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Neutrophil diversity and function in health and disease.

Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells,

Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.

Nucleocytoplasmic transport (NCT) regulates the spatial distribution of proteins and RNA between the nucleus and cytoplasm. NCT dysregulation can mislocalize tumor suppressors, DNA-repair factors, transcription factors, and drug targets in cancer. In this review, we conceptualize NCT-dependent protein mislocalization as a spatial regulatory framework for anticancer drug resistance, rather than as a catalogue of transport components. We systematically discuss how nuclear pore complex (NPC) remodeling, transport-receptor imbalance, post-translational modification (PTM)-regulated cargo routing, s

Plasma Cell Myeloma: Биохимический анализ диагноза, лечения и умного нанокарьера - терапевтического развития.

Плазменная миелома (ПХМ) классифицируется как рак крови и характеризуется аномальным распространением плазменных клеток в костном мозге и чрезмерным производством моноколональных иммуноглобулинов, что приводит к постоянному повреждению жизненно важных органов. Несмотря на то, что стратегии лечения улучшились благодаря разработке протеазонных ингибиторов (ИП), иммуноводных препаратов (ИМИД) и моноклонных антител (mAbs), ПХМ остается неизлечимым заболеванием из-за молекулярной неоднородности и развития сопротивляемости лекарствам. В этом обзоре мы обсуждаем биохимические и молекулярные основы, л

Targeting neuroinflammation: 3-monothiopomalidomide a new drug candidate to mitigate traumatic brain injury and neurodegeneration.

BACKGROUND: Traumatic Brain Injury (TBI) is a major risk factor for neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD), with neuroinflammation playing a critical role in the secondary cell death that exacerbates the initial injury. While targeting neuroinflammation holds significant therapeutic promise, clinical trials of available anti-inflammatory agents have fallen short. 3-Mono-thiopomalidomide (3-MP), a novel immunomodulatory imide drug (IMiD), was designed to curb inflammation without the adverse effects of traditional IMiDs and was evaluated across

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

Rare Hematologic Malignancies and Pre-Leukemic Entities in Children and Adolescents Young Adults.

There are a variety of rare hematologic malignancies and germline predispositions syndromes that occur in children and adolescent young adults (AYAs). These entities are important to recognize, as an accurate diagnosis is essential for risk assessment, prognostication, and treatment. This descriptive review summarizes rare hematologic malignancies, myelodysplastic neoplasms, and germline predispositions syndromes that occur in children and AYAs. We discuss the unique biology, characteristic genomic aberrations, rare presentations, diagnostic challenges, novel treatments, and outcomes associate

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… ANKRD26 (thrombocytopenia 2) * ETV6 (thrombocytopenia 5) * With risk of organ dysfunction GATA2 ( GATA2 -deficiency) SAMD9 (MIRAGE syndrome) SAMD9L ( SAMD9L -related ataxia pancytopenia syndrome) Biallelic germline BLM (Bloom syndrome) Inherited bone marrow failure syndromes Fanconi anemia Shwachman-Diamond …

Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches.

Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for

Precision medicine: The use of tailored therapy in primary immunodeficiencies.

Primary immunodeficiencies (PID) are rare, complex diseases that can be characterised by a spectrum of phenotypes, from increased susceptibility to infections to autoimmunity, allergy, auto-inflammatory diseases and predisposition to malignancy. With the introduction of genetic testing in these patients and wider use of next-Generation sequencing techniques, a higher number of pathogenic genetic variants and conditions have been identified, allowing the development of new, targeted treatments in PID. The concept of precision medicine, that aims to tailor the medical interventions to each patie

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… Microbiol Spectr ( 2016 ) 4 ( 4 ): 1–43 . doi: 10.1128/microbiolspec.DMIH2-0026-2016 PMC8428766 27726779 17 Diamond G Beckloff N Weinberg A Kisich KO . The roles of antimicrobial peptides in innate host defense . …

Targeting cancer stem cells in drug discovery: Current state and future perspectives.

In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways (e.g., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic st

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… R Freitas C Duarte A Isoniemi H Laakkonen P Christofori G Ylä-Herttuala S Shibuya M Pytowski B Eichmann A Betsholtz C Alitalo K Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation Nature 2008 454 656 660 18594512 10.1038/nature07083 100 Chiorean EG LoRusso P Strother RM Diamond …

Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases.

Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neur

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… Diamond S., Freitag F., Phillips S.B., Bernstein J.E., Saper J.R. Intranasal civamide for the acute treatment of migraine headache. Cephalalgia. 2000;20:597–602. doi: 10.1046/j.1468-2982.2000.00088.x. 123. Saper J.R., Klapper J., Mathew N.T., Rapoport A., Phillips S.B., Bernstein J.E. …

Ocular toxicity associated with antibody-drug conjugates in cancer therapy: a comprehensive review.

Ocular toxicity from anti-cancer drugs is frequently overlooked, largely because it is non-life-threatening, whereas clinical priorities often center on adverse events that pose immediate risks to survival. Antibody-drug conjugates (ADCs) have emerged as an important therapeutic modality in oncology, offering potent cytotoxicity against tumor cells through the targeted delivery of payloads. However, this potency also introduces a spectrum of toxicities, among which ocular toxicity has gained increasing attention. ADC-induced ocular toxicity can impair visual function and significantly compromi

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… Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. (2019) 380:741–51. doi: 10.1056/NEJMoa1814213. PMID: 108. U.S. Food and Drug Administration . …

T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occ

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… Johnston RJ, Choi YS, Diamond JA, Yang JA, Crotty S. STAT5 is a Potent Negative Regulator of TFH Cell Differentiation. J Exp Med (2012) 209(2):243–50. doi: 10.1084/jem.20111174 105. Nguyen V, Luzina I, Rus H, Tegla C, Chen C, Rus V. …

Hiv and Lymphoma: from Epidemiology to Clinical Management.

Patients infected with human immunodeficiency virus (HIV) are at increased risk for developing both non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common acquired immune deficiency syndrome (AIDS)-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop

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… Remick SC, Diamond C, Migliozzi JA, Solis O, Wagner H, Jr, Haase RF, Ruckdeschel JC. Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome: a retrospective analysis and review of the literature. …

Significance of long chain polyunsaturated fatty acids in human health.

In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators. In this sense, new familie

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… Davidson A, Diamond B. Autoimmune diseases. New Engl J Medicine Adv Inmunol. 2001;345:340–350. doi: 10.1056/NEJM200108023450506. 23. Nakazawa DJ. The autoimmune epidemic: bodies gone haywire in a world out of balance. New York: Touchstone/Simon & Schuster; 2009. 24. Simopoulos AP. …

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically

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… . | NCT01458392 NCT01727336 NCT01720173 http://www.acceleronpharma.com/products/dalantercept/ Soluble fusion protein of receptor type IIA (ActRIIA) linked to the Fc protein of human IgG1 | Sotatercept ACE-011 | II | Anemia in rare blood diseases, including β-thalassemia, MDS, and diamond blackfan; chronic …

Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.

The development of brain metastasis is a major cause of significantly reduced survival in breast cancer patients. The initiation and progression of breast cancer brain metastasis (BCBM) involve multiple distinct molecular pathways and reprogramming of the tumor microenvironment (TME). This review systematically summarizes key mechanisms underlying BCBM, including epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and the spatiotemporal dynamics of metabolic reprogramming regulated by critical signaling pathways during brain colonization. In particular, we highlight

Recommendations for the effective use of T-cell-redirecting therapies: a Canadian consensus statement.

BackgroundT-cell-redirecting therapies, such as bispecific antibodies and chimeric antigen receptor T-cells, exploit the cytotoxic capabilities of the immune system to destroy cells expressing specific surface antigens, including malignant cells. These therapies have demonstrated unprecedented rates, depth, and duration of responses in relapsed and refractory multiple myeloma. However, there are significant challenges in implementing these therapies into practice, which require multidisciplinary and multicenter coordination and significant healthcare resources to effectively manage these patie

Tumor Vaccines: Unleashing the Power of the Immune System to Fight Cancer.

This comprehensive review delves into the rapidly evolving arena of cancer vaccines. Initially, we examine the intricate constitution of the tumor microenvironment (TME), a dynamic factor that significantly influences tumor heterogeneity. Current research trends focusing on harnessing the TME for effective tumor vaccine treatments are also discussed. We then provide a detailed overview of the current state of research concerning tumor immunity and the mechanisms of tumor vaccines, describing the complex immunological processes involved. Furthermore, we conduct an exhaustive analysis of the con

Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper.

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatmen

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies.

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic dr

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… Diamond E.L. Durham B.H. Ulaner G.A. Drill E. Buthorn J. Ki M. Bitner L. Cho H. Young R.J. Francis J.H. Efficacy of MEK inhibition in patients with histiocytic neoplasms Nature 2019 567 521 524 10.1038/s41586-019-1012-y 30867592 PMC6438729 53. Yoshida K. Sanada M. Shiraishi Y. Nowak D. Nagata Y. …