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A patient with minimal myeloma treatment who survived for 20 years.

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The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers.

Purpose of reviewWe aim to review the most recent findings in the use of NK cells in childhood cancers.Recent findingsNatural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less li

Expected benefits and concerns regarding virtual reality in caring for terminally ill cancer patients - a qualitative interview study.

BackgroundMany palliative cancer patients require inpatient hospital treatment for medical reasons, which contrasts their frequent desire to be at home. Virtual reality (VR) could be a way of bringing the home environment closer to them. First observations have shown benefits from VR for inpatients in palliative care. The aim of this qualitative, descriptive study was to explore the expectations of in-patients suffering from incurable cancer and their relatives about VR, in particular individualized VR images of the patients' own home.MethodsSemi-structured interviews with inpatients suffering

От статического риска до динамического мониторинга заболеваний: роль MRD и иммунного профилирования в множестве миелом.

Терапевтический ландшафт множественной миеломы (ММ) претерпел глубокие изменения, при этом высокоэффективные комбинированные режимы и иммунная терапия позволили обеспечить беспрецедентные темпы глубоких и устойчивых ответных мер. В результате этого одной традиционной стратификации базовых рисков становится все более недостаточно для объяснения неоднородности клинических результатов или для направления лечения на протяжении всего курса лечения. Эта эволюционирующая парадигма сместила внимание на динамическое, адаптированное к реакциям наблюдение за заболеваниями, сосредоточенное на поддающихся

Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.

The dynamic changes in chromatin conformation alter the organization and structure of the genome and further regulate gene transcription. Basically, the chromatin structure is controlled by reversible, enzyme-catalyzed covalent modifications to chromatin components and by noncovalent ATP-dependent modifications via chromatin remodeling complexes, including switch/sucrose nonfermentable (SWI/SNF), inositol-requiring 80 (INO80), imitation switch (ISWI) and chromodomain-helicase DNA-binding protein (CHD) complexes. Recent studies have shown that chromatin remodeling is essential in different stag

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… During fear learning, H3K4 trimethylation, a transcription active mark, is increased, while H3K9 dimethylation, a silencing mark, is decreased at specific gene promoters, such as the key genes of memory consolidation Zif268 and Bdnf. … In contrast, HDAC3, which is highly expressed in the substantia nigra, can enhance LTP in acute hippocampal slices and memory consolidation under contextual fear conditions [ 146 ]. …

Urgent and emergent radiotherapy for hematologic malignancies of the central nervous system: a review of the literature and practical approach.

IntroductionHematologic malignancies, including leukemias, lymphomas, and myeloma, can involve the central nervous system (CNS) at the time of diagnosis or later in relapse. CNS involvement can lead to acute neurologic symptoms or signs that need prompt evaluation and treatment. Radiotherapy (RT) can lead to quick disease response, but how it can best be incorporated early into multi-modality treatment in the urgent clinical setting is often unclear.MethodsHere, we outline a practical approach to planning and incorporating urgent RT in patients with hematologic malignancies involving the CNS.

Primary central nervous system lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS.The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.Algorithms for first-line and salvage treatments are provided.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion.

Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu

Гендерное неравенство в когнитивных расстройствах между неврологическими аутоиммунными расстройствами: систематический обзор.

ВВЕДЕНИЕ: Неврологические аутоиммунные расстройства (НКД) часто переплетаются с когнитивными расстройствами (КИ), что представляет собой многоуровневую проблему как с клиническим пониманием, так и с терапевтическим управлением. Усугубленное бремя NAD и CI не только оказывает значительное влияние на качество жизни пациента (QoL), прогнозы состояния и результаты лечения, но и оказывает несоразмерное воздействие на женщин, которые по своей сути более подвержены автоматическому иммунитету. Этот обзор направлен на изучение гендерных когнитивных недостатков, их основополагающих механизмов и их клини

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… Additionally, excessive thyroid hormone may disrupt hippocampal function, impairing memory consolidation. … All the while, sleep disturbances, as previously mentioned, particularly obstructive sleep apnea, contribute to intermittent hypoxia, oxidative stress, and impaired memory consolidation. …

Смягчение катастрофического забвения при рассеянии множественных склерозов с помощью эластичной консолидации веса.

Сегментация множественных склерозов (MS) имеет решающее значение для мониторинга развития заболеваний. Методы углубленного обучения дают многообещающие результаты, однако при оценке данных, полученных с помощью различных протоколов или сканеров, сталкиваются с проблемами, связанными с переключением доменов. Передача обучения (ТЛ) обеспечивает успешную адаптацию к доменам, но может привести к катастрофическому забвению, что приведет к значительному снижению эффективности в исходный домен. Непрерывное обучение направлено на решение этой проблемы путем сохранения знаний, полученных в предыдущих о

A systematic review of the last two decades of NK cell-based clinical trials: state of the art of AML therapy.

BACKGROUND: Acute myeloid leukemia (AML) remains a significant challenge in hematologic oncology, with high relapse rates and limited treatment options. Natural killer (NK) cells, as key effectors of innate immunity, have shown strong anti-leukemic activity, making them promising candidates for immunotherapy. Despite increasing clinical interest, a comprehensive evaluation of NK cell-based therapies in AML is still needed. METHODS: This systematic review follows the PRISMA guidelines to analyze clinical trials evaluating NK cell therapy in AML, either as a standalone treatment or in combinatio

Current Main Topics in Multiple Myeloma.

Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consol

Cancer related cognitive impairment: a downside of cancer treatment.

Cancer treatment is associated with long lasting cognitive impairment in cancer survivors. This cognitive impairment is often termed cancer related cognitive impairment (CRCI). Cancer survivors treated for tumors outside the central nervous system are increasingly diagnosed with CRCI. The development of strategies to mitigate the negative effects of cancer treatment on the brain are crucial. Although neuroimaging research has proposed several candidate mechanisms, the pathogenic underpinnings of CRCI remain uncertain. As such, preventative and treatment strategies have not been identified. To

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… adenocarcinoma) on right flank | Single dose of 50ug IP Anti-CLTA4 antibody followed by 20Gy ECRT one week later | Day 4 after ECRT | Impairment in recognition memory Impairment of spatial recognition memory Chen et al., 2002 ( 149 ) | Swiss mice | Single dose of 1mg/kg IP tamoxifen | 30 minutes | Impairment in memory … consolidation processes Single dose of 10mg/kg IP tamoxifen | 30 minutes | Impairment in memory consolidation and retrieval processes Single dose of 3mg/kg IP toremifene | 30 minutes | Impairment in memory acquisition processes Single dose of 10mg/kg IP toremifene | 30 minutes | Impairment in memory …

Realizing Innate Potential: CAR-NK Cell Therapies for Acute Myeloid Leukemia.

Next-generation cellular immunotherapies seek to improve the safety and efficacy of approved CD19 chimeric antigen receptor (CAR) T-cell products or apply their principles across a growing list of targets and diseases. Supported by promising early clinical experiences, CAR modified natural killer (CAR-NK) cell therapies represent a complementary and potentially off-the-shelf, allogeneic solution. While acute myeloid leukemia (AML) represents an intuitive disease in which to investigate CAR based immunotherapies, key biological differences to B-cell malignancies have complicated progress to dat

Current and future role of carfilzomib-based quadruplet combinations as therapy for newly diagnosed multiple myeloma.

The treatment of newly diagnosed multiple myeloma (NDMM) has advanced rapidly in recent years, with the standard of care (SOC) now including not only triplet combinations of proteasome inhibitors (PIs), immunomodulatory agents, and steroids but also quadruplet combinations that add the anti-CD38 monoclonal antibodies isatuximab (Isa) or daratumumab (D) to a triplet backbone. In addition to the widely used bortezomib-lenalidomide-dexamethasone (VRd) combination, an alternative triplet option that can be considered is the combination of the second-generation PI carfilzomib (K) with lenalidomide-

Autologous hematopoietic stem cell transplantation for multiple myeloma in the age of CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the management of relapsed and refractory myeloma, with excellent outcomes and a tolerable safety profile. High dose chemotherapy with autologous hematopoietic stem cell transplantation (AHCT) is established as a mainstream of newly diagnosed multiple myeloma (NDMM) management in patients who are young and fit enough to tolerate such intensity. This standard was developed based on randomized trials comparing AHCT to chemotherapy in the era prior to novel agents. More recently, larger studies have primarily shown a progression fr

Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.

Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be co

CD8+ CD28-нормативные T клетки после вводного лечения предсказывают, что пациенты миэломы выживут без прогрессирования: результат GMMG-HD6 Исследование по многоцентральной фазе III.

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Evidence of brain-derived neurotrophic factor in ameliorating cancer-related cognitive impairment: A systematic review of human studies.

Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis and neuroplasticity and may be a key protein in cancer-related cognitive impairment (CRCI). This systematic review assessed the relationship between BDNF biomarkers and neurocognitive outcomes in cancer patients and survivors. A search in PubMed, Scopus, and PsycINFO yielded 638 articles, of which 26 were eligible. Fourteen (54 %) studied BDNF protein levels while 15 (58 %) analyzed BDNF rs6265 polymorphism. Of the nine observational studies reporting BDNF plasma/serum levels, five (56 %) exhibited a positive asso

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… In particular, BDNF’s involvement in neurotransmitter release and long-term potentiation is important to learning and memory consolidation ( Morris et al., 1986 ). …

Перспективы Талкетамаба и его полезности в лечении множественной миеломы: безопасность, эффективность и место в терапии.

Несмотря на недавние достижения, большинство пациентов с множественной миэломой в конечном итоге развивают сопротивление имеющимся методам лечения, подчеркивая необходимость новых терапевтических стратегий. G Класс рецептора с протеиновыми соединениями C 5 Член D (GPRC5D) стал жизнеспособной новой терапевтической целью для клеток миэломы, которая привела к клиническому развитию талькетамаба, первого GPRC5D-directed bi специфичный Т-активист (TCE). В августе Талкетамаб получил ускоренное утверждение 2023 Управление по контролю за продуктами питания и лекарствами. Помимо ожидаемой краткосрочной