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High-Affinity DARPin Allows Targeting of MeV to Glioblastoma Multiforme in Combination with Protease Targeting without Loss of Potency.

Measles virus (MeV) is naturally cytolytic by extensive cell-to-cell fusion. Vaccine-derived MeV is toxic for cancer cells and is clinically tested as oncolytic virus. To combine the potential of MeV with enhanced safety, different targeting strategies have been described. We generated a receptor-targeted MeV by using receptor-blind viral attachment protein genetically fused to designed ankyrin repeat protein (DARPin) binding domains specific for the epidermal growth factor receptor (EGFR). To reduce on-target toxicity for EGFR+ healthy cells, we used an engineered viral fusion protein activat

Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая

Oxygen targets in critically ill patients: from pathophysiology to population enrichment strategies.

Oxygen supplementation is widely used to enhance oxygen delivery and to treat or prevent hypoxia; however, it requires careful management to avoid the harmful effects of excessive oxygen exposure. Both hyperoxia (inspiratory oxygen fraction exceeding 0.21) and hyperoxemia (arterial oxygen tension oxygen partial pressure [PaO2] > 100 mmHg) can contribute to lung injury, promote systemic vasoconstriction, and increase the production of reactive oxygen species, which can impair macromolecular and cellular functions. Conversely, in certain situations, hyperoxemia may provide benefits, such as hemo

Efficacy and Safety of Filgrastim and Its Biosimilars to Prevent Febrile Neutropenia in Cancer Patients: A Prospective Study and Meta-Analysis.

Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrop

Миграционный арест и трансэндотелиальная торговля патогенными клетками, подобными ТH17, осуществляются с помощью дифференцированных хемокинов.

Человеческие TH17/тип 17 клетки выражают хемокиновый рецептор CCR6, но функции CCR6 и других химокиновых рецепторов в экстравазации клеток типа 17 Т не были полностью определены. Здесь мы показываем, что периферийные клетки крови человека CD4+CCR6+T, которые одновременно выражают CCR2, имеют патогенную сигнатуру TH17, могут производить подстрекательские цитокины без активации Т клеточного рецептора, и демонстрируют более широкое выражение генов, связанных с патогенностью и активацией, в цереброспинной жидкости пациентов с множественным склерозом по сравнению с контролем. В газовых камерах с ак

Liquid biopsies in myeloid malignancies.

Hematologic malignancies are the most common type of cancer affecting children and young adults, and encompass diseases, such as leukemia, lymphoma, and myeloma, all of which impact blood associated tissues such as the bone marrow, lymphatic system, and blood cells. Clinical diagnostics of these malignancies relies heavily on the use of bone marrow samples, which is painful, debilitating, and not free from risks for leukemia patients. Liquid biopsies are based on minimally invasive assessment of markers in the blood (and other fluids) and have the potential to improve the efficacy of diagnosti

Всемирный конгресс молекулярного воображения 2022.

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mRNA vaccine development and applications: A special focus on tumors (Review).

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronaviru

Student Summer Research Awards - SSRAAbstracts of the SSRA September 2022 meeting, UCD School of Medicine.

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Sclerostin Alters Tumor Cell Characteristics of Oral Squamous Cell Carcinoma and May Be a Key Player in Local Bone Invasion.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin tr

Will a mAb-Based Immunotherapy Directed against Cancer Stem Cells Be Feasible?

The cancer stem cell (CSC) hypothesis suggests that within a tumor, there is a small subpopulation of cells with stem cell properties responsible for tumor maintenance and metastasis generation. This hypothesis also implies that new antitumor drugs, rather than targeting the bulk of the tumor mass, would be more effective if they directly targeted the CSC subpopulation. The CSCs from several types of tumors have been identified with mAbs recognizing surface antigens in these cells; however, antigens specifically or exclusively expressed in the CSC population have not yet been identified. Thus,

Обязательный экзамен по патологии: лишний или необходимый?

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Epidemiology, Risk Factors, and Outcomes of Neutropenic Enterocolitis in Onco-Hematological Patients According to Chemotherapy Regimen.

BackgroundWhile neutropenic enterocolitis (NEC) is a well-known life-threatening complication during intensive chemotherapy, its incidence, impact, and outcome on specific at-risk populations remain ill defined.MethodsWe report 178 NEC episodes during 1963 myeloablative chemotherapy courses among 1259 adult patients with acute myeloid (AML) or lymphoblastic (ALL) leukemia or receiving autologous hematopoietic stem cell transplantation (auto-HCT) for lymphoma or multiple myeloma. Risk factors were assessed by multivariate logistic regression models.ResultsMost NEC cases (93.3%) occurred during

Machine learning-based prognostic model for bloodstream infections in hematological malignancies using Th1/Th2 cytokines.

OBJECTIVE: Bloodstream infection (BSI) is a significant cause of mortality in patients with hematologic malignancies(HMs), particularly amid rising antibiotic resistance. This study aimed to analyze pathogen distribution, drug-resistance patterns and develop a novel predictive model for 30-day mortality in HM patients with BSIs. METHODS: A retrospective analysis of 231 HM patients with positive blood cultures was conducted. Logistic regression identified risk factors for 30-day mortality. Th1/Th2 cytokines were collected at BSI onset, with LASSO regression and restricted cubic spline analysis

Роман CCL3-HMGB1 Ось сигнала регулирует выражение остеоцита РАНКЛ в множестве миеломы.

Множественная миелома (ММ) — клональная плазменная клетка, вызывающая изнурительное заболевание костей. Остеолитическое разрушение, которое является отличительной чертой MM, вызвано увеличением остеокластного числа и усилившейся ресорбцией костей, главным образом в результате чрезмерного производства RANKL, главного регулятора образования остеокласта, в пределах ниши опухоли. Ранее мы сообщали, что остеоциты, самые изобилие клеток в костной нише, поощряют прогрессию опухоли и поддерживают болезнь костей MM, перепроизводяя RANKL. Однако молекулярные механизмы, лежащие в основе регулирования РАН

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 week

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer.

PurposeAdoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.Materials and methodsMultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally r

The Effect of Docosahexaenoic Acid and α-Lipoic Acid as Prevention of Bortezomib-Related Neurotoxicity in Patients With Multiple Myeloma.

Background and Aims: In cancer patients, a common complication during chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). For this reason, we decided to conduct a phase II prospective study on 33 patients with multiple myeloma at first diagnosis, to evaluate whether a nutraceutical compound given for 6 months during bortezomib (BTZ) treatment succeeded in preventing the onset of neurotoxicity. Methods: Neurological evaluation, electroneurography, and functional and quality of life (QoL) scales were performed at baseline and after 6 months. We administered a tablet containing doc

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XRK3F2 Inhibition of p62-ZZ Domain Signaling Rescues Myeloma-Induced GFI1-Driven Epigenetic Repression of the Runx2 Gene in Pre-osteoblasts to Overcome Differentiation Suppression.

Multiple myeloma bone disease (MMBD) is characterized by non-healing lytic bone lesions that persist even after a patient has achieved a hematologic remission. We previously reported that p62 (sequestosome-1) in bone marrow stromal cells (BMSC) is critical for the formation of MM-induced signaling complexes that mediate OB suppression. Importantly, XRK3F2, an inhibitor of the p62-ZZ domain, blunted MM-induced Runx2 suppression in vitro, and induced new bone formation and remodeling in the presence of tumor in vivo. Additionally, we reported that MM cells induce the formation of repressive chro

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati