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Thrombotic microangiopathy following chimeric antigen receptor T-cell therapy.

INTRODUCTION: Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia and is associated with a variety of conditions and following hematopoietic stem cell transplantation. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel immunotherapeutic approach using genetically modified autologous T cells. CAR-T therapy has been linked with injuries to vascular endothelium, but a direct association between CAR-T and TMA has not been reported. CASE REPORTS: Two cases of TMAs following CAR-T treatment are reported here. In each case, clinical evidence of kidney inju

:: 8th Европейский конгресс фармацевтики: выдержки из выступлений

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Serum Onconeural Antibodies in Dogs and Cats for Early Diagnosis of Cancer.

Cancer is one of the leading causes of death in dogs and cats worldwide, and effective early detection techniques and reliable therapies are still lacking. Given the high demand for early cancer detection and differentiation in veterinary diagnostics, we developed and validated a new diagnostic approach to assess onconeural antibodies, also known as high-risk antibodies, in dog and cat blood serum samples. We determined the presence of systemic onconeural/high-risk (ONHR) antibodies, their suitability for early cancer diagnostics, and the feasibility of differentiating various malignancies. Ou

Целенаправленная деградация белка разрушает ненаркомные цели, чтобы обратить вспять иммунное уклонение и терапию устойчивости к раку.

Таргетированная деградация белков (ТД) использует эндогенные протеолитические системы — систему убиквина и протеасомы и лизосомальные пути — для селективного удаления белков, вызывающих болезни, которые не реагируют на традиционное ингибирование. В онкологической иммунотерапии ТД разрушает критические иммунодепрессивные узлы в экзоцитоплазматическом, мембранном и цитоплазматическом компартментах, перепрограммируя микросреду опухоли от иммунологически «холодной» к «горячей» состоянию. Эта статья рассматривает молекулярные принципы инженерии бифункциональных деградаторов и обобщает клинические д

Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage-Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities.

Philadelphia chromosome (Ph) results from a translocation between the breakpoint cluster region (BCR) gene on chromosome 9 and ABL proto-oncogene 1 (ABL1) gene on chromosome 22. The fusion gene, BCR-ABL1, is a constitutively active tyrosine kinase which promotes development of leukemia. Depending on the breakpoint site within the BCR gene, different isoforms of BCR-ABL1 exist, with p210 and p190 being the most prevalent. P210 isoform is the hallmark of chronic myeloid leukemia (CML), while p190 isoform is expressed in majority of Ph-positive B cell acute lymphoblastic leukemia (Ph+ B-ALL) case

Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics.

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell-neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to

Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of

JunB is a key regulator of multiple myeloma bone marrow angiogenesis.

Bone marrow (BM) angiogenesis significantly influences disease progression in multiple myeloma (MM) patients and correlates with adverse prognosis. The present study shows a statistically significant correlation of the AP-1 family member JunB with VEGF, VEGFB, and IGF1 expression levels in MM. In contrast to the angiogenic master regulator Hif-1α, JunB protein levels were independent of hypoxia. Results in tumor-cell models that allow the induction of JunB knockdown or JunB activation, respectively, corroborated the functional role of JunB in the production and secretion of these angiogenic fa

Сипонимод поддерживает воспоминание в неподдерживающей среде.

Воспаление, характерное для множественных повреждений склероза (MS), приводит к функциональным повреждениям и постепенной потере аксона с течением времени. Хотя, как считается, ремилеляция защищает аксоны, внутренние регенерационные процессы часто являются неполными или полностью неэффективными у многих пациентов с синдромом MS. Хотя точные причины провала воспоминаний остаются неясными, неоднократное обезвоживание в ранее затронутых районах с белыми телами является признанным фактором, способствующим этому. В одном из предыдущих исследований мы продемонстрировали, что модификатор Siпонimod с

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy.

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening co

Non-diabetic hypoglycemia: bridging gaps in diagnosis and treatment: a position statement report by the Arabic Association for the Study of Diabetes and Metabolism (AASD).

BACKGROUND: Non-diabetic hypoglycemia presents a substantial diagnostic challenge due to its diverse and often nonspecific symptomatology. The resultant delay in diagnosis can lead to a myriad of misdiagnoses. This misidentification not only prolongs patient suffering but also elevates the risk of severe complications, such as permanent neurologic damage and mortality. Recognizing the clinical nuances of non-diabetic hypoglycemia is paramount for timely and accurate diagnosis, which ultimately enhances patient outcomes and safety. MAIN BODY: A position statement has been formulated by the Ara

Сравнительный анализ нервно-воспалительных путей болезни Альцгеймера, болезни Паркинсона и множественного склероза: понимание сходства и различий.

Растет интерес к нейродегенеративным болезням, усугубляющим значительное социально-экономическое бремя, вызванное старением общества. Несмотря на то, что каждая болезнь имеет различные этиологии, нейроинфламмация, как считается, играет решающую роль в болезни Альцгеймера (AD), болезни Паркинсона (PD) и множественном склерозе (MS). Помимо патогенной функции воспаления мозга, растет число свидетельств того, что иммунная реакция необходима для нейрорегенерации. Этот обзор сравнивает и контрастирует с нейроинфламационными путями, которые характерны для различных нейродегенеративных заболеваний. В

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

Acupuncture for cancer-induced bone pain?

Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acu

Совпадение в полном тексте источника
… Myofascial Trigger Points Another manifestation of chronic pain is the presence of reactive muscle spasm which in turn causes additional pain and shortening of the muscle, affecting function [ 63 ]. … The use of acupuncture for myofascial trigger points (MTPs) may be a useful way of both alleviating discomfort and improving functional status. A recent study using anesthetic injected into MTPs in chronic neck pain has confirmed that function can be improved by eradicating these points [ 64 ]. …

Challenges in the Diagnosis and Management of the Miller Fisher Variant of Guillain-Barré Syndrome: A Case Report.

Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS), characterized by the triad of ophthalmoplegia, ataxia, and areflexia, often following a bacterial or viral illness. This case report presents a 58-year-old Hispanic female patient with a preceding streptococcal pharyngitis who developed symptoms of bilateral facial nerve palsy and lower limb ataxia. Cerebrospinal fluid (CSF) analysis revealed albuminocytologic dissociation and, combined with her presentation of ophthalmoplegia, ataxia, and areflexia, supported the diagnosis of MFS. Magnetic resonance imaging (MRI)

Периодическое заболевание и нейроинфламмация при множественном склерозе: систематический обзор текущих данных.

Множественный склероз (MS) — хроническое, иммунопосредованное неврологическое расстройство, характеризующееся обезвоживанием и нейродегенерацией. Появляющиеся данные свидетельствуют о наличии связи между MS и периодонтальными заболеваниями (PD) через общие иммуновоспалительные пути. В ходе этого обзора оценивается связь между периодонтальными заболеваниями и множественным склерозом с уделением особого внимания взаимодействию между иммунной и воспалением и клинической корреляции. Несмотря на появляющиеся данные, прочность связей остается неясной из-за методологической неоднородности. AIM: Обзор

Theranostics - a sure cure for cancer after 100 years?

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted d

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

Rapid Recognition of Carfilzomib-Induced Thrombotic Microangiopathy and Early Application of Eculizumab Successfully Rescued Two Relapsed Myeloma Patients.

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Programmed Cell Death in Health and Disease.

Programmed cell death is a conserved evolutionary process of cell suicide that is central to the development and integrity of eukaryotic organisms [...].