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Оценка причинно-следственного воздействия метаболомы на риск психических и нейродегенеративных расстройств.

Данные свидетельствуют о фенотипическом и биологическом переплетении между психическими и нейродегенеративными расстройствами. Дальнейшее выявление лежащих в основе взаимных и уникальных биологических механизмов может привести к появлению новых, многопорядковых и многопорядковых терапевтических целей. Метаболом представляет собой важную область для идентификации целей, поскольку метаболиты играют важнейшую роль в модуляции разнообразных биологических процессов.Мы использовали менделианскую случайность (MR) для проверки причинного воздействия ~ 1000 плазменных метаболитов и ~ 300 метаболитов на

Antitumoral Agent-Induced Constipation: A Systematic Review.

BackgroundConstipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly defined. This systematic review aimed to analyze and synthesize the available information related to the prevalence, etiology, and treatment of ATAIC.MethodsA systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. The review included human studies written in English, French, or Spanish involving patients with cancer and containing information abou

Lenalidomide-associated B-cell ALL: clinical and pathologic correlates and sensitivity to lenalidomide withdrawal.

Lenalidomide is an effective component of induction and maintenance therapy for multiple myeloma, though with a risk of secondary malignancies, including acute lymphoblastic leukemia (ALL). In contrast to therapy-related myeloid neoplasia, lenalidomide-associated lymphoblastic neoplasia remains poorly characterized. We conducted a dual institution retrospective study of 32 ALL cases that arose after lenalidomide maintenance (all B-lineage, 31/32 BCR::ABL-negative). B-cell ALL (B-ALL) was diagnosed at median 54 months (range, 5-119) after first exposure to lenalidomide and after median 42 month

Absence of Biomarker-Driven Treatment Options in Small Cell Lung Cancer, and Selected Preclinical Candidates for Next Generation Combination Therapies.

Lung cancer is the second most common cancer in the United States, and small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. In SCLC, more than other malignancies, the standard of care is based on clinical demonstration of efficacy, and less on a mechanistic understanding of why certain treatments work better than others. This is in large part due to the virulence of the disease, and lack of clinically or biologically relevant biomarkers beyond routine histopathology. While first line therapies work in the majority of patients with extensive stage disease, development of re

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… The drug covalently binds to central guanine in trinucleotide triplets in the minor groove of DNA, forming adducts capable of inducing DNA double-strand breaks ( Markham, 2020 ). It may also induce immunogenic cell death and increase anti-tumor immunity. …

The dark side of immunotherapy.

Immunotherapy has broadened the therapeutic scope and response for many cancer patients with drugs that are generally of higher efficacy and less toxicity than prior therapies. Multiple classes of immunotherapies such as targeted antibodies and immune checkpoint inhibitors (ICI), cell-based immunotherapies, immunomodulators, vaccines, and oncolytic viruses have been developed to help the immune system target and destroy malignant tumors. ICI targeting programmed cell death protein-1 (PD-1) or its ligand (PD-L1) are among the most effective immunotherapy agents and are a major focus of current

Role of Cyclin-Dependent Kinase Inhibitors in Endometrial Cancer.

Endometrial Cancer (EC) is an important cause of death in women worldwide. Despite early diagnosis and optimal treatment of localized disease, relapsed patients have few therapeutic options because after first line therapy, currently no standard of care exists. On the basis of endocrine positivity of most endometrioid ECs, Endocrine Therapy (ET) is a reasonable and widely accepted option. Better knowledge of molecular mechanisms involved in cancer highlighted the deregulated activity of Cyclin-Dependent Kinases (CDKs) in the cell cycle as a hallmark of carcinogenesis supporting the development

Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma.

Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of t

The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acqui

Immunotherapy in Multiple Myeloma.

Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.

Эффективность и безопасность Belantamab Mafodotin с Бортезомибом плюс Dexametasone у пациентов с повторной/отправленной миеломой: DREAMM-6 Судебное разбирательство по делу Б.

ЦЕЛЬ: Этап I/II DREAMM-6 ручка В (измерение)NCT03544281) исследованный белантамб мафодотин в сочетании с бортезомиб/дексаметазоном (BVd) в регрессивной/редактированной множественной миеломе (RRMM). ПАТИЕНТЫ И МЕТОДЫ: Взрослые с RRMM последовательно зачислялись в учебные заведения two belantamab mafodotin (внутренний) когорты " доза-эскалация " (DE)2.5 Тогда 3.4 мг/кг каждый 3 Неделями). Дополнительные пациенты, зачисленные в eight Классы " доза-расширение " : 1.9, 2.5, или 3.4 мг/кг каждый 3 недель; 2.5 или 3.4 мг/кг каждый 3 :: разделение недель (сутки) 1 и 8); 1.9 или 2.5

Прогресс и перспективы на будущее в химерикском антигенном рецепторе Т-клетке и биконкретной антителной терапии для множественных миелом.

Начавшаяся терапия перенаправления Т-клеток значительно изменила условия лечения повторной/изъятий множественной миеломы (RRMM), особенно у пациентов с тремя классами обнаженных или рефрактных заболеваний. Лечение химерных антигенных рецепторов (CAR) Т-клеток и биконкретные антитела (BSAbs), которые в первую очередь нацелены на антигены созревания клеток B (BCMA), показали замечательную эффективность в ключевых испытаниях и реальных условиях мира. В последнее время группа рецепторов G с протеиновым сцеплением C 5 В качестве многообещающих вариантов были выбраны агенты D, особенно для пациентов

Проблемы с многократной терапией миеломы у пациентов постарше и посторонних.

Каждый год больше, чем 150,000 во всем мире диагностируются случаи множественной миеломы (ММ) и более 100,000 Зарегистрированы случаи смерти в результате этого злонамеренного поведения. Уровень заболеваемости ММ растет во всем мире, особенно в странах с высоким уровнем дохода и среди мужского населения в возрасте ≥ 50. Хотя прогресс в осуществлении стратегий лечения привел к повышению уровня выживания за последние десятилетия, ММ остается неизлечимым во многих случаях. Важно то, что one- треть пациентов с диагнозом MM - >75 возраст и характеризуется относительно низкой трудоспособностью или сл

Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators.

BACKGROUND: High-dose glucocorticoids are the standard treatment for acute relapses in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Therapeutic apheresis can be considered for the escalation of relapse therapy, but some patients still do not recover sufficiently. We aimed to explore the effects of apheresis on humoral and cellular immune parameters and to identify features that correlate with beneficial clinical outcomes. METHODS: We studied two cohorts comprising a total of 63 patients with MS or NMOSD who were undergoing relapse therapy with eithe

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… The average of the measured OD values per sample (doublets or triplets) was normalized by subtracting the mean OD value of blank wells and the OD value of the respective uncoated control. For the statistical analysis, negative values in the data were truncated to zero. …

A review of recent clinical trials to evaluate disease-modifying therapies in the treatment of cardiac amyloidosis.

Cardiac amyloidosis (CA) is a serious condition that results in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF) that is caused by the extracellular deposition of amyloid fibrils within heart tissue. While many important features of CA have been known for years, its prevalence in elderly patients with HF is increasingly being recognized. Plasma cells produce monoclonal immunoglobulin light chains which results in the formation and aggregation of amyloid fibrils that are responsible for AL amyloidosis. CA is classified as originating from either transthyret

Joint AI-driven event prediction and longitudinal modeling in newly diagnosed and relapsed multiple myeloma.

Multiple myeloma management requires a balance between maximizing survival, minimizing adverse events to therapy, and monitoring disease progression. While previous work has proposed data-driven models for individual tasks, these approaches fail to provide a holistic view of a patient's disease state, limiting their utility to assist physician decision-making. To address this limitation, we developed a transformer-based machine learning model that jointly (1) predicts progression-free survival (PFS), overall survival (OS), and adverse events (AE), (2) forecasts key disease biomarkers, and (3)

The prevalence and outcomes of frail older adults in clinical trials in multiple myeloma: A systematic review.

Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials an

The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies.

Cancer associated thrombosis (CAT) is associated with significant morbidity and mortality, highlighting an unmet clinical need to improve understanding of the pathophysiology of CAT. Multiple myeloma (MM) is associated with one of the highest rates of thrombosis despite widespread use of thromboprophylactic agents. The pathophysiology of thrombosis in MM is multifactorial and patients with MM appear to display a hypercoagulable phenotype with potential contributory factors including raised von Willebrand factor (VWF) levels, activated protein C resistance, impaired fibrinolysis, and abnormal t

Chromosome 1q21 abnormalities in multiple myeloma.

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q rem

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… Additionally, the majority of this benefit was driven by the MAIA study, when daratumumab was added to a doublet, lenalidomide/dexamethasone, as opposed to PI/IMiD triplets in the other studies. Notably, data regarding the impact of CD38 mAbs in patients with +1q are extremely limited. …

Allogeneic Hematopoietic Transplantation for Multiple Myeloma in the New Drugs Era: A Platform to Cure.

Allogeneic hematopoietic cell transplantation (alloHCT) represents a treatment option for multiple myeloma (MM) patients. As shown in several studies, alloHCT is highly effective, but it is hampered by a high toxicity, mainly related to the graft-versus-host disease (GVHD), a complex immunological reaction ascribable to the donor's immune system. The morbidity and mortality associated with GVHD can weaken the benefits of this procedure. On the other side, the high therapeutic potential of alloHCT is also related to the donor's immune system, through immunological activity known as the graft-ve

Treatment of elderly patients with refractory/relapsed multiple myeloma: oral drugs adherence and the COVID-19 outbreak.

Once the treatment of refractory/relapsed multiple myeloma in the elderly is greatly influenced by the adherence of patients and family members, clinicians should be aware of patients' behavior and lifestyle, as it may influence the individual treatment plan for each patient. Furthermore, treatment with oral chemotherapy is of special value during the COVID-19 outbreak. Multidisciplinary healthcare involvement is crucial in the management of polypharmacy, adverse events and dose adjustment due to comorbidities and natural loss of renal function with age. Oral drugs simplify intake, reduce hosp