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In vitro models of breast cancer bone metastasis: analyzing drug resistance through the lens of the microenvironment.

Even though breast cancers usually have a good outcome compared to other tumors, the cancer can progress and create metastases in different parts of the organism, the bone being a predilection locus. These metastases are usually the cause of death, as they are mostly resistant to treatments. This resistance can be caused by intrinsic properties of the tumor, such as its heterogeneity, but it can also be due to the protective role of the microenvironment. By activating signaling pathways protecting cancer cells when exposed to chemotherapy, contributing to their ability to reach dormancy, or ev

Combined inhibition of JAK1,2/Stat3‑PD‑L1 signaling pathway suppresses the immune escape of castration‑resistant prostate cancer to NK cells in hypoxia.

Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects,

The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies.

Cancer associated thrombosis (CAT) is associated with significant morbidity and mortality, highlighting an unmet clinical need to improve understanding of the pathophysiology of CAT. Multiple myeloma (MM) is associated with one of the highest rates of thrombosis despite widespread use of thromboprophylactic agents. The pathophysiology of thrombosis in MM is multifactorial and patients with MM appear to display a hypercoagulable phenotype with potential contributory factors including raised von Willebrand factor (VWF) levels, activated protein C resistance, impaired fibrinolysis, and abnormal t

The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tum

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… N1 TANs can activate the effector T cells to prevent tumor development, promote tumor cell apoptosis via tumor necrosis factor-associated apoptosis-inducing ligand, and promote the release of matrix metalloproteinase 8 (MMP8) to degrade the ECM, which favors tumor metastasis ( 49 ). …

Роль и функции " Ирисина " : перспективы последних изменений и неевродегенеративных заболеваний.

Irisin — пептид, полученный из фибронектина типа III, содержащего домен белка 5 (FNDC5) и производимый главным образом мышечными волокнами в соответствии с регулированием пероксисомных прорациатрированных рецепторов гамма-коативатора 1-альфа (PGC1α) во время упражнения. Ирисин стал объектом обширных исследований в силу его потенциала как метаболического регулятора и его антиоксидантных свойств. В частности, она связана с защитными действиями в мозгу. Несмотря на растущий интерес, остается много вопросов относительно молекулярных механизмов, лежащих в основе их воздействия. В настоящем обзоре р

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

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

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

The role of myeloid derived suppressor cells in musculoskeletal disorders.

The immune system is closely linked to bone homeostasis and plays a pivotal role in several pathological and inflammatory conditions. Through various pathways it modulates various bone cells and subsequently sustains the physiological bone metabolism. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid-derived cells that can exert an immunosuppressive function through a direct cell-to-cell contact, secretion of anti-inflammatory cytokines or specific exosomes. These cells mediate the innate immune response to chronic stress on the skeletal system. In chronic

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

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

Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia.

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibr

The skeleton: an overlooked regulator of systemic glucose metabolism in cancer?

Recent discoveries demonstrated the skeleton's role as an endocrine organ regulating whole-body glucose homeostasis. Glucose metabolism is critical for rapid cell proliferation and tumour growth through increasing glucose uptake and fermentation of glucose to lactate despite being in an aerobic environment. This hypothesis paper discusses emerging evidence on how bones can regulate whole-body glucose homeostasis with potential to impact on tumour growth and proliferation. Moreover, it proposes a clinical link between bone glucose metabolism and prognosis of cancer based on recent clinical tria

The impact of anxiety and depression on hematologic malignancy outcomes: a systematic review and meta-analysis.

BackgroundHematologic malignancies (HMs) are associated with high morbidity and mortality. Depression and anxiety, prevalent in patients with HM, may adversely impact survival, but their prognostic role remains unclear.Materials and methodsThis systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD42024568789). We searched PubMed, SCOPUS, and Web of Science for studies examining the association between depression or anxiety and survival outcomes in patients with HMs. Data extraction and quality assessment (using the Newcastle-Ottawa Scale and RoB2) w

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

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

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