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Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that f

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

2,4 Dinitrophenol as Medicine.

In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescri

The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We e

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the

Advancement and Challenges in Monitoring of CAR-T Cell Therapy: A Comprehensive Review of Parameters and Markers in Hematological Malignancies.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to 80% of patients following CAR-T cell therapy. CRS results from the uncontrolled overproduction of proinflammatory cytokines, which leads to symptoms such as fever, headache, hypoxia, or neurological complications. CAR-T cell detection is p

Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases.

Each year, the number of patients who are diagnosed with kidney disease too late is increasing, which leads to permanent renal failure. This growing problem affects people of every age, sex and origin, and its full etiopathogenesis is not fully understood, although the involvement of genetic susceptibility, infections, immune disorders or high blood pressure is suggested. Difficulties in making a correct and quick diagnosis are caused by the lack of research on early molecular markers, as well as educational and preventive activities among the public, which leads to the late detection of kidne

Antibody-drug conjugates in cancer therapy: current advances and prospects for breakthroughs.

Antibody-drug conjugates (ADCs), often referred to as "intelligent biological missiles," have garnered significant attention in the rapidly evolving landscape of cancer therapy. ADCs represent a sophisticated approach by integrating monoclonal antibodies (mAbs), which are particular targeting tumor antigens, with cytotoxic payloads, which deliver lethal effects. Compared with the combination of chemotherapy and mAbs, ADCs precisely deliver highly potent cytotoxins directly to tumor cells while minimizing damage to healthy tissues. However, limitations such as significant adverse effects, subop

Antibody drug conjugate: the "biological missile" for targeted cancer therapy.

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreove

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivi

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… This mechanism effectively shields melanoma cells from various chemotherapeutic agents, including DNA intercalating agents and topoisomerase inhibitors (e.g., cisplatin, etoposide, daunorubicin, and doxorubicin), as well as cytoskeleton-disrupting toxins, like vinblastine, irrespective of their mode …

Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following forma

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

Интеграция нанотехнологий в онкологию для передовых стратегий наночастиц в целевую диагностику и лечение рака.

Рак остается одной из основных глобальных проблем в области здравоохранения. Обычная терапия часто ограничивается низкой избирательностью опухолей, системной токсичностью, резистентностью к многочисленным лекарствам и неоптимальными фармакокинетиками. Нанотехнология предлагает преобразующий подход в онкологии. Она позволяет осуществлять целенаправленные поставки наркотиков, контролировать или стимулировать их высвобождение и использовать многофункциональные платформы, сочетающие в себе терапию и диагностику. Нанопчасти повышают растворимость наркотиков, продлевают циркуляцию и повышают внутрик

Митохондриальная ДНК (mtDNA) в качестве жидкого биомаркера в нейродегенеративных расстройствах: систематический обзор.

ИСТОРИЯ ВОПРОСА: В ряде исследований была проведена оценка периферийных и цереброспинных жидкостей (CSF) mtDNA как предполагаемого биомаркера нейродегенеративных заболеваний, что зачастую приводит к непоследовательным выводам. Мы систематически анализировали текущие данные, позволяющие оценить уровни крови и CSF mtDNA и возможное бремя в болезни Паркинсона (PD), болезни Альцгеймера (ALS) и амиотропическом боковом склерозе (ALS). Множественный склероз (MS) был также включен в качестве парадигмы хронического нейроинфламмации под воздействием нейродегенерации. МЕТОДЫ: Медлин, Эмбаза, Скопус и веб

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

Developments in nanotechnology approaches for the treatment of solid tumors.

Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology pla