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Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

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… Among the ornithine decarboxylase inhibitors, α-difluoromethylornithine (DFMO) is the most widely used both for parasitic infections, excess of facial hair in women, and chemotherapy. … Alpha-methyl-(plus or minus)-ornithine, an inhibitor of ornithine decarboxylase . J. Med. Chem . 17 , 447 – 451 . 4830542 10.1021/jm00250a016 Aboud-Pirak E. Hurwitz E. Pirak M. E. Bellot F. Schlessinger J. Sela M. ( 1988 ). …

Hemoadsorption and plasma adsorption: two current options for the 3rd dimension of dialysis purification.

The adsorption technique has opened a new frontier in the field of purification through hemodialysis. This technique has proved to be effective in removing uremic toxins previously deemed inaccessible due to their size or charge, as well as to their molecular interactions with blood proteins. In this context, this review provides a detailed explanation of the role of Polyester-polymer alloy (PEPA®) membranes and hemodiafiltration with endogenous reinfusion. The polyester-polymer alloy membrane is a three-layered dialysis membrane with adsorbent properties, representing an innovative approach t

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… Ornithine, phenylalanine, tryptophan, and cystine are lost in greater quantities during hemodialysis with both hydrophilic and non-hydrophilic polyester-polymer alloy membranes. Careful monitoring of amino acid loss is essential to enhance nutritional management in HD patients [ 20 ]. … using two dialyzers per session | RR of albumin was similar between three filters (PMMA 15%, FDX-PEPA 10%, FDY-PEPA 9%) Japan | Yokomatsu et al. [ 20 ] | 2013 | 9 patients/1 | FDX and FLX PEPA versus PAN in HD | Standard HD for 3–4 h, Qb 100–200 mL/min, Qd 500 mL/min, 3 sessions/week | The loss of ornithine …

Chemotherapy-Induced Neuropathy and Drug Discovery Platform Using Human Sensory Neurons Converted Directly from Adult Peripheral Blood.

Chemotherapy-induced peripheral neuropathy (PN) is a disorder damaging the peripheral nervous system (PNS) and represents one of the most common side effects of chemotherapy, negatively impacting the quality of life of patients to the extent of withdrawing life-saving chemotherapy dose or duration. Unfortunately, the pathophysiological effects of PN are poorly understood, in part due to the lack of availability of large numbers of human sensory neurons (SNs) for study. Previous reports have demonstrated that human SNs can be directly converted from primitive CD34+ hematopoietic cells, but was

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… tested for iNPCs expansion Condition 1 | Condition 2 | Condition 3 RHB‐A basal medium | DMEM/F12 basal medium | DMEM/F12 basal medium N2 (1×) | N2 (1×) | N2 (1×) B27 (1×) | B27 (1×) | B27 (1×) bFGF (10 ng/ml) | bFGF (20 ng/ml) | bFGF (20 ng/ml) EGF (10 ng/ml) | EGF (10 ng/ml) | EGF (10 ng/ml) Poly‐ l ‐ornithine‐laminin … coated plates | Poly‐ l ‐ornithine‐laminin coated plates | Matrigel coated plates Sensory Neuron Differentiation of Directly Converted Neural Precursors Using combined small‐molecule inhibition (SU5402, DAPT, and CHIR99021) to induce sensory neuron (nociceptors; iSNs) differentiation 34 of the directly …

Targeting erythroid progenitor cell metabolism to enhance cancer immunotherapy.

While cancer immunotherapy has transformed clinical management for cancer patients, its low response rates remain a critical challenge to be addressed. Tumor immune evasion now extends beyond the tumor microenvironment (TME), as advanced tumors induce extramedullary hematopoiesis (EMH) in the spleen, leading to a substantial expansion of erythroid progenitor cells (EPCs) with potent immunosuppressive capacity. EPCs are typically transient populations in erythroid maturation and differentiation; however, under tumor burden, they undergo profound metabolic reprogramming that exacerbates their im

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… Arginine metabolism of EPCs Arginase is a manganese-centered metalloenzyme that catalyzes the conversion of L-arginine to L-ornithine and urea, serving as a key enzyme in the urea cycle. … Similar to MDSCs, EDMCs secrete ARG-1 to catabolize L-arginine into ornithine, depleting arginine in the TME 23 . Extensive research demonstrates that L-arginine deficiency downregulates CD3ζ chain expression in T cells, inhibiting their proliferation 79 . …

Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia.

Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients' lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field s

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… In addition to tumorigenesis, another safety issue arose in a trial for ornithine transcarbamylase (OTC) deficiency, where a patient died from a severe immune reaction to a recombinant adenoviral vector delivering the OTC gene [ 15 – 17 ]. … advanced therapies Cerebrospinal fluid Centre for the technologies of gene and cell therapy Diffuse large B-cell lymphoma European medicines agency Immune checkpoint inhibitors Interleukin 12 Lipid nanoparticle Metachromatic leukodystrophy Mucopolysaccharidosis National institute of chemistry Ornithine …

Nutritional supplementation for hip fracture aftercare in older people.

BACKGROUND: Older people with hip fractures are often malnourished at the time of fracture, and subsequently have poor food intake. This is … high dose bolus vitamin D, different oral doses or sources of vitamin D, intravenous or oral iron, ornithine alpha-ketoglutarate versus an isonitrogenous peptide supplement, taurine versus placebo, and a supplement with vitamins, minerals and amino acids, provided low- or very low-quality evidence of no clear effect on mortality or complications, where rep …

Концептуализация комплексного ухода за многими миеломами: роль питания, дополнительных услуг и дополнительных услуг.

Множественная миелома (ММ) — вторая по распространенности гематологическая гелингология, масштабы которой в последние годы значительно возросли. Прогноз ММ радикально изменился с введением новых лекарственных средств, повышающих ожидаемую продолжительность жизни; рецидивы являются обычным явлением во время болезни и характеризуются увеличением числа отказов от лечения. Кроме того, пациенты ММ сталкиваются с проблемами, связанными с качеством жизни, в то время как обычное лечение может быть ограничено. Это включает боль в костях и диализ из-за осложнений острой почечной недостаточности. Поэтому

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… The pathophysiology seems to function by decreasing ornithine [ 99 ]. Last but not least, acupuncture-related safety concerns should be recognized in patients with MM and decreased immune system activity. … Acupuncture Synergized with Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine. Front. Oncol. 2021;11:779562. doi: 10.3389/fonc.2021.779562. 100. Lyu J., Wang S., Zhang H., Liu S. …

mTOR Cross-Talk in Cancer and Potential for Combination Therapy.

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understandi

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… Furthermore, mTORC1 is also involved in the regulation of other proteins including Ornithine DeCarboxylase (ODC), glycogen synthase, Hypoxia-Inducible Factor 1α (HIF-1 α), lipin, Protein Phosphatase 2A (PP2A) and Signal Transducer and Activator of Transcription (STAT) 3 [ 43 , 44 , 45 , 46 , 47 , 48 … Inhibition by rapamycin of ornithine decarboxylase and epithelial cell proliferation in intestinal IEC-6 cells in culture. Br. J. Pharmacol. 1997;120:571–574. doi: 10.1038/sj.bjp.0700936. 45. Yokogami K., Wakisaka S., Avruch J., Reeves S.A. …

20 Years of Legislation - How Australia Has Responded to the Challenge of Regulating Genetically Modified Organisms in the Clinic.

•In contrast to the prior voluntary system, since 2001, gene technology in Australia has been regulated under a legislated national Gene Technology Regulatory Scheme which is administered by the Gene Technology Regulator.•The Scheme provides science-based assessment of the potential risks of gene technology to the health and safety of people and the environment.•It complements the role of the Australian Therapeutic Goods Administration which regulates all therapeutic products in Australia to ensure they are safe and effective.•Recent reforms to the Scheme contribute to, and anticipate, the con

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… Unfortunately, in 1999 a participant died in a gene therapy trial for ornithine transcarbamylase deficiency ( 9 , 10 ). This led to a suspension of research at the host institution, a major investigation, and a tightening of regulatory oversight. … Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab. ( 2009 ) 96 : 151 – 7 . 10.1016/j.ymgme.2008.12.016 19211285 10. Smaglik P . Gene therapy institute denies that errors led to trial death. …

Amino acids metabolism: a potential target for cancer treatment.

Metabolic reprogramming of amino acids has been recognized as a significant characteristic in various types of cancers. Numerous studies have indicated that the metabolic reprogramming of amino acids in tumors significantly supports certain malignant behaviors, including tumor proliferation, survival, invasion, and even immune escape. Amino acids can provide biomolecules such as nucleotides and glutathione (GSH) for tumors, and the bioavailability of amino acids influences tumor progression. Meanwhile, as essential metabolites, amino acids are closely associated with immune cell activation and

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… Arginine metabolism (right): Arginine is catabolized through the urea cycle by arginase to generate ornithine, urea, nitric oxide (NO), and citrulline. In addition, it will be methylated into monomethylarginine (MMA) through protein arginine methyltransferases (PRMTs). … Arginase Arginase is a key metabolic enzyme that can hydrolyze arginine to urea and ornithine and is classified into ARG1 and arginase 2 (ARG2). Both isoforms participate in arginine metabolism and share similar functions. …

The Controversial Role of IL-33 in Lung Cancer.

Interleukin-33 (IL-33) belongs to the interleukin-1 (IL-1) family, and its structure is similar to IL-18. When cells are damaged or undergo necrosis, mature form of IL-33 is secreted as a cytokine, which can activate the immune system and provide danger signals. The IL-33/ST2 signaling pathway is composed of IL-33, suppression of tumorigenicity 2 (ST2), and IL-1 receptor accessory protein (IL-1RAcP). IL-33 has been reported to be strongly associated with lung cancer progression, and can exhibit opposite effects on lung cancer under different conditions. In this review, we have summarized the s

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… By activating ornithine decarboxylase, which catalyses the synthesis of polyamines, IL-33 induces M2-like macrophage polarization ( 50 ). IL-33 is also able to induce the gene expression of Th2-associated cytokines such as IL-5 and IL-13 ( 34 ). … Oesophageal Squamous Cell Carcinoma-Associated IL-33 Rewires Macrophage Polarization Towards M2 via Activating Ornithine Decarboxylase. Cell Prolif. (2021) 54:e12960. doi: 10.1111/cpr.12960 51. Wang J, Zhong M, Liu J. Research Progress on the Biological Function of IL-33 and its Effect on Tumors. …

MGluR5 Agonist, CHPG, увеличивает число дифференцированных человеческих олигодендроцитов.

Предыдущие исследования на взрослых мышах показывают, что 2-хлор-5-гидроксифениловый гликин (CHPG) MGluR5 сокращает потери в миелине, вызванные купризоной. Этот эффект частично привязывается CHPG к рецепторам mGluR5 для реактивных астроцитов, что приводит к высвобождению нервно-партрофного фактора мозга (BDNF), что приводит к увеличению миелина и уменьшает поведенческий дефицит. Однако остается неясным, оказывает ли CHPG аналогичное благотворное воздействие на клетки человека. Для решения этой проблемы мы изучили воздействие CHPG на клетки человека, используя как индуцированные плюрипотентными

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… On day 30, spheres were plated on poly-L-ornithine/laminin-coated dishes. On day 45, the medium was changed to Glia medium. …

Artificial Intelligence for Risk Stratification in Diffuse Large B-Cell Lymphoma: A Systematic Review of Classification Models and Predictive Performances.

Background: Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous malignancy, with various outcomes despite significant advances in therapeutic options. Current conventional prognostic tools, e.g., the International Prognostic Index (IPI), lack sufficient precision at an individual patient level. However, artificial intelligence (AI), including machine learning (ML) and deep learning (DL), can enable specialists to navigate complex datasets, with the final aim of improving prognostic models for DLBCL. Objectives: This scoping review aims to systematically map the current litera

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… A similar approach falls partly into the multi-omics domain, documenting the importance of the stromal ambient, uncovering a stem cell-like, immune-deserted subgroup marked by ornithine decarboxylase 1 (ODC1) expression [ 75 ]. … Legend: RNA-seq, RNA sequencing; OS, overall survival; ML, machine learning; TP53, tumor protein p53; VAF, variant allele frequency; PD-L1, programmed death-ligand 1; CD20, cluster of differentiation 20; ODC1, ornithine decarboxylase 1. …

Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were

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… Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency Mol. Genet. Metab. 96 2009 151 157 19211285 10.1016/j.ymgme.2008.12.016 77 Tros de Ilarduya C. Sun Y. Düzgüneş N. Gene delivery by lipoplexes and polyplexes Eur. J. Pharm. … Targeting ornithine decarboxylase reverses the LIN28/Let-7 axis and inhibits glycolytic metabolism in neuroblastoma Oncotarget 6 2015 196 206 25415050 10.18632/oncotarget.2768 PMC4381588 109 Chien C.-S. Wang M.-L. Chu P.-Y. Chang Y.L. Liu W.H. Yu C.C. Lan Y.T. Huang P.I. Lee Y.Y. Chen Y.W. …

Bright Spots in The Darkness of Cancer: A Review of Starfishes-Derived Compounds and Their Anti-Tumor Action.

The fight against cancer represents a great challenge for researchers and, for this reason, the search for new promising drugs to improve cancer treatments has become inevitable. Oceans, due to their wide diversity of marine species and environmental conditions have proven to be precious sources of potential natural drugs with active properties. As an example, in this context several studies performed on sponges, tunicates, mollusks, and soft corals have brought evidence of the interesting biological activities of the molecules derived from these species. Also, echinoderms constitute an import

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… In a previous study [ 46 ] it was demonstrated that polysaccharides extracted from A. pectinifera inhibited the cytochrome P450 1A1- mediated ethoxyresorufin O-deethylase activity and reduced significantly the ornithine decarboxylase activity in polysaccharide-treated MCF-7 breast cancer cells. … Then, the activity of phase II detoxification enzymes, such as quinone reductase (QR), glutathione S-transferase (GST) and ornithine decarboxylase (ODC) in HT-29 human colon adenocarcinoma cells was investigated [ 45 ]. …

[Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)].

Drug-induced liver injury (DILI) is one of the most common adverse reactions of anti-tuberculosis treatment. To improve the diagnosis and ma … plasma exchange, dual plasma molecular adsorption system, etc.) may be a beneficial option (4, C); ornithine aspartate may help reduce blood ammonia levels in patients with severe disease or liver failure (4, C).Recommendation 23: Rational drug use during the recovery period: During or after liver function recovery, clinicians should comprehensively assess …

Aminoglycosides, vancomycin, and metronidazole for people with cirrhosis and hepatic encephalopathy.

RATIONALE: Hepatic encephalopathy is a common complication of cirrhosis. Its development is associated with increased morbidity and mortalit … ides, other antibiotics, or other potentially beneficial agents (e.g. branched-chain amino acids, L-ornithine L-aspartate, nitazoxanide (a broad-spectrum antiparasitic/antiviral agent), and nicotinohydroxamic acid (a potent urease inhibitor). We included trials irrespective of publication status, outcomes reported, language, or blinding. We excluded trials …

Exploring Human Brain Metabolism via Genome-Scale Metabolic Modeling with Highlights on Multiple Sclerosis.

Cerebral dysfunctions give rise to a wide range of neurological diseases due to the structural and functional complexity of the human brain stemming from the interactive cellular metabolism of its specific cells, including neurons and glial cells. In parallel with advances in isolation and measurement technologies, genome-scale metabolic models (GEMs) have become a powerful tool in the studies of systems biology to provide critical insights into the understanding of sophisticated eukaryotic systems. In this study, brain cell-specific GEMs were reconstructed for neurons, astrocytes, microglia,

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… Carbamoyl-phosphate, acetate, and ornithine were computed as top reporter metabolites ( p -value < 0.025). …

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review.

BackgroundPeripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN.MethodsThe PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched fr

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… Acupuncture Synergized with Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine. Front Oncol . 2021;11:779562. doi: 10.3389/fonc.2021.779562 12. Zhou Y, Garcia MK, Chang DZ, et al. Multiple myeloma, painful neuropathy, acupuncture? …

Isolation of a Highly Purified HSC-enriched CD34+CD90+CD45RA- Cell Subset for Allogeneic Transplantation in the Nonhuman Primate Large-animal Model.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common treatment for patients suffering from different hematological disorders. Allo-HCT in combination with hematopoietic stem cell (HSC) gene therapy is considered a promising treatment option for millions of patients with HIV+ and acute myeloid leukemia. Most currently available HSC gene therapy approaches target CD34-enriched cell fractions, a heterogeneous mix of mostly progenitor cells and only very few HSCs with long-term multilineage engraftment potential. As a consequence, gene therapy approaches are currently limited

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… Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003; 80:148–158. doi:10.1016/j.ymgme.2003.08.016 22. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. …