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Mitochondrial Determinants of Anti-Cancer Drug-Induced Cardiotoxicity.

Mitochondria are key organelles for the maintenance of myocardial tissue homeostasis, playing a pivotal role in adenosine triphosphate (ATP) production, calcium signaling, redox homeostasis, and thermogenesis, as well as in the regulation of crucial pathways involved in cell survival. On this basis, it is not surprising that structural and functional impairments of mitochondria can lead to contractile dysfunction, and have been widely implicated in the onset of diverse cardiovascular diseases, including ischemic cardiomyopathy, heart failure, and stroke. Several studies support mitochondrial t

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

An actionable sterol-regulated feedback loop modulates statin sensitivity in prostate cancer.

ObjectiveThe statin family of cholesterol-lowering drugs has been shown to induce tumor-specific apoptosis by inhibiting the rate-limiting enzyme of the mevalonate (MVA) pathway, HMG-CoA reductase (HMGCR). Accumulating evidence suggests that statin use may delay prostate cancer (PCa) progression in a subset of patients; however, the determinants of statin drug sensitivity in PCa remain unclear. Our goal was to identify molecular features of statin-sensitive PCa and opportunities to potentiate statin-induced PCa cell death.MethodsDeregulation of HMGCR expression in PCa was evaluated by immunohi

Keyword Index for Volume 93

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Cancer and Obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

BackgroundThis Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides an overview of cancer and increased body fat.MethodsThe scientific information for this CPS is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership.ResultsTopics include the increased risk of cancers among patients with obesity, cancer risk factor population-attributable fractions, genetic and epigenetic links between obesity and cancer, adiposopathic and mechanistic processes accounting for increased cancer risk

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.

CRISPR-Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targ

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

Therapeutic Targeting of Cancer Stem Cells in Human Glioblastoma by Manipulating the Renin-Angiotensin System.

Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection and adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs can be identified by embryonic stem cell markers, express components of the renin-angiotensin system (RAS) and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB patients rarely develop distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in r

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, and Huntington's Diseases and Amyotrophic Lateral Sclerosis.

Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Hunti

Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in hematologic diseases by modulating immune responses, supporting hematopoiesis, and remodeling the bone marrow microenvironment. Clinically, MSCs have been explored for graft-versus-host disease and hematopoietic stem cell transplantation support, while their applications in hematologic malignancies, including acute myeloid leukemia, multiple myeloma, and myelodysplastic syndromes, remain under investigation. However, therapeutic heterogeneity, safety concerns, and standardization challenges limit their clinical transla

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… | BM-MSCs derived from AML patients and healthy donors | In vitro and vivo | / | BM-MSC-derived miR-222-3p modulates the Th1/Th2 balance and triggers AML cell apoptosis through IRF2 signaling | BM-MSC-derived miR-222-3p modulates apoptosis and immune responses by targeting IRF2, AKT1, and RNA methylation … methylation axis | Inhibiting METTL3 could serve as a potential therapeutic strategy to counteract AML chemoresistance | Lack of in clinical validation | 2023 | Liao et al.[ 15 ] | Fujian Medical University Union Hospital, China | BM-MSCs derived from AML patients and healthy donors | In vitro and …

Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly

Targeted protein degradation: advances in drug discovery and clinical practice.

Targeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing a stark contrast to traditional therapeutic approaches like small molecule inhibitors that primarily focus on inhibiting protein function. This advanced technology capitalizes on the cell's intrinsic proteolytic systems, including the proteasome and lysosomal pathways, to selectively eliminate disease-causing proteins. TPD not only enhances the efficacy of treatments but also expands the scope of protein degradation applications. Despite its considerable potential, TPD faces chal

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

Research advances of lactylation modification in breast cancer.

Breast cancer (BC), a leading cause of cancer mortality in women, involves complex molecular mechanisms including post-translational modifications (PTMs). While common PTMs are well-studied, lactylation-a novel PTM linking metabolism to epigenetics-has emerged as a critical regulator in BC pathogenesis. The high concentration of lactate caused by the Warburg effect makes lactylation in tumor tissue possible. Machine learning enhances the discovery and analysis of lactylation sites by processing large datasets, revealing patterns that influence tumor behavior and patient outcomes. This review o

Mechanistic study of pre-eclampsia and macrophage-associated molecular networks: bioinformatics insights from multiple datasets.

BACKGROUND: Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the molecular mechanism of macrophages in pre-eclampsia is not well understood. METHODS: In this study, the key biomarkers during the development of pre-eclampsia were identified using bioinformatics analysis. The GSE75010 and GSE74341 datasets from the GEO database were obtained and merged for differential analysis. A weighted gene co-expression network analysis (WGCNA) was constructed based on macrophage content, and

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

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… The integration of AI into the identification of treatment-resistant cancer cells has been used with machine learning to unveil distinct RNA methylation regulators in pan-cancer neoadjuvant therapy, potentially leading to more effective personalized treatment plans [ 133 ]. …

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

Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review.

The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Although the advancement of modern immunotherapeutic approaches can increase the survival rate of cancer patients, new modalities are essential for improved therapeutic outcomes. Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration. It has been thought that EVs can reduce the risks and side eff

Proceedings of the CIMAGO Congress - Environment, Genetics and Oncobiology in the 21st Century - Challenges and Opportunities.

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