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Circadian clock and cancer.

Circadian rhythms play a critical role in regulating physiological and behavioral processes, such as the sleep-wake cycle, hormone secretion, and metabolism. These rhythms are controlled by endogenous biological clocks, which are synchronized with environmental cues, primarily the light-dark cycle. Notably, disruption or reprogramming of circadian rhythms is closely associated with cancer initiation, progression, and treatment response. At the molecular level, the dysregulation of core clock genes can disturb normal cellular rhythms, leading to aberrant cell proliferation, impaired DNA repair,

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidenc

Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43

Therapeutic potential of cytokine-induced killer cell therapy for renal cell carcinoma and prostate cancer.

Renal cell carcinoma (RCC) and prostate cancer (PCa) are among the most prevalent and therapeutically challenging malignancies of the genitourinary system, particularly in advanced or metastatic stages. For advanced/metastatic RCC, targeted agents such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have improved progression-free and overall survival. For metastatic castration-sensitive PCa, androgen deprivation therapy (ADT) combined androgen receptor pathway inhibitors (ARPIs) with or without chemotherapy remains the standard of care. Despite these advances, ther

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL).

Aging is a multifaceted process characterized by a gradual decline in physiological function and increased susceptibility to a range of chronic diseases. Among the molecular and cellular mechanisms driving aging, genomic instability is a fundamental hallmark, contributing to increased mutation load and genetic heterogeneity within cellular populations. This review explores the role of genomic instability and genetic heterogeneity in aging in the hematopoietic system, with a particular focus on clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined signifi

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… The neurovascular unit and its correlation with cognitive performance in patients with cerebral small vessel disease: a canonical correlation analysis approach. Geroscience. 2024;46:5061–73. 10.1007/s11357-024-01235-8. 169. …

Mediterranean Diet Food Components as Possible Adjuvant Therapies to Counteract Breast and Prostate Cancer Progression to Bone Metastasis.

Bone metastasis is a serious and often lethal complication of particularly frequent carcinomas, such as breast and prostate cancers, which not only reduces survival but also worsens the patients' quality of life. Therefore, it is important to find new and/or additional therapeutic possibilities that can counteract the colonization of bone tissue. High adherence to the Mediterranean diet (MD) is effective in the prevention of cancer and improves cancer patients' health, thus, here, we considered its impact on bone metastasis. We highlighted some molecular events relevant for the development of

Notch signaling deregulation in multiple myeloma: A rational molecular target.

Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell localization in the bone marrow milieu allows direct interactions between tumor cells and non-tumor bone marrow cells which promote neoplastic cell growth, survival, bone disease, acquisition of drug resistance and consequent relapse. Twenty percent of MM patients are at high-risk of treatment failure as defined by tumor markers or presentation as plasma cell leukemia. Cumulative evidences indicate a key role of Notch signaling in multiple

Improved oncolytic and immunostimulatory activity of the spontaneous jin-3 reovirus mutant in preclinical bladder cancer models.

Immunotherapy has emerged as a promising strategy for treatment of urothelial carcinoma of the bladder (UCB) but not all patients show clinically desirable responses upon treatment with immune-checkpoint inhibition. Oncolytic viruses may unleash the full potential of immunotherapy. Besides tumor-lysing properties, oncolytic viruses can induce durable and systemic anti-viral and anti-tumor immune responses. Here, we evaluated and compared oncolytic and immunostimulatory properties of wild-type reovirus (R124) and the junction-adhesion molecule-independent mutant reovirus (jin-3) in preclinical

Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.

Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins. We underscore the significance of 14-3-3 proteins in the regulation of osteoblasts, osteoclasts, chon

Renal Involvement in Cancer Patients Undergoing Oncology Therapies: Implications for Personalized Treatment Strategies.

Introduction: Oncological therapies have significantly improved patient outcomes but are increasingly associated with renal toxicity, which can markedly influence therapeutic decisions. Integrating early identification of kidney injury into clinical workflows is essential for personalized medicine, allowing treatment tailoring based on individual risk profiles. Aim: To evaluate the incidence of acute kidney injury (AKI) and chronic kidney Disease (CKD); assess indices of renal function recovery in patients who developed AKI; and investigate the incidence of renal immune-related adverse events

Ferroptosis and its emerging role in esophageal cancer.

The occurrence and development of tumors involve a series of life activities of cells, among which cell death has always been a crucial part in the research of tumor mechanisms and treatment methods. Ferroptosis is a non-apoptotic form of cell death, which is characterized by lipid peroxidation accumulation and further cell membrane rupture caused by excessive production of intracellular oxygen free radicals dependent on iron ions. Esophageal cancer is one of the common digestive tract tumors. Patients in the early stage are mainly treated with surgery, and the curative effect is awe-inspiring

Onco-Hem Connectome-Network-Based Phenotyping of Polypharmacy and Drug-Drug Interactions in Onco-Hematological Inpatients.

We introduce the Onco-Hem Connectome (OHC), a patient similarity network (PSN) designed to organize real-world hemato-oncology inpatients by exploratory phenotypes with potential clinical utility. Background: Polypharmacy and drug-drug interactions (DDIs) are pervasive in hemato-oncology and vary with comorbidity and treatment intensity. Methods: We retrospectively analyzed a 2023 single-center cohort of 298 patients (1158 hospital episodes). Standardized feature vectors combined demographics, comorbidity (Charlson, Elixhauser), comorbidity polypharmacy score (CPS), aggregate DDI severity scor

Relationship between sodium and diffusion MRI metrics in multiple sclerosis.

Sodium MRI can measure in vivo sodium concentrations in people with multiple sclerosis, but the extent to which these alterations reflect metabolic dysfunction in the absence of tissue damage or neuroaxonal loss remains uncertain. Increases in total sodium concentration and extracellular sodium concentration are believed to be indicative of tissue disruption and extracellular space expansion. Conversely, increase in intracellular sodium concentration may represent early and transient responses to neuronal insult, preceding overt tissue damage. Here, we explored the relationship between total s

Провоспалительные молекулы, имплицитно связанные с множественным склерозом Divert Development of Human Oligodendrocyte Lineage Cells.

ИСТОРИЯ И ЗАДАЧИ: Олигодендроциты (ОИ) и их процессы формирования миелина теряются во время заболевания, вызванного множественным склерозом (МС), цель которого заключается в проникновении лейкоцитов и их эффектных цитокинов. Считается, что ремонт миелин зависит от набора и дифференциации ячеек потомков олигодендроцитов. До сих пор не определены основания для отказа от воспоминаний во время болезни MS. Цель этого исследования состояла в том, чтобы определить влияние на дифференциацию опухолей человека факторов некроза (ОКП) и интерферона (ИФН).Мы создали человека OPC из индуцированных плюрипоте

Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells.

Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents

Dynamic roles of inflammasomes in inflammatory tumor microenvironment.

The inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysreg

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.

Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches: IRE1, ATF6, and PERK, each of which is crucial for regulating stress responses, protein homeostasis, and apoptosis. These pathways normally help cells handle stress effectively; however, excessive or prolonged activati

IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via i

Clinical relevance of extracellular vesicles in hematological neoplasms: from liquid biopsy to cell biopsy.

In the era of precision medicine, liquid biopsy is becoming increasingly important in oncology. It consists in the isolation and analysis of tumor-derived biomarkers, including extracellular vesicles (EVs), in body fluids. EVs are lipid bilayer-enclosed particles, heterogeneous in size and molecular composition, released from both normal and neoplastic cells. In tumor context, EVs are valuable carriers of cancer information; in fact, their amount, phenotype and molecular cargo, including proteins, lipids, metabolites and nucleic acids, mirror nature and origin of parental cells rendering EVs a