ABSTRACT
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) by providing patients with long-term survival. Although most patients who receive TKI treatment have shown satisfactory tolerance, second malignancies (SMs) should not be ignored because of lifetime treatment. We designed a retrospective study to evaluate the incidence and possible risk factors of SMs in CML patients treated with TKIs. PATIENTS AND METHODS: Records of 223 patients with Philadelphia chromosome-positive CML treated with imatinib were reviewed to investigate frequencies and characteristics of SMs. The data of SMs were compared with the number expected from the National Central Cancer Registry. The possible risk factors of SM in CML patients treated with TKIs were also evaluated using Poisson regression in this study. RESULTS: After a median follow-up of 64 months (range, 4-253 months) from CML diagnosis, 7 patients (3.14%) developed 6 different SMs including colon, stomach, breast, kidney, cervical, and lymphonodus tissue. The risk of second cancer was higher than expected (observed-to-expected ratio, 2.45; 95% confidence interval, 1.17-5.14; P = .018). No associated elements were found in terms of influencing the incidence of SM in CML patients treated with TKIs. CONCLUSION: We found patients with CML treated with TKIs had a higher relative incidence of SM compared with the expected incidence among the general Chinese population. However, the correlations between second cancer and the potential risk factors including the length of exposure and cumulative dose of TKIs were not found in this study.
Subject(s)
Antineoplastic Agents/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/etiology , Protein Kinase Inhibitors/adverse effects , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Child , Female , Follow-Up Studies , Humans , Incidence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Neoplasms, Second Primary/diagnosis , Protein Kinase Inhibitors/therapeutic use , Registries , Retrospective Studies , Young AdultABSTRACT
Marine diatom Skeletonema costatum is an important prey in the marine food web and is often used as a standard test organism in ecotoxicological studies. In this study, in vivo experiments were performed to analyze the effects of 1-octyl-3-methylimidazolium bromide ([C8mim]Br) on the growth, photosynthetic activity, and oxidative stress in S. costatum using 96h growth tests with a batch-culture system. The growth of S. costatum was significantly inhibited by [C8mim]Br with 48 and 96h-EC50 of 17.9 and 39.9mgL(-1), respectively. The maximum quantum yield (Fv/Fm) and the light use efficiency (α) were inhibited by [C8mim]Br, which affected the growth of S. costatum. Subsequent biochemical assays in S. costatum revealed that [C8mim]Br induced changes of Chl a content, soluble protein content, and SOD activity, which had significant increases in low [C8mim]Br treatments (≤20mgL(-1)), but decreased in high [C8mim]Br exposures (≥40mgL(-1)). The increase of SOD activity at low concentrations (≤20mgL(-1)) may be considered as an active defense of S. costatum against [C8mim]Br stress by reactive oxygen species (ROS) quenching. In addition, [C8mim]Br increased ROS level and malondialdehyde (MDA) content in S. costatum, suggesting that the physiological effects of [C8mim]Br are resulted from ROS generation.
Subject(s)
Diatoms/drug effects , Imidazoles/toxicity , Water Pollutants, Chemical/toxicity , Chlorophyll/metabolism , Chlorophyll A , Diatoms/growth & development , Diatoms/metabolism , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Photosynthesis/drug effects , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Isocitrate Dehydrogenase/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Mutation , Adolescent , Adult , Aged , Aged, 80 and over , Asian People , China , Female , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Nucleophosmin , Prognosis , Time Factors , Young AdultABSTRACT
Polysaccharides extracted from various sources are natural active substances, which may lead to the activation of macrophage via multiple pathways and mechanisms. This article intends to illustrate the signaling pathways of polysaccharides from plants, fungi, algae and other sources, to identify the mechanisms on the molecular level, and to explore the novel target immunomodulatory agents.
Subject(s)
Macrophage Activation/immunology , Macrophages/metabolism , Polysaccharides/pharmacology , Animals , Humans , Macrophage Activation/drug effects , Macrophages/drug effects , Macrophages/immunology , Signal TransductionABSTRACT
Astragalus polysaccharide (APS) was obtained by hot water extraction, alcohol precipitation, gel-permeation chromatography and ultrafiltration. Fluorescence material 2-aminoacridone (2-AMAC) labeled APS bind to macrophage in a time- dependent manner and the binding can be remarkably inhibited by APS. Furthermore, the effect of APS on RAW264.7 macrophage demonstrated APS increase the level of cytokines including TNF-α, GM-CSF and the production of NO. NF-κB protein levels are increased in response to APS. Blocking NF-κB with specific inhibitor resulted in decreased levels of NO and TNF-α. The results suggested that APS possess potent immunomodulatory activity by stimulating macrophage and could be used as an immunotherapeutic adjuvant.
