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Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following forma

A comprehensive update of extracutaneous involvement of mycosis fungoides: A narrative review of literature.

Mycosis fungoides, the most prevalent subtype of cutaneous T-cell lymphoma, primarily targets areas of the skin that of not exposed to sunlight. Nevertheless, it can involve extracutaneous tissues at any disease stage, especially during its advanced phases. Research suggests that all extracutaneous organs might be susceptible, though such cases are more commonly reported in autopsy studies and less so in clinical setting. The most recent comprehensive review of such extracutaneous manifestations in mycosis fungoides occurred almost a decade ago. With the aim of enhancing clinicians' understand

Association of Epistatic Effects of lncRNA GAS5, miR-146a, IRAK-1, and miR-155 Genetic Variants with Multiple Sclerosis Risk and Severity.

The complex genetic architecture of heritability in multiple sclerosis (MS) remains undisclosed mainly. Epistasis (gene-gene interaction) substantially impacts MS; however, it is largely unexplored, especially among the non-coding RNA genes and their targets. The long non-coding RNA GAS5 exacerbates demyelination and sponges miR-146a and miR-155, impeccable contributors to MS pathogenesis. miR-146a negatively regulates the immune responses by targeting IRAK-1. We investigated the association of epistatic effects and haplotypes of five single nucleotide polymorphisms (SNPs), GAS5 rs2067079, miR

Harnessing CAR-Extracellular Vesicles for Next-Generation Cancer Immunotherapy.

Cancer immunotherapy has experienced substantial progress in recent years, particularly with the advancement of chimeric antigen receptor (CAR) technology, which enables immune cells to selectively target tumor-associated antigens. CARs, now in their fifth generation, are engineered by combining monoclonal antibody fragments with signaling and co-stimulatory domains and have been successfully applied to T cell, natural killer (NK) cell, and macrophage-based therapies. Notable clinical successes, such as tisagenlecleucel and lisocabtagene maraleucel underscore the therapeutic potential of CAR-T

Recent advances in the bench-to-bedside translation of cancer nanomedicines.

Cancer remains a complex and challenging medical problem, driving extensive research efforts. Despite significant progress in understanding its genetic and molecular aspects, the quest for effective treatments continues. Nanomedicines have shown great potential for revolutionizing cancer treatment by offering targeted and controlled drug delivery, reducing side effects, and improving patient outcomes. Accordingly, nanomedicines have been the focus of extensive research and development for clinical translation. As of September 2024, a search on the ClinicalTrials.gov website using the term "nan

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… Similarly, Zeng et al. 42 found that polydopamine NPs (PDA NPs) in hydrogels accelerated the healing of bacteria-infected wounds through photothermal effects, while the hydrogels' strong adhesive properties promoted rapid re-epithelialization 43 . …

Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich ass

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Immune monitoring, immune phenotyping, and precision intervention in severe pneumonia: current evidence and translational challenges

Severe pneumonia remains a major cause of mortality in critically ill patients, with severe community-acquired pneumonia representing a clinically important and representative scenario. This review focuses primarily on severe community-acquired pneumonia as the clinical context, in which outcomes are determined by the interplay between pathogen burden and heterogeneity of host responses. Beyond pathogen-directed therapies, severe pneumonia is frequently characterized by dynamic and partially overlapping states of hyperinflammation, immune dysfunction, and subsequent immunosuppression. Differen

Объем хориоидного плефуса при нарушениях мозга: систематический обзор.

БАКGROUND: Чороидный плефус — это сильно сосудистая структура, расположенная в боковом, третьем и четвертом желудочках мозга. Недавние исследования показывают, что изменения объема чороидного плефуса связаны с прогрессированием различных заболеваний мозга. Алгоритмы сегментации значительно улучшили нашу способность изучать объем чороидного плефуса в связи с различными патологиями. Таким образом, конкретная цель данного обзора заключалась в описании насколько оценка объема чороидного плефуса предоставляет клинически значимую информацию в заболеваниях мозга. МЕТОДЫ: Была проведена обширная поис

Brazilian Position Statement on the Use Of Multimodality Imaging in Cardio-Oncology - 2021.

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Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu

The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?

Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptiv

Cancer immunotherapy insights: key takeaways from the ADSCC bone marrow and cellular therapy congress 2024.

The rising global cancer burden underscores the urgent need for innovative and effective therapies. Molecular and cellular immunology advances have revolutionized cancer immunotherapy, transforming laboratory discoveries into clinical breakthroughs. The Second Bone Marrow Transplant and Cellular Therapy Congress, held in Abu Dhabi, United Arab Emirates (UAE), on October 26th - 27th, 2024, and sponsored by the Abu Dhabi Stem Cells Center (ADSCC), convened global experts to discuss cutting-edge developments in adoptive cell transfer (ACT); chimeric antigen receptor T-cell (CAR-T) therapy, tumor-

Последовательность BCMA- и GPRC5D-targeting Иммунотерапия в множестве миеломы: практическое руководство Европейской сети миеломы.

В последние годы с появлением нового BCMA- и GPRC5D-directed Иммунотерапия, включая терапию ЦАР-Т-клеток, биконкретные антитела (BSAbs) и антитела-наркотики (ADC). Выбор и последовательность лечения становятся все более сложными с учетом широкого круга вариантов лечения. В этом обзоре Европейская сеть < < Миэлома > > дает рекомендации о том, как лучше всего включить эти новые методы лечения в нынешнюю систему лечения с использованием имеющихся данных. Оптимальная последовательность лечения зависит от различных особенностей, связанных с пациентом и опухолью, а также от компенсации и

From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis despite advances in treatment strategies. Standard treatment regimens induce remissions in many patients, but relapse occurs in approximately half, highlighting the urgent need for novel therapeutic strategies. Antibody-based therapies have significantly improved the treatment of acute lymphoblastic leukemia (ALL), but progress in AML has been slower, with only gemtuzumab ozogamicin (GO) receiving FDA approval to date. This is largely due to the absence of AML-specific surface antigens and the challeng

Diagnosis, Treatment, and Prevention of Cardiovascular Toxicity Related to Anti-Cancer Treatment in Clinical Practice: An Opinion Paper from the Working Group on Cardio-Oncology of the Korean Society of Echocardiography.

Cardiovascular (CV) toxicity associated with anti-cancer treatment is commonly encountered and raises critical problems that often result in serious morbidity or mortality. Most cardiac toxicities are related to the cumulative dose of chemotherapy; however, the type of chemotherapy, concomitant agents, and/or conventional CV risk factors have been frequently implicated in CV toxicity. Approximately half of the patients exhibiting CV toxicity receive an anthracycline-based regimen. Therefore, serologic biomarkers or cardiac imagings are important during anti-cancer treatment for early detection

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment.

Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers cur

Extraglandular Manifestations of Sjögren’s Syndrome (SS): Dermatologic, Arthritic, Endocrine, Pulmonary, Cardiovascular, Gastroenterology, Renal, Urology, and Gynecologic Manifestations

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Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential.

Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects t