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TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.

TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a biologically and clinically distinct subset of myeloid malignancies characterized by poor prognosis, resistance to standard therapies, and high rates of relapse. TP53 mutations, particularly biallelic are frequently associated with complex karyotypes and confer profound chemoresistance. Although hypomethylating agents and venetoclax-based combinations provide modest benefit, durable remissions remain rare. Novel therapeutic strategies targeting mutant p53, restoring wild-type function, or exploiting synth

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… Arsenic trioxide (ATO) ATO is a drug used for the treatment of acute promyelocytic leukemia ( 180 ). … Arsenic trioxide, a therapeutic agent for APL. Oncogene. (2001) 20:7146–53. doi: 10.1038/sj.onc.1204762, PMID: 181. Chen S, Le W, Liang Y, Tang YG, Song HX, Wu LL, et al. Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site. …

A randomized exploratory phase 2 study in patients with chemotherapy-related peripheral neuropathy evaluating whole-body vibration training as adjunct to an integrated program including massage, passive mobilization and physical exercises.

BackgroundChemotherapy-induced polyneuropathy (CIPN) is a common toxicity after chemotherapy, immunomodulatory drugs or proteasome inhibitors, which is difficult to treat and may also have impact on quality of life. The objective of the study was to evaluate whole-body vibration (WBV) on the background of an integrated program (IP) including massage, passive mobilization and physical exercises on CIPN.Patients and methodsIn an exploratory phase-2 study patients with CIPN (NCI CTC grade 2/3) were randomized for WBV plus IP (experimental) to IP alone (standard). 15 training sessions within 15 we

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… Background Chemotherapy induced polyneuropathy (CIPN) is a frequent toxicity observed after chemotherapy [ 1 ], immunomodulatory drugs or proteasome inhibitors [ 2 ], but may also occur with a lower incidence after other novel anti-cancer drugs such as arsenic trioxide [ 3 ] or brentuximab [ 4 ]. … Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol. 2005;82:224–229. doi: 10.1532/IJH97.05044. 4. Peggs KS. …

The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review.

Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and tra

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… The anti-carcinogenic effect of arsenic trioxide has previously been associated with apoptosis and mitochondrial oxidative stress, and the effect of AA or GSH depletion on its pharmacokinetic and possible resistance should be explored [ 59 ]. … Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin. Cancer Res. 2002;8:3658–3668. 56. …

Application of High Throughput Technologies in the Development of Acute Myeloid Leukemia Therapy: Challenges and Progress.

Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by extensive heterogeneity in genetics, response to therapy and long-term outcomes, making it a prototype example of development for personalized medicine. Given the accessibility to hematologic malignancy patient samples and recent advances in high-throughput technologies, large amounts of biological data that are clinically relevant for diagnosis, risk stratification and targeted drug development have been generated. Recent studies highlight the potential of implementing genomic-based and phenotypic-based screen

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… One successful example is the identification of all-trans retinoic acid (ATRA) and arsenic trioxide therapy for acute promyelocytic leukemia (APL). … The discovery of this translocation has clinical significance due to its responsiveness to arsenic trioxide and ATRA which promote degradation of PML-RAR-α [ 12 ]. …

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

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… Among outcomes: assessment of functional leukemia stem cells | ( 168 ) Also arsenic trioxide is used for the therapy of APL where it induces differentiation and apoptosis of leukemic cells. … In vivo , arsenic trioxide decreased recurrence rates after radical resection and prolonged survival in a mouse model. Arsenic trioxide is being studied, in combination with tyrosine kinase inhibitors in a clinical trial for its capacity to target the CML stem cell population (Table 4 ). …

Совместное управление триазолами с хемапаевыми и/или иммунозопрессивными агентами, известными умеренным взаимодействием между наркотиками и наркотиками у пациентов с гематологическими заболеваниями, госпитализировано в связи с инвазивным аспергиллозом.

ОБРАЩЕНИЕ: Триазолы широко используются для лечения и профилактики инвазивного аспергиллоза (ИА), но могут вызывать серьезное взаимодействие с наркотиками (ДПИ) с химиотерапией (ХТ) и иммунодепрессантами (ИС) посредством ингибирования CYP3A4. Частота получения трехазол-ХТ или одновременного лечения в случае гематологовых заболеваний (ГМ) вновь принятых в ПА пациентов в целом неизвестна. Мы изучили американские претензии IQVIA, в том числе в отношении взрослых ≥ 1 требование о пребывании в стационаре с диагностическим кодом для АИ с октября 1, 2015- ноябрь 30, 2022 и доказательства существовани

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… trioxide | 1 (0.3) Discussion In this contemporary cohort of HM patients newly hospitalized with IA, triazoles were used in nearly all cases. … Specific CT agents to treat HM that are associated with important QTc prolongation include a wide range of compounds: arsenic trioxide, cyclophosphamide (alkylating agent), gilteritinib and midostaurin (FLT3 inhibitors), glasdegib (Hedgehog inhibitor), lenalidomide (immunomodulatory amide), and nilotinib …

Extracellular vesicles: a new frontier in diagnosing and treating graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Graft-versus-host disease (GvHD) is a prevalent complication following allogeneic hematopoietic stem cell transplantation (HSCT) and is characterized by relatively high morbidity and mortality rates. GvHD can result in extensive systemic damage in patients following allogeneic HSCT (allo-HSCT), with the skin, gastrointestinal tract, and liver frequently being the primary target organs affected. The severe manifestations of acute intestinal GvHD often indicate a poor prognosis for patients after allo-HSCT. Endoscopy and histopathological evaluation remain employed to diagnose GvHD, and auxiliar

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… Both hucMSC-EVs and arsenic trioxides (ATOs) have been shown to treat aGvHD through immunomodulation. In addition to immunomodulation, hucMSC-EVs have a unique drug delivery function, which is believed to improve their activity (Fig. 4 ). … EVs, Extracellular vesicles; APC cell, Antigen presenting cell; NK cell, Natural killer cell; Treg cell, Regulatory T cell; MSC/MSCs, Mesenchymal Stromal/Stem Cells; M1 and M2, M1 and M2 macrophages; miR-204, miRNA-204; ATOs, Arsenic trioxides; IL-6, Interleukin 6; GvHD, Graft-versus-host disease; aGvHD …

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results.

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have f

Intrathoracic manifestations of hematologic malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Although the global incidence of hematologic malignancies is decreasing, the risk of developing these cancers is increasing due to increased lifespan and modern treatments including targeted therapy, chemotherapy, and radiation. Intrathoracic manifestations of hematologic malignancies may be the presenting sign leading to diagnosis or result from various treatment toxicity. The most common respiratory manifestation of hematologic malignancies is infectious, but up to half of pulmonary findings are from non-infectious etiologies. We aim to summarize the current literat

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… Imatinib, used in CML treatment, and arsenic trioxide, which is used to treat refractory or relapsed acute promyelocytic leukemia, can cause pericardial effusions ( 18 , 19 ). … Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia. J Cell Physiol 2019;234:14500-6. 10.1002/jcp.28292 19. Medeiros BC, Possick J, Fradley M. …

Analysis of differential gene immune infiltration and clinical characteristics of skin cutaneous melanoma based on systems biology and drug repositioning methods to identify drug candidates for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) has a low early detection rate and a high mortality rate. There are many problems such as side effects and drug resistance in existing therapeutic drugs. Current studies have confirmed that SKCM pathogenesis-related genes promote the invasion and metastasis of cutaneous melanoma, but their roles in the tumor microenvironment (TME) remain unclear. Network pharmacology provides new opportunities for drug repurposing and repositioning, and is a fast, safe, and inexpensive drug discovery method to find new drugs for the treatment of SKCM. In this study, based on 3 da

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… FDA-approved drugs for the treatment of lymphatic blood system diseases such as vorinostat, prednisolone acetate, arsenic trioxide, and tazemetostat are now found to have a certain effect on SKCM. … Arsenic trioxide has now been found that it can downregulate the tumor procoagulant activity of MCF-7 and WM-115 cell lines and induce growth inhibition and apoptosis of melanoma cell lines (Hoffman et al. 2015 ). …

Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives.

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of "onco-channelopathy". Here, we review the contribution of ion channels and transporters in multiple myeloma (

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… Furthermore, the pharmacological treatment with arsenic trioxide (ATO), which decreases Ik v currents and depolarizes cells in a concentration-dependent manner, inhibits MM cell proliferation by arresting RPMI8226 cells at the G0/G1 phase [ 24 ]. … Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide. Oncogene. 2004;23:1239–1247. doi: 10.1038/sj.onc.1207205. 77. …

Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma.

Haematopoiesis is a tightly orchestrated process where a pool of hematopoietic stem and progenitor cells (HSPCs) with high self-renewal potential can give rise to both lymphoid and myeloid lineages. The HSPCs pool is reduced with ageing resulting in few HSPC clones maintaining haematopoiesis thereby reducing blood cell diversity, a phenomenon called clonal haematopoiesis. Clonal expansion of HSPCs carrying specific genetic mutations leads to increased risk for haematological malignancies. Therefore, it comes as no surprise that hematopoietic tumours develop in higher frequency in elderly peopl

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… Li et al. reported recently that autophagy cell death occurred upon arsenic trioxide (As2O3) treatment. … Chronic Myeloid Leukaemia Goussetis et al. first reported the autophagic degradation of the BCR-ABL oncoprotein in CML cells under arsenic trioxide (ATO) treatment in 2012 [ 282 ]. …

Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.

Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, poss

Trends in overall survival and costs of multiple myeloma, 2000-2014.

Little real-world evidence is available to describe the recent trends in treatment costs and outcomes for patients with multiple myeloma (MM). Using the Truven Health MarketScan Research Databases linked with social security administration death records, this study found that the percentage of MM patients using novel therapy continuously increased from 8.7% in 2000 to 61.3% in 2014. Compared with MM patients diagnosed in earlier years, those diagnosed after 2010 had higher rates of novel therapy use and better survival outcomes; patients diagnosed in 2012 were 1.25 times more likely to survive

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… The non-novel treatments included arsenic trioxide, bendamustine, busulfan, cisplatin, cyclophosphamide, doxorubicin, etoposide, melphalan, prednisone, dexamethasone, rituximab, vincristine and vorinostat. … Non-novel treatment include: arsenic trioxide, bendamustine, busulfan, cisplatin, cyclophosphamide, doxorubicin, etoposide, melphalan, prednisone, dexamethasone, rituximab, vincristine and vorinostat. …

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox

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… In fact, studies have found that most chemotherapeutic drugs can kill cancer cells by directly or indirectly facilitating reactive oxygen species (ROS) accumulation, such as doxorubicin, cisplatin, 5-fluorouracil and arsenic trioxide (ATO) [ 12 , 13 ]. … Metformin potentiates the effect of arsenic trioxide suppressing intrahepatic cholangiocarcinoma: roles of p38 MAPK, ERK3, and mTORC1. J. Hematol. Oncol. 2017;10:59. doi: 10.1186/s13045-017-0424-0. 72. …

Drug-induced herpes zoster: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024.

BACKGROUND: Herpes zoster severely impacts patients' quality of life and therapeutic results. This research utilized data from the FDA Adverse Event Reporting System (FAERS) to examine the prevalence and attributes of drug-induced herpes zoster. METHODS: We analyzed FAERS reports about zoster from Q1 2004 to Q3 2024 and developed a list of possible pathogenic agents. Ranked the 30 medicines with the greatest incidence of reported herpes zoster cases. Statistical disproportionality analysis was employed to identify an elevated reporting frequency of herpes zoster linked to a particular medicat

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… Radioimmunoconjugate drugs such as ibritumomab, anti-tumor drugs like bortezomib, arsenic trioxide, and cladribine also mention herpes zoster risk in their labels. … Phase ii multicenter study of arsenic trioxide in patients with myelodysplastic syndromes . J. Clin. Oncol. official J. Am. Soc. Clin. Oncol. 24 ( 16 ), 2456 – 2464 . 10.1200/JCO.2005.03.7903 16651647 Serra F. Cassaniti I. Lilleri D. Pedrazzoli P. Baldanti F. Lasagna A. ( 2022 ). …

A Case of Syphilis with High Bone Arsenic Concentration from Early Modern Cemetery (Wroclaw, Poland).

Venereal syphilis is a sexually transmitted disease caused by Treponema pallidum - Gram-negative, slowly growing bacteria. The spread of the disease in the Old World was due to increased birth rate, urban population growth, migration and lack of knowledge concerning the epidemiology. In the past, the treatment was mainly symptomatic and included application of mercury compounds. The goal of the study was to present the case of advanced venereal syphilis found in early modern (16th-18thc) graveyard localized in Wroclaw, Poland. The object of the study is a cranium of a male whose age at death h

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… Selected mechanisms of the therapeutic effect of arsenic trioxide in cancer treatment. Postepy Hig Med Dosw (Online) 2008;62:463–467. [70] Petres J, Baron D, Hagedorn M. Effects of arsenic cell metabolism and cell proliferation: cytogenetic and biochemical studies. …

Нанотехнология в области гематологии: усиление терапевтической эффективности с помощью нанопчастей.

Фон и цели Гематологические заболевания, такие, как лейкемия, лимфома и множественная миелома, вносят значительный вклад в глобальный диагноз рака. Несмотря на прогресс в традиционных методах лечения, таких, как химиотерапия и иммунотерапия, эти методы лечения сталкиваются с ограничениями, включая неконкретную адресность, побочные эффекты и резистентность к лекарствам. Цель этого обзора заключается в изучении потенциала нанотехнологии, в частности наночастиц (НФ), для улучшения терапевтических последствий для этих раковых заболеваний путем расширения поставок наркотиков и снижения токсичности.

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… . | [ 24 ] Arsenic trioxide loaded double oligopeptide coupled NPs | Enhanced stability and loading efficiency of Arsenic trioxide as well as targeting in the lesions. | [ 25 ] Aptamer–methotrexate conjugate | Targeting the biomarker CD117, which is overexpressed on AML cells with no effect on the background … Su J., Liu G., Lian Y., et al., “Preparation and Characterization of Erythrocyte Membrane Cloaked PLGA/Arsenic Trioxide Nanoparticles and Evaluation of Their In Vitro Anti‐Tumor Effect,” RSC Advances 8, no. 36 (2018): 20068–20076. 143. …

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and objectiveAnnexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help ad

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… Arsenic trioxide, which functions by inducing apoptosis, was originally used as a treatment for patients with acute promyelocytic leukemia. … One study reported that the specific silencing of ANXA1 enhanced the sensitivity of cancer cells to a low concentration of arsenic trioxide by inhibiting MAPK/ERK activation ( 81 ). …

Bioinformatics-Guided Discovery of miRNAs Involved in Apoptosis Modulated by Parthenolide Combined with Vincristine in The NALM6 Cell Line.

ObjectiveAcute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the Tanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induce apoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone on the apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line.Materials and met

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… These findings support those of another study that found parthenolide enhanced the toxicity of arsenic trioxide (ATO) in T-cell leukemia/lymphoma cells in vitro ( 20 ). … Synergy between parthenolide and arsenic trioxide in adult T-cell leukemia/lymphoma cells in vitro. Iran J Basic Med Sci. 2020;23(5):616–622. doi: 10.22038/ijbms.2020.40650.9610. 21. Freund RRA, Gobrecht P, Fischer D, Arndt HD. Advances in chemistry and bioactivity of parthenolide. …