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Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy.

Osteocytes are terminally differentiated cells of the osteoblast lineage. They are involved in the regulation of bone remodeling by increasing osteoclast formation or decreasing bone formation by the secretion of the osteoblast inhibitor sclerostin. Monoclonal antibody anti-sclerostin, Romosozumab, has been developed and tested in clinical trials in patients with osteoporosis. In the last years, the role of osteocytes in the development of osteolytic bone lesions that occurs in multiple myeloma, have been underlined. Myeloma cells increase osteocyte death through the up-regulation of both apop

The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (N

Всеобъемлющий мета-анализ сердечно-сосудистых неблагоприятных последствий биконкретной антителной терапии в гематологовых злодеяниях.

Введение: Биотечные антитела (BSAbs) являются перспективным и мощным терапевтическим вмешательством в случае рецидивных или рефрактных (R/R) гематологических магнестов, включая острую лимфоболическую лейкемию (ALL), множественные миеломы (MM) и лимфомы B-клеток. Эти рекомбинантные молекулы предназначены для целей two отдельные антигены или эпитопы. Хотя БСАБ продемонстрировали значительную эффективность в управлении гематологическими паразитами, токсины должны тщательно контролироваться, а их характеристики безопасности требуют дальнейшего изучения. В ходе этого метаанализа изучаются последств

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге

Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF).

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… The glycosylated version, lenograstim, produced in CHO cells, was approved in Europe in 1993. They are eliminated in vivo by renal excretion, degradation via G-CSF receptors, or serum elastase. The serum half-life of filgrastim is 3.5 h, with a concentration of 10 ng/ml over 8–16 h [ 10 ]. …

ISEV2019 Abstract Book

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Management of keratinocyte carcinoma - Special considerations in the elderly.

Keratinocyte carcinomas (KCs) are now an epidemic in The United States of America, especially in elderly patients. KCs, including basal cell carcinoma and squamous cell carcinoma, can lead to disfigurement and occasionally death. However, the lower mortality rate associated with KC compared with melanoma allows for increased flexibility in the selection of treatment. Flexibility in treatment is particularly important in the elderly given that this patient population often has medical comorbidities that should be considered. These patients may have multiple KCs, higher risk tolerance to recurre

DNA Binding, DNA Photocleavage, Molecular Docking Studies and Photo-Induced Effect on Melanoma Cells of 2-Methyl-3-OR Quinazolinone Derivatives.

Thirty 2-methyl-quinazolinone fussed hydroxamic acids (3-OH) and their 3-OEt and 3-OBn derivatives were evaluated for their affinity towards calf-thymus (CT) DNA using UV-vis absorption, viscosity and fluorescence spectroscopy. DNA photocleavage activity was assessed by incubating the compounds with plasmid DNA followed by UV-A and visible light irradiation, which enabled identification of the most potent derivatives active at concentrations of 100 nΜ and 10 μΜ, respectively. Mechanistic studies on the most active compounds indicated the formation of oxygen radical species and a decrease in ef

Defibrotide for prophylaxis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in pediatric high-risk patients: consensus guidelines from the European Society for Blood and Marrow Transplantation (EBMT).

SOS/VOD is a life-threatening complication of hematopoietic stem cell transplantation, especially in children, with incidences reaching up to 15-20%. Despite efforts, SOS/VOD remains unpredictable with significant morbidity and mortality. High-risk criteria are clearly defined, and the pediatric EBMT diagnostic criteria have improved sensitivity, reducing treatment delays and enhancing outcomes. A meta-analysis combining retrospective and prospective studies found a risk ratio of 0.30 for SOS/VOD with defibrotide (DF) prophylaxis. Additionally, two prospective trials were conducted: the pediat

Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity.

The use of modern therapies such as thalidomide, bortezomib and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM). However, patients with relapsed/refractory multiple myeloma (RRMM) often have poorer clinical outcomes and might benefit from novel therapeutic strategies. Emerging therapies, such as deacetylase inhibitors, monoclonal antibodies and new proteasome inhibitors, appear promising and may change the therapeutic landscape in RRMM. A limited number of stu

Canine Cancer: Strategies in Experimental Therapeutics.

Cancer is the most common cause of death in adult dogs. Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model. These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leverage

Rare Diseases of the Nose, the Paranasal Sinuses, and the Anterior Skull Base.

Due to their low incidence and thus resulting limited diagnostic criteria as well as therapeutic options, rare diseases of the nose, the paranasal sinuses, and the anterior skull base are a significant challenge. The value as of which a disease has to be considered as rare amounts to a maximum of 5 patients per 10 000 people. Within these diseases, however, there are extreme differences. Some rare or orphan diseases like for example the inverted papilloma belong to regularly diagnosed and treated diseases of larger departments of oto-rhino-laryngology whereas other rare diseases and malformati

Lenalidomide use in multiple myeloma (Review).

Lenalidomide is a second-generation new immunomodulatory medication used to treat multiple myeloma (MM). Its mechanism of action involves affecting the expression of vascular endothelial growth factor, interleukin-6, cytochrome c, caspase-8, as well as other factors including immunological modulation and the direct killing of cells, among others, rendering it a fundamental medication, useful for the treatment of MM. Combining lenalidomide with other medications such dexamethasone, bortezomib, ixazomib, carfilzomib and daratumumab can markedly alleviate MM. When autologous-hematopoietic stem ce

Упражнения и питание в гематологических заболеваниях: свидетельства перевода и новые меры вмешательства.

Пациенты, страдающие гематологическими микроорганизмами, включая лейкемию, лимфому и миелому, живут дольше из - за прогресса в лечении. Тем не менее такое лечение часто приводит к токсичным последствиям, влияющим на качество жизни пациентов (QoL). Хотя мероприятия, связанные с образом жизни, такие, как упражнение и питание, приносят пользу, снижая риск заболевания раком и улучшая результаты лечения твердых опухолей, их применение в гематологических опухолей по-прежнему недостаточно изучено. В настоящем описательном обзоре рассматриваются текущие данные о роли физических упражнений и питания в

Безопасность и эффективность антиклеточных антигенных (Анти-БКМА) антител для релапсированных/отверженных миеломы: систематический обзор клинических испытаний.

Многократная миелома (RRMM) по-прежнему является сложным заболеванием и нуждается в более эффективных вариантах лечения. В настоящее время проводятся клинические испытания, в ходе которых проводится анализ воздействия антиклеточного антигена (BCMA) биконкретного антитела (Abs) против RRMM с ранними многообещающими результатами. Целью этого исследования является систематическая оценка безопасности и эффективности антибиологических антител для пациентов с RRMM. На сайте PubMed, Embase, Web of Science и Американского общества гематологии (ASH) были найдены опубликованные данные о безопасности и э

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

NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells.

Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously reported that NK3.3EVs, extracellular vesicles (EVs) derived from the normal human natural killer (NK) cell line, NK3.3, have strong cytotoxic activity against leukemia and breast cancer cell lines, without harming normal cells. Here, we used a three-dimensional (3D) MCF7 breast cancer mammosphere model to repro

Understanding the Mechanisms of Diet and Outcomes in Colon, Prostate, and Breast Cancer; Malignant Gliomas; and Cancer Patients on Immunotherapy.

Cancer patients often ask which foods would be best to consume to improve outcomes. This is a difficult question to answer as there are no case-controlled, prospective studies that control for confounding factors. Therefore, a literature review utilizing PubMed was conducted with the goal to find evidence-based support for certain diets in specific cancer patients-specifically, we reviewed data for colon cancer, prostate cancer, breast cancer, malignant gliomas, and cancer patients on immunotherapy. Improved outcomes in colon cancer and patients on immunotherapy were found with high-fiber diet

A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical

Th17 and Treg cells in bone related diseases.

Bone-related diseases share the process of immune response that targets bone tissue and bone marrow and then induce adverse effects on structure and function. In recent years, reciprocal relationship between immune cells and bone systems has been uncovered gradually. Regulatory T (Treg) and T helper 17 (Th17) cells are newly identified subsets of CD4+ T cells, and the balance between them is particularly essential for maintaining immune homeostasis. Accumulated data have demonstrated quantitative or functional imbalance between Th17 and Treg in bone related diseases, suggesting that Th17 and T