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Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

Immunosenescence and cancer predisposition in pediatric transplant recipients: An emerging paradigm.

Pediatric solid organ and hematopoietic stem cell transplant recipients paradoxically experience accelerated immune aging despite chronological youth, establishing a paradigm with profound implications for cancer risk and long-term outcomes. This comprehensive review synthesizes current evidence demonstrating how transplantation-related factors, anti-thymocyte globulin-mediated T cell depletion, cytomegalovirus reactivation, chronic immunosuppression, and thymic dysfunction, induce premature immunosenescent phenotypes. These processes converge to generate T cell populations exhibiting CD28 los

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil

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… particularly those involving PARPi in conjunction with histone deacetylase inhibitors (HDACI), cyclin-dependent kinase inhibitors (CDKI), androgen receptor signaling inhibitors (ARSIs), immune checkpoint inhibitors (ICI), ionizing radiation (IR), oncolytic herpes simplex viruses (oHSVs), proteolysis-targeting chimeras …

Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.

BACKGROUND: CAR-T cell therapy represents a major breakthrough in hematological malignancies. However, the trade-off between insufficient treatment persistence and treatment-related toxicities (especially cytokine release syndrome, CRS) still limits its wider clinical application. MAIN BODY: Our review aims to reframe the understanding of this central dilemma. It posits that the dynamic imbalance of intracellular signaling networks and external inflammation in the tumor microenvironment (TME) are the causes of insufficient persistence of CAR-T cells and the severe CRS. The intracellular signa

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… Natural Killer Non-Structural Protein 3 Oxidative Phosphorylation Programmed Death-1 Programmed Death-Ligand 1 Phosphatidylinositol 3-Kinase Phosphatidylinositol 4,5-Bisphosphate Phosphatidylinositol 3,4,5-Trisphosphate Protein Kinase C Theta Phospholipase C Gamma 1 Proteolysis Targeting Chimera …

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbio

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… FX-C is a chimera of human FX with an inserted 99 loop of snake FX from Pseudonaja textilis . 194 This makes the molecule insensitive to FXa DOACs. Functionality has been proven in vitro and in vivo, and the molecule is currently undergoing phase 1 testing (source: VarmX Web site). …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Immune reprogramming in the bone marrow microenvironment: a new perspective on the bone immune microenvironment of postmenopausal osteoporosis.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.

Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and

Расширение горизонта: потенциальное применение элементов ЦАР-Т сверх нынешних показателей.

Проектирование иммунных клеток для лечения гематологических заболеваний стало одним из основных направлений исследований с тех пор, как в B-ALL были достигнуты первые заметные успехи в лечении CAR-T-клеток. В настоящее время можно лечить несколько заболеваний в условиях высокой терапии или рецидива. В настоящее время для острого лимфоболического лейкемии (ALL), диффузной лимфомы B-клеток (DLBCL), лимфомы мантичной клетки (MCL), множественной миеломы (MM) и фолликулярной лимфомы (FL) утвержден ряд методов лечения CD19- или BCMA-клеток. Применение этих методов значительно улучшило результативнос

Gene editing and CRISPR in the clinic: current and future perspectives.

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases whic

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… Importantly, the crRNA and tracrRNA can be fused to form a single guide RNA (sgRNA) chimera that retains the ability to target and cleave specific nucleic acid target sequences [ 16 ]. …

Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая

:: 45th Ежегодное совещание Европейского общества по трансплантации крови и костного мозга: Врачи - сессия плаката.

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Abstracts of the 5(th) Cachexia Conference, Barcelona, Spain, December 5-8, 2009.

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Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular p

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… Among the different DC subsets, using bone marrow chimera experiments, Diamond and collaborators have demonstrated that Ifnar1 −/− CD8α + DCs lose their capability to cross present tumor antigens and as a consequence, when regressor tumors are transplanted, the host is no longer able to immune reject …

Monoclonal Antibodies Approved for Cancer Therapy

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is

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… Surprisingly, they observed that BM chimeras showed no defects in hematopoiesis or lymphopoiesis despite the absence of β-catenin. 101 In a subsequent experiment, Koch et al examined whether the persistence of normal hematopoiesis and lymphopoiesis could be explained by the compensatory function of γ-catenin …

Applications of synthetic biology in medical and pharmaceutical fields.

Synthetic biology aims to design or assemble existing bioparts or bio-components for useful bioproperties. During the past decades, progresses have been made to build delicate biocircuits, standardized biological building blocks and to develop various genomic/metabolic engineering tools and approaches. Medical and pharmaceutical demands have also pushed the development of synthetic biology, including integration of heterologous pathways into designer cells to efficiently produce medical agents, enhanced yields of natural products in cell growth media to equal or higher than that of the extract

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… Li et al. used an in silico designed cationic chimera near-infrared fluorescent protein and anionic carboxylate-terminated PEG to prepare a protein-PEG nanocarrier. 221 The nanoprotein is amphiphilic, resulting in the aggregation and phase separation in aqueous solutions to form nanoparticles. 221 The …

Angioprevention of Urologic Cancers by Plant-Derived Foods.

The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many of these tumors are detected in early stages lengthens the duration of their treatment, with a significant increase in health care costs. In this scenario, prevention offers the most cost-effective long-term strategy for the global control of these diseases. Although specialized diets are not the only way to

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… Thalidomide (Thalomid ® ) | Amino acid | Multiple myeloma in combination with dexamethasone | VEGF-A bFGF, FGFR | 2006 Temsirolimus (Torisel ® ) | TKI | RCC | mTOR | 2007 Vandetanib (Caprelsa ® ) | TKI | Unresectable or metastatic TC | VEGFR2 | 2011 Ziv-Aflibercept (Zaltrap ® ) | Fusion protein (VEGFR chimera …

References

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… Graft-versus-leukemia reactions in allogeneic chimeras. Blood. 2004;103:767–776. doi: 10.1182/blood-2003-02-0342. 34. Ruggeri L, Mancusi A, Burchielli E, Capanni M, Carotti A, Aloisi T. NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. …