Результаты поиска

Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume.

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to tradition

Генетическое или терапевтическое нарушение траектории подачи сигналов Reelin/Apoer2 улучшает воспалительные результаты артрита.

Ремутатоидный артрит (RA) — хроническое аутоиммунное заболевание, характеризующееся синновальным воспалением, образованием паннуса и постепенным совместным разрушением. Вспыльчивая среда в RA приводит к активации эндотелиальных клеток и к повышению регулирования молекул сцепления, что облегчает проникновение лейкоцитов в синовый. Релин, циркулирующий гликопротеин, ранее связанный с активацией эндотели и вербовкой лейкоцитов для лечения таких заболеваний, как атеросклероз и множественный склероз, стал потенциальным регулятором этих процессов. Однако его роль в патогенезе РА остается слабой. Зде

Adequate IVIG dosing is associated with an improved long-term outcome in secondary immunodeficiency: A prospective, non-interventional study.

OBJECTIVE: To assess the safety, tolerability, and effectiveness of the intravenous immunoglobulin (IVIG) Intratect 50 g/L in immunoglobulin replacement therapy (IgRT) in a prospective, large-scale non-interventional study (NIS). The analysis focused upon patients with secondary immunodeficiency (SID), the most frequent indication for IgRT in this NIS. MATERIALS AND METHODS: Patients were enrolled at 123 centers in Germany. Each patient received IVIG as prescribed by the physician, guided by the Summary of Product Characteristics. Data were acquired from medical records and patients' question

Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma.

Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/β-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 a

Oncology distress screening within predominately Black Veterans: Outcomes on supportive care utilization, hospitalizations, and mortality.

BackgroundWe evaluated whether patients' initial screening symptoms were related to subsequent utilization of supportive care services and hospitalizations, and whether patient-level demographics, symptoms, hospitalizations, and supportive care service utilization were associated with mortality in primarily low-income, older, Black Veterans with cancer.MethodsThis quality improvement project created collaborative clinics to conduct cancer distress screenings and refer to supportive care services at an urban, VA medical center. All patients completed a distress screen with follow-up screening e

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… Veterans' Diseases Associated with Agent Orange . U.S. Department of Veteran's Affairs ; 2010 . 6 Hwa KJ , Dua MM , Wren SM , Visser BC . Missing the obvious: psychosocial obstacles in veterans with hepatocellular carcinoma . …

Peroral Endoscopic Myotomy (POEM) in a Patient with Complete Heart Block-a Case Report.

UNLABELLED: The ATP-binding cassette, subfamily G, member 2 (ABCG2) transporter, or breast cancer resistance protein (BCRP), plays a crucial role in the absorption and distribution of various compounds, including anti-seizure medications (ASMs). ABCG2 genetic polymorphisms have been shown to affect the pharmacokinetics of several drugs, including anti-cancer drugs and statins. Clinical studies suggested an association between the ABCG2 variations and ASMs pharmacokinetics. Thus, the aim of the present study was to evaluate the effect of the coding ABCG2 variants, 742T > G and 886G > C on the A

Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics.

Multiple myeloma (MM) is a clinical disorder characterized by aberrant plasma cell growth in the bone marrow microenvironment. Globally, the prevalence of MM has been steadily increasing at an alarming rate. In the United States, more than 30,000 cases will be diagnosed in 2024 and it accounts for about 2% of cancer diagnoses and more than 2% of cancer deaths, more than double the worldwide figure. Both symptomatic and active MM are distinguished by uncontrolled plasma cell growth, which results in severe renal impairment, anemia, hypercalcemia, and bone loss. Multiple drugs have been approved

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… GSEA ( analysis ) Subramanian et al. (2005) Multiple risk factors have been identified for the development of MM, including male gender, overweight status, occupational exposure to certain industries, and exposure to dioxin or Agent Orange. However, the precise etiology of MM remains elusive. …

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer.

PurposeAdoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.Materials and methodsMultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally r

CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma.

Clinical development of chimeric antigen receptor (CAR)-T-cell therapy has been enabled by advances in synthetic biology, genetic engineering, clinical-grade manufacturing, and complex logistics to distribute the drug product to treatment sites. A key ambition of the CARAMBA project is to provide clinical proof-of-concept for virus-free CAR gene transfer using advanced Sleeping Beauty (SB) transposon technology. SB transposition in CAR-T engineering is attractive due to the high rate of stable CAR gene transfer enabled by optimized hyperactive SB100X transposase and transposon combinations, en

Gene expression signatures that predict radiation exposure in mice and humans.

BackgroundThe capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.Methods and findingsWe have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, rang

Воздействие нового биотинового соединения в гиппокампальной ремиилизации в крысах.

Обезвоживание обычно наблюдается в нейродегенеративных расстройствах, включая множественный склероз (MS). Добавление биотина, как известно, стабилизирует прогрессирование MS. Чтобы уменьшить эффективную дозу биотина, мы синтезировали новую и превосходящую форму биотина, комплекс магния, который ионологически связан биотином (MgB), и сравнили его зависимое от дозы воздействие с биотином в одиночку после демиелинации с использованием лизолицитина (LPC) у крыс. Myelination была оценена с помощью быстрого синего пятна и иммуностаза от белка MBP, что свидетельствует о том, что наиболее значительное

Витамины в профилактике и терапии нейродегенеративных заболеваний.

Нейродегенеративные заболевания, такие, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS) и множественный склероз (MS), которые являются следствием постепенной потери нейронной функции и структуры, вызывают значительное когнитивное расстройство. Заболеваемость этими заболеваниями среди населения мира постоянно растет в результате старения населения. Хотя генетические и экологические факторы чаще всего упоминаются в качестве патогенетических факторов этих заболеваний, все больше фактов свидетельствует о важной роли надлежащего питания в профилактике и

The role of bone-modifying agents in myeloma bone disease.

Bone disease is common in patients with multiple myeloma (MM), which manifests as bone pain and skeletal-related events (SREs) such as pathological fractures and spinal cord compression. Myeloma bone disease (MBD) can adversely affect the quality of life of patients and have negative effects on morbidity and mortality. The pathogenesis of MBD is complex, and several factors are involved in the dysregulation of bone metabolism and uncoupling of bone remodeling, which result in net bone loss and devastating SREs. Broadly speaking, elevated osteoclast activity, suppressed osteoblast activity, and

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Governs GVHD and Immunosuppression Need, Reducing Late Toxicities in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a l

агитационные рамки ИИ, связывающие языковые модели с электронными медицинскими записями, и график биомедицинских знаний для реальных доказательств.

Доступ к крупномасштабным клиническим и биомедицинским базам данных по-прежнему является серьезным препятствием для клинических и научных работников, требующим значительных вычислительных знаний. Агентские системы искусственного интеллекта, в которых крупные языковые модели (МПМ) организуют многоэтапное рассмотрение и выполнение запросов под интерактивным контролем человека, открывают возможности для демократизации доступа к данным и ускорения процесса получения доказательств. MethodsWe применяли Типовой контекстный протокол (МКП) для интеграции в рамках одного агентского рабочего процесса ста

Clinical and Genomic Epidemiology of Carbapenem-Nonsusceptible Citrobacter spp. at a Tertiary Health Care Center over 2 Decades.

Carbapenem-nonsusceptible Citrobacter spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (P = 0.03), as did daily defined carbapenem doses/1,000 patient days (6.52 to 34.5; R2 =

HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line.

While papillary thyroid cancer (PTC) has largely favorable prognosis, anaplastic thyroid cancer (ATC) is a rare but extremely aggressive malignancy with grim clinical outcome. Even though new therapeutic options are emerging for ATC, additional preclinical models and novel combinations are needed for specific subsets of patients. We established a novel cell line (PF49) from the malignant pleural effusion of a 68-year-old male patient with ATC that rapidly transformed from a BRAF and TERT promoter mutant PTC. PF49 cells demonstrated a robust migratory activity in vitro and strong invasive capac

The therapeutic potential of colchicine in oncology studies: from structural modification and targeted delivery to clinical management.

Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of "toxicity reduction and efficacy enhancement," this review comprehensively summarizes colchicine's multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanism

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncol