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Перевозка и сдерживание движения sphingosine-1-phosphate Экспортеры SPNS2.

Sphingosine-1-phosphate (S1P) — сигнал лизолипида, имеющий решающее значение для развития сердца, иммунитета и слуха. Соответственно, мутации в переносчике S1P SPNS2 связаны с уменьшением числа белых клеток и нарушениями слуха. СПНС2 также экспортирует S1P-mimicking FTY720-P (Финголимод) и, таким образом, является центральным элементом фармакокинетики этого препарата при лечении множественного склероза. Здесь мы используем комбинацию крио-электронной микроскопии, иммунофлюоресценции, связывания in vitro и в vivo S1P-оценки экспорта, а также молекулярное моделирование динамики для исследования

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… After three washing steps (two times blocking buffer, one-time 1x PBS), the slides we mounted with ProLong medium diamond (Invitrogen) and stored at 4 °C. …

Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment.

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop m

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… Vandyke K., Zeissig M.N., Hewett D.R., Martin S.K., Mrozik K.M., Cheong C.M., Diamond P., To L.B., Gronthos S., Peet D.J., et al. HIF-2α Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12/CXCR4 and CCR1. …

Моноклональная антитела в Смолдингах Множественная Миелома и Моноклональная Гаммопатия Неопределенной Значимости: Текущий статус и будущие направления.

Моноклональные антитела (MoAbs), предназначенные для нескольких клеточных рецепторов, значительно улучшили прогноз множественных миелом (MM). Их высокая эффективность и безопасность поднимают вопрос о том, влияет ли на естественный ход болезни более раннее терапевтическое вмешательство в моноколональную гаммопатию неопределенного значения (МГУС) и задушающую миелому (ШМ). ММ предшествует клинически признанным условиям, таким, как МГУС и SMM. В рамках многочисленных исследований изучается биология заболеваний и иммунный профиль SMM и MGUS, с тем чтобы разгадать сложную связь между иммуноконтрол

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… Diamond B. Maura F. Hillengass J. Turesson I. Landgren C.O. Kazandjian D. Second malignancies in multiple myeloma; emerging patterns and future directions Best Pract. Res. Clin. Haematol. 2020 33 101144 10.1016/j.beha.2020.101144 32139010 PMC7544243 93. Musto P. Anderson K. Attal M. Richardson P. …

Noncoding RNAs improve the predictive power of network medicine.

Network medicine has improved the mechanistic understanding of disease, offering quantitative insights into disease mechanisms, comorbidities, and novel diagnostic tools and therapeutic treatments. Yet, most network-based approaches rely on a comprehensive map of protein-protein interactions (PPI), ignoring interactions mediated by noncoding RNAs (ncRNAs). Here, we systematically combine experimentally confirmed binding interactions mediated by ncRNA with PPI, constructing a comprehensive network of all physical interactions in the human cell. We find that the inclusion of ncRNA expands the nu

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… Barabási , A DIseAse MOdule Detection (DIAMOnD) algorithm derived from a systematic analysis of connectivity patterns of disease proteins in the human interactome . PLoS Comput. Biol. 11 , e1004120 ( 2015 ). 25853560 10.1371/journal.pcbi.1004120 PMC4390154 63 A. …

Mass Spectrometry-Based Proteomics: Analyses Related to Drug-Resistance and Disease Biomarkers.

Mass spectrometry-based proteomics is a key player in research efforts to characterize aberrant epigenetic alterations, including histone post-translational modifications and DNA methylation. Data generated by this approach complements and enrich datasets generated by genomic, epigenetic and transcriptomics approaches. These combined datasets can provide much-needed information on various mechanisms responsible for drug resistance, the discovery and validation of potential biomarkers for different diseases, the identification of signaling pathways, and genes and enzymes to be targeted by futur

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… Farber S., Diamond L.K. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N. Engl. J. Med. 1948;238:787–793. doi: 10.1056/NEJM194806032382301. 56. Greger V., Passarge E., Höpping W., Messmer E., Horsthemke B. …

Pathogenesis and treatment of Sjogren's syndrome: Review and update.

Sjogren's syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, and lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 and IL-23), and B cell-related cytokines (TNF and BAFF) are crucial for the pathogenesis of SS. We also summarize the advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, targeting BAFF, inhibiting JAK pathway, et al. Similar

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… Lazear HM, Schoggins JW, Diamond MS. Shared and distinct functions of type I and type III interferons. Immunity (2019) 50(4):907–23. doi: 10.1016/j.immuni.2019.03.025 49. Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM, et al. …

CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.

The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM. However, their shortcomings deal with logistical and clinical challenges, including limited availability, manufacturing times, and toxicities. This article provides an overview of rec

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… Maura F, Weinhold N, Diamond B, et al. The mutagenic impact of melphalan in multiple myeloma. Leukemia . 2021;35(8):2145–2150. …

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies.

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bo

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… Diamond T., Golombick T., Manoharan A. Vitamin D status may effect the skeletal complications of multiple myeloma. Am. J. Hematol. 2010;85:302–303. doi: 10.1002/ajh.21619. 98. Park W.H., Seol J.G., Kim E.S., Binderup L., Koeffler H.P., Kim B.K., Lee Y.Y. …

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of infected-coronavirus cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to establ

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… Bekerman Elena, Neveu Gregory, Shulla Ana, Brannan Jennifer, Pu Szu-Yuan, Wang Stanley, Xiao Fei, Barouch-Bentov Rina, Bakken Russell R., Mateo Roberto, Govero Jennifer, Nagamine Claude M., Diamond Michael S., De Jonghe Steven, Herdewijn Piet, Dye John M., Randall Glenn, and Einav Shirit. …

The Production Processes and Biological Effects of Intravenous Immunoglobulin.

Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it ca

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… Diamond B. Antibodies elicited by pneumococcal antigens bear an anti-DNA-associated idiotype J. Clin. Investig. 1991 87 842 846 10.1172/JCI115088 1999497 PMC329872 12. Knezevic-Maramica I. Kruskall M.S. …

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, December 5th 2015

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… Vanpouille-Box C Diamond JM Pilones KA Zavadil J Babb JS Formenti SC TGFbeta is a master regulator of radiation therapy-induced antitumor immunity Cancer Res 2015 75 11 2232 42 10.1158/0008-5472.CAN-14-3511 25858148 PMC4522159 60. …

Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes.

The discovery of JAK2 (V617F) a decade ago led to optimism for a rapidly developing treatment revolution in Ph(-) myeloproliferative neoplasms. Unlike BCR-ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) syndromes. JAK-STAT inhibitors have ch

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… 21220608 10.1200/JCO.2010.32.8021 PMC4979099 83 Harrison CN Cortes JE Cervantes F Results of a randomized, double-blind, placebo-controlled phase iii study (JAKARTA) of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis (MF) Blood 2013 122 21 393 84 Zhang Q Zhang Y Diamond …

Notch signaling deregulation in multiple myeloma: A rational molecular target.

Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell localization in the bone marrow milieu allows direct interactions between tumor cells and non-tumor bone marrow cells which promote neoplastic cell growth, survival, bone disease, acquisition of drug resistance and consequent relapse. Twenty percent of MM patients are at high-risk of treatment failure as defined by tumor markers or presentation as plasma cell leukemia. Cumulative evidences indicate a key role of Notch signaling in multiple

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… Jimeno A LP, Strother RM, Robinson Diamond J, Plato L, Younger A, Messersmith WA, Kittaneh M, Sawyer D, Adriaens L, Liu L, Kao RJ, DiCioccio AT, Brownstein CM, Lowy I, Trail P, Chiorean EG. …

In silico investigations of the anti-catabolic effects of pamidronate and denosumab on multiple myeloma-induced bone disease.

It is unclear whether the new anti-catabolic agent denosumab represents a viable alternative to the widely used anti-catabolic agent pamidronate in the treatment of Multiple Myeloma (MM)-induced bone disease. This lack of clarity primarily stems from the lack of sufficient clinical investigations, which are costly and time consuming. However, in silico investigations require less time and expense, suggesting that they may be a useful complement to traditional clinical investigations. In this paper, we aim to (i) develop integrated computational models that are suitable for investigating the ef

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… Diamond T, Levy S, Day P, Barbagallo S, Manoharan A, et al. (1997) Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity. British Journal of Haematology 97 3:641–648. 37. …

The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?

Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptiv

Кровавая добавка и болезни человека: обзор клинических испытаний.

Медицинальные свойства турмеров (Curcuma longa L.) — растения, использовавшегося на протяжении веков в качестве противовоспалительного средства, объясняются его полифеноловыми каркуминоидами, где преобладает кёркумин. Хотя «куркуминовые» добавки являются топ-продаваемыми ботаническими с перспективными доклиническими эффектами, остаются вопросы о биологической активности у человека. Для решения этой проблемы был проведен обзор аналитического исследования с целью оценки клинических испытаний человека, в ходе которых сообщалось о пероральном воздействии каркумина на результаты лечения. Eight :: п

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

Advanced Diagnostic Techniques

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… If only one slide is available, it may be used divided into test and negative reagent control by circling the areas of interest with a diamond or wax pen or using the cell transfer technique already mentioned ( DeLellis and Hoda, 2006 ). … Processing of Fixed Samples Fixed samples are dehydrated and embedded in a liquid resin that polymerizes to produce a hard block that is cut using special glass or diamond knives in an ultramicrotome. …

FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial.

Fc receptor-homolog 5 (FcRH5) is a membrane protein that is ubiquitously expressed on myeloma cells. Cevostamab is a first-in-class, FcRH5×CD3 bispecific antibody. GO39775 is a phase 1 dose-escalation and dose-expansion study evaluating fixed-duration cevostamab in relapsed or refractory multiple myeloma. Cevostamab was initiated with step-up dosing and continued at the target dose (TD) once every 3 weeks for 17 cycles (~12 months) unless disease progression or unacceptable toxicity occurred. Primary objectives were to evaluate safety, including determination of the maximum tolerated dose (MTD

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… Peer review Peer review information Nature Medicine thanks Benjamin Diamond, Carsten Müller-Tidow and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Saheli Sadanand, in collaboration with the Nature Medicine team. …

Инфекционные токсичные вещества, связанные с биконкретными антителами и клетками CAR-T в множестве миеломы: систематический обзор.

Лечение с перенацеливанием клеток изменило лечение повторной/охлажденной множественной миэломы (RRMM), но связано со значительным риском инфицирования. Мы систематически анализировали инфекционные заболевания после терапии Т-клеток CAR и биконкретных антител (BSAbs) с уделением особого внимания частотности, времени, патогенам, факторам риска и профилактике. Следуя руководящим принципам PRISMA, мы обыскали Паббмеда до мая. 22, 2026, и включает исследования, содержащие информацию о инфекционных результатах у пациентов, проходящих курс лечения с помощью клеток CAR-T или BsAbs. Всего 123 Был прове

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… Kowalski A, Lykon J, Diamond BT, Coffey DG, Kaddoura M, Maura F et al (2025) Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies. Blood Adv 63. …