Результаты поиска

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in

Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o

Cancer stem cells: advances in knowledge and implications for cancer therapy.

Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still i

The Role of Interleukin-1 in the Pathogenesis of Cancer and its Potential as a Therapeutic Target in Clinical Practice.

Interleukin-1 (IL-1) has long been known to be a key mediator of immunity and inflammation. Its dysregulation has been implicated in recent years in tumorigenesis and tumor progression, and its upregulation is thought to be associated with many tumors. Overexpression of the IL-1 agonists IL-1α and IL-1β has been shown to promote tumor invasiveness and metastasis by inducing the expression of angiogenic genes and growth factors. IL-1 blockers such as anakinra and canakinumab are already approved and widely used for the treatment of some autoimmune and autoinflammatory diseases and are currently

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

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases.

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing seve

CD70-targeted CAR-T/NK therapy: Rationale, advances, and future directions.

Chimeric antigen receptor T and natural killer (CAR-T/NK) cells is a rapidly evolving cellular immunotherapy technology that has made great achievements in the treatment of hematologic diseases. CD70, as a surface antigen expressed on tumor cells in a variety of hematologic malignancies, including acute myeloid leukemia, non-Hodgkin lymphoma, multiple myeloma, etc., and solid tumors such as renal cell carcinoma, osteosarcoma, and glioma, is a potential target for CAR-T/NK cells. Several preclinical studies and clinical trials on CAR-T/NK cells targeting CD70 are currently underway, bringing ne

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

Osteoporosis: the current status of mesenchymal stem cell-based therapy.

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves

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

Mesenchymal stem cells lineage and their role in disease development.

BackgroundMesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for differen

Myeloma bone disease: Pathophysiology and management.

Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases t

Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process.

Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients' quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence,

Совпадение в полном тексте источника
… Stromal fibroblast activation protein alpha promotes gastric cancer progression via epithelial-mesenchymal transition through Wnt/β-catenin pathway. BMC Cancer. 2018;18:1099. doi: 10.1186/s12885-018-5035-9. 89. Yi Y., Zeng S., Wang Z., Wu M., Ma Y., Ye X., Zhang B., Liu H. …

Association between circulating inflammatory proteins and temporomandibular disorders: insight from a two-sample Mendelian randomization analysis.

BackgroundPast studies have indicated links between specific inflammatory proteins in the bloodstream and temporomandibular disorders (TMDs). Nonetheless, there remains the need for further solid research pinpointing the exact causes behind these associations. This Mendelian randomization (MR) study aims to examine the association between 91 circulating inflammatory proteins and TMDs.MethodologyThe most comprehensive genome-wide association studies available for circulating inflammatory proteins and TMDs was used in this two-sample MR analysis. The association between genetic predispositions t

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, V

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function.

Estrogens exert their physiological and pathophysiological effects via cellular receptors, named ERα, ERβ, and G-protein coupled estrogen receptor (GPER). Estrogen-regulated physiology is tightly controlled by factors that regulate estrogen bioavailability and receptor sensitivity, while disruption of these control mechanisms can result in loss of reproductive function, cancer, cardiovascular and neurodegenerative disease, obesity, insulin resistance, endometriosis, and systemic lupus erythematosus. Restoration of estrogen physiology by modulating estrogen bioavailability or receptor activity