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Cancer stem cell impact on clinical oncology.

Cancer is a widespread worldwide chronic disease. In most cases, the high mortality rate from cancer correlates with a lack of clear symptoms, which results in late diagnosis for patients, and consequently, advanced tumor disease with poor probabilities for cure, since many patients will show chemo- and radio-resistance. Several mechanisms have been studied to explain chemo- and radio-resistance to anti-tumor therapies, including cell signaling pathways, anti-apoptotic mechanisms, stemness, metabolism, and cellular phenotypes. Interestingly, the presence of cancer stem cells (CSCs), which are

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… Disulfiram is a drug used for treating alcoholism, and it shows anti-cancer activity in vitro and in vivo , further potentiating the chemotherapeutic response. … Sandstrom SK Murphy RF McLain D Tuason L Peereboom D Bukowski RM Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer Clin Cancer Res 1998 4 635 642 9533531 151 Liu P Kumar IS Brown S Kannappan V Tawari PE Tang JZ Jiang W Armesilla AL Darling JL Wang W Disulfiram …

Lost in transcription: molecular mechanisms that control HIV latency.

Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover,

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… Disulfiram reactivates latent HIV–1 expression through depletion of the phosphatase and tensin homolog AIDS 2013 27 F7 F11 10.1097/QAD.0b013e3283570620 22739395 172. Xing S. Bullen C.K. Shroff N.S. Shan L. Yang H.C. … Disulfiram reactivates latent HIV–1 in a Bcl–2–transduced primary CD4+ T cell model without inducing global T cell activation J. Virol. 2011 85 6060 6064 21471244 10.1128/JVI.02033-10 PMC3126325 173. Siegel D.S. Zhang X. Feinman R. Teitz T. Zelenetz A. Richon V.M. Rifkind R.A. Marks P.A. …

Drug Delivery Approaches for the Treatment of Cervical Cancer.

Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods.

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… Other thermoplastic vaginal rings were shown to hold and release disulfiram, an anticancer drug, at levels far beyond the IC 50 value for HeLa cells [ 108 ]. 3.2. Nanofibers Nanofibers have various applications, one of which is drug delivery, especially in local chemotherapy. … Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer Eur. J. Pharm. Biopharm. 2014 88 945 953 10.1016/j.ejpb.2014.08.002 25128854 109. Hu X. Liu S. Zhou G. Huang Y. Xie Z. Jing X. Electrospinning of polymeric nanofibers for drug delivery applications J. …

Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer.

The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields. Such drug repurposing promises faster access of drugs to patients while reducing costs in the long and difficult process of drug development. However, the number of existing drugs and diseases, together with the heterogeneity of patients and diseases, notably including cancers, can make repurposing time consuming and inefficient. The key question we address is how to efficiently repurpose an existing drug to treat a given indication. As drug efficacy rem

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… Pain, fever | | | + | | + | | | [ [60] , [61] , [62] ] Treatment Amantadine (Symmetrel TM ) | Dopamine agonist | Viral infections, Parkinson disease | + | | | | | + | | [ 63 ] Pleconaril (Picovir TM ) | Capsid inhibitor | Viral infections, Parkinson disease | + | | | | + | | | [ 63 ] Disulfiram … potrace 1.16, written by Peter Selinger 2001-2019 </metadata><g transform="translate(1.000000,15.000000) scale(0.019444,-0.019444)" fill="currentColor" stroke="none"><path d="M0 440 l0 -40 480 0 480 0 0 40 0 40 -480 0 -480 0 0 -40z M0 280 l0 -40 480 0 480 0 0 40 0 40 -480 0 -480 0 0 -40z"/></g></svg> C2 Disulfiram …

Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.

Medulloblastomas are the most common malignant pediatric brain tumors, representing approximately 20% of the central nervous system cancers in children. These tumors are highly heterogeneous and classified into four molecular subgroups-WNT, SHH, Group 3, and Group 4-each with distinct genetic and epigenetic profiles that influence tumor behavior, therapeutic response, and patient outcomes. Advances in molecular diagnostics have improved the subclassification of medulloblastomas, yet treatment outcomes for high-risk subtypes, particularly Group 3, remain poor, with current modalities often asso

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… , normalizes tumor vasculature, enhances drug delivery | Enhances drug delivery by normalizing vasculature | Preclinical studies Atorvastatin | Blocks RAS/RAF signaling via HMG-CoA inhibition, anti-angiogenic effects | Prevents leptomeningeal spread and anti-angiogenic effects | Preclinical studies Disulfiram … Disulfiram, an alcohol dependence treatment, generates reactive oxygen species through ALDH inhibition and induces copper-dependent apoptosis, with potential for targeting hypoxic tumor regions [ 90 ]. …

Pharmacotherapy for anxiety and comorbid alcohol use disorders.

BACKGROUND: Anxiety disorders are a potentially disabling group of disorders that frequently co-occur with alcohol use disorders. Comorbid a … s. Trials assessing drugs administered for the treatment of drinking behaviour, such as naltrexone, disulfiram and acomprosate were not eligible for inclusion in this systematic review. DATA COLLECTION AND ANALYSIS: A systematic review is a standardised evaluation of all research studies that address a particular clinical issue.Two review authors independen …

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

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… Accordingly, pharmacologic approaches such as disulfiram that suppress both GSDMD-FL and GSDMD-N have been proposed as targeted strategies to prevent RILD ( 252 - 255 ). RILD pathogenesis also involves complex cytokine network regulation. … In preclinical models, disulfiram inhibits GSDMD-mediated pyroptosis and reduces irradiation-induced hepatocyte injury and neutrophil infiltration ( 252 , 254 ). …

Keyword Index for Volume 104

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… 1791 desmoid tumour 37 desmoid-type fibromatosis 37 dexamethasone 605, 620 diagnosis 110, 1325, 1418 diagnostic imaging 1482 diagnostic marker 893 dietary patterns 524, 1493 diethylstilbestrol 605, 620 differentiation therapy 229 disseminated tumour cells 1434 distant metastasis 1724 distress 255, 419 disulfiram …

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

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… Disulfiram has also shown promise in cancer therapy. It inhibits EMT and metastasis by affecting the NF‐κB and TGF‐β signaling pathways. Its potential effectiveness against hepatocellular carcinoma stems from its ability to tackle issues related to EMT [ 136 ]. … Recent studies have shown improved therapeutic efficacy for patients with advanced metastatic cancer and associated fibrotic alterations by combining novel compounds, such as disulfiram, with existing anti‐fibrotic medicines, such as pirfenidone and nintedanib [ 127 ]. …

Nanoparticles for Effective Combination Therapy of Cancer.

Cancer continues to remains a major healthcare problem across the world despite strong translational research efforts towards tackling the disease. Surgery, when possible, along with radiation and chemotherapy continue to remain the mainstay of cancer treatment. Novel targeted therapies or biologics and immunotherapies have recently been approved to improve treatment efficacies while reducing collateral damage to normal, non-cancerous tissues. Combination therapies have shown better results than individual monotherapies in the clinic but often the improvements in therapeutic indices remain mar

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… Another example emphasizing on MDR is combination treatment using DOX and disulfiram, P-gp inhibitor, encapsulating pH sensitive polymeric micelles nanosystem. The pH sensitive nanosystem comprise of disulfram loaded poly (styrene-co-maleic anhydride)- adipic dihydrazide conjugated DOX. … PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance Biomaterials 35 2391 2400 24360574 10.1016/j.biomaterials.2013.11.086 35 Duan X Xiao J Yin Q Zhang Z Yu H 2013 Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram …

Keyword Index for Volume 107

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… health 888 depression 1644 deprivation 765 developing countries 1445 diabetes 1608 diagnosis 260, 1220, 1876 diagnostics 1987 diet 537 dietary cadmium 895 differential splicing 675 digit ratio 1631 direct sequencing 626 discrimination 1025 disease outcome 370 disseminated tumour cell 1345 disulfiram …

Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.

Neutrophil extracellular traps (NETs) are complex, web-like structures consisting of DNA intertwined with antimicrobial proteins, which neutrophils release upon immune activation. These structures play a crucial role in pathogen elimination, particularly in infectious diseases. However, their involvement in various pathological conditions is multifaceted and context-dependent, while NETs contribute to host defense against infections, they can also exacerbate sterile inflammation, autoimmune disorders, and tumor progression. This review provides a comprehensive analysis of the molecular mechani

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… Notably, disulfiram, an aldehyde dehydrogenase inhibitor, exhibits anti-inflammatory and anticancer properties by simultaneously limiting both NET formation and pyroptosis [ 112 ]. Conversely, within the TME, NETs actively suppress NK-cell cytotoxicity through multiple mechanisms. … Disulfiram, an aldehyde dehydrogenase inhibitor, works as a potent drug against sepsis and cancer via NETosis, pyroptosis, apoptosis, ferroptosis, and cuproptosis. Blood Sci. 2022;4(3):152–4. 10.1097/BS9.0000000000000117. 113. Gao J, et al. …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… Cyclopamine | Steroidal alkaloid | Basal cell carcinoma | Bind to the Smo protein to inhibit the Hh pathway 199 14 | Diclofenac | Anti-inflammatory | Colorectal, breast, pancreatic, ovarian, and prostate cancer | Immunomodulation, apoptosis, angiogenesis, actions on Myc, and glucose metabolism 200 15 | Disulfiram … the 3 other drugs was determined. 10 | Combination of 9 repurposed drugs with low-dose chemotherapy for brain cancer | Monocentric proof of concept clinical trial assessing the safety of the coordinated undermining of survival paths by 9 repurposed drugs (aprepitant, auranofin, celecoxib, captopril, disulfiram …

Neutrophil extracellular traps in homeostasis and disease.

Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the

Роль антиоксидантов в множестве миеломы: диагностика, прогнозирование и терапевтическое применение: обзор сюжета.

Множественная миэлома (ММ) — злокачественная клетка B-клеток с моноклональными плазменными клетками, производящими нефункциональные иммуноглобулины. Она по-прежнему неизлечима из-за de novo или приобретенного сопротивления злокачественных клеток стандартным химиотерапиям. Таким образом, понимание механизма терапевтического сопротивления имеет важнейшее значение для разработки более эффективных мер вмешательства и определения новых целей лечения. MM - это разнородная болезнь, характеризующаяся сложными генетическими изменениями, которые имеют решающее значение для прогнозирования стратификации.

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… A study on human MM cell lines reported that a copper chelating agent and inhibitor of SOD1, disulfiram (DSF), showed anti-myeloma effect. … ABC, As 2 O 3 /BTZ/vitamin C; AIF1, apoptosis-inducing factor 1; BM, bone marrow; BMMCs, bone marrow myeloma cells; BTZ, bortezomib; DSF, disulfiram; GSH, glutathione; GST, glutathione S -transferase; GSTP, glutathione S -transferase P1; HMCLs, human myeloma cell lines; KLF6, Krüppel-like factor 6; LIP …

Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists' arsenal.

Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of dist

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… inhibits growth of colorectal cancer liver metastases in the regenerating liver Clin Exp Metastasis 2014 31 4 395 405 10.1007/s10585-014-9635-8 24442969 109 Kast RE Karpel-Massler G Halatsch ME CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram … nelfinavir impairs proteasome activity and inhibits the proliferation of multiple myeloma cells in vitro and in vivo Haematologica 2012 97 7 1101 1109 22271897 10.3324/haematol.2011.049981 PMC3396684 145 Kast RE Halatsch ME Matrix metalloproteinase-2 and -9 in glioblastoma: a trio of old drugs – captopril, disulfiram …

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

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… antiemetic for pregnancy, but has now been repurposed and approved for multiple myeloma [ 16 , 17 ]; itraconazole, a triazole antifungal developed in the 1980s, showed anticancer activities in preclinical in vitro and in vivo models of pancreatic ductal adenocarcinoma derived from liver metastasis [ 18 ]; disulfiram … Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram. Cell Communication and Signaling. 2020;18(1):p. 36. doi: 10.1186/s12964-019-0507-3. 20. Xia C., Chen R., Chen J., et al. …

Keyword Index for Volume 109

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… 242 diastolic heart function 891 DICER1 2744 diet 257, 1914, 2904 diethylstilboestrol 1079 differential expression 1848 diffuse large B-cell lymphoma 312 diffusion-weighted MRI 615, 1562 disease progression 121 disease-specific survival 1093 disparities 1302 disseminated tumour cells 1264 disulfiram …

Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case-control study.

AbstractPrevious studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and se

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… obstructive pulmonary disease or use of bronchodilating inhalation agents containing an antimuscarinic component), markers of autoimmune diseases (AD) (diagnosis codes or prescription of immunomodulating drugs), and diagnoses related to excessive alcohol consumption (diagnose codes and prescription of disulfiram …

The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.

The unfolded protein response (UPR) mediated by IRE1/XBP1, PERK/eIF2α/ATF4, and ATF6/GRP78 governs tumor adaptation to hypoxia, nutrient deprivation, and therapy stress. In gynecologic malignancies (ovarian, endometrial, cervical), persistent endoplasmic reticulum (ER)-stress signaling underlies proliferation, invasion, immune evasion, and treatment resistance but also creates druggable liabilities. We conducted a narrative review of peer-reviewed literature indexed in MEDLINE (PubMed), Embase, Scopus, and Web of Science from inception through 13 September 2025. Search terms combined ER-stress

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… For example, NCT04648033 is evaluating the ER-stress inducers auranofin and disulfiram in platinum-resistant ovarian cancer, while NCT03456700 combines the procaspase-activating compound PAC-1 with gemcitabine to potentiate ER-stress-mediated apoptosis [ 53 ]. …