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Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.

Histone deacetylase inhibitors (HDAC inhibitors, HDACi) have garnered considerable attention due to their potential in treating various types of malignant tumors. Histone deacetylases (HDACs) not only influence chromatin structure and gene transcription by regulating histone acetylation status but also acetylate various non-histone proteins. They are widely involved in several key biological processes, such as cell cycle regulation, apoptosis induction, and immune responses. HDACi exert their effects by inhibiting HDAC activity; however, these effects are highly concentration-dependent and non

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… Combination therapy with gemcitabine further enhanced efficacy, with the mechanism involving increased lipogenic fibroblasts and reduced myofibroblasts to achieve “dual-chamber targeting.” Ent also attenuates the effects of TGF-β and TGF-α and antagonizes transcriptional activation ( 113 ). …

Decoding multiple myeloma: single-cell insights into tumor heterogeneity, immune dynamics, and disease progression.

BackgroundMultiple myeloma (MM) is a biologically heterogeneous malignancy of clonal plasma cells, often progressing from MGUS or smoldering MM. It causes anemia, bone lesions, and immune dysfunction due to abnormal plasma cell expansion in the bone marrow. Neuroinflammatory and neurotrophic factors may influence MM progression by affecting immune cells and the bone marrow niche. Growing evidence points to a role for neuroimmune regulation in tumor immunity. Despite therapeutic progress, disease heterogeneity and resistance highlight the need for new strategies targeting the tumor microenviron

Targeting super enhancers for liver disease: a review.

BackgroundSuper enhancers (SEs) refer to the ultralong regions of a gene accompanied by multiple transcription factors and cofactors and strongly drive the expression of cell-type-related genes. Recent studies have demonstrated that SEs play crucial roles in regulating gene expression related to cell cycle progression and transcription. Aberrant activation of SEs is closely related to the occurrence and development of liver disease. Liver disease, especially liver failure and hepatocellular carcinoma (HCC), constitutes a major class of diseases that seriously endanger human health. Currently,

CAR-T cell therapy: Where are we now, and where are we heading?

Chimeric antigen receptor (CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies, with 9 CAR-T-cell products currently available. Furthermore, CAR-T cells have shown promising potential for expanding their therapeutic applications to diverse areas, including solid tumors, myocardial fibrosis, and autoimmune and infectious diseases. Despite these advancements, significant challenges pertaining to treatment-related toxic reactions and relapses persist. Consequently, current research efforts are focused on addressing these issues to enhance the safe

Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.

Bone marrow is the primary site of blood cell production in adults and serves as the source of osteoblasts and osteoclasts that maintain bone homeostasis. The medullary microenvironment is also involved in malignancy, providing a fertile soil for the growth of blood cancers or solid tumors metastasizing to bone. The cellular composition of the bone marrow is highly complex, consisting of hematopoietic stem and progenitor cells, maturing blood cells, skeletal stem cells, osteoblasts, mesenchymal stromal cells, adipocytes, endothelial cells, lymphatic endothelial cells, perivascular cells, and n

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… Leptin-receptor-expressing bone marrow stromal cells are myofibroblasts in primary myelofibrosis. Nat. Cell Biol. 2017;19(6):677–688. doi: 10.1038/ncb3530. Deeb G., et al. …

Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in recent years as key regulators of the tumor microenvironment. Indeed, they are now considered active players in the pathophysiology of hematologic malignancies rather than passive bystanders in the hematopoietic microenvironment. Onc

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… After their activation, dependent on Mk-produced Cxcl4, these cells are metabolically reprogrammed, particularly in fatty acids, and differentiate into matrix-producing myofibroblasts. …

Application of cell-derived exosomes in the hematological malignancies therapy.

Exosomes are small membrane vesicles of endocytic origin that are produced by both tumor and normal cells and can be found in physiological fluids like plasma and cell culture supernatants. They include cytokines, growth factors, proteins, lipids, RNAs, and metabolites and are important intercellular communication controllers in several disorders. According to a vast amount of research, exosomes could support or inhibit tumor start and diffusion in a variety of solid and hematological malignancies by paracrine signaling. Exosomes are crucial therapeutic agents for a variety of illnesses, such

Interstitial Lung Disease and Pulmonary Fibrosis: A Practical Approach for General Medicine Physicians with Focus on the Medical History.

Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors may be particularly confusing, and are often extrapolated to radiologic imaging patterns which may further add to the confusion. We propose that rather than focusing on precise histologic findings, focus should be on identifying an accurate etiology of ILD through a comprehensive and detailed m

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… OP, or area of organization, is recognized microscopically by multiple round or oval pale-staining deposits consisting of extracellular matrix proteins and spindle-shaped fibroblasts or myofibroblasts [ 12 , 29 , 30 ]. …

Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application.

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) is a tyrosine kinase signaling pathway that has a fundamental role in many biologic processes including embryonic development, tissue regeneration, and angiogenesis. Increasing evidence indicates that this pathway plays a critical role in oncogenesis via gene amplification, activating mutations, or translocation in tumors of various histologies. With multiplex sequencing technology, the detection of FGFR aberrations has become more common and is tied to cancer cell proliferation, resistance to anticancer therapies, and n

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

Резюме: 31 Европейский конгресс патологии.

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Targeted therapies in pediatric oncology: A start.

The treatment of cancers was revolutionized by the use of combination "conventional" chemotherapy, first in children, during the 20th century. That foundation of therapy, while having achieved significant advances in survival, has reached its limits. Innovations in targeted therapies are now building upon that foundation to further improve outcomes in pediatric oncology. These targeted agents are designed to narrowly utilize specific biologic processes for greater efficacy and optimally fewer generalized toxicities. I will provide an overview of the current spectrum of targeted therapies avail

Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with part

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… Myofibroblasts also play a key role in the development of OSMF, and curcumin was shown to inhibit their proliferation more effectively than fibroblasts. This effect was accompanied by induction of apoptosis through downregulation of BCL-2 and upregulation of BAX. …

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects,

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… Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth Cancer Cell 2011 19 257 272 10.1016/j.ccr.2011.01.020 21316604 PMC3060401 27. Taheri M. Tehrani H.A. Dehghani S. Alibolandi M. Arefian E. Ramezani M. …

Emerging Roles of Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy.

Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs)

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… Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth. Cancer Cell. 2011;19:257–272. doi: 10.1016/j.ccr.2011.01.020. 10. Timaner M., Tsai K.K., Shaked Y. The multifaceted role of mesenchymal stem cells in cancer. Semin. …

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

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… Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 2017;214:579–596. doi: 10.1084/jem.20162024. 22. Biffi G., Oni T.E., Spielman B., Hao Y., Elyada E., Park Y., Preall J., Tuveson D.A. …

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

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… High levels of CCN5 hinder adipogenic differentiation as they dedifferentiate 3T3-L1 adipose cells into pluripotent myofibroblasts expressing α-SMA (Grünberg et al. 2014 ). …

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

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… Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer J. Exp. Med. 2017 214 579 596 10.1084/jem.20162024 28232471 PMC5339682 57. Chen C.T. Chen Y.C. Yamaguchi H. Hung M.C. …

Expert consensus on resection of chest wall tumors and chest wall reconstruction.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forw

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

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… Lung fibrosis-associated soluble mediators and bronchoalveolar lavage from idiopathic pulmonary fibrosis patients promote the expression of fibrogenic factors in subepithelial lung myofibroblasts. Pulm. Pharmacol. Therapeut. 2017;46:78–87. doi: 10.1016/j.pupt.2017.08.012. 120. …