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Эпштейн-Барр Вирус: больше чем просто инфекция.

Хотя вирус Эпштейн-Барр обычно ассоциируется с доброкачественным инфекционным мононуклеозом, он в настоящее время признается в качестве одного из основных движителей сложных иммунопатологических расстройств. Замыкаясь между литическими репликациями и стратегическими программами запоздалости, EBV перепрограммирует биологию B-клеток, чтобы избежать иммунного наблюдения и нарушить гомеостаз. Центральным элементом этого патогенеза является вирусный протеин EBNA1, который приводит к автоматическому иммунитету с помощью молекулярной имитации с принимающими антигенами, включая GlialCAM в множестве ск

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… Primary Infection: Transmission and Route of Entry Oral transmission via saliva is the principal route of EBV transmission; primary infection targets the oropharynx, with viral tropism for both epithelial cells and B lymphocytes [ 1 , 7 ]. … Because the cellular reservoir of EBV differs between patients, therapeutic strategy is tailored to viral tropism: in B-cell-driven EBV-HLH, rituximab depletes the infected B-cell reservoir and rapidly reduces viral load, whereas a persistently elevated EBV PCR despite adequate B-cell depletion should …

Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment.

The skeletal system is of paramount importance in advanced stage prostate cancer (PCa) as it is the preferred site of metastasis. Complex mechanisms are employed sequentially by PCa cells to home to and colonize the bone. Bone-resident PCa cells then recruit osteoblasts (OBs), osteoclasts (OCs), and macrophages within the niche into entities that promote cancer cell growth and survival. Since PCa is heavily reliant on androgens for growth and survival, androgen-deprivation therapy (ADT) is the standard of care for advanced disease. Although it significantly improves survival rates, ADT detrime

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… PCa displays a preferential tropism toward bone which is the primary site of metastasis in 80% of patients with advanced disease ( 4 ). … Bone Metastasis of PCa Prostate cancer cells show an almost exclusive tropism for bone. Although the exact mechanisms that drive bone metastasis are unknown, it has been proposed that the BM microenvironment may provide the ideal condition for the PCa cells to thrive. …

Kinetics of hematologic response in AL amyloidosis: Insights from clinical and cytogenetic subgroup analysis in the daratumumab era.

Rapid and profound reduction of free light chains (FLCs) improves outcomes in AL amyloidosis; however, early FLC kinetics with daratumumab-based frontline therapy remain undefined. We retrospectively analyzed 315 patients treated with daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCd) or Dara-Vd at eight centers. Involved FLC (iFLC), the difference between iFLC and uninvolved FLC (dFLC), and hematologic response (≥very good partial response [VGPR]) were assessed at baseline and at 1, 3, and 6 months, and correlated with light chain isotype, disease burden (bone-marrow plasma-cell

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… Kappa and Lambda FLC isotypes represent distinct entities with differing proteotoxicity, immunoglobulin variable gene usage, organ tropism, and survival. 30 , 31 , 32 , 33 Lambda light chains—particularly IGLV1‐44—show cardiac tropism, IGLV6‐57 skews renal (glomerular) involvement, while kappa AL is … The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood. 2001;98:714‐720. 32. Sidiqi MH, Aljama MA, Muchtar E, et al. …

Recent advances in understanding and treating immunoglobulin light chain amyloidosis.

Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body, resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical presentations and a tendency to mimic common medical conditions, AL amyloidosis is often diagnosed late and results in dismal outcomes. Early referral to a specialized center with expertise in management of AL amyloidosis is always recommended. The availability of sensitive biomarkers and novel therapies is reforming our approach to how we manage AL amy

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… Organ toxicity and tropism in amyloid The exact mechanism of amyloid deposition in various organs of the body and consequent toxicity is not completely understood. Several mechanisms of amyloid-related proteotoxicity leading to organ dysfunction have been reported in the literature. … It has been hypothesized that AL amyloid manifests organ tropism which may be a function of LC variable region gene polymorphisms 13 , 14 . Studies have shown that LC variable region gene subtypes predispose to specific organ involvement in AL. …

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms

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… In addition, ESCs and iPSCs can be potential sources for the production of anti-cancer vaccines. (3) MSCs/NSCs are effective to deliver genes, NPs, and OVs to tumor niche due to their intrinsic tumor tropism. … Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: New nanotools for cancer treatment. Pharmacol. Res. 2016;111:487–500. doi: 10.1016/j.phrs.2016.07.006. 91. …

Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteo

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… The tropism that cancer cells exhibit towards certain organs depends in part on their chemokine/chemokine receptors expression profile. … Breast cancer organ-specific tropism has been a hot topic in research for many years and major insights are mostly derived from studies with animal models. …

Targeted therapy in the treatment of malignant gliomas.

Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In additi

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… Aboody KS Brown A Rainov NG Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas Proc Natl Acad Sci U S A 2000 97 23 12846 12851 11070094 10.1073/pnas.97.23.12846 PMC18852 105. … Zhao D Najbauer J Garcia E Neural cell tropism to glioma: critical role of tumor hypoxia Mol Cancer Res 2008 6 12 1819 1829 19074827 10.1158/1541-7786.MCR-08-0146 107. …

Центральная нервная система Множественная миелома: обновление 2026 года.

Множественная миелома центральной нервной системы (CNS-MM) — редкая, но очень агрессивная дизракразия плазменных клеток с плохим прогнозом. КНС-ММ представляет собой отдельную клиническую структуру, характеризующуюся уникальными диагностическими проблемами и терапевтическими сопротивлениеми. Традиционная терапия исторически приводила к мрачным результатам, а медиана выживаемости за несколько месяцев. Современная диагностика основана на интеграции неврологических симптомов, усовершенствованной цитометрии потока CSF и изображений с высоким разрешением; однако единых диагностических критериев по-

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… 0% | 30.5 months | Combination regimens including novel agents Risk factors for CNS involvement Lactate dehydrogenase (LDH) and extramedullary disease (EMD) Elevated serum LDH is a frequently reported predictor of CNS-MM, but it primarily reflects aggressive systemic EMD rather than CNS-specific tropism … Loss of CD56 (NCAM) is the most frequently cited marker associated with enhanced migratory capacity and CNS tropism, although heterogeneity exists [ 10 – 13 ]. Expression of CD28 and CD20 remains under investigation but shows less consistent correlation in recent studies. …

Castleman Disease and Kaposi Sarcoma: A Review of the Literature and a Case Series.

Castleman disease and Kaposi sarcoma (KS) are both associated with infection by human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). This virus plays a critical role in the pathogenesis of both conditions, particularly in immunocompromised individuals, such as those with HIV/AIDS. Multicentric Castleman disease (MCD) generally presents with systemic inflammatory symptoms, lymphadenopathy, and organ dysfunction, while Kaposi sarcoma typically appears as vascular tumors on the skin, with occasional involvement of mucous membranes or internal organs. We prese

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… HHV-8 has oncogenic potential and a tropism for B cells. HHV-8 has oncogenic potential and a tropism for B cells. …

The Impact of Immune System in Regulating Bone Metastasis Formation by Osteotropic Tumors.

Bone metastases are frequent and debilitating consequence for many tumors, such as breast, lung, prostate, and kidney cancer. Many studies report the importance of the immune system in the pathogenesis of bone metastasis. Indeed, bone and immune system are strictly linked to each other because bone regulates the hematopoietic stem cells from which all cells of the immune system derive, and many immunoregulatory cytokines influence the fate of bone cells. Furthermore, both cytokines and factors produced by immune and bone cells promote the growth of tumor cells in bone, contributing to supporti

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… Some types of tumors are characterized by a selective bone tropism, out of which are prostate, breast, lung, and kidney cancers. Bone metastases can give osteolytic, osteosclerotic, or mixed lesions. … Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature. British Journal of Cancer. 2013;108(12):2525–2536. doi: 10.1038/bjc.2013.271. 27. Conley-LaComb M. K., Saliganan A., Kandagatla P., Chen Y. Q., Cher M. L., Chinni S. R. …

Mesenchymal stem/stromal cells in cancer therapy.

The multipotent mesenchymal stem/stromal cells (MSCs), initially discovered from bone marrow in 1976, have been identified in nearly all tissues of human body now. The multipotency of MSCs allows them to give rise to osteocytes, chondrocytes, adipocytes, and other lineages. Moreover, armed with the immunomodulation capacity and tumor-homing property, MSCs are of special relevance for cell-based therapies in the treatment of cancer. However, hampered by lack of knowledge about the controversial roles that MSC plays in the crosstalk with tumors, limited progress has been made with regard to tran

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… Furthermore, the tumor tropism of MSCs allows them to precisely release the drug near the tumor site, which, theoretically, increases the safety and efficacy of the treatment. … Therefore, the feasibility of tumor-tropism of MSC might differ from cancer to cancer. Besides, the source of MSC and the route of administration may also affect the efficacy of the genetically modified MSCs. …

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

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… Breast and prostate cancers exhibit a marked tropism for bone tissue, while lung, kidney, and thyroid cancers, as well as multiple myeloma, also show a high frequency of skeletal involvement [ 2 , 6 , 7 ]. … Breast cancer exhibits a marked tropism for bone tissue, and in patients with metastatic disease, bone is one of the most frequent sites of dissemination. …

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.

CRISPR-Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targ

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… Together, the in vivo delivery platform, its persistence, tropism, and immunological profile, defines both tissues and the dominant safety liabilities that must be monitored in CRISPR-based gene therapies [ 66 ]. 2.4. … Second, delivery remains the key determinant of both efficacy and risk, because biodistribution, exposure time, and tissue tropism shape the therapeutic window as well as immunogenicity and toxicity. …

Hijacking the helpers: platelet and neutrophil trafficking in AML and therapeutic exploitation.

Acute myeloid leukemia (AML) remains one of the most aggressive and treatment-resistant hematologic malignancies, driven by clonal expansion of immature myeloid blasts in the bone marrow and peripheral blood. Current therapies-chemotherapy and targeted agents-are limited by poor marrow penetration, systemic toxicity, and rapid development of resistant clones, leaving long-term survival rates low. Clinicians face the persistent challenge of delivering effective therapy while minimizing harm. Platelets and neutrophils-beyond their classical roles in hemostasis and innate immunity-actively suppor

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… Beyond tropism, cell-based carriers offer modular engineering advantages: membrane coatings preserve surface-targeting ligands and immune-evasion signals. At the same time, payloads can be tuned for rapid release or intracellular delivery once the carrier reaches its niche [ 37 ]. … These cells persist in the bloodstream only for hours to days, necessitating careful timing for ex vivo manipulations or consideration of aged/subset neutrophils with predictable marrow tropism to ensure effective delivery [ 120 ]. …

New understanding of the damage of SARS-CoV-2 infection outside the respiratory system.

Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associa

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… Evidence from previous studies about SARS proved that coronavirus has a tropism to the gastrointestinal tract. The viral nucleic acid could be readily detected in stool specimens of patients who have been infected with SARS. … The kind of tropism above may explain the frequent occurrence of diarrhoea in coronavirus infection. Wong et al’s research showed that SARS-CoV-2 has the ability of encoding and expressing the spike (S) glycoproteins that could bind to the entry receptor ACE2. …

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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… MSC-EVs show excellent biocompatibility and exceptional biodistribution properties, including the capability to cross biological barriers, low toxicity and immunogenicity, and strong tumor tropism. … In addition, unlike liposomes, they are generally less immunogenic, are well tolerated due to their natural origin, and are much more efficient at entering tumor loci, linked to their strong tumor tropism. …

Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine.

BackgroundMedulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus t

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… As derivatives of the Edmonston vaccine strain, these viruses display a natural tropism for the CD46 membrane protein, an inhibitory complement regulator strongly over-expressed by many types of tumor relative to normal tissue [ 8 , 9 ]. … potential of oncolytic measles virus: promises and challenges Clin Pharmacol Ther 2010 88 5 620 625 10.1038/clpt.2010.211 20881957 Leber MF Bossow S Leonard VH Zaoui K Grossardt C Frenzke M Miest T Sawall S Cattaneo R von Kalle C MicroRNA-sensitive oncolytic measles viruses for cancer-specific vector tropism …

Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence.

On 4 September 2024, the Reagan-Udall Foundation for the FDA (FDA Foundation) in collaboration with the Food and Drug Administration (FDA) and the Gates Foundation hosted a workshop titled "Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence". The event brought together a diverse group of experts, including international regulatory bodies, regulated industries, healthcare professionals, patients, academic researchers and global health advocates, to discuss the rapid advancements in gene therapy and the pressing need for equitable access in low-and middle-

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… However, challenges remain with its natural tropism, which results in a low efficacy in certain tissues following intravenous administration. These challenges are typically addressed by increasing the dosage of the vector. … These vectors are also engineered to improve tropism, facilitating the delivery of therapeutic genes to cells such as HSCs. …

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer

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… In addition, the adaptation of microRNA-responsive regulatory elements enables selective activation of the CRISPR system, while capsid-modified Ad can enhance tumor tropism through targeted binding to cancer-specific surface markers, thereby improving the precision of CRISPR delivery in cancer therapy … Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. Cell Prolif. 2022;55:e13339. 73. Lee BR, Jo E, Yoon HY, Yoon CJ, Lee HJ, Kwon KC, et al. Nonimmunogenetic viral capsid carrier with cancer targeting activity. …

Биология и болезни крыс

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