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1.
Article in Chinese | WPRIM | ID: wpr-880079

ABSTRACT

OBJECTIVE@#To identify differentiation related miRNA and evaluate roles of miRNA during ATRA induced myeloid differentiation.@*METHODS@#The small RNA sequencing was used to analyze differential expressed miRNAs in ATRA induced NB4 cells. Then the several up or down-regulated miRNA were selected as the research candidates. SgRNAs targeting the genome of each miRNA were designed and NB4 cells with inducible expression of Cas9 protein were generated. After transduced sgRNA into NB4/Cas9 cells, the mutation level by PCR and surveyor assay were evaluated. The cell differentiation level was investigated by surface CD11b expression via flow cytometry.@*RESULTS@#A total of 410 mature miRNAs which expressed in NB4 cells were detected out after treated by ATRA, 74 miRNAs were up-regulated and 55 were down-regulated miRNAs with DNA cleavage generated by CRISPR/Cas9 was assayed directly by PCR or surveyor assay, quantitative PCR showed that the expression of miRNA was downregulated, which evaluated that gene edition successfully inhibitied the expression of mature miRNA. MiR-223 knockout showed the myeloid differentation of NB4 significantly inhibitied, while miRNA-155 knockout showed the myeloid differentation of NB4 cells significantly increased.@*CONCLUSION@#CRISPR/Cas9 is a powerful tool for gene editing and can lead to miRNA knockout. Knockouts of miR-223 and miR-155 have shown a differentiation-related phenotype, and the potential mechanism is the integrative regulation of target genes.


Subject(s)
CRISPR-Cas Systems , Cell Differentiation , Gene Editing , MicroRNAs/genetics , Sequence Analysis, RNA , Tretinoin
3.
Rev. Nutr. (Online) ; 33: e180232, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057195

ABSTRACT

ABSTRACT Objective Acrylamide is a potentially neurotoxic and carcinogenic chemical and naturally creates during the heating process of carbohydrate-rich foods, such as potato chips and breakfast cereals. Acrylamide might be ingested by people via consuming food that contains it. Therefore, we investigated the effect of acrylamidegiven orally to male and female rats on plasma retinoic acid and α-tocopherol and serum sialic acid and malondialdehyde levels. Method A total of 50 Wistar rats were used (25 female and 25 male, three-four weeks old). The rats of each sex were given 2 and 5mg/kg/day acrylamide via drinking water for 90 days. At the end of the treatment, the animals were euthanized by cervical dislocation. Blood specimens were collected through cardiac puncture, and serum and plasma samples were analysed using the high-performance liquid chromatography technique with a Ultraviolet detector. Results The analysis of the plasma and serum samples revealed that serum sialic acid and malondialdehyde levels in both sexes given 5mg/kg/day acrylamide were significantly increased, and the serum sialic acid levels were higher in female rats given 2mg/kg/day acrylamide. The plasma retinoic acid and α-tocopherol levels significantly decreased in both sexes given only the highest dose. Conclusion The results show that acrylamide causes an increase in oxidative stress and leads to a decrease in the levels of retinoic acid and α-tocopherol which play a role in the defense mechanism against this stress.


RESUMO Objetivo A acrilamida é um químico potencialmente neurotóxico e carcinogênico, sendo naturalmente criada durante o processo de aquecimento de alimentos ricos em carboidratos, como batatas fritas e cereais matinais. Dado que o composto pode ser ingerido através do consumo de alimentos, o presente trabalho teve por objetivo investigar o seu efeito, quando administrado oralmente a ratos, medindo-se os níveis plasmáticos de ácido retinoico e α-tocoferol, bem como os níveis séricos de ácido siálico e malondialdeído Métodos Foram utilizados cinquenta ratos Wistar, sendo metade de cada sexo, com idade entre três e quatro semanas. Os animais foram divididos em dois grupos, os quais receberam diferentes doses diárias de acrilamida, via água potável, durante noventa dias: o primeiro ingeriu 2mg/kg/dia; e o segundo, 5mg/kg/dia. Ao final do tratamento, os animais foram eutanasiados por meio de luxação cervical. Amostras de sangue foram coletadas através de punção cardíaca, assim como amostras de soro e plasma foram medidas usando-se a técnica de cromatografia líquida de alta performance com detector de Ultravioleta. Resultados A análise das amostras de plasma e soro revelou que os níveis de ácido siálico e malondialdeído, em ratos de ambos os sexos tratados com acrilamida de 5mg/kg/dia, foram significativamente aumentados, ao passo que os níveis séricos de ácido siálico foram maiores em ratas tratadas com 2mg/kg/dia de acrilamida. Já os níveis plasmáticos de ácido retinoico e α-tocoferol diminuíram significativamente em ratos de ambos os sexos, quando tratados com a dose mais elevada.Concl Conclusão Os resultados mostram que a acrilamida causa um aumento no estresse oxidativo e leva a uma diminuição nos níveis de ácido retinoico e α-tocoferol, que desempenham um papel no mecanismo de defesa contra esse estresse.


Subject(s)
Animals , Rats , Acrylamide , Tretinoin , Biomarkers , Rats, Wistar , Oxidative Stress , N-Acetylneuraminic Acid , Tocopherols , Malondialdehyde
4.
Rev. Hosp. El Cruce ; (27): 35-42, 2020.
Article in Spanish | LILACS | ID: biblio-1282916

ABSTRACT

Acute promyelocytic leukemiais a subtype of acute my eloid leukemia characterized by the presence of the PML:RAR aonco proteindueto a specific geneticalteration, translocation (15;17), which avoids my eloid differentiation, generating the accumulation of leukemic promyelocytes with posterior alteration of hemostasis. It presents with symptoms related to pancytopenia and thrombohemorrhagic coagulopathy, and there are few report sof cases with vasculitis secondary to promyelocytic leukemia. The clinical case aimed to describe a particular form of presentation of acute promyelocytic leukemia with vasculitis.


La leucemia promielocítica aguda es un subtipo de leucemia mieloide aguda caracterizada por la presencia de la oncoproteína PML-RARa debido a una alteracióngenéticaespecífica, la translocación (15;17), que impide la diferenciación mieloide generando la acumulación de promielocitos leucémicos y una alteración compleja de la hemostasia. Se presenta con síntomas relacionados a pancitopenia y coagulopatía trombo-hemorrágica existiendo escasos reportes de casos de vasculitis asociada a leucemia. El caso clínico descrito representa una forma particular de presentación de una leucemia promielocítica aguda con vasculitis.


Subject(s)
Leukemia, Promyelocytic, Acute , Tretinoin , Vasculitis
5.
Dermatol. argent ; 26(1): 32-34, 2020. ilus
Article in Spanish | LILACS | ID: biblio-1146323

ABSTRACT

Las poroqueratosis son un grupo heterogéneo de trastornos de la queratinización epidérmica, de presentación infrecuente. Se caracterizan clínicamente por pápulas hiperqueratósicas que confluyen y forman placas anulares con un centro atrófico y bordes sobreelevados. Hay seis variantes clínicas. El examen histopatológico evidencia la característica laminilla cornoide. Se presenta el caso de una niña de 2 años con diagnóstico de poroqueratosis de Mibelli y respuesta parcial al tratamiento tópico con tretinoína al 0,025%, que actualmente continúa en seguimiento clínico (AU)


Porokeratosis is a heterogeneous group of disorders in epidermal keratinization. It is an infrequent entity characterized clinically by hyperkeratotic papules that converge forming annular plaques with an atrophic center and raised borders. There are six clinical variants. The histopathological examination evidences the typical cornoid lamella. We present a 2-year-old girl diagnosed with porokeratosis of Mibelli and partial response to topical treatment of tretinoin 0,025%, still under clinical control (AU)


Subject(s)
Humans , Female , Child, Preschool , Porokeratosis/diagnosis , Tretinoin/therapeutic use , Porokeratosis/pathology , Porokeratosis/drug therapy , Keratolytic Agents/therapeutic use
7.
Journal of Experimental Hematology ; (6): 1083-1087, 2019.
Article in Chinese | WPRIM | ID: wpr-775760

ABSTRACT

OBJECTIVE@#To investigate the differentiation of acute promyelocytic leukemia (APL) cells induced by adenosine targeting Prx III.@*METHODS@#HL-60 cells were divided into four groups: control group, all-trans retinoic acid (ATRA) group, adenanthin group and ATRA+adenanthin group. Cell morphologic changes were observed under optical microscope. The influence of adenanthin on the differentiation of HL-60 was observed by nitro blue tetrazolium chloride (NBT) test. Cell surface differentiation antigens CD11b expression was measured by flow cytometry. The protein expression of Prx III was detected by immunohistochemical assay.@*RESULTS@#Adenanthin could induce the differentiation of HL-60 cells; the NBT reduction positive rate in ATRA+adenanthin group was significantly higher than that in ATRA group and adenanthin group (P<0.05). The percentage of CD11b positive cells in ATRA+adenanthin group (43.62%±1.38%) was higher than that in adenanthin group (28.15%±1.78%), ATRA group (36.72%±1.33%) and control group (7.99%±1.78%) (P<0. 05). The content of Prx Ⅲ protein in adenanthin group was significantly higher than that in control group and ATRA group (P<0.05).@*CONCLUSION@#Adenanthin and ATRA have a synergistic effect on the differentiation and maturation of HL-60 cells, and its mechanism may be related with regulation of Prx III expression.


Subject(s)
Cell Differentiation , Diterpenes, Kaurane , HL-60 Cells , Humans , Leukemia, Promyelocytic, Acute , Peroxiredoxin III , Tretinoin
8.
Journal of Experimental Hematology ; (6): 2024-2029, 2019.
Article in Chinese | WPRIM | ID: wpr-781500

ABSTRACT

Abstract  Among myeloid leukemias, the acute promyelocytic leukemia (APL) was found to be specifically sensitive to all-trans retinoic acid (ATRA), almost all APL patients respond to ATRA therapy. The ATRA induces remission of APL patients by stimulating the differentiation of the leukemia cells. However, with the long-term application of ATRA alone, ATRA resistance has become one of the main causes of chemotherapy failure in the patients with acute promyelocytic leukemia. At present, the mechanism of ATRA-resistance is not completely clear, this review discusses the mechanism of drug-resistance in terms of signal pathways, genes, proteins and enzyme.


Subject(s)
Antineoplastic Agents , Cell Differentiation , Humans , Leukemia, Promyelocytic, Acute , Tretinoin
9.
Article in Korean | WPRIM | ID: wpr-719664

ABSTRACT

Neutrophilic leukemoid reaction may occur in many situations, including hemolysis, malignancy, infection, and exposure to certain toxins. It usually shows morphological overlap with chronic myeloid leukemia in which promyelocytes are not majorly associated. Here, we present a case of promyelocytic leukemoid reaction in a patient with sepsis. A 28-year-old man was admitted for renal stone removal. After percutaneous nephrolithotomy, his condition deteriorated with fever (37.8℃), tachycardia (130/min), acute renal failure, pleural effusion, and pulmonary edema. Complete blood count indicated a white blood cell count of 73.39×10⁹/L including 82% promyelocytes, hemoglobin 8.9 g/dL, and platelet count of 85×10⁹/L. A bone marrow aspirate showed that promyelocytes accounted for 73.8% of all nucleated cells. Following bone marrow examination, treatment with all-trans retinoic acid (ATRA) was started immediately. Reverse transcription polymerase chain reaction (RT-PCR) study revealed the absence of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) and other RARA (retinoic acid receptor alpha) rearrangements. Once the chromosome analysis of bone marrow cells demonstrated the normal karyotype, ATRA was discontinued.


Subject(s)
Acute Kidney Injury , Adult , Blood Cell Count , Bone Marrow , Bone Marrow Cells , Bone Marrow Examination , Fever , Granulocyte Precursor Cells , Hemolysis , Humans , Karyotype , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Promyelocytic, Acute , Leukemoid Reaction , Leukocyte Count , Nephrostomy, Percutaneous , Neutrophils , Platelet Count , Pleural Effusion , Polymerase Chain Reaction , Pulmonary Edema , Reverse Transcription , Sepsis , Tachycardia , Tretinoin
10.
Article in English | WPRIM | ID: wpr-719618

ABSTRACT

BACKGROUND: Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1. METHODS: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks. RESULTS: When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks. CONCLUSION: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.


Subject(s)
Animals , Apoptosis , Bleomycin , Blotting, Western , Cell Differentiation , Epithelial Cells , Fibroblasts , Fibrosis , In Vitro Techniques , Lung Injury , Mice , Mitogen-Activated Protein Kinase Kinases , Mitogen-Activated Protein Kinases , Models, Animal , p38 Mitogen-Activated Protein Kinases , Phosphorylation , Protein Kinases , Smad Proteins , Transforming Growth Factor beta , Transforming Growth Factors , Tretinoin
11.
Article in English | WPRIM | ID: wpr-742352

ABSTRACT

PURPOSE: To investigate the effects of all-trans retinoic acid (ATRA) in cisplatin (CP)-induced testicular damage in rats. MATERIALS AND METHODS: Twenty-eight male Wistar rats were divided into four groups: Control, ATRA alone, ATRA+CP, and CP alone. Body weight, testicular weight, sperm count, sperm motility, percentage of abnormal sperm, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in testicular tissue, and testicular histopathology were compared among groups. RESULTS: The sperm count and motility significantly decreased and the percentage of abnormal sperm significantly increased in the CP group compared to the control and ATRA groups. CP+ATRA administration significantly increased the sperm count and motility, but reduced the abnormal sperm count. CP administration significantly increased TOS and OSI compared to the control group and the other groups. Administering CP+ATRA significantly decreased TOS and the OSI in testicular tissue and reduced spermatogenesis, but increased the Johnsen score. CONCLUSIONS: The destructive effects of CP treatment on testicular tissue and spermatogenesis were reduced by administering ATRA.


Subject(s)
Animals , Body Weight , Cisplatin , Humans , Male , Oxidative Stress , Rats , Rats, Wistar , Sperm Count , Sperm Motility , Spermatogenesis , Spermatozoa , Testis , Tretinoin , Vitamin A
12.
Article in English | WPRIM | ID: wpr-776625

ABSTRACT

OBJECTIVE@#To examine the effects of ursolic acid (UA) on mitigating retinoic acid (RA)-induced osteoporosis in rats.@*METHODS@#Fifty female Sprague-Dawley rats were randomly divided into the control group (n=10) and the osteoporosis group (n=40). The 40 osteoporosis rats were induced by 75 mg/(kg•d) RA once daily for 2 weeks, and then were randomly assigned to vehicle control (model), low-, middle-, and high-dose UA [(UA-L, UA-M, UA-H; 30, 60, 120 mg/(kg•d), respectively] groups (10 rats each). UA were administered once daily to the rats from the 3rd weeks for up to 4 weeks by gavage. Bone turnover markers [serum alkaline phosphatase (ALP), osteocalcin (OCN), urine deoxypyridinoline (DPD)] and other parameters, including serum calcium (S-Ca), serum phosphorus (S-P), urine calcium (U-Ca), urine phosphorus (U-P), and bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia, bone biomechanical properties and trabecular microarchitecture, were measured.@*RESULTS@#The osteoporosis in rats was successfully induced by RA. Compared with the model group, UA-M and UA-H significantly reversed the RA-induced changes in S-P, U-Ca, U-P, ALP, OCN and urine DPD ratio and markedly enhanced the BMD of right femur, 4th lumbar vertebra and tibia (Plt;0.05 or Plt;0.01). Further, biomechanical test and microcomputed tomography evaluation also showed that UA-H drastically improved biomechanical properties and trabecular microarchitecture (Plt;0.05 or Plt;0.01).@*CONCLUSION@#UA could promote bone formation, increase osteoblastic activity and reduce osteoclastic activity in rats, indicating that UA might be a potential therapeutic of RA-induced acute osteoporosis.


Subject(s)
Animals , Biomechanical Phenomena , Bone Density , Bone Remodeling , Female , Osteoporosis , Diagnostic Imaging , Drug Therapy , Rats , Rats, Sprague-Dawley , Tretinoin , Toxicity , Triterpenes , Pharmacology , Therapeutic Uses , X-Ray Microtomography
13.
Article in English | WPRIM | ID: wpr-764078

ABSTRACT

BACKGROUND AND OBJECTIVES: Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification. METHODS AND RESULTS: We used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34⁺CD45⁺ cells with progenitor functions, even in the CD43⁻ population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision. CONCLUSIONS: Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.


Subject(s)
Dexamethasone , Humans , Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Progesterone , Regenerative Medicine , Tretinoin
14.
Immune Network ; : e15-2019.
Article in English | WPRIM | ID: wpr-764016

ABSTRACT

To this date, the criteria to distinguish peritoneal macrophages and dendritic cells (DCs) are not clear. Here we delineate the subsets of myeloid mononuclear cells in the mouse peritoneal cavity. Considering phenotypical, functional, and ontogenic features, peritoneal myeloid mononuclear cells are divided into 5 subsets: large peritoneal macrophages (LPMs), small peritoneal macrophages (SPMs), DCs, and 2 MHCII⁺CD11c⁺CD115⁺ subpopulations (i.e., MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺). Among them, 2 subsets of competent Ag presenting cells are demonstrated with distinct functional characteristics, one being DCs and the other being MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells. DCs are able to promote fully activated T cells and superior in expanding cytokine producing inflammatory T cells, whereas MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells generate partially activated T cells and possess a greater ability to induce Treg under TGF-β and retinoic acid conditions. While the development of DCs and MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells are responsive to the treatment of FLT3 ligand and GM-CSF, the number of LPMs, SPMs, and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells are only influenced by the injection of GM-CSF. In addition, the analysis of gene expression profiles among MHCII⁺ peritoneal myeloid mononuclear cells reveals that MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells share high similarity with SPMs, whereas MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells are related to peritoneal DC2s. Collectively, our study identifies 2 distinct subpopulations of MHCII⁺CD11c⁺CD115⁺ cells, 1) MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells closely related to peritoneal DC2s and 2) MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells to SPMs.


Subject(s)
Animals , Antigen Presentation , Dendritic Cells , Granulocyte-Macrophage Colony-Stimulating Factor , Macrophages , Macrophages, Peritoneal , Mice , Peritoneal Cavity , T-Lymphocytes , Transcriptome , Tretinoin
15.
Article in English | WPRIM | ID: wpr-758904

ABSTRACT

The development of long-term surviving fetal cell cultures from primary cell tissue from the developing brain is important for facilitating studies investigating neural development and for modelling neural disorders and brain congenital defects. The field faces current challenges in co-culturing both progenitors and neurons long-term. Here, we culture for the first time, porcine fetal cells from the dorsal telencephalon at embryonic day (E) 50 and E60 in conditions that promoted both the survival of progenitor cells and young neurons. We applied a novel protocol designed to collect, isolate and promote survival of both progenitors and young neurons. Herein, we used a combination of low amount of fetal bovine serum, together with pro-survival factors, including basic fibroblast growth factor and retinoic acid, together with arabinofuranosylcytosine and could maintain progenitors and facilitate in vitro differentiation into calbindin 1+ neurons and reelin+ interneurons for a period of 7 days. Further improvements to the protocol that might extend the survival of the fetal primary neural cells would be beneficial. The development of new porcine fetal culture methods is of value for the field, given the pig's neuroanatomical and developmental similarities to the human brain.


Subject(s)
Brain , Calbindins , Cell Culture Techniques , Congenital Abnormalities , Cytarabine , Fibroblast Growth Factor 2 , Humans , In Vitro Techniques , Interneurons , Neurons , Stem Cells , Telencephalon , Tretinoin
16.
Journal of Experimental Hematology ; (6): 1033-1039, 2019.
Article in Chinese | WPRIM | ID: wpr-771843

ABSTRACT

@#]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups.@*RESULTS@#There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P>0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037,0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770).@*CONCLUSION@#For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.


Subject(s)
Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Humans , Leukemia, Promyelocytic, Acute , Remission Induction , Retrospective Studies , Treatment Outcome , Tretinoin
17.
Journal of Experimental Hematology ; (6): 1380-1386, 2019.
Article in Chinese | WPRIM | ID: wpr-775710

ABSTRACT

OBJECTIVE@#To investigate the effect of chromosomal karyotype on the prognosis of patients with acute promyelocytic leukemia (APL) in condition of the maintenance treatment based on arsenic trioxide.@*METHODS@#The patients with acute promyelocytic leukemia for last 12 years in our hospital were retrospectively collected. The patients mainly treated with arsenic trioxide in maintenance protocol were selected and followed up. All the patients were divided into 3 groups according to cytogenetic data: single t (15; 17) group, t (15; 17) with additional chromosomal abnormality (ACA) group, and normal karyotype group. Then, the prognostic significance of ACAs and complex karyotype were investigated in APL patients.@*RESULTS@#There were 57 cases in the single t (15; 17) group, in which 8 cases died in the first month after induction treatment with early mortality rate of 14%. There were 21 patients in t (15; 17) with ACA group, in which 4 cases died in the first month with early mortality rate of 19%. There were 15 cases in normal chromosome group, in which 5 cases died in the first month with the early mortality rate of 33.3%. There was no statistical difference in the early mortality among 3 groups. All the remaining 76 patients achieved complete hematological remission. These patients were followed up. The median follow-up time was 43.9 months. Among them, only 2 patients in single t (15; 17) group and 1 patient in t (15; 17) with ACA group relapsed. No patient relapsed in normal karyotype group. The relapse rate was 3.5% in single t (15; 17) group and 4.2% in t (15; 17) with ACA group, respectively. There was no statistical difference in the overall survival and disease-free survival rates among 3 groups. Further analysis showed that the patients with complex chromosome karyotypes had lower relapse-free survival rates, but overall survival rates were not significantly different in 3 group.@*CONCLUSION@#In general, ACA can not affect the prognosis of patients with acute promyelocytic leukemia in condition of the maintenance treatment based on arsenic trioxide, but the complex chromosomal karyotype may reduce the relapse-free survival rates.


Subject(s)
Arsenic Trioxide , Therapeutic Uses , Humans , Karyotype , Leukemia, Promyelocytic, Acute , Drug Therapy , Prognosis , Remission Induction , Retrospective Studies , Treatment Outcome , Tretinoin
18.
Article in Chinese | WPRIM | ID: wpr-775053

ABSTRACT

OBJECTIVE@#To study the clinical effect of the SCMC APL-2010 regimen in the treatment of acute promyelocytic leukemia (APL) in children.@*METHODS@#A retrospective analysis was performed for the clinical data of 44 children with APL who received treatment with the SCMC APL-2010 regimen between April 2010 and July 2016. The Kaplan-Meier survival analysis was used to evaluate event-free survival (EFS) rate and overall survival (OS) rate.@*RESULTS@#Of the 44 children with APL, 42 (95%) achieved a complete remission (CR) after one course of treatment and 1 achieved CR after two courses of treatment, with an overall CR rate of 98%. The 9-year EFS and OS rates were 96%±3% and 97.7%±2.2% respectively. As for adverse events, 41 (93%) had infection, 29 (66%) had granulocyte reduction, 12 (27%, 1 died) had differentiation syndrome, 16 (36%) had liver dysfunction, 12 (27%) had adverse gastrointestinal reactions, and 7 (16%) had QT prolongation, 1 (2%) had orchitis, and no secondary neoplasm was observed.@*CONCLUSIONS@#Children with APL receiving the SCMC APL-2010 regimen have a good prognosis and can achieve a long-term survival, while treatment-related infection is commonly seen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Child , Disease-Free Survival , Humans , Leukemia, Promyelocytic, Acute , Male , Remission Induction , Retrospective Studies , Treatment Outcome , Tretinoin
19.
Article in Chinese | WPRIM | ID: wpr-813317

ABSTRACT

Retinoic acid, an active metabolite of vitamin A, exerts multiple effects on regulating embryonic development and inducing differentiation, proliferation, apoptosis as well as resistance in various cancer cells. Apart from the classic genomic action (binding to the nuclear receptors to regulate the expression of its downstream target genes), retinoic acids also play important roles in anti-cancer effect through non-genomic pathways (via extranuclear and non-transcriptional effects).


Subject(s)
Apoptosis , Cell Differentiation , Genomics , Humans , Neoplasms , Drug Therapy , Receptors, Retinoic Acid , Tretinoin
20.
J. appl. oral sci ; 27: e20180317, 2019. tab, graf
Article in English | LILACS | ID: biblio-984571

ABSTRACT

Abstract Bone morphogenetic protein type 2 (BMP-2) and retinoic acid (RA) are osteoinductive factors that stimulate endogenous mechanisms of bone repair which can be applied on management of osseous defects in oral and maxillofacial fields. Objective Considering the different results of RA on osteogenesis and its possible use to substitute/potency BMP-2 effects, this study evaluated the outcomes of BMP-2, RA, and BMP-2+RA treatments on in vitro osteogenic differentiation of human adipose-derived stem cells (ASCs) and the signaling pathway(s) involved. Material and Methods ASCs were treated every other day with basic osteogenic medium (OM) alone or supplemented with BMP-2, RA, or BMP-2+RA. Alkaline phosphatase (ALP) activity was determined using the r-nitrophenol method. Extracellular matrix mineralization was evaluated using von Kossa staining and calcium quantification. Expression of osteonectin and osteocalcin mRNA were determined using qPCR. Smad1, Smad4, phosphorylated Smad1/5/8, BMP-4, and BMP-7 proteins expressions were analyzed using western blotting. Signaling pathway was evaluated using the IPA® software. Results RA promoted the highest ALP activity at days 7, 14, 21, and 28, in comparison to BMP-2 and BMP-2+RA. BMP-2+RA best stimulated phosphorylated Smad1/5/8 protein expression at day 7 and Smad4 expression at days 7, 14, 21, and 28. Osteocalcin and osteonectin mRNA expressions were best stimulated by BMP-2+RA at day 7. Matrix mineralization was most improved by BMP-2+RA at days 12 and 32. Additionally, BMP-2+RA promoted the highest BMP signaling pathway activation at days 7 and 14, and demonstrated more activation of differentiation of bone-forming cells than OM alone. Conclusions In summary, RA increased the effect of BMP-2 on osteogenic differentiation of human ASCs.


Subject(s)
Humans , Osteogenesis/drug effects , Tretinoin/pharmacology , Cell Differentiation/drug effects , Bone Morphogenetic Protein 2/drug effects , Mesenchymal Stem Cells/drug effects , Osteoblasts/drug effects , Osteogenesis/physiology , Reference Values , Time Factors , Osteocalcin/analysis , Osteocalcin/drug effects , Osteonectin/analysis , Osteonectin/drug effects , Cell Differentiation/physiology , Cells, Cultured , Blotting, Western , Reproducibility of Results , Analysis of Variance , Alkaline Phosphatase/analysis , Alkaline Phosphatase/adverse effects , Bone Morphogenetic Protein 2/metabolism , Mesenchymal Stem Cells/metabolism
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