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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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… However, it played a significant role in the development and marketing of more potent insulin sensitizers, such as pioglitazone (PGZ), rosiglitazone (RGZ), and troglitazone (TGZ). … Pioglitazone PGZ represents the second generation of TZDs that received approval from the FDA for T2D in 1999. PGZ inhibits the growth and invasion of glioma cells and reduces the abundance of β-catenin in a PPAR-γ-dependent manner in vitro and in xenografts [ 73 ]. …

Metronomic chemotherapy: changing the paradigm that more is better.

The introduction of the "maximum tolerated dose" in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy-a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs

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… Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors. Cancer. 2003;98:2251–6. doi: 10.1002/cncr.11775. 70. Kopp HG, Kanz L, Hartmann JT. … Antiangiogenic therapy with pioglitazone, rofecoxib, and trofosfamide in a patient with endemic Kaposi sarcoma. Arch Dermatol. 2004;140:1504–7. doi: 10.1001/archderm.140.12.1504. 72. Kong DS, Lee JI, Kim WS, et al. …

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines a

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… PPARγ Agonists Peroxisome proliferator-activated receptor gamma (PPARγ- agonists, rosiglitazone and pioglitazone, are drugs in clinical use for diabetes ( 61 ). … Pioglitazone, in clinical studies on diabetic patients, was able to reduce the plasma level of different inflammatory factors among which CPR, IL-1, IL-6, and TNF-α ( 64 ). …

Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials.

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlini

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… The DURATION-2 trial demonstrated the effectiveness and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide. … Patients who switched from daily sitagliptin or pioglitazone to once-weekly exenatide experienced better or sustained glycemic control and weight loss [ 139 ]. …

Clinical Practice Guidelines for management of Sexual Disorders in Elderly.

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… Recent studies have reported that metformin and pioglitazone used in diabetes enhance the effect of Sildenafil in treating ED. Various PDE-5 inhibitors have been compared in table 11 . … & Row 58 Kaplan HS The new sex therapy: Active treatment of sexual dysfunctions 1974 New York Brunner/Mazel 59 Hawton K The behavioral treatment of sexual dysfunction British J Psychiatry 1982 140 94 101 10.1192/bjp.140.1.94 7059745 60 Gholamine B Shafiei M Motevallian M Mahmoudian M Effects of pioglitazone …

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidan

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… As shown in clinical trials ( NCT02888964 ; EudraCT 2009‐011675‐79), the combination of Pioglitazone with Imatinib was well tolerated in CML patients with a better molecular response (MR 4.5) in 56% versus 23% found in patients treated with Imatinib alone ( 85 ). … Finally, there is a current phase II study that aims to further characterize the use of Pioglitazone in patients with TKIs failure after first TFR to proceed with the second discontinuation attempt ( NCT02889003 ). …

New insight into adiponectin role in obesity and obesity-related diseases.

Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined "adipocytokines," protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production tha

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… Drugs like rosiglitazone and pioglitazone, belonging to the thiazolidinedione (TZD) class of PPAR γ agonists, have been clinically and experimentally proven to be potent inducers of adiponectin expression [ 153 – 155 ]; accordingly, many of the metabolic effects of rosiglitazone or pioglitazone are absent … reduces obesity-related inflammation in adipose tissue: comparison of activation of PPAR α , PPAR γ , and their combination Diabetes 2005 54 12 3358 3370 2-s2.0-33644664433 16306350 10.2337/diabetes.54.12.3358 154 Phillips SA Ciaraldi TP Oh DK Savu MK Henry RR Adiponectin secretion and response to pioglitazone …

Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry.

Werner syndrome is an adult-onset progeria syndrome that results in various complications. This study aimed to clarify the profile and secular variation of the disease. Fifty-one patients were enrolled and registered in the Werner Syndrome Registry. Their data were collected annually following registration. A cross-sectional analysis at registration and a longitudinal analysis between the baseline and each subsequent year was performed. Pearson's chi-squared and Wilcoxon signed-rank tests were used. Malignant neoplasms were observed from the fifth decade of life (mean onset: 49.7 years) and we

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… Regarding diabetes treatments, similar to findings in a previous report [ 9 ], pioglitazone, metformin, and insulin sensitizers were often used. … While, longitudinally, the percentage of metformin use has increased more than that of pioglitazone, suggesting that the negative effects of pioglitazone on osteoporosis may be considered. Among those with dyslipidemia, statins were used in 58.8% of patients. …

Балансирование иммунотерапии рака клеток CIK и PPAR Ligands: One Потенциальное терапевтическое приложение для злоумышленников CNS.

Клеточная терапия, вызванная цитокином (CCK), оказалась успешной в клинических испытаниях на глиобластому. Не менее важное значение имеют и намеки на то, что в центральной нервной системе (КНС) сосуществуют пероксисомные рецепторы (PPARs) с активированными рецепторами. Это служит обоснованием для изучения возможного синергического эффекта клеток CIK и PPAR. Methodology Мы изучали нейробластому и глиобластомные клеточные линии со зрелыми клетками CIK и PRAR antagonist GW-9662 для оценки воздействия на жизнеспособность клеток, потенциальное генное выражение (Wnt/β-ctenin сигнализация, DNMT1) и г

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… K., Alphonse‐Sullivan N., Isom S., et al., “Safety of Pioglitazone During and After Radiation Therapy in Patients With Brain Tumors: A Phase I Clinical Trial,” Journal of Cancer Research and Clinical Oncology 145, no. 2 (2019): 337–344, 10.1007/s00432-018-2791-5. 10. …

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

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… In another study, pioglitazone was found to suppress benzo(a)pyrene induced lung cancer by 63%, and a combination of pioglitazone and budesonide could achieve 90% reduction in tumor burden ( Fu et al., 2011 ). … Former smokers treated with pioglitazone showed mild improvement in the worst biopsy scores, and recorded a decreased Ki-67 labeling index of bronchial biposies. However, slight worsening was seen in current smokers administered with pioglitazone ( Keith et al., 2019 ). …

Иммунотерапевтический ландшафт амиотропического бокового склероза: библиометрический анализ тенденций в области исследований, приоритетов в области перевода и сетей сотрудничества (см.2006-2025).

Амиотрофный боковой склероз (ALS) по-прежнему является серьезной терапевтической проблемой, при этом иммунная диагностика все чаще признается в качестве одного из важнейших факторов развития заболеваний. Несмотря на обширные механистические исследования, никакой иммунотерапевтический подход не привел к последовательному изменению болезней, в связи с чем возникают вопросы о том, отражает ли этот переводный пробел биологическую сложность или структурную несогласованность в исследовательской экосистеме. Чтобы охарактеризовать интеллектуальную эволюцию исследований иммунотерапевтии ALS, определить

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… The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J Neurosci. 2005;25(34):7805–7812. doi: 10.1523/JNEUROSCI.2038-05.2005. 41. … A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLOS ONE. 2012;7(6):e37885. doi: 10.1371/journal.pone.0037885. 42. Kriz J, Nguyen MD, Julien JP. …

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

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… Numerous studies have revealed that treatment of rosiglitazone, pioglitazone, T0070907, and GW9662 on lymphoma cell lines inhibited cell growth or proliferation and induced apoptosis [ 142 , 143 ]. … Pertaining to PPARs, TZDs molecules like RGZ (Avandia) and pioglitazone (Actos) were synthesized in the 1990s. However, their application in oncology is limited. …

Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical

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… (pamapimod/pioglitazone) KIN001 is a combination of pamapimod, a selective inhibitor of p38 mitogen-activated protein kinase alpha (p38 MAPKα), and pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist. … Therefore, KIN001, the combination of a p38 MAPK inhibitor with pioglitazone, might have synergistic antiviral activity against SARS-CoV-2 with anti-inflammatory effects. 166 A phase 2 study to evaluate the efficacy and safety of KIN001 (pamapimod/pioglitazone) in non-hospitalized COVID-19 patients …

Клемастин фумарат ускоряет аккумуляцию инвалидности в прогрессивном множественном склерозе, усиливая пироптоз.

Множественный склероз (MS) — иммунопосредованное демиелинизирующее заболевание CNS. Клемастин фумарат, внезапный антигистамин и мускариновый блокатор рецепторов, обладает ремиелионирующим потенциалом в MS. Климастичная рука была добавлена в текущее клиническое исследование платформы, нацеленное на остаточную активность на основе точности, биомаркированной комбинированной терапии множественных склерозов (TRAP-MS) (Clinical Procures.gov). NCT03109288), для выявления сигнатуры ремиелинирования цереброспиновой жидкости (CSF) и для сбора данных о безопасности клемастина у пациентов независимо от ре

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… chance is 0.015% ( P = 0.00015; χ 2 test comparing CLM arm with remaining TRAP-MS treatments, where 0 out of 63 treatment-specific patient slopes [representing 42 patients] triggered safety criteria after 84.3 patient/years on the remaining 6 tested drugs: montelukast, losartan, hydroxychloroquine, pioglitazone … Forty-two patients were enrolled into an additional 6 treatment arms (dantrolene, hydroxychloroquine, losartan, montelukast, pioglitazone, and pirfenidone) of TRAP-MS. Both sexes were included in the study. …

Novel Treatment Strategies Utilizing Immune Reactions against Chronic Myelogenous Leukemia Stem Cells.

Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.

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… Another example is pioglitazone, which is known to sensitize CML-LSCs to TKIs by repressing the transcription of STAT5 , which up-regulates stemness-related genes [ 124 ]. … Fu, et al. have shown that pioglitazone could also induce IFN-γ production in tumor-infiltrating invariant natural killer T from both human patients and mouse melanoma models through alteration of metabolic status in these cells [ 125 ], suggesting that the immune-activating effects of these drugs might …

Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enaside

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… I Recruiting NCT03290443 A Phase 1, 2-Part, Multicenter, Open-label, 3-Arm Study to Determine the Effect of Enasidenib (CC-90,007) on the Pharmacokinetics of Single Doses of Caffeine, Dextromethorphan, Flurbiprofen, Midazolam, Omeprazole, Digoxin, Rosuvastatin and Pioglitazone in Subjects With Acute … Arm 3 will receive pioglitazone. …

PPARs in Irradiation-Induced Gastrointestinal Toxicity.

The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in i

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… The antidiabetic class of thiazolidinedione drugs includes troglitazone, rosiglitazone, pioglitazone and ciglitazone, all synthetic ligands of PPAR- γ . … The PPAR-γ agonist pioglitazone post-transcriptionally induces p21 in PC3 prostate cancer but not in other cell lines. Cell Cycle. 2005;4(4):582–584. 108. Chen GG, Lee JFY, Wang SH, Chan UPF, Ip PC, Lau WY. …

Revolutionary drug repositioning: the preventive and therapeutic potential of metformin and other antidiabetic drugs in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections remain the first-line therapy for AMD. However, their high cost and the need for frequent administration pose challenges to long-term adherence, highlighting the need for accessible and cost-effective preventive strategies. Emerging evidence suggests that traditional antidiabetic drugs, such as metformin, sulfonylureas, and thiazolidinediones, may offer neuroprotective benefits, opening new avenues for AMD prevention. Among these, me

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… TZDs, while improving insulin resistance, carry risks such as cardiovascular events with rosiglitazone and bladder cancer with pioglitazone ( Tseng, 2012 ). Their association with macular edema further restricts their potential use in retinal disease prevention ( Nien and Tseng, 2014 ). … Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities? J. Formos. Med. Assoc. 111 , 123 – 131 . 10.1016/j.jfma.2011.10.003 22423665 Tseng C. H. ( 2018 ). …

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

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… Preliminary clinical studies in 3 CML patients showed that combined use of pioglitazone and IM accomplished sustained complete molecular remission for up to 4.7 years in all patients, even after pioglitazone withdrawal [ 141 ]. … Phase II ACTIM trial showed that IM and pioglitazone had no drug interactions, yet their combination achieved MR4.5 at 12 months in 56% of patients [ 138 ]. …