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Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib.

Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit β5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route i

Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions.

Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body's defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the appro

Mesenchymal Stem Cell Therapy for Neurological Complications of Prematurity: A Narrative Review.

Background: Preterm birth is a leading cause of neonatal mortality and long-term disability worldwide. Injury in premature infants is demonstrated by disrupted organ development from inflammation, oxidative stress, hypoxia, and impaired vascular maturation. Current therapies largely provide supportive care and do not directly promote tissue regeneration. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential strategy to enhance endogenous repair across organ systems commonly affected by prematurity. Results: Evidence indicates that MSCs exert therapeutic effects primarily thro

Инструменты и наборы инструментальных средств по лечению рака и психическому здоровью: обзор с целью анализа в соответствии с Руководящими принципами ПОРСМА-СКР.

Справочная информация: Наборы инструментальных средств/наборы инструментальных средств представляют собой перспективный инструмент для лечения раковых заболеваний и охраны психического здоровья. Однако для определения их ключевых компонентов и эффективных стратегий осуществления необходимы исследования. Методы: В соответствии с PRISMA-ScR поиск проводился по пяти базам данных с использованием ключевых терминов. Включены исследования по вопросам психического здоровья или лечения раковых заболеваний с использованием комплектов инструментов или инструментов для взрослых, документируются стратегии

Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Randomized Clinical Trials.

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the parti

Neurologic adverse events of cancer immunotherapy.

Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neu

Bortezomib in mantle cell lymphoma: comparative therapeutic outcomes.

Mantle cell lymphoma (MCL) is an incurable, typically aggressive subtype of non-Hodgkin lymphoma, accounting for 4%-7% of newly diagnosed non-Hodgkin lymphoma cases. Chemoresistance commonly ensues in MCL, and patients with this heterogeneous disease invariably relapse, underscoring the unmet need for better therapies. Over the past few years, several novel agents with promising activity and unique mechanisms of action have been deemed effective in MCL. Bortezomib is a reversible proteasome inhibitor, approved as a single agent for patients with relapsed/refractory MCL who have received at lea

Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease.

Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-deriv

Bone-targeted therapies in metastatic castration-resistant prostate cancer: evolving paradigms.

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibi

Ginsenoside-Mediated Ferroptosis Regulation: Bidirectional Effects and Therapeutic Potential in Diseases.

Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism p

Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females.

Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; an

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… Our study was also culturally and ethnically diverse, whereby participants followed their own lifestyle and food preferences. However, they were controlled (via photos and daily dietary diary) for each meal throughout the day during the 9-week experimental period. …

Всемирный конгресс по болезням остеопороза, остеоартрита и мускулоскелета 2025).

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A Comprehensive Review of Modern Cancer Therapies Utilizing Oncolytic Viruses.

Oncolytic viruses (OVs) are gaining traction as advanced tools in cancer therapy. They are distinguished by their ability to destroy malignant cells while sparing normal tissue specifically. In addition to their direct tumor-lysing properties, an essential benefit of oncolytic virus therapy is its capacity to activate both the innate and adaptive immune systems. To enhance these therapeutic actions, many OVs have been genetically engineered to encode immune-modulating factors that reestablish or strengthen antitumor immune responses. Recent studies show that combining OVs with other forms of i

Аспекты достоинства в семьях, обеспечивающих уход за лицами, страдающими множественным склерозом.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Основное внимание в этом исследовании уделяется сохранению достоинства и посягательству на достоинство членов семьи, обеспечивающих уход за лицами, страдающими множественным склерозом. АИМ: Цель исследования заключалась в углублении понимания того, как семьи, ухаживающие за лицами, страдающими множественным склерозом, воспринимают сохранение или лишение их достоинства. Применялся герменевый подход. МЕТОДЫ ИССЛЕДОВАНИЙ: Авторы провели научные опросы в форме бесед с восемью лицами, обеспечивающими уход за членами семьи. АНАЛИЗ И МЕТОДЫ ТОЛКОВАНИЯ: Нашим компасом и руководс

Данные наблюдений и генетических данных свидетельствуют о наличии связи между изменяемыми факторами риска и распространенностью и серьезностью нейроиммунологических расстройств.

Гравис (MG), множественный склероз (MS) и расстройства спектра нейромиэлита (NMOSD) являются разнородной группой редких нейроиммунологических расстройств, частотность которых в последние годы возросла. Взаимосвязь между изменяемыми факторами риска и нейромнологическими расстройствами не в полной мере понятна. МЕТОДЫ: Мы использовали многократную логистическую регрессию для оценки взаимосвязи между 38 факторы риска и two Нейроиммунологические заболевания с использованием данных почти 500,000 :: отдельные лица из Биобанка Великобритании. Кроме того, мы подали заявление two- выборка менделианских

Нетипичные неблагоприятные явления в реальном мире в исследовании долгосрочной иммуномодуляции в связи с множественным склерозом и расстройством спектра нейромилита.

КОЛИЧЕСТВО: Иммунотерапии являются неотъемлемой частью борьбы с множественным склерозом (МС) и связанными с ним демиелиническими заболеваниями, однако негативные реакции на наркотики существенно сказываются на терпимости методов лечения, позволяющих регулировать заболевания (ДМТ). ЦЕЛИ: Цель настоящего исследования заключается в оценке характеристик безопасности ДМТ в рамках реальной группы населения, затронутой МЗ и связанными с ними заболеваниями, и в выявлении нетипичных неблагоприятных явлений (АЭ) и явлений исключительной тяжести. МЕТОДЫ: Был проведен ретроспективный анализ 3850 больные с

Ruxolitinib for the treatment of acute graft-versus-host disease: a retrospective analysis.

Steroid-refractory acute graft-versus-host disease (aGvHD) is a serious complication after allogeneic hematopoietic stem cell transplantation, associated with significant mortality. Ruxolitinib was the first drug approved for aGvHD, based on results of the REACH2 trial; however, real-world data are limited. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of aGvHD at our center from March 2016 to August 2022 and assessed biomarkers of risk. We identified 49 patients receiving ruxolitinib as second- (33/49), third- (11/49), fourth- (3/49), or fifth-line (2/49) tr

Safety and Efficacy of Extracorporeal Photopheresis for Acute and Chronic Graft-versus-Host Disease.

Background/Objectives: Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; Methods: We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients w

Proteasomal adaptations to FDA-approved proteasome inhibitors: a potential mechanism for drug resistance?

With proteasome inhibitors (PIs) becoming clinically available since 2003, outcomes for patients with multiple myeloma (MM) have dramatically changed, improving quality of life and survival. Despite the impressive treatment success, however, almost all MM patients who initially respond to these PIs eventually develop resistance. Furthermore, a portion of MM patients is inherently unresponsive to the PIs. Extensive mechanistic investigations identified several non-proteasomal signaling pathways suspected to be linked to the PI resistance, for which several excellent reviews are currently availa