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МикроРН в связи с иммунными заболеваниями: механизм, функции и терапевтические аспекты.

МикроРНК (миРНК) представляют собой эволюционно сохранившиеся, некодирующие молекулы РНК приблизительно 18-25 нуклеотидов по длине, которые регулируют генное выражение на посттранарном уровне. Их главным механизмом действий является пост-ранарное заглушение генов с помощью интерференции РНК, которое достигается путем привязки к дополнительным последовательности в рамках целевых посыльных РНК (mRNA). Накопляемые данные свидетельствуют о ключевой роли miRNA в развитии, дифференциации и функционировании иммунных клеток, а также в сохранении иммунной гомеостазии. Более полное понимание сложных мол

Autophagy in tumor immune escape and immunotherapy.

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of immune resistance remains significant. Autophagy, a cellular response to various stressors, involves the degradation of damaged proteins and organelles via lysosomal pathways, maintaining cellular homeostasis. This process not only supports tumor cell survival but also profoundly impacts the efficacy of cancer immunotherapies. The modulation of autophagy in tumor cells or immune cells exerts dual effects on tumor immune escape and immunotherapy. However,

Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume.

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to tradition

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… A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis. BMC Neurol. 2008;8(1):38. doi: 10.1186/1471-2377-8-38. 45. Wågø KJ, Skarsvåg TI, Lundbom JS, Tangen, LF, Ballo, S, Hjelseng, T, Finsen, V et al. …

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (ei

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media

Iron in the Tumor Microenvironment-Connecting the Dots.

Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic im

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects.

The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for

Новые границы для лечения множественных склерозов: от целесообразных молекулов до биконкретных антител.

Множественный склероз (MS) — аутоиммунное демиелинирующее заболевание центральной нервной системы. С 1990-х годов был достигнут значительный прогресс в развитии терапевтического ландшафта MS, в результате чего было разработано более 20 различных методов лечения заболеваний (ДМТ). Эта терапия эффективно решает проблемы рецидивов и воспаления, но большинство из них не смогли реально предотвратить прогрессирование заболеваний. В то время как классически понимается как состояние с Т-камерой, наиболее эффективные DMT в замедлении движения также нацелены на клетки B. Новые классы методов лечения MS

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… A significant positive correlation between EDSS and MFI values of phosphorylated NF κ B after CD40 stimulation has also been demonstrated in patients that received interferon beta-1a and combined mycophenolate mofetil combination therapy, indicating that reduced phosphorylation of NF κ B correlates with …

К лечению множественных склерозов

Множественный склероз (MS) является воспалительным и демиелинизирующим заболеванием центральной нервной системы (CNS). У большинства пациентов болезнь начинается с острого наступления, за которым следует этап ремиссии, последующие рецидивы и позднее переход к устойчивой хронической прогрессии. В меньшинстве пациентов эта постепенная фаза развивается с самого начала. Для рецидивов MS характерно в основном деновое образование побочного повреждения CNS и инфильтрация иммунных клеток, в то время как патологические особенности MS прогрессирования включают медленно расширяющиеся повреждения, глобаль

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… Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis N. Engl. J. Med. 2016 376 221 234 10.1056/NEJMoa1601277 28002679 44. Hawker K. O’Connor P. Freedman M.S. Calabresi P.A. Antel J. Simon J. Hauser S. Waubant E. Vollmer T. Panitch H. …

Predicting chemotherapy toxicity in multiple myeloma: the prognostic value of pre-treatment serum cytokine levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor.

IntroductionMultiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients.

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount

Circadian rhythms and cancers: the intrinsic links and therapeutic potentials.

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting cycles, and activity-rest cycles, coordinating the behavior and physiology of all organs for whole-body homeostasis. Acute disruption of circadian rhythm may lead to transient discomfort, whereas long-term irregular circadian rhythm will result in the dysfunction of the organism, therefore increasing the risks of numerous diseases especially cancers. Indeed, both epidemiological and experimental evidence has demonstrated the intrinsic li

Mesenchymal Stromal Cells in Neuroblastoma: Exploring Crosstalk and Therapeutic Implications.

Neuroblastoma (NB) is the second most common solid cancer in childhood, accounting for 15% of cancer-related deaths in children. In high-risk NB patients, the majority suffers from metastasis. Despite intensive multimodal treatment, long-term survival remains <40%. The bone marrow (BM) is among the most common sites of distant metastasis in patients with high-risk NB. In this environment, small populations of tumor cells can persist after treatment (minimal residual disease) and induce relapse. Therapy resistance of these residual tumor cells in BM remains a major obstacle for the cure of NB.

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

A review on how to do hematology consults during COVID-19 pandemic.

The ongoing COVID-19 pandemic is the most trending and talked topic across the World. From its point of origin in Wuhan, China to clinical laboratory at NIH, a mere six-month-old SARS-CoV-2 virus is keeping the clinicians, and scientists busy at various fronts. However, COVID-19 is an emerging and evolving disease and each day brings in more data, new figures, and findings from the field of clinical practice. The role of hematologists has been increasingly recognized during the current pandemic because of several reasons. Most important of them are the characteristic hematological findings of

Автономная гематопоэтическая трансплантация уменьшает воспаление мозга и аксоглиальные повреждения биомаркеров при множественном склерозе.

Аутологическая трансплантация стволовых клеток (AHSCT) может вызвать долгосрочную иммунную терпимость и остроту болезней у пациентов с сильным множественным склерозом (MS), однако основные механизмы не вполне понятны. Мы гипотезуем, что AHSCT вызовет постоянное снижение в провокационных цитокинах, хемокинах и аксолиальных повреждениях биомаркеров в сыворотке и CSF.МЕТОДЫ: Продольная сыворотка и пробы CSF были получены из 24 :: участники процесса по делу HALT-MS с сильными MS, проходящими через AHSCT ( &lt; &lt; AHSCT &gt; &gt; )NCT00288626), с сывороткой, собираемой в 9 период времени с момент

Exploring Serum Biomarkers for Neuropathic Pain in Rat Models of Chemotherapy-Induced Peripheral Neuropathy: A Comparative Pilot Study with Oxaliplatin, Paclitaxel, Bortezomib, and Vincristine.

Blood biomarkers, including neurofilament light chain (NfL), have garnered attention as potential indicators for chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting adverse effect of neurotoxic anticancer drugs. However, no blood biomarker has been established for routine application or translational research. This pilot study aimed to evaluate a limited panel of blood biomarkers in rat models of CIPN and their correlations with neuropathic pain. CIPN models were induced through repeated injections of oxaliplatin, paclitaxel, bortezomib, and vincristine. Electronic von Frey test

A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.

BACKGROUND: CAR-T cell gene therapy has advanced from an experimental concept to a standard curative treatment for selected hematologic malignancies. Substantial clinical evidence has established CAR-T therapy as a cornerstone for relapsed/refractory B-cell malignancies and multiple myeloma, demonstrating durable, long-term remissions. In 2025, the U.S. Food and Drug Administration (FDA) eliminated the Risk Evaluation and Mitigation Strategy (REMS) requirement, reflecting improved clinical management of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome