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Updates in novel immunotherapeutic strategies for relapsed/refractory AML.

Acute myeloid leukemia (AML) is a severe hematological malignancy with poor outcomes, particularly in older adults. Traditional treatment options like high-dose chemotherapy often lead to refractory or relapsed AML, with even worse outcomes. New therapies for relapsed and refractory AML are needed, and this review explores the most recent advancements in immunotherapy in AML. Checkpoint Inhibitors utilizing innate or adaptive immune targeting have shown potential to improve AML outcomes when combined with hypomethylating agents and chemotherapy. The use of adoptive cell therapy in AML demonstr

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… Primarily injection site reactions. … Related AEs mainly injection site reactions. …

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhib

The feasibility and efficacy of subcutaneous plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA-identical sibling donors: results of the HOVON-107 study.

BackgroundPlerixafor (PFX) mobilizes CD34+ cells into circulation by disrupting the CXCR4 binding of the hematopoietic stem cell in its bone marrow niche.Study design and methodsin the prospective HOVON-107 study (www.hovon.nl) 23 allogeneic HLA-identical sibling donors received one or two subcutaneous (sc) injections of plerixafor 0.320 mg/kg.The primary endpoint, was defined as feasibility to mobilize a minimum of 2.0 x106 CD34+ cells/kg recipient weight obtained by leukopheresis in at least 90% of the donors.Resultsmedian 3.3 x 106 CD34+ cells/kg (1.9-6.5) were collected after 1 (n=12) or 2

Diseases of the Nervous System

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Skin Telocytes Could Fundament the Cellular Mechanisms of Wound Healing in Platelet-Rich Plasma Administration.

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopec

Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials.

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlini

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… Injection site reactions were rare but more common with ExQW. No major hypoglycemia occurred. Therefore, ExQW was found to result in superior glycemic control with less nausea than ExBID in patients with type 2 diabetes. Both groups also experienced weight loss [ 142 ]. … N = 364, 28 weeks | Average 1.12 kg and, respectively, 1.19 kg decrease of bodyweight in exenatide and sitagliptin groups versus 0.15 kg increase in the placebo | Gastrointestinal events and injection-site reactions | [ 142 ] 8. …

P57 PRE-EXPOSURE PROPHYLAXIS FOR COVID-19 WITH TIXAGEVIMAB/CILGAVIMAB (EVUSHELD) IN PATIENTS WITH MULTIPLE MYELOMA

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Лечение связанного с лекарствами остеонекроза челюсти с помощью клеточной терапии.

Введение: Остеонекроз челюсти (MRONJ), связанный с лекарственными препаратами, представляет собой серьезную проблему с учетом отсутствия «золотого стандартного» лечения. Клеточная терапия и тканевая инженерия предлагают перспективные терапевтические альтернативы. Цель этого исследования заключалась в использовании регенеративных свойств стромальной сосудистой фракции (AT-SVF) и лейкоцитного фибрина с высоким содержанием лейкоцита (L-PRF) для обработки MRONJ. AT-SVF содержит мезенхимальные стромальные клетки (MSC) и эндотелиальные клетки потомства (EPC), которые способствуют образованию костей,

A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.

Acute leukemia is a highly heterogeneous disease; therefore, combination therapy is commonly used for patient treatment. Drug-drug interaction is a major concern of combined therapy; hence, dual/multi-target inhibitors have become a dominant approach for cancer drug development. HDACs and HSP90 are involved in the activation of various oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, and RAF/MEK/ERK, which are also highly enriched in acute leukemia gene expression profiles. Therefore, we suggest that dual HDAC and HSP90 inhibitors could represent a novel therapeutic approach fo

Thirty years from FDA approval of pegylated liposomal doxorubicin (Doxil/Caelyx): an updated analysis and future perspective.

In 2025, it will be 30 years since the initial clinical approval of pegylated liposomal doxorubicin (PLD) by the Food and Drug Administration. PLD predated the field of nanomedicine and became a model nanomedicine setting key pharmacological principles (prolonged circulation, slow drug release and the enhanced permeability and retention (EPR) effect) for clinical application of other nano-drugs in cancer therapy. The impressive reduction of cardiotoxicity conferred by PLD is the most valuable clinical asset. While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breas

Терапевтические достижения в педиатрии с множественным склерозом.

Педиатрический множественный склероз (POMS) является хроническим и иммунным расстройством, которое влияет на центральную нервную систему детей и подростков. Примерно 3-10% пациентов, страдающих синдромом MS, имеют место до достижения 18-летнего возраста. Подавляющее большинство случаев заболевания педиатрическим синдромом MS характеризуется повторной эрозией с высоким уровнем заболеваемости. Пациенты педиатрии, страдающие синдромом MS, традиционно проходили лечение без маркировки с различной степенью успеха. С одобрением многих новых методов лечения для взрослых МР быстро начали появляться аль

Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

Synthesis and biological evaluation of a new polymeric conjugate and nanocarrier with osteotropic properties.

Bone-seeking (osteotropic) drug delivery systems (ODDS) represent an interesting solution for targeting different types of drugs to the bones. In particular, anticancer and antibacterial agents could take advantage of such therapeutic strategy. We have recently developed an innovative approach to this aim: a new osteotropic biomaterial was prepared, based on the conjugation of a poly(lactide-co-glycolide) (PLGA) with the bisphosphonate drug alendronate (PLGA-ALE); its hemo- and cytocompatibility were verified. Starting with this copolymer, an osteotropic nanoparticle system (NP) was produced f

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.

Myelodysplastic Syndromes (MDSs) affect the elderly and can progress to Acute Myeloid Leukemia (AML). Epigenetic alterations including DNA methylation and chromatin modification may contribute to the initiation and progression of these malignancies. DNA hypomethylating agents such as decitabine and azacitidine are used as therapeutic treatments and have shown to promote expression of genes involved in tumor suppression, apoptosis, and immune response. Another anti-cancer drug, the proteasome inhibitor bortezomib, is used as a chemotherapeutic treatment for multiple myeloma (MM). Phase III clin

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… Most common adverse reactions associated with the DNMT inhibitor treatment are thrombocytopenia, neutropenia and leukopenia (grade 3/4), gastrointestinal events including nausea, vomiting, and injection site reactions [ 91 , 101 ]. … Moreover, the route of oral administration will alleviate the injection site reactions associated with vidaza. Currently, there are no effective treatments to suppress leukemic transformation and increase survival outcomes in patients with higher-risk MDS. …

A novel nonlive, adjuvanted herpes zoster subunit vaccine: a report on the emerging clinical data and safety profile.

Herpes zoster (HZ) is an acute vesicular dermatitis with a typical dermatomal distribution, caused by the varicella zoster virus (VZV), often preceded and accompanied by prodromal pain or pruritus. HZ may be related to several complications such as postherpetic neuralgia (PHN). The incidence and severity of the disease increase with aging, due to immunosenescence and in particular to the decline of the specific cell-mediated immunity (CMI). The impact of HZ in terms of morbidity and short- and long-term complications, the availability of suboptimal treatment options to date, and the high costs

The various therapeutic applications of the medical isotope holmium-166: a narrative review.

Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it emits high-energy beta radiation which can be used for a therapeutic effect and gamma radiation which can be used for nuclear imaging purposes. Furthermore, holmium-165 can be visualized by MRI because of its paramagnetic properties and by CT because of its high density. Since holmium-165 has a natural abundance of 100%, the only by-product is metastable holmium-166 and no costly chemical purification steps are necessary for pro

Расширенный полиглутамин в ATAXIN1 приводит к потере функции, которая усугубляет остроту множественного склероза в модели мыши EAE.

Ataxin-1 (ATXN1) — белок, в котором расширение его полиглутаминового тракта вызывает нервно-дегенеративное расстройство спинномозговой системы 1 (SCA1) в результате повышения функциональности. Недавно было продемонстрировано, что АТXN1 дикая порода играет защитную роль в регулировании жесткости экспериментального аутоиммунного энцефаломиелита (EAE) — хорошо зарекомендовавшей себя модели мыши для мультиклероза (MS). В этом исследовании дополнительно изучается роль ATXN1 с расширенным полиглутаминым трактом в контексте MS с использованием модели мыши EAE.МЕТОДЫ: Гемизигиозные мыши Atxn1 (Atxn12Q

Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review.

BACKGROUND AND OBJECTIVE: Denosumab is a valuable and safe therapy for skeletal disorders in adults and has received regulatory approval to treat osteoporosis and bone metastases. However, denosumab is not licensed for pediatric use due to a lack of high-quality prospective research on children. This study aimed to describe and discuss the benefits and disadvantages of denosumab in treating bone diseases in children and to summarize the current understanding of the role of denosumab therapy in children. METHODS: A narrative review was conducted using the literature retrieved from the PubMed,

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-