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Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

Emerging mechanism and therapeutic potential of neurofibromatosis type 1-related nerve system tumor: Advancing insights into tumor development.

Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 gene, which increases susceptibility to various nervous system tumors, including plexiform neurofibromas, malignant peripheral nerve sheath tumors, and optic pathway gliomas. Recent research has shown that these tumors are intricately connected to the complex, dynamic interactions within neurons, culminating in neuronal signaling that fosters tumor growth. These interactions offer crucial insights into the molecular mechanisms underpinning tumor development, as well as broader implications for therapeutic

The history of cancer pain and bone-targeted agents: 10 most commonly asked questions.

The prevalence of pain and skeletal complications of metastatic bone disease is high and an important factor, which contributes to decreased quality of life and low survival rate. Bone-targeted agents are well-established therapies to reduce the skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications is still controversial. The objective of this review is to summarize the existing evidence about the use of bone-targeted agents in the treatment of metastatic bone pain, trying to answer to the 10 most commonly asked questions in this matter. T

Последствия " Читинас " 3-like 1 Протеин в патогенезе множественных склерозов в аутопсиированных мозгах и муриновой модели.

Chitinase-3-like белок 1 (CHI3L1) был замешан в патологии множественных склерозов (MS), однако его конкретная роль остается неясной. Чтобы прояснить его участие, мы провели протеомический анализ цереброспиновой жидкости (CSF) пациентов, вновь выделяющих MS (RRMS) two- размерная разница в геле электрофорезе (2D-DIGE). CHI3L1 стал наиболее регулируемым белком в регулярных RRMS. ELISA подтвердила значительное повышение уровней CHI3L1 у пациентов с периодическими RRMS и вторичными прогрессивными MS (SPMS), при этом уровни снижаются у лиц, реагирующих на стероиды, но увеличиваются у лиц, не предста

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines a

Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review.

Hyperhomocysteinemia (HHcy) influences the development and progression of neurodegenerative disorders in different ways. Homocysteine (Hcy) metabolism is related to that of asymmetric dimethylarginine (ADMA) and group B vitamins. The breakdown of the pathway involving nitric oxide (NO) and ADMA can be considered one of the causes of endothelial alteration that represents a crucial step in the development of several neurodegenerative disorders. Deficiencies of vitamins other than group B ones, such as D and A, have also been associated with central nervous system disorders. The aim of this narr

Disease Milestones through Bibliometric Analysis of the Top 100 Cited Articles in Multiple Myeloma.

Multiple myeloma (MM) accounts for 1.6% of all cancers and 5%-10% of all hematologic malignancies in the United States (US). Despite marked progress in disease management, it remains incurable with high rates of relapse. We conducted a bibliographic analysis on the Web of Science (WOS) from July 25, 2017 and July 29, 2017. Among the top 100 most-cited articles (1901-2012), the most cited article received 2404 citations and least cited article received 336 citations. Forty-four of 100 articles were published in journals with impact factors greater than 20. We observed that over the years, the f

Resolving the Complexity: A Comprehensive Review on Carbon Monoxide Diffusion Capacity in Chronic Obstructive Pulmonary Disease Patients.

This review comprehensively examines the intricate relationship between carbon monoxide (CO) diffusion capacity and chronic obstructive pulmonary disease (COPD). COPD, comprising chronic bronchitis and emphysema, presents a substantial global health burden, necessitating a nuanced understanding of pulmonary function parameters for effective diagnosis and management. The review delves into the physiological underpinnings, measurement techniques, and factors influencing CO diffusion capacity, emphasizing its pivotal role in assessing alveolar gas exchange efficiency. Key findings elucidate corre

Effects of exosomes from different origins on osteoclasts.

Abnormal osteoclast function is closely related to the development of osteolytic diseases such as osteoporosis and tumor bone metastasis, which seriously affects patients' quality of life. The cellular microenvironment is complex and variable, and exosomes, as an important pathway mediating intercellular communication, can be secreted by a variety of cells in the human body, which carry "cargo" that can affect the biological function of recipient cells. Osteoclasts receive a variety of cellular exosomes to regulate and influence the body's bone homeostasis. In this narrative review, we summari

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… In addition, RaimondiL et al . found that multiple myeloma cell-derived exosomes can promote osteoclast differentiation by inducing the expression of osteoclast differentiation genes, including cathepsin K (CTSK), matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase (TRAP) [ 89 …

Targeting the Endocannabinoidome in Pancreatic Cancer.

Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic

Mesenchymal stem cell transplantation plays a role in relieving cancer pain.

Tumors can invade, compress, and damage nerves, leading to persistent pain and seriously affecting the quality of life of patients. However, their treatment is challenging. Sensitization of peripheral receptors, abnormal activity of primary sensory neurons, activation of glial cells, enhanced inflammatory responses, and sensory information transmission contribute towards cancer pain. Therefore, considerable attention has been paid to exploring prospective methods to inhibit the occurrence of these factors and relieve cancer pain. Studies on different types of pains have revealed that the trans

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis.

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metast

A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis.

ObjectiveThis meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models.MethodsA systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle's RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias.ResultsThis meta-analysis included 24 studies involving 440 animals with methodological quality scores

Monoclonal Antibodies-Anchored Quantum Dots-Based Delivery Strategies for Glioblastoma Treatment: Challenges and Applications.

Treatment of glioblastoma multiforme (GBM) has been a great challenge before medical fraternity since last century owing to a median survival of less than 15 months, despite of intensive therapy. Neurosurgeries, intense chemotherapy, advanced radiotherapy, and targeted therapies have bought some extension to the life of GBM patients. Combination and targeted therapies could bring a concrete approach to tackle the complexities of GBM treatment. Monoclonal antibodies (mAbs) have already proved their potential, owing to their high affinity and target-specificity, as a promising cancer immunothera

Cystatin M/E Ameliorates Multiple Myeloma-Induced Hyper Osteolytic Bone Resorption.

Multiple myeloma (MM) is a malignancy of terminally differentiated B-cells that is localized primarily in the bone marrow (BM) but also can be present in peripheral blood and tissue/organs [...].

Читинас-3-подобный-1: многообразный игрок в нейроинфламмации и дегенеративной патологии с терапевтическими последствиями.

Читинас-3-подобный-1 (CHI3L1) — эволюционно сохранившийся белок, содержащийся в ключевых биологических процессах, включая реконструирование тканей, ангиогенез и нейроинфламмацию. Она стала важным игроком в различных нейродегенеративных заболеваниях и расстройствах мозга. Повышенные уровни CHI3L1 наблюдались в таких неврологических условиях, как травматическое повреждение мозга (TBI), болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS), болезнь Креуцфельда-Якоба (CJD), множественный склероз (MS), оптика нейромиелита (NMO), вызванная ВИЧ деменция (HAD), цереб

Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.

Bone metastases remain one of the most clinically devastating complications of advanced cancer, particularly in breast, prostate, and lung malignancies, where they drive pain, fractures, hypercalcemia, and progressive functional decline. Their management is further complicated by a highly immunosuppressive bone microenvironment characterized by osteoclast-driven bone destruction, myeloid cell dominance, impaired antigen presentation, and weak effector T-cell infiltration, all of which limit the activity of conventional immunotherapies. In this setting, nanoparticles are emerging not merely as

Role of TRP Channels in Cancer-Induced Bone Pain.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in

Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.

Medulloblastomas are the most common malignant pediatric brain tumors, representing approximately 20% of the central nervous system cancers in children. These tumors are highly heterogeneous and classified into four molecular subgroups-WNT, SHH, Group 3, and Group 4-each with distinct genetic and epigenetic profiles that influence tumor behavior, therapeutic response, and patient outcomes. Advances in molecular diagnostics have improved the subclassification of medulloblastomas, yet treatment outcomes for high-risk subtypes, particularly Group 3, remain poor, with current modalities often asso

Integrative Hematology: State of the Art.

Blood cancers are a group of diseases with thus far frequently poor prognosis. Although many new drugs, including target therapies, have been developed in recent years, there is still a need to expand our therapeutic armamentarium to better deal with these diseases. Integrative hematology was conceived as a discipline that enriches the patient's therapeutic possibilities with the use of supplements, vitamins and a nutritional approach aiming at improving the response to therapies and the clinical outcome. We will analyze the substances that have proved most useful in preclinical and clinical s