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Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer.

Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significantrole in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Someof the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeuticwindow and undesired side effects of available anticancer drugs and the limitations of anticancerdrugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranosticcarriers, liposomes, carbon nano

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.

Protein quality control allows eukaryotes to maintain proteostasis under the stress of constantly changing conditions. In this review, we discuss the current literature on PQC, highlighting flaws that must exist for malignancy to occur. At the nidus of PQC, the expression of BAG1-6 reflects the cell environment; each isoform directs proteins toward different, parallel branches of the quality control cascade. The sum of these branches creates a net shift toward either homeostasis or apoptosis. With an established role in ALP, Bag3 is necessary for cell survival in stress conditions including th

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

Skeletal muscle dysfunction induced by cancer immunotherapy: mechanistics insights and surgical implications.

Cancer immunotherapy has revolutionized cancer treatment, yet its effects extend far beyond tumor eradication. Accumulating evidence indicates that immunotherapy-associated skeletal muscle dysfunction represents a complex, cross-organ pathological process driven by dynamic crosstalk between the tumor microenvironment and peripheral tissues. Rather than an isolated adverse event, muscle injury emerges from integrated mechanisms including inflammatory cytokine spillover, aberrant immune cell infiltration, metabolic reprogramming, vascular dysfunction, and impaired regenerative signaling. Central

Purinergic Signalling: Therapeutic Developments.

Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and the

MicroRNA in Acromegaly: Involvement in the Pathogenesis and in the Response to First-Generation Somatostatin Receptor Ligands.

Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNA

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… growth factor 2. … This miRNA is also known as a tumor suppressor, as it is negatively correlated with different kinds of cancer, targeting IGF-1R , genes that are involved in the EMT, as well as fibroblast growth factor 2 ( FGF2 ), which plays a role in differentiation and proliferation [ 72 ]. …

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review.

PurposeBone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis.MethodsA comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analys

Mesenchymal Stem Cell Therapy for Neurological Complications of Prematurity: A Narrative Review.

Background: Preterm birth is a leading cause of neonatal mortality and long-term disability worldwide. Injury in premature infants is demonstrated by disrupted organ development from inflammation, oxidative stress, hypoxia, and impaired vascular maturation. Current therapies largely provide supportive care and do not directly promote tissue regeneration. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential strategy to enhance endogenous repair across organ systems commonly affected by prematurity. Results: Evidence indicates that MSCs exert therapeutic effects primarily thro

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program.

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retin

An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma.

The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed multiple myeloma (MM) patients who have a long-term response to thalidomide (THAL), lasting at least 18 months. The study was carried out on 234 patients who received THAL for relapsed/refractory myeloma. Out of the 234 patients, 129 patients (55.1%) responded to THAL with a mean response duration of 11.9 months (ranging from 1 to 48) and an overall survival rate of 20.3 months (ranging 1-55 months). In 64 patients (27.4% of the whole group), the response to THA

Assessment of Knowledge, Awareness, and Perception of Platelet-Rich Plasma among Oral Surgeons.

AimThe current survey was conducted to assess the knowledge and awareness of platelet-rich plasma (PRP) among oral surgeons in the state of Tamil Nadu.MethodologyThe cross-sectional questionnaire survey was conducted among oral surgeons in the state of Tamil Nadu. The self-administered questions related to knowledge and awareness of PRP were collected from 500 participants. The statistical analysis was done using Statistical Package for the Social Sciences SPSS (V 22.0). The frequency distribution was computed.ResultsThis survey exposed that 454 (90.4%) respondents had knowledge and awareness

Beyond Darwin: reactive heredity, burst-drift dynamics and eco‑evolutionary control of cancer.

Darwinian clonal evolution provides a necessary framework for understanding tumour progression, yet emerging evidence shows that some cancers depart from a strictly gradualist tempo through episodic "macroevolutionary" leaps. We propose a unifying Burst-Drift-Control (BDC) model in which short-lived genomic reconfigurations ("bursts") that transiently alter heritable genomic states ("reactive heredity") precede longer intervals of constrained expansion, creating time-bounded vulnerabilities that clinicians may strategically steer ("control"). In this usage, the Drift component refers specifica

Utilization of Stem Cells in Medicine: A Narrative Review.

Regenerative medicine holds significant promise for addressing diseases and irreversible damage that are challenging to treat with conventional methods, making it a prominent research focus in modern medicine. Research on stem cells, a key area within regenerative medicine due to their self-renewal capabilities, is expanding, positioning them as a novel therapeutic option. Stem cells, utilized in various treatments, are categorized based on their differentiation potential and the source tissue. The term 'stem cell' encompasses a broad spectrum of cells, which can be derived from embryonic tiss

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

Enhanced sialylation of bone marrow mesenchymal stromal cells contributes to immune remodeling through macrophage polarization in multiple myeloma patients.

INTRODUCTION: In multiple myeloma (MM), the immune system is disrupted, partly due to tumor-modified bone marrow mesenchymal stromal cells (BM-MSCs). These MSCs show altered glycosylation, including increased sialylation, which may promote immune evasion through Siglec interactions. METHODS: We quantified sialic acids and Siglec ligands on healthy donors-, MM-, T-MM-(treated multiple myeloma) and MGUS (monoclonal gammopathy of undetermined significance)-MSCs, and examined how different culture conditions (myeloma coculture, conditioned medium, hypoxia, inflammation, 3D culture) affect MSC gly

Current approach to the diagnosis and treatment of femoral-popliteal arterial disease. A systematic review.

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis affecting 5 million adults in the United States, with an age-adjusted prevalence of 4% to 15% and increasing up to 30% with age and the presence of cardiovascular risk factors. In this article we focus on lower extremity PAD and specifically on the superficial femoral and proximal popliteal artery (SFPA), which are the most common anatomic locations of lower extremity atherosclerosis. We summarize current evidence and perform a systematic review on the diagnostic evaluation as well as the medical, endovascular and s

Inflammasomes in Cancer Progression and Anti-Tumor Immunity.

The inflammasomes are critical regulators of innate immunity, inflammation and cell death and have emerged as important regulators of cancer development and control. Inflammasomes are assembled by pattern recognition receptors (PRR) following the sensing of microbial- or danger-associated molecular patterns (MAMPs/DAMPs) and elicit inflammation through the oligomerization and activation of inflammatory caspases. These cysteinyl-aspartate proteases cleave the proinflammatory cytokines IL-1β and IL-18 into their biologically active mature form. The roles of the inflammasomes and associated pro-i

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges.

Gastrointestinal (GI) cancer remains the deadliest cancer in the world. The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery, and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer. There is well-established evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies, which should routinely be incorporated into treatment strategies for GI cancer. Other potential therapeutic targets involve the PI3K/AKT pathwa

Picropodophyllin inhibits the growth of pemetrexed-resistant malignant pleural mesothelioma via microtubule inhibition and IGF-1R-, caspase-independent pathways.

BackgroundAcquired pemetrexed resistance leads to treatment interruption in patients with malignant pleural mesothelioma (MPM). Insulin-like growth factor-I receptor (IGF-1R) inhibitor is a candidate for treating pemetrexed-naïve MPM. However, the efficacy of cytotoxic and targeted drugs in acquired-pemetrexed resistant MPM is unclear. We explored anticancer drugs, including the IGF-1R inhibitor picropodophyllin, against acquired pemetrexed-resistant MPMs.MethodsAcquired pemetrexed-resistant human MPM cell lines, named as H2452/PEM and 211H/PEM after their parental lines H2452 and 211H, respec

Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen rece