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Preclinical B cell depletion and safety profile of a brain-shuttled crystallizable fragment-silenced CD20 antibody.

BACKGROUND: The blood-brain barrier (BBB) presents a major challenge for the development of monoclonal antibody (mAb)-based therapies for brain disorders. To improve the likelihood of success of such therapies, Roche Brainshuttle technology utilizes a single anti-transferrin receptor 1 (TfR1)-antigen-binding antibody fragment linked to a therapeutic antibody, allowing engagement with TfR1 to transport the therapeutic antibody into the brain via receptor-mediated transcytosis. METHODS: We compared Fc-silenced and Fc-competent variants of the Brainshuttle and the parental (non-shuttled) type II

Nanomaterial-Driven Precision Immunomodulation: A New Paradigm in Therapeutic Interventions.

Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could

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… Evidence of nanomaterial-based therapies in both preclinical and clinical applications has shown promise and has been successful in a range of autoimmune disorders including RA, multiple sclerosis (MS), and systemic lupus erythematosus [ 185 , 186 ]. …

Bone metastases in thyroid cancer.

Whereas preemptive screening for the presence of lymph node and lung metastases is standard-of-care in thyroid cancer patients, bone metastases are less well studied and are often neglected in thyroid cancer patient surveillance. Bone metastases in thyroid cancer are, however, independently associated with poor/worse prognosis with a median overall survival from detection of only 4 years despite an otherwise excellent prognosis for the vast majority of thyroid cancer patients. In this review we summarize the state of current knowledge as pertinent to bony metastatic disease in thyroid cancer,

СРП 2013

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Развитие микробиотерапии: роль синтетической биологии в инженерных микробных сообществах для точной медицины.

В последние годы исследования в области микробиотических исследований и синтетической биологии были посвящены изучению новых подходов к микробным манипуляциям в терапевтических целях. Тем не менее, по этому аспекту имеется фрагментированная информация с ключевыми идеями, разбросанными по различным дисциплинам, таким, как молекулярная биология, генетика, биоинженерия и медицина. Цель этого обзора заключается в создании преобразующего потенциала синтетической биологии в плане развития исследований и лечения микробиоме, что имеет значительные последствия для здравоохранения, сельского хозяйства и

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… Engineered probiotics that alter immune responses have the potential to improve autoimmune disorders like rheumatoid arthritis and multiple sclerosis ( Wang et al., 2024 ). …

GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases.

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers1. T cells participate in a wide range of inflammatory diseases such as psoriasis2, Crohn's disease3, oesophagitis4 and multiple sclerosis5,6, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7. Chronic rhinosinusitis affects more than 10% of the general population8. Am…

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are invol

Emerging and underexplored ginsenosides in cancer therapy (2020-2025): Beyond cytotoxic mechanisms.

Ginsenosides from Panax plants have long been studied as potential anticancer agents. In earlier years, most research focused on a few well-known ginsenosides that showed strong direct cytotoxicity, such as Rg3 and Rh2. As a result, many other ginsenosides were considered less active and received limited attention. However, studies published between 2020 and 2025 indicate that several previously underexplored ginsenosides also exhibit meaningful anticancer activity. These compounds often do not function as strongly cytotoxic agents. Instead, they act through broader and more indirect mechanism

NAD+‒circadian rhythm coupling in dementia.

The circadian rhythm system and sleep coordinate whole-body functions across the 24-h cycle, yet these rhythms progressively deteriorate with neurodegenerative diseases, including dementia. Growing evidence indicates that nicotinamide adenine dinucleotide (NAD+) interacts with the circadian system through multiple molecular pathways and that NAD+ levels decline with dementia. In this review, we synthesize current evidence on the bidirectional relationship between NAD+ metabolism and circadian regulation in several dementia disorders, emphasizing the key circadian pathways, the nicotinamide pho

Precision Medicine Through Network Language: Integrating Clinical Insight and Data Expertise.

Precision medicine is facing a critical transition driven by the growing complexity of biological data and the insufficient ability of current models to translate such data into clinically meaningful information. Linear, single-gene approaches are no longer adequate to explain the multifactorial nature of most modern diseases, whose phenotypes emerge from combinations of genetic, molecular, and environmental factors. Network-based precision medicine addresses this by providing a systemic framework capable of integrating heterogeneous omics data, interactomes, and clinical information to identi

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… Through the analysis of networks of relationships, it is possible to make diagnoses, identify new drugs, find computational biomarkers, and estimate risk factors for complex diseases, such as cancer, cardiovascular diseases, autoimmune diseases (e.g., multiple sclerosis) and diabetes [ 27 , 54 ]. …

Profile of tocilizumab and its potential in the treatment of giant cell arteritis.

Giant cell arteritis (GCA) remains a medical emergency due to the threat of permanent sight loss. High-dose glucocorticoids (GCs) are effective in inducing remission in the majority of patients, however, relapses are common which lengthen GC therapy. GC toxicity remains a major morbidity in this group of patients, and conventional steroid-sparing therapies have not yet shown enough of a clinical benefit to change the standard of care. As the understanding of the underlying immunopathophysiology of GCA has increased, positive clinical observations have been made with the use of IL-6 receptor in

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… IL-6 therefore has a critical role in altering the balance between Treg and Th17 cells, and its overproduction contributes to the pathogenesis of GCA and other inflammatory disorders, including RA, pancreatitis, multiple sclerosis, systemic lupus erythematosus (SLE), Crohn’s disease, asthma, multiple …

New Directions in the Study and Treatment of Metastatic Cancer.

Traditional cancer therapy has relied on a strictly cytotoxic approach that views non-metastatic and metastatic tumor cells as identical in terms of molecular biology and sensitivity to therapeutic intervention. Mounting evidence suggests that, in fact, non-metastatic and metastatic tumor cells differ in key characteristics that could explain the capacity of the metastatic cells to not only escape the primary organ but also to survive while in the circulation and to colonize a distant organ. Here, we lay out a framework for a new multi-pronged therapeutic approach. This approach involves modif

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… FTY720 (Fingolimod) was developed as an immunomodulating drug mostly for treating the relapsing form of multiple sclerosis. Fingolimod is phosphorylated forming fingolimod-phosphate. …

Abstracts of the Cell Therapy Transplant Canada 2022 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2022 Annual Conference. The conference was held in-person 15-18 June 2022, in Niagara Falls, Ontario. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 16 June, and oral abstract authors were featured during the oral abstract session in the afternoon on Friday, 17 June 2022. Thirty-three (33) abstracts were selected for presentation as posters and six (6) as oral presentations. The top abstracts in each of four (4) categories, (1) Basic/Translati

ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to p

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy.

Viral mimicry refers to an active antiviral response triggered by the activation of endogenous retroviruses (ERVs), usually manifested by the formation of double-stranded RNA (dsRNA) and activation of the cellular interferon response, which activates the immune system and produces anti-tumor effects. Epigenetic studies have shown that epigenetic modifications (e.g. DNA methylation, histone modifications, etc.) play a crucial role in tumorigenesis, progression, and treatment resistance. Particularly, alterations in DNA methylation may be closely associated with the suppression of ERVs expressio

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

Longitudinal validity and reliability of the Myeloma Patient Outcome Scale (MyPOS) was established using traditional, generalizability and Rasch psychometric methods.

PURPOSE: The Myeloma Patient Outcome Scale (MyPOS) was developed to measure quality of life in routine clinical care. The aim of this study was to determine its longitudinal validity, reliability, responsiveness to change and its acceptability. METHODS: This 14-centre study recruited patients with multiple myeloma. At baseline and then every two months for 5 assessments, patients completed the MyPOS. Psychometric properties evaluated were as follows: (a) confirmatory factor analysis and scaling assumptions (b) reliability: Generalizability theory and Rasch analysis, (c) responsiveness and min

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… Hobart JC Cano SJ Improving the evaluation of therapeutic interventions in multiple sclerosis: The role of new psychometric methods Health Technology Assessment 2009 13 1 177 10.3310/hta13120 19216837 59. …

The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is among the most penetrative malignancies affecting humans, with mounting incidence prevalence worldwide. This cancer is usually not diagnosed in the early stages. There is also no effective therapy against PDAC, and most patients have chemo-resistance. The combination of these factors causes PDAC to have a poor prognosis, and often patients do not live longer than six months. Because of the failure of conventional therapies, the identification of key biomarkers is crucial in the early diagnosis, treatment, and prognosis of pancreatic cancer. 65% of the

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… Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases . Lancet Neurology . ( 2011 ) 10 : 649–56 . doi: 10.1016/S1474-4422(11)70121-1 21683930 95 Darlington PJ Boivin M-N Bar-Or A . … Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis . Expert Rev neurotherapeutics . ( 2011 ) 11 : 1295–303 . doi: 10.1586/ern.11.113 PMC3234364 21864075 96 Huang G-L Sun J Lu Y Liu Y Cao H Zhang H . MiR-200 family and cancer: From a meta-analysis view . …

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r