摘要 :
Белки, связывающие ретиноевую кислоту (РК), CRABP1 и CRABP2 являются молекулярными шаперонами, обеспечивающими реализацию внутрикл...
展开
Белки, связывающие ретиноевую кислоту (РК), CRABP1 и CRABP2 являются молекулярными шаперонами, обеспечивающими реализацию внутриклеточной активности РК, важнейшего стимулятора клеточной дифференцировки, обладающего опухоль-супрессорной активностью. Одной из основных функций CRABP2 является доставка и передача ретиноевой кислоты ядерным рецепторам RAR/RXR, что приводит к активации транскрипции широкого спектра ретиноид-респонсивных генов. Функции CRABP1 менее изучены, но связаны, по-видимому, с удержанием ретиноевой кислоты в цитоплазме и ограничением ее активности в отношении регуляции транскрипции генов, что предполагает участие данного белка в формировании РК-резистентности. Также малопонятны и механизмы, регулирующие активность CRABP1. Впервые проведенное в данной работе сравнение уровней CRABP1 в линиях опухолевых клеток различного происхождения показало отсутствие этого белка в клетках опухолей, считающихся РК-резистентными, и его выраженную продукцию в РК-чувствительных клетках. Вместе с тем анализ, проведенный на панели клеточных линий рака молочной железы с различным уровне?
收起
摘要 :
The application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the treatment of acute promyelocytic leukemia (APL). More than 80-90% of patients are expected to be cured with a combination of ATRA,...
展开
The application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the treatment of acute promyelocytic leukemia (APL). More than 80-90% of patients are expected to be cured with a combination of ATRA, ATO and/or chemotherapy. In this review, we focus on the remaining obstacles to a cure for all patients with APL. We review the issue of early death and coagulopathy and discuss the particular challenges in the care of patients with high-risk APL and patients with relapsed APL. We also give recommendations and highlight ongoing efforts to improve the persistently high early death rate and the outcomes of high risk and relapsed APL patients.
收起
摘要 :
Introduction All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated a...
展开
Introduction All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. Case Report A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. Management & Outcome Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. Discussion This case highlights the importance of monitoring ATRA's side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.
收起
摘要 :
Despite the impressive results obtained with standard chemotherapy, approximately 20% of acute promyelocytic leukemia (APL) patients undergo disease relapse thereby requiring salvage therapy. Few data is available on long-term pro...
展开
Despite the impressive results obtained with standard chemotherapy, approximately 20% of acute promyelocytic leukemia (APL) patients undergo disease relapse thereby requiring salvage therapy. Few data is available on long-term prognosis in relation to time to complete remission (CR): we reviewed 142 patients treated with AIDA protocols and we found that 42 out of 142 (29.6%) patients achieved CR after 35 days (median time, 42 days). No significant differences in presenting features, including FAB subtype, type of PML/RARA transcript and relapse risk at presentation between the two patient groups achieving CR > or <35 days were revealed, except for male sex and older age that were significantly associated with delayed CR. Rate of relapse was 31% in patients with delayed CR compared to 17% in the group of patients who achieved CR < 35 days (p=0.001), with a 5-year CIR of 29.6% compared to 12% (p=0.03). APL patients with delayed CR should be more closely monitored during follow-up for early identification of relapse and prompt administration of pre-emptive salvage therapy. ? 2012 Elsevier Ltd.
收起
摘要 :
Seasonal and spatial variability of trace metal concentrations and of a battery of antioxidant parameters were evaluated in digestive gland of the ribbed mussel Aulacomya atra atra. Fe, Al and Cu accumulated in tissue exhibited ma...
展开
Seasonal and spatial variability of trace metal concentrations and of a battery of antioxidant parameters were evaluated in digestive gland of the ribbed mussel Aulacomya atra atra. Fe, Al and Cu accumulated in tissue exhibited maximum values in winter, coinciding partially with the highest labile concentrations of Fe and Cu in sediment. Metals, as other pollutants, are known to influence the oxidative status of organisms and antioxidant enzymes have been often proposed as biomarkers of contaminant effects. Seasonal variations of trace metals did not appear to influence those of biochemical parameters, which generally showed an opposite trend with higher enzymatic activities in summer when trace metal concentrations were lower. Organisms from Punta Cuevas (control site) showed higher induction of reactive oxygen species production than those from both considered impacted sites, suggesting the possibility of some biochemical adaptation in organisms or a higher modulation of environmental and physiological factors on antioxidant responses than levels of trace metals. This study, which is the first in the area in this matter, showed that seasonal variations of potential biomarkers should be incorporated into interpretation of long-term biomonitoring studies in this marine coastal ecosystem.
收起
摘要 :
In this study, we assessed in gills of native ribbed mussels Aulacomya atra atra from three sites within Nuevo Gulf (Northern Patagonia) several biomarkers such as reactive oxygen species (ROS), lipid radicals (LR), malondialdehyd...
展开
In this study, we assessed in gills of native ribbed mussels Aulacomya atra atra from three sites within Nuevo Gulf (Northern Patagonia) several biomarkers such as reactive oxygen species (ROS), lipid radicals (LR), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and metallothionein (MT). Furthermore, concentrations of main trace metals (Fe, Al, Zn, Cu, Cd and Pb) were quantified in mussel tissue. Results showed significant induction of SOD, GST, MT and MDA, as well as, higher concentration of Fe, Al and Cd in winter than in summer. The high MDA content measured in mussels from Folias Wreck seemed to be caused by the very high levels of Fe that would come from the corrosion of the vessel. Mussels from the control site Punta Cuevas presented the lowest levels of Cd and the highest of Al in winter. Despite positive correlations were found between Al and GST and MT, no spatial differentiation was detected in those biomarkers. On the other hand, MT was only related to Al been most likely influenced by environmental variables than by the trace metals. It has to be highlighted that the relationship detected among water temperature, nutrients and antioxidant responses in gills is probably related to the fact that this tissue is in direct contact with water and it is sensitive to its fluctuations. Taking into account that mussel gill is a tissue actively proliferating and the first target of contaminants present in water, so that changes in its antioxidant system can provide an earlier warning signal than in other tissues.
收起
摘要 :
Echinostoma atrae, new species (Digenea: Echinostomatidae) is described from intestine of the bird Black Coot Fulica atra of Manchhar Lake, Sindh, Pakistan. Although the present specimens resemble with type species Echinostoma rev...
展开
Echinostoma atrae, new species (Digenea: Echinostomatidae) is described from intestine of the bird Black Coot Fulica atra of Manchhar Lake, Sindh, Pakistan. Although the present specimens resemble with type species Echinostoma revolutum but are distinguished from it in having aspinose body, 38 collar spines, absence of collar spines on oral sucker, more elongated and widely separated testes and tubular excretory bladder.
收起
摘要 :
A little number of current autophagy inhibitors may have beneficial effects on the acute myeloid leukemia (AML) patients. However, there is a strong need to figure out which settings should be activated or inhibited in autophagy p...
展开
A little number of current autophagy inhibitors may have beneficial effects on the acute myeloid leukemia (AML) patients. However, there is a strong need to figure out which settings should be activated or inhibited in autophagy pathway to prevail drug resistance and also to improve current treatment options in leukemia. Therefore, this study aimed to compare the effects of well-known inhibitors of autophagy (as 3-MA, BafA1, and HCQ) in leukemia KG-1 and HL-60 cells exposed to arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Cell proliferation and cytotoxicity of cells were examined by MTT assay. Autophagy was studied by evaluating the development of acidic vesicular organelles, and the autophagosomes formation was investigated by acridine orange staining and transmission electron microscopy. Moreover, the gene and protein expressions levels of autophagy markers (ATGs, p62/SQSTM1, and LC-3B) were also performed by qPCR and western blotting, respectively. The rate of apoptosis and cell cycle were evaluated using flow cytometry. We compared the cytotoxic and apoptotic effects of ATO and/or ATRA in both cell lines and demonstrated that some autophagy markers upregulated in this context. Also, it was shown that autophagy blockers HCQ and/or BafA1 could potentiate the cytotoxic effects of ATO/ATRA, which were more pronounced in KG-1 cells compared to HL-60 cell line. This study showed the involvement of autophagy during the treatment of KG-1 and HL-60 cells by ATO/ATRA. This study proposed that therapy of ATO/ATRA in combination with HCQ can be considered as a more effective strategy for targeting leukemic KG-1 cells.
收起
摘要 :
Background and aims: We investigated oral delivery of transforming growth factor beta 1 [TGF beta]- and all-trans retinoic acid [ATRA]-loaded microspheres as therapy for gut inflammation in murine models of inflammatory bowel disease [IBD].
原文获取