечения (DMT) влияют на эпохи имунные биомаркеры, только частично понимаются. Мы проанализировали 771 образец сыворотки 147 здоровых органов управления и 289 человек с MS (PwMS) с помощью мультиплексных иммуномасс. Мы определили серостатус цитомегаловируса (CMV) и собрали ретроспективную клиническую информацию. Мы провели неконтролируемый и многообразный анализ.Неконтролируемый анализ по

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… Notably, EGF can induce cellular senescence; activation of the cognate receptor, EGFR, can trigger the secretion of SASP-related factors. 71 Moreover, bFGF exhibits both anti- and pro-senescence activity. 72 , 73 Further investigations will be necessary to determine whether EGF and bFGF are double-edged … swords promoting remyelination/repair while enhancing cellular senescence in the context of MS. …

Targeting Oxidative Stress as a Therapeutic Approach for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in precl

Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately ex

Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.

Cancer is one of the leading causes of disease-related death worldwide, and targeting key regulatory genes to induce programmed cell death in tumor cells has emerged as a crucial therapeutic strategy, following surgery, radiotherapy, and chemotherapy. As a mitochondrial outer membrane protein, NIX/BNIP3L can both mediate apoptosis to inhibit tumor cell growth and promote tumor cell survival by clearing intracellular reactive oxygen species (ROS) through mitophagy. Therefore, we summarize a brief overview of the structure and function of NIX/BNIP3L, as well as the mechanisms of NIX/BNIP3L gener

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… Furthermore, platycodin D2 (PD2) induces NIX-mediated mitophagy in HCC cells, activating the p21/cyclin A2 pathway to promote cellular senescence. This senescence exerts dual anti-tumor effects: as a typically irreversible process, it directly suppresses HCC progression. …

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy.

Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulat

Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy.

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasivene

IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K/Akt/mTOR Pathway to Regulate Autophagy.

Interferon regulatory factor 4 (IRF4), a critical member of the IRF transcription factor family, harbors an elusive biological role in cervical cancer. Through immunohistochemical staining and immunoblotting, CCK-8 viability assays, EdU incorporation tests, clonogenic survival experiments, flow cytometric detection, transmission electron microscopy, immunofluorescence staining and heterotopic transplantation model, we discover that IRF4 expression was markedly decreased in cervical cancer tissues and cell lines compared to normal controls. Overexpression of IRF4 suppressed proliferation, migra

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… D., et al., “Guidelines for Minimal Information on Cellular Senescence Experimentation in Vivo,” Cell 187 (2024): 4150–4175, 10.1016/j.cell.2024.05.059. 31. …

Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells.

Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents

The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing.

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the 'guardian of the genome' and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni syndrome (LFS), the inherited cance

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… Interestingly, BACH1 is also a negative regulator of p53 which binds to p53 and impedes cellular senescence [ 147 ]. The binding of BACH1 to p53 is inhibited by p19ARF, like MDM2 [ 148 ]. … Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin. Nat. Struct. Mol. Biol. 2008;15:1246–1254. doi: 10.1038/nsmb.1516. 148. Nishizawa H., Ota K., Dohi Y., Ikura T., Igarashi K. …

Role of Toll-Like Receptors in Myeloid Neoplasms: Focuses on the Molecular Mechanisms and Clinical Impact on Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myeloid Leukemia.

Toll-like receptors (TLRs) are essential components of the innate immune system, functioning as pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In hematological malignancies, particularly myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), TLRs influence inflammation, disease progression, and therapeutic response. This review highlights the prognostic relevance of TLR expression, the role of the MyD88 signaling pathway in clonal evolution, and the dual

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… expression of TLR4, induced by the S100A9 protein, reduces the process of cellular senescence, decreasing the rate of apoptosis of neoplastic cells, also contributing to the progression of the disease [ 41 ]. … Shi L., Zhao Y., Fei C., et al., “Cellular Senescence Induced by S100A9 in Mesenchymal Stromal Cells Through NLRP3 Inflammasome Activation,” Aging 11, no. 21 (2019): 9626–9642, https://www.aging‐us.com/article/102409 . 42. …

Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics.

Six decades have passed since the foundational recognition of the primary properties of the stem cells. Research on stem cells has since remained at the forefront of efforts to combat a spectrum of diseases, most notably cancer. Despite remarkable progress in medical science, a definitive cure for cancer has remained elusive, spurring the pursuit of diverse therapeutic strategies, among which stem cell therapy is a particularly promising avenue. Moreover, the utilization of cancer stem cells as a therapeutic source holds immense potential for addressing intractable diseases. The strategy of ta

Lactylation in health and disease: physiological or pathological?

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles in different aspects of energy metabolism and signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as a novel posttranslational modification (PTM). Research indicates that Kla is an essential balancing mechanism in a variety of organisms and is involved in many key cellular biological processes through different pathways. Kla is closely related to disease development and represents a potential and important new drug target

Opinion: more mouse models and more translation needed for ALS.

Amyotrophic lateral sclerosis is a complex disorder most of which is 'sporadic' of unknown origin but approximately 10% is familial, arising from single mutations in any of more than 30 genes. Thus, there are more than 30 familial ALS subtypes, with different, often unknown, molecular pathologies leading to a complex constellation of clinical phenotypes. We have mouse models for many genetic forms of the disorder, but these do not, on their own, necessarily show us the key pathological pathways at work in human patients. To date, we have no models for the 90% of ALS that is 'sporadic'. Potenti