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Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review.

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical feat

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… Finally, endothelial activation evident by an increase in angiotensin 2: angiotensin 1 ratio in response to inflammatory cytokines also contributes to ICANS by causing further disruption of BBB, vascular dysfunction, increased capillary permeability, and coagulation cascade activation [ 75 ]. …

Biosensors, Artificial Intelligence Biosensors, False Results and Novel Future Perspectives.

Medical biosensors have set the basis of medical diagnostics, and Artificial Intelligence (AI) has boosted diagnostics to a great extent. However, false results are evident in every method, so it is crucial to identify the reasons behind a possible false result in order to control its occurrence. This is the first critical state-of-the-art review article to discuss all the commonly used biosensor types and the reasons that can give rise to potential false results. Furthermore, AI is discussed in parallel with biosensors and their misdiagnoses, and again some reasons for possible false results

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

Приобретенный изолированный фактор VII Недостаток в ячейке Плазмы: краткое представление Two Дела, связанные с Плазмой-Келл-Леукемией, и обзор литературы.

Приобретенный изолированный фактор VII (FVII) недостаток является редким, но важным открытием у пациентов с расстройствами плазменных клеток, имеющими значительные терапевтические и прогнозные последствия. Цель настоящего анализа и обзора случаев, о которых сообщается в литературе, состоит в том, чтобы высветить связанные с болезнями характеристики, связанные с этим редким свертываемым дефектом, клиническими проявлениями и результатами, а также потенциальными основополагающими механизмами и дать руководящие указания в отношении методов лечения этих пациентов с точки зрения профилактических и т

Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play a vital role in the pathogenesis of multiple myeloma (MM), especially for tumor invasion and osteolytic osteopathy. By breaking down extracellular matrix (ECM) components and releasing the proteins composing the ECM and growth factors, as well as their receptors, MMPs affect tissue integrity and promote cancer cell invasion and metastasis. A vital pathophysiological characteristic of MM is the progress of osteolytic lesions, which are brought on by interactions between myeloma cells and the bone marrow mic

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… In the BM microenvironment of MM patients, microvessel density (MVD), endothelial activity, capillary permeability, as well as perfusion are enhanced, and the increase in MVD is triggered by oncogene-mediated expression and secretion of cytokines and proangiogenic growth factors ( 47 ). …

Допересадка эндотелиального активационного и стрессового индекса (EASIX) и Albumin-Modificed MEASIX (mEASIX_alb) Предсказание выживания при пересадке нескольких стволовых клеток, находящихся под контролем пациентов, страдающих от миеломы.

Справочная информация и цели: Эндотелиальная дисфункция все чаще признается в качестве одного из ключевых факторов, определяющих результаты трансплантации. Индекс Эндотелиальной активации и стресса (EASIX), первоначально подтвержденный при трансплантации стволовых клеток, включает маркеры эндотелиального стресса в один сводный счет. Его прогнозируемая роль в автоматической трансплантации стволовых клеток (ASCT) в случае множественной миеломы (MM) остается неопределенной. Мы провели оценку предтрансплантационной ценности EASIX, альбом-модифицированной формулы (mEASIX_alb) и индексов питания (Пр

Adverse events associated with chimeric antigen receptor T-cell therapy in ophthalmology: a narrative review.

Chimeric antigen receptors are synthetically produced receptors engineered to engage with target cells with high specificity. These cells are created by inserting an artificial T-cell receptor into an immunoglobulin's antigen-binding region, allowing the cells to combine and target specific antigens. The use of chimeric antigen receptor (CAR) T-cell therapy has been a remarkable achievement in the field of immunotherapy, particularly in the treatment of ophthalmic tumors like retinoblastoma and uveal melanoma. However, there are some documented side effects, such as cytokine release syndrome (

Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.

Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes

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

Стратегии защиты от нейропии в множестве склерозов: обновление статуса и формирующиеся парадигмы.

ВВЕДЕНИЕ: MS представляет собой континуум заболеваний, в котором с момента начала и с течением времени происходит злокачественное воспаление и нейродегенерация. Недавний прогресс в недостатке патобиологии MS создает новые перспективы для новых терапевтических стратегий нейрозащиты. ОБЛАСТЬ ПРИМЕНЕНИЯ: Авторы кратко рассматривают механизмы, лежащие в основе воспаления и нейродегенерации в MS, и обсуждают нынешние и формирующиеся стратегии поощрения нейрозащиты в MS. Данные были получены в значительной степени на основе обширного обзора опубликованной литературы, имеющейся на PubMed (до 5 марта

Chest and Mediastinum

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Skin manifestations associated with systemic diseases - Part I.

The skin demonstrates what is happening in the body in many diseases, as it reflects some internal processes on the surface. In this sense, skin as an organ, goes beyond its protective and barrier functions, as it provides clues for the identification of some systemic diseases. The dermatologist then raises diagnostic hypotheses for conditions related to all systems and refers them to the appropriate specialty. With easy access to examination by trained eyes and biopsies, the skin can present specific or non specific alterations on histopathology. In the first case this combination establishes

Zoledronic Acid Modulation of TRPV1 Channel Currents in Osteoblast Cell Line and Native Rat and Mouse Bone Marrow-Derived Osteoblasts: Cell Proliferation and Mineralization Effect.

Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10-8 to 5 × 10-4 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10-

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome.

The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specificall

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… Intercellular cement and capillary permeability. Physiol. Rev. 1947;27:436–463. doi: 10.1152/physrev.1947.27.3.436. 17. Hawley E.E., Frazer J.P., Button L.L., Stevens D.J. …

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of C

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their m

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy.

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tum

Multimodal imaging of bone metastases: From preclinical to clinical applications.

Metastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cir