Результаты поиска

CAR-T cell therapies in autoimmune rheumatic diseases: a brief report on the clinical trial landscape, current status, and future perspectives.

Autoimmune rheumatic diseases (ARDs) are chronic inflammatory disorders where B cells play a key role. Traditional B-cell-targeted therapies have limitations, whereas CAR-T-cell therapy, which aims for a broader reset of the B-cell compartment by targeting B-cell surface markers such as CD19 or B-cell maturation antigen (BCMA), has unique advantages. Currently, most CAR-T cell trials for ARDs are in the early stages, with 64.29% (36/56 trials) of studies being phase I trials and only 7.14% (4/56 trials) progressing to phase II trials, primarily focusing on conditions, such as systemic lupus er

S1PR4-dependent Воздействие этрасимод на первичную активацию миэлоидных иммунных клеток человека.

ИСТОРИЯ ВОПРОСА: Sphingosine-1-phosphate (S1P) и его five Рецепторы S1PR1-5 играть важную роль в миграции, дифференциации и активации различных иммунных клеток. Недавно было утверждено несколько модуляторов S1PR с особой избирательностью для лечения различных подстрекательских заболеваний. Среди них Озанимод, S1PR1/5 Модулятор, утвержденный для лечения язвительного колита и множественных склерозов, и Etrasimod, S1PR1/4/5 Модулятор, утвержденный для лечения язвительного колита. Хронические самовоспалительные заболевания, такие, как вспыльчивые болезни кишечника (ББК) и язвительный колит, характ

Antibody-Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives.

Background: The clinical landscape for antibody-drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensiv

The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (N

Neurophysiological mechanisms of cancer-induced bone pain.

BackgroundCancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected.Aim of reviewTherefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and u

PIM1 kinase and its diverse substrate in solid tumors.

The PIM kinase family, consisting of PIM1, PIM2, and PIM3, is a group of serine/threonine protein kinases crucial for cellular growth, immunoregulation, and oncogenesis. PIM1 kinase is often overexpressed in solid and hematopoietic malignancies, promoting cell survival, proliferation, migration, and senescence by activating key genes. In vitro and in vivo studies have established the oncogenic potential of PIM1 kinases. These kinases have been implicated in tumor progression, metastasis, and resistance to chemotherapy, underscoring their potential as a therapeutic target for cancer therapy. Th

Curcumol inhibits the malignant progression of prostate cancer and regulates the PDK1/AKT/mTOR pathway by targeting miR‑9.

Curcumol has been reported to exert anti‑tumor activity, but its intrinsic molecular mechanism in prostate cancer remains to be elucidated. The present study aimed to analyze the effect of curcumol on prostate cancer and identify its possible internal regulatory pathway using in vitro cell culture and in vivo tumor model experiments. The cytotoxicity of curcumol was detected using a Cell Counting Kit‑8 assay and it was found that curcumol had no obvious toxicity or side effects on RWPE‑1 cells. Wound healing, Transwell and flow cytometry assays demonstrated that curcumol could affect the activ

Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy.

IntroductionPrimary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN.MethodsPatients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point w

Palbociclib as an Antitumor Drug: A License to Kill.

Neoplastic cells are characterized by uncontrolled cell divisions caused by cell cycle dysregulation. Key regulatory proteins governing the transition from the G1 to the S phase are the CDK4 and CDK6 kinases, which are controlled by D-type cyclins. The CDK4/6 kinases enable the use of these proteins as targets for anticancer therapy because they prevent the growth and the development of malignant cells by inhibiting their activity. This paper surveys the clinical trial results concerning palbociclib, the first in-class FDA-approved anticancer drug for hormone-dependent breast cancer. It discus

Whole genome sequencing in adults with clinical hallmarks of hypophosphatasia negative for ALPL variants.

BackgroundHypophosphatasia (HPP) is a rare disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP), encoded by the ALPL gene. The primary objective was to explore novel ALPL variants by whole genome sequencing (WGS) in patients with HPP who previously tested negative by standard methods for ALPL variants. The secondary objective was to search for genes beyond ALPL that may reduce ALP activity or contribute to HPP symptoms.Methods and resultsWGS was performed in 16 patients clinically diagnosed with HPP who had ALP activity below the normal range and tested negativ

The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and su

Машинное прогнозирование развития заболеваний в первичном прогрессивном множественном склерозе.

Первичный постепенный множественный склероз (ППМС) затрагивает 10-15% пациентов, страдающих множественным склерозом, и свидетельствует о значительной изменчивости темпов развития инвалидности. Определение ключевых биологических особенностей и пациентов, подверженных повышенному риску быстрого развития, имеет решающее значение для разработки и оптимизации стратегий лечения. Переписка периферальных кровяных клеток может дать ценную информацию для прогнозирования исхода пациентов. В этом исследовании мы использовали систему машинного обучения, применяемую к исходным профилям транскрипции крови и

Prospects for repurposing CNS drugs for cancer treatment.

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drug

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment str

A systems-pharmacology analysis of herbal medicines used in health improvement treatment: predicting potential new drugs and targets.

For thousands of years, tonic herbs have been successfully used all around the world to improve health, energy, and vitality. However, their underlying mechanisms of action in molecular/systems levels are still a mystery. In this work, two sets of tonic herbs, so called Qi-enriching herbs (QEH) and Blood-tonifying herbs (BTH) in TCM, were selected to elucidate why they can restore proper balance and harmony inside body, organ and energy system. Firstly, a pattern recognition model based on artificial neural network and discriminant analysis for assessing the molecular difference between QEH an

Proteasome Inhibitors and Their Potential Applicability in Osteosarcoma Treatment.

Osteosarcoma (OS) is the most common type of bone cancer, with ~30% of patients developing secondary/metastatic tumors. The molecular complexity of tumor metastasis and the lack of effective therapies for OS has cultivated interest in exploiting the proteasome as a molecular target for anti-cancer therapy. As our understanding towards the behavior of malignant cells expands, it is evident that cancerous cells display a greater reliance on the proteasome to maintain homeostasis and sustain efficient biological activities. This led to the development and approval of first- and second-generation

Совпадение в полном тексте источника
… These work in parallel to ameliorate ER stress by transcribing UPR target genes (i.e., heat shock proteins to aid in protein folding in ER), inhibiting mRNA translation through phosphorylation of eIF2α, and increasing the activity of transcription factors ATF4 and spliced X-box binding protein 1 (XBP1 …

Талидомид взаимодействует с воспалением в идиопатическом фиброзе легких.

" Трагедия Талидомида " является важной вехой в истории фармацевтической промышленности. Несмотря на ограниченные клинические испытания, прилагаются постоянные усилия по изучению Талидомида в качестве лекарства от рака и подстрекательских заболеваний, таких, как ревматуидный артрит, проказа, и COVID-19. В рамках этого обзора основное внимание уделяется возможностям борьбы с воспалением путем повторного использования талидомида для лечения идиопатического фиброза легких (ИПФ). Статьи были найдены в базе данных Scopus, сортированы и рассмотрены отдельные статьи. Содержание включает в с

Bispecific and multispecific T-cell engagers: advancing the future of immunotherapy.

T-cell engagers (TCEs) represent an emerging class of immunotherapies that harness T cells' cytotoxic power to eliminate diseased cells-a transformative future therapeutic strategy. TCEs form immunological synapses to trigger potent immune responses, with proven efficacy in blood cancers; research expands their use to solid tumors via innovative molecular design and improved safety profiles. Beyond oncology, TCEs hold promise in autoimmune disorders by eliminating autoreactive cells, offering novel avenues for diseases like lupus. However, achieving optimal outcomes without disrupting immune h

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