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Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?

Cholangiocarcinoma (CCA) is a refractory cancer with limited treatment options and poorly understood molecular mechanisms underlying tumor development. The most effective treatment is surgical resection; however, patients are highly prone to recurrence. Moreover, considering that most patients are diagnosed in advanced stages, treatment options are restricted to palliative care, which results in poor prognosis. Due to the limited effect of chemotherapy and radiotherapy, targeted therapy is becoming a hot topic in the field of biliary cancer treatment. The fibroblast growth factor/fibroblast gr

Osteoimmunology in bone malignancies: a symphony with evil.

Bone marrow is pivotal for normal hematopoiesis and immune responses, yet it is often compromised by malignancies. The bone microenvironment (BME), composed of bone and immune cells, maintains skeletal integrity and blood production. The emergence of primary or metastatic tumors in the skeletal system results in severe complications and contributes significantly to cancer-related mortality. These tumors set off a series of interactions among cancer, bone, and immune cells, and disrupt the BME locally or distantly. However, the drivers, participants, and underlying molecules of these interactio

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… DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25 Nature 583 2020 133 138 10.1038/s41586-020-2394-6 32528174 144 Cools-Lartigue J. Spicer J. McDonald B. … Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis J Clin Invest 123 2013 3446 3458 10.1172/JCI67484 23863628 PMC3726160 145 Mousset A. Lecorgne E. Bourget I. …

Are All Patients with Cancer at Heightened Risk for Severe Coronavirus Disease 2019 (COVID-19)?

Cancer patients are traditionally considered at high risk for complicated respiratory viral infections, due to their underlying immunosuppression. In line with this notion, early case series reported high mortality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with malignancy. However, subsequent large, prospective, epidemiological surveys indicate that the risk for severe coronavirus disease 2019 (COVID-19) may be largely attributed to the multiple confounders operating in this highly heterogeneous population of patients, rather than the cancer or

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… trap formation ( Table 2 ). … Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med 2020; 217:e20200652. 34. Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID-19. JCI Insight 2020; 5:e138999. doi: 10.1172/jci.insight.138999 35. Middleton EA, He XY, Denorme F, et al. …

Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia.

Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-β, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoi

Фактор XII-А Новая терапевтическая цель? Систематический обзор.

Фактор XII — это молекула нечеткой физиологической функции, которая привлекает все больший интерес к исследованиям в различных медицинских дисциплинах. В последние годы был накоплен значительный объем данных о вкладе фактора XII в патогенез подстрекательских и протромботических заболеваний. Было продемонстрировано, что FXII играет защитную роль в коагуляции на основе FXII во время хостинговой защиты от инфекций и защищает от многоорганических неудач в моделях сепсиса животных. В случае синдрома острой дыхательной недостаточности (АРДС) деятельность FXII способствует высвобождению провоспалител

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… Upon activation, neutrophils release extracellular DNA structures known as neutrophil extracellular traps (NETs), which serve as a substrate for FXII activation and subsequent fibrin trap formation, thereby limiting the spread of infection. … CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. Immunity. 2020;52:856–871. doi: 10.1016/j.immuni.2020.03.001. 10. …

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

Myeloma cell-derived CXCL7 facilitates proliferation of tumor cells and occurrence of osteolytic lesions through JAK/STAT3 pathway.

Osteolytic lesions and pathological fractures are hallmark manifestations of multiple myeloma (MM), profoundly influencing the quality of life and self-care ability of MM patients. By analyzing transcriptome data and single-cell RNA-seq data from our center and the GEO database, a subset of MM cells with high expression levels of chemokine CXCL7 was identified. This subset of MM cells possesses a high capacity for proliferation and activation of osteoclast signaling pathway. CXCL7 might be a crucial regulator of osteolytic damage in MM. Subsequently, the association between the expression leve

Pulmonary origin and risk assessment of cancer-associated thrombosis.

Cancer-associated thrombosis (CAT) is a serious complication frequently observed in patients with cancer; however, its exact mechanism is not yet fully understood. Recent research in 2025 suggests that the lungs play a significant role in providing prothrombotic factors. Both primary and metastatic lung tumors have the potential to induce a state of hypercoagulability through various pathways, such as the secretion of procoagulant molecules, such as tissue factor (TF), triggering local inflammatory responses, platelet activation, and alterations in the function of vascular endothelial cells. F

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… Fourth, tumor cells can stimulate neutrophils to release neutrophil extracellular traps (NETs), which act as scaffolds that trap platelets and activate the coagulation system. … The emerging role of neutrophil extracellular traps in Arterial, venous and Cancer-Associated thrombosis. Front Cardiovasc Med. 2021;8:786387. 10.3389/fcvm.2021.786387. Published 2 Dec 2021. 34926629 10.3389/fcvm.2021.786387 PMC8674622 31. …

Exosomes Derived from Pancreatic Cancer Cells Induce Osteoclast Differentiation Through the miR125a-5p/TNFRSF1B Pathway.

BackgroundPancreatic cancer (PC) was regarded as the 4th principal cause of cancer-related fatalities in the United States and patients usually suffered from severe nutrition deficiency, muscle wasting, as well as bone loss. In our previous research, we have found that PC-derived exosomes potentially initiate insulin resistance in skeletal muscle cells. However, the role of exosomes in the PC-related bone loss remains unknown.MethodsThe effect of PC-derived exosomes on the osteoclast differentiation and femoral bone structure in the orthotopic xenograft mouse model were investigated. MiRNA exp

Current progress in CAR-based therapy for kidney disease.

Despite significant breakthroughs in the understanding of immunological and pathophysiological features for immune-mediated kidney diseases, a proportion of patients exhibit poor responses to current therapies or have been categorized as refractory renal disease. Engineered T cells have emerged as a focal point of interest as a potential treatment strategy for kidney diseases. By genetically modifying T cells and arming them with chimeric antigen receptors (CARs), effectively targeting autoreactive immune cells, such as B cells or antibody-secreting plasma cells, has become feasible. The emerg

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… trap. … Furthermore, additional data have indicated that ANCAs can trigger the formation of neutrophil extracellular traps (NETs), which in turn activate dendritic cells and autoreactive B-cells. …

The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis.

Current methods for testing bone density lack the capability to detect patients with early bone loss, and existing osteoporosis therapies have limitations in their efficacy and safety. Therefore, the development of more precise and convenient diagnostic technologies and novel treatments is of paramount importance. Extracellular vesicle (EV)-mediated non-coding RNA (ncRNA) interaction networks enable both the detection of early bone loss and targeted therapy for enhanced treatment outcomes. In this review, we highlight the utility of EVs for carrying various ncRNAs (e.g., miRNAs, lncRNAs, and c

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchy

An Early Myeloma Bone Disease Model in Skeletally Mature Mice as a Platform for Biomaterial Characterization of the Extracellular Matrix.

Multiple myeloma (MM) bone disease is characterized by osteolytic bone tissue destruction resulting in bone pain, fractures, vertebral collapse, and spinal cord compression in patients. Upon initial diagnosis of MM, almost 80% of patients suffer from bone disease. Earlier diagnosis and intervention in MM bone disease would potentially improve treatment outcome and patient survival. New preclinical models are needed for developing novel diagnostic markers of bone structural changes as early as possible in the disease course. Here, we report a proof-of-concept, syngeneic, intrafemoral MOPC315.BM

Targeting inflammation as cancer therapy.

Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators i

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… Table 1 Key inflammatory cells in cancer with antitumor or protumoral activities TGF-β, transforming growth factor-β; NETs, neutrophil extracellular traps; NK, natural killer; TAM, tumor-associated macrophage; VEGF, vascular endothelial growth factor Cell type | Protumor activities | Antitumor activities … A unique way for neutrophils to combat infection is the release of neutrophil extracellular traps (NETs), a net-like structure primarily composed of DNA-histone complexes from neutrophils, which are identified as a critical type of innate immune response [ 29 ]. …

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation.

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cel

New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities.

Approximately one-third of advanced renal cell carcinoma (RCC) patients develop osteolytic bone metastases, leading to skeletal complications. In this review, we first provide a comprehensive perspective of seminal studies on bone metastasis of RCC describing the main molecular modulators and growth factor signaling pathways most important for the RCC-stimulated osteoclast-mediated bone destruction. We next focus on newer developments revealing with in-depth details, the bidirectional interplay between renal cancer cells and the immune and stromal microenvironment that can through epigenetic r

Beyond oncology: Selinexor's journey into anti-inflammatory treatment and long-term management.

Selinexor, a selective inhibitor of nuclear export (SINE), is gaining recognition beyond oncology for its potential in anti-inflammatory therapy. This review elucidates Selinexor's dual action, highlighting its anti-tumor efficacy in various cancers including hematologic malignancies and solid tumors, and its promising anti-inflammatory effects. In cancer treatment, Selinexor has demonstrated benefits as monotherapy and in combination with other therapeutics, particularly in drug-resistant cases. Its role in enhancing the effectiveness of bone marrow transplants has also been noted. Importantl

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… Furthermore, Selinexor’s ability to prevent the creation of neutrophil extracellular traps (NETs) while maintaining neutrophil function provides strategic benefits in the treatment of illnesses defined by high NET activity ( 40 ). … Selinexor, a selective inhibitor of nuclear export, inhibits human neutrophil extracellular trap formation in vitro . Front Pharmacol . ( 2022 ) 13 : 1030991 . doi: 10.3389/fphar.2022.1030991 36506529 PMC9730241 40 Kashyap T Murray J Walker CJ Chang H Tamir S Hou B . …

Antiphospholipid Antibodies and Lipids in Hematological Malignancies.

One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-β2 glycoprotein I (anti-β2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL.

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… Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 2018;18:134–147. doi: 10.1038/nri.2017.105. 48. Scandolara T.B., Panis C. Neutrophil traps, anti-myeloperoxidase antibodies and cancer: Are they linked? Immunol. Lett. 2020;221:33–38. doi: 10.1016/j.imlet.2020.02.011. 49. …

Экстраклектные везикли для клинической диагностики: от массовых измерений до одновидового анализа.

Экстраклектные везикулы (ЭМ) играют ключевую роль в межклеточном общении, сигнальных путях и патогенезе заболеваний, перевозя биомолекулы, такие, как ДНК, РНК, белки и липиды, полученные из клеток их происхождения, и они продемонстрировали значительный потенциал в области клинического применения. Их клиническое значение подчеркивает необходимость применения чувствительных методов для полной реализации их диагностического потенциала. В рамках этого всеобъемлющего обзора мы изучаем гетерогенность ЭМ, связанную с биогенезом, структурой, содержанием, происхождением, типом выборки и функциональными

Supra-Physiological Levels of Magnesium Counteract the Inhibitory Effect of Zoledronate on RANKL-Dependent Osteoclastogenesis.

Bisphosphonates (BPs) are drugs used to cure metabolic diseases like osteoporosis and oncological conditions, such as multiple myeloma and bone metastases. The pharmacological activity of these compounds is mediated by their capacity to induce a systemic osteoclast depletion, finally resulting in reduced bone resorption. In spite of their efficacy, the clinical application of BPs is sometimes associated with a frightening side effect known as osteonecrosis of the jaw (ONJ). In principle, a therapeutic approach able to elicit the local re-activation of osteoclast production could counteract the