Search results for "Arsenic Trioxide"
showing 10 items of 22 documents
Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology
2018
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug’s activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1.88). Drug-resistant U87.MG ΔEGFR glioblastoma cells harboring mutated epidermal growth factor receptor were even more sensitive (collateral sensitive) than wild-type U87.MG cells (…
Traditional Chinese medicines (TCMs) for molecular targeted therapies of tumours.
2009
Scientific progress in genetics, cell and molecular biology has greatly ameliorated our comprehensive understanding of the molecular mechanisms of neoplastic transformation and progression. The rapidly advancing identification of molecular targets in human cancers during the last decade has provided an excellent starting point for the development of novel therapeutics. A huge variety of potential molecular targets have been identified, many of which are already in the market for therapeutic purposes. It is now becoming possible to target pathways and/or molecules that are crucial in maintaining the malignant phenotype. Traditional Chinese medicine (TCM) is often considered as alternative or…
Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA a…
2019
Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of ≥2 ACA, and a very CK (CK+) as ≥3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with <2 ACA (p=.09). Among patients wi…
Real Life Experience with ATRA-Arsenic Trioxide Based Regimen in Acute Promyelocytic Leukemia - Updated Results of the Prospective German Intergroup …
2016
Abstract Background: Standard therapy of acute promyelocytic leukemia has long relied on the combination of All-trans-retinoic acid (ATRA) and chemotherapy. The introduction of arsenic trioxide (ATO) in APL treatment has allowed achievement of similarly high remission and survival rates coupled with significantly reduced myelosuppression. Recent results of the APL0406 trial by the GIMEMA-AMLSG-SAL study groups showed that the combination of ATRA and arsenic trioxide (ATO) is superior to standard ATRA and chemotherapy (CHT) in front-line therapy of low/intermediate risk acute promyelocytic leukemia (APL). The implications of these results for the clinical practice of APL patients in Germany …
Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy
2018
Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk-and age-adapted protocol (Programa Espanol de Tratamientos en Hematologia (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged >= 60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA tria…
As2O3-induced oxidative stress and cycle progression in a human intestinal epithelial cell line (Caco-2)
2007
Foods and drinking water are the main routes for human exposure to inorganic arsenic, the intestinal epithelium being the first barrier against such exogenous toxicants. The present study evaluates the effect of As(III) (0.5-25 microM) upon Caco-2 cells as an intestinal epithelia model. Cell viability, intracellular formation of reactive oxygen species (ROS), mitochondrial membrane potential (Deltapsim) changes, and cell cycle distribution in exposed cultures were evaluated. The intracellular production of ROS was seen to increase in a non-dose dependent manner at all concentrations tested, with impairment of cell mitochondrial enzyme function secondary to a loss of Deltapsim. Concentration…
Improved Outcome with ATRA-Arsenic Trioxide Compared to ATRA-Chemotherapy in Non-High Risk Acute Promyelocytic Leukemia - Updated Results of the Ital…
2014
Abstract Background: We recently showed that the combination of ATRA and arsenic trioxide (ATO) is at least not inferior and possibly superior to standard ATRA and chemotherapy (CHT) in the front-line management of low/intermediate risk APL (Italian-German APL 0406 trial; Lo-Coco et al., NEJM 2013). We report herein on the extended and final series of 276 patients (162 were in the previous report) with the last case being enrolled into the study in January 2013. Methods: The APL0406 study was a prospective, open-label, randomized intergroup trial conducted by the Italian GIMEMA and the German SAL and AMLSG study groups. Eligible patients were adults aged 18-<71 years with newly diagnosed…
Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet
2015
In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-u…
Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide
2015
Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of comp…
From traditional Chinese medicine to rational cancer therapy
2007
Many natural products and derivatives thereof belong to the standard repertoire of cancer chemotherapy. Examples are Vinca alkaloids, taxanes and camptothecins. In recent years, the potential of natural products from plants, notably from medicinal plants used in traditional Chinese medicine (TCM), has been recognized by the scientific community in the Western world. To provide an example of the most recent developments in this field, we have selected several compounds, namely artesunate, homoharringtonine, arsenic trioxide and cantharidin, that are found in natural TCM products and that have the potential for use in cancer therapy. Controlled clinical studies have shown that homoharringtoni…