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1.
Journal of Experimental Hematology ; (6): 1242-1246, 2021.
Article in Chinese | WPRIM | ID: wpr-888545

ABSTRACT

OBJECTIVE@#To explore the expression level of ETV6-ABL fusion gene in different cell populations in patients with myeloproliferative neoplasm (MPN) and therapeutic effect of tyrosine kinase inhibitor (TKI).@*METHODS@#A 42-year-old man who presented with fever, marked leukocytosis and chronic myelogenous leukemia (CML) like MPN was reported. ETV6-ABL fusion gene was detected by real-time PCR and confirmed by direct sequencing. ETV6-ABL mRNA expression in each cell population sorted from peripheral blood by flow cytometry was detected by real-time PCR.@*RESULTS@#ETV6-ABL fusion gene was found out in bone marrow cells and confirmed as type A by direct sequencing. ETV6-ABL fusion gene transcript level in polymorphonuclear cells was nearly 3.6-fold relative to that in total cells, which was significantly higher than that in T cell, B cell and monocyte subsets. The complete blood count (CBC) returned to normal level after treatment with imatinib (400 mg) daily for three months. After TKI treatment for 6 months, the ratio of ETV6-ABL/ABL decreased from 174.1% to 1.9%.@*CONCLUSION@#ETV6-ABL fusion gene positive MPN may have a CML clinical presentation and is sensitive to TKI. ETV6-ABL fusion gene is specifically expressed in polymorphonuclear cells.


Subject(s)
Adult , Fusion Proteins, bcr-abl/genetics , Genes, abl , Hematopoietic Stem Cell Transplantation , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Myeloproliferative Disorders/genetics
2.
Article in Chinese | WPRIM | ID: wpr-880097

ABSTRACT

OBJECTIVE@#To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP).@*METHODS@#Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment.@*RESULTS@#Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABL@*CONCLUSION@#In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , China , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines , Pyrimidines/therapeutic use , Treatment Outcome
3.
Article in Chinese | WPRIM | ID: wpr-880087

ABSTRACT

OBJECTIVE@#To investigate the effect of etoposide (ETO) on elimination of chronic myeloid leukemia (CML) stem cells by imatinib mesylate(IM) in vivo.@*METHODS@#SCL-tTA/BCR-ABL mice were used as CML animal model. Flow cytometry was used to assess the effect of ETO alone or in combination with IM on the number of leukemia stem cell (LSC) in bone marrow and spleen, and peripheral blood neutrophils in CML mice and normal control FVB mice.@*RESULTS@#The results showed that in CML mice, the number and proportion of LSC in bone marrow and the proportion of neutrophils in peripheral blood decreased significantly after ETO and IM combined treatment, and the degree of decrease was more significant than that of both alone. While in wild type FVB mice, the combination of ETO and IM showed no significant effect on the number and proportion of LSK cells in bone marrow and the proportion of neutrophils in spleen.@*CONCLUSION@#ETO can selectively enhance elimination of CML LSC by IM in vivo.


Subject(s)
Animals , Drug Resistance, Neoplasm , Etoposide , Fusion Proteins, bcr-abl , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Mice , Stem Cells
4.
Journal of Experimental Hematology ; (6): 1752-1756, 2021.
Article in Chinese | WPRIM | ID: wpr-922329

ABSTRACT

OBJECTIVE@#To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients.@*METHODS@#The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR.@*RESULTS@#There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months.@*CONCLUSION@#For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.


Subject(s)
Adult , Dasatinib , Female , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Protein Kinase Inhibitors , Young Adult
5.
Journal of Experimental Hematology ; (6): 1714-1718, 2021.
Article in Chinese | WPRIM | ID: wpr-922323

ABSTRACT

OBJECTIVE@#To investigate the regulation of chronic myelogenous leukemia (CML) imatinib resistant genes, in order to improve the therapeutic effect of CML imatinib resistant patients.@*METHODS@#The human CML cell line K562 and imatinib-resistant K562 cells (K562/G01) were collected, and transcriptome of the cells were achieved by RNA-seq. The sequencing data were analyzed by using standard procedures.@*RESULTS@#Compared with K562 cells, 464 genes were significantly changed in K562/G01 cells, including 163 up-regulated and 301 down-regulated genes. The GO function annotation analysis and KEGG pathway analysis results showed that the differentially expressed genes were mainly involved in biological processes such as oxidative phosphorylation, localization to protein organelle, ribonucleoprotein complex biogenesis and so on. Gene Set Enrichment Analysis (GSEA) plots showed that 5 gene-sets were up-regulated in K562/G01 significantly, including the pathway of TGF-beta, mTOR and CML.@*CONCLUSION@#CML imatinib resistance is associated with oxidative phosphorylation, during which the pathway of TGF-beta and mTOR are significantly up-regulated.


Subject(s)
Drug Resistance, Neoplasm , Gene Expression Profiling , Humans , Imatinib Mesylate/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
7.
Brasília; s.n; 2 jul. 2020.
Non-conventional in Portuguese | PIE, LILACS, BRISA, PIE | ID: biblio-1117621

ABSTRACT

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 17 artigos e 9 protocolos.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Technology Assessment, Biomedical , Zinc/therapeutic use , Ivermectin/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Vaccines/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Fingolimod Hydrochloride/therapeutic use , Imatinib Mesylate/therapeutic use , Abatacept/therapeutic use , Glucocorticoids/therapeutic use , Hydroxychloroquine/therapeutic use
8.
Rev. méd. Chile ; 148(3): 404-408, mar. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1115806

ABSTRACT

Hypophosphatemia is a relatively frequent and a potentially serious adverse drug effect. Clinically it is characterized by bone pain and muscle weakness. There are several mechanisms by which a drug can induce hypophosphatemia and they can be classified according to whether or not they are mediated by an excess of Fibroblast Growth Factor 23 (FGF23). We report two patients with the condition: (i) A 49-year-old woman with Chronic Myeloid Leukemia (CML) and gastric sleeve surgery at 46 years of age. After receiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary phosphate losses associated with high FGF23 levels were confirmed. Plasma phosphate returned to normal values 90 days after the iron administration. (ii) A 40-year-old man with a history of CML in whom imatinib was started. He developed symptomatic hypophosphatemia due to non FGF23-mediated hyperphosphaturia. As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases illustrate the importance of recognizing and treating drug-induced hypophosphatemia in a timely manner, and thus avoid the morbidity associated with this entity.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Hypophosphatemia , Phosphates , Administration, Intravenous , Imatinib Mesylate , Iron
9.
J. coloproctol. (Rio J., Impr.) ; 40(1): 12-19, Jan.-Mar. 2020. tab, graf, ilus
Article in English | LILACS | ID: biblio-1090846

ABSTRACT

Abstract Background This study defines the disease profile in south Indian population and determine the clinic-pathological aspects of Gastro-Intestinal Stromal Tumors. Method In this prospective study patients diagnosed of gastrointestinal stromal tumors were taken thorough clinical examination and a database of Anthropometric details and clinical details were analyzed. Pathological data included tumor size, presence or absence necrosis, mitotic counts, immunohistochemistry for CD-117, CD-34. Results There were 44 patients with confirmed diagnosis of gastro-intestinal stromal tumor. The highest incidence was found in the 6th decade. The most common symptoms were abdominal pain and gastrointestinal bleed. Stomach was most frequent site for gastro-intestinal stromal tumors. Immunochemistry for CD-117 was positive in 93.18% cases. Majority of tumors (79.5%) had pure spindle cell morphology and mitotic activity showed that 34% of the GISTs were of the high risk group. Forty two patients were suggestive of surgery as the primary treatment after presentation. Conclusion Abdominal pain was the most common presenting complaint. Majority of the tumors aroused from the stomach. The majority of the tumors had pure spindle cell morphology and 93% of the tumors were CD-117 positive. A significant relationship between tumor size, tumor necrosis and mitotic activity with large tumors having necrosis and high mitotic rate having high risk of malignancy, was observed. Surgical resection is considered mainstay of treatment of gastro-intestinal stromal tumor. Imatinib therapy should be given to patients in moderate to severe risk categories.


Resumo Justificativa Este estudo define o perfil da doença na população do sul da Índia e determina os aspectos clínicos e patológicos dos tumores estromais gastrointestinais. Método Neste estudo prospectivo, os pacientes diagnosticados com tumor estromal gastrointestinl foram submetidos a um exame clínico completo, e uma série de dados dos pacientes, incluindo detalhes antropométricos e clínicos, foram analisados. Os dados patológicos incluíram tamanho do tumor, presença ou ausência de necrose, contagem mitótica e imuno-histoquímica para CD-117, CD-34. Resultados Havia 44 pacientes com diagnóstico confirmado de tumor estromal gastrointestinal. A maior incidência foi encontrada na 6ª década de vida. Os sintomas mais comuns foram dor abdominal e sangramento gastrointestinal. O estômago foi o local mais frequente para tumores estromais gastrointestinais. A imuno-histoquímica para CD-117 foi positiva em 93,18% dos casos. A maioria dos tumores (79,5%) apresentava morfologia pura de células fusiformes e a atividade mitótica mostrou que 34% dos GISTs pertenciam ao grupo de alto risco. Quarenta e dois pacientes receberam indicação para cirurgia como tratamento primário após a apresentação. Conclusão A dor abdominal foi a queixa mais comum. A maioria dos tumores afetava o estômago, apresentava morfologia pura de células fusiformes e 93% eram CD-117 positivos. Foi observada uma relação significativa entre o tamanho do tumor, a necrose tumoral e a atividade mitótica, com os tumores grandes apresentando necrose e alta taxa mitótica com alto risco de malignidade. A ressecção cirúrgica é considerada o principal tratamento do tumor estromal gastrointestinal. A terapia com imatinibe deve ser administrada a pacientes em categoria de risco de moderadas a grave.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Neoplasms , Proto-Oncogene Proteins c-kit/immunology , Antigens, CD34/immunology , Imatinib Mesylate/therapeutic use , India , Antineoplastic Agents/therapeutic use
10.
J. coloproctol. (Rio J., Impr.) ; 40(1): 89-93, Jan.-Mar. 2020. ilus
Article in English | LILACS | ID: biblio-1090838

ABSTRACT

Abstract Here we describe an infrequent case of gastrointestinal stromal tumor of the rectum in a 57 year-old man with spindle cell neoplasm probably gastrointestinal stromal tumor and CT scan showed tumor from the anterior rectal wall and offered abdominoperineal resection for the same. The patient was started on imatinib and had a significant reduction in symptoms. The patient was reassessed with the CT scan, which showed a reduction in tumor size and Transanal minimally invasive surgery was planned for the patient. Use of imatinib prior to surgical resection to attain the reduced size of the tumor within the limit of resection is an attractive approach. Since tumor development can happen rapidly again after substantial tumor shrinkage, the best time to operate depending on resectability and the maximum therapeutic outcome remains divisive.


Resumo No presente estudo, os autores descrevem um caso raro de tumor estromal gastrointestinal no reto em um homem de 57 anos que se apresentou com neoplasia de células fusiformes, com provável tumor estromal gastrointestinal. A tomografia computadorizada demonstrou tumor na parede anterior do reto e foi sugerida sua ressecção abdominoperineal. O paciente iniciou tratamento com imatinibe e apresentou uma redução significativa nos sintomas. O paciente foi reavaliado por tomografia computadorizada, que evidenciou redução do tamanho do tumor; portanto, foi indicada cirurgia transanal minimamente invasiva. O tumor era ressecável e foi necessário um extenso acompanhamento para romper o órgão, de forma a alcançar a ressecção máxima; caso contrário, o tumor estromal gastrointestinal também seria irressecável. O uso de imatinibe antes da ressecção cirúrgica para reduzir o tamanho do tumor dentro do limite de ressecção é uma abordagem interessante. Como o tumor pode se crescer rapidamente após ser substancialmente reduzido, a literatura ainda apresenta controvérsias quanto ao melhor momento para operar e quanto ao melhor desfecho terapêutico.


Subject(s)
Humans , Male , Middle Aged , Rectal Neoplasms/therapy , Gastrointestinal Stromal Tumors/therapy , Imatinib Mesylate/therapeutic use , Transanal Endoscopic Surgery , Antineoplastic Agents/therapeutic use , Rectal Neoplasms/diagnosis , Gastrointestinal Stromal Tumors/diagnosis
11.
Article in Chinese | WPRIM | ID: wpr-829042

ABSTRACT

OBJECTIVE@#To investigate the effect and mechanism of miR-124-3p-targeing regulating ABCA2 on chronic myelogenous leukemia cell K562-R.@*METHODS@#CML cells with miR-124-3p-overexpression and ABCA2-over-expression as well as subcutaneoustrans planted tumor nude mice were used as study objects. And the CML cells were divided into four groups: K562-R blank control, miR-124-3p mimic control, ABCA2-overexpression and mimic+PC ABCA2. The effects of miR-124-3p and ABCA2 on CML cells were analyzed. The levels of proliferation-, apoptosis- and autophagy- related protein were determined by Western blot. qRT-PCR was employed to detect the levels of miR-124-3p and ABCA2 in K562-R cells. The relationship between miR-124-3p and ABCA2 was validated by luciferase reporter system assays and bioinformatics. Hoechst/immunohistochemical staining and CCK-8 assay were performed to investigate the function involved.@*RESULTS@#miR-124-3p highly expressed in K562-S cells and lowly expressed in K562-R cells, however, ABCA2 lowly expressed in K562-S cells and highly expressed in K562-R cells. Over-expression of miR-124-3p significantly decreased ABCA2 level and cell growth, but increased autophagy and apoptosis in K562-R cells (P<0.01). When ABCA2 was over-expressed, the K562-R cell growth was promoted and autophagy and apoptosis were inhibited (P<0.01). The miR-124-3p promoted cell autophagy and apoptosis but inhibited cell growth in nude mice transplant tumor model (P<0.01).@*CONCLUSION@#miR-124-3p can target ABCA2 to inhibit the growth of CML cells and promote the cell autophagy and apoptosis of CML cells.


Subject(s)
ATP-Binding Cassette Transporters , Animals , Apoptosis , Cell Proliferation , Humans , Imatinib Mesylate , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Mice , Mice, Nude , MicroRNAs
12.
Journal of Experimental Hematology ; (6): 1885-1891, 2020.
Article in Chinese | WPRIM | ID: wpr-879988

ABSTRACT

OBJECTIVE@#To investigated the anti-tumor in vivo effect and mechanism of the acid RNA protein complex (FA-2-b-β) of Agaricus blazei Murrill extract.@*METHODS@#CCK-8 method was used to detected the inhibitory effect of FA-2-b-β on proliferation of primary CML cells from newly diagnosed CML patients, the CML mouse model was established by trail-venous injection of primary CML cells, and the survival time, blood cell count and body weight were observed, the immunoflouresence and immunehistochemistry analysis, RT-qPCR, Western bolt were used to detemine the expression of caspase-3 signal pathway-related apoptosis genes and proteins.@*RESULTS@#The experiments in vitro showed that the proliferative inhibitory rate in drug-treated group increased with concentration- and time-dependent manner (r@*CONCLUSION@#The FA-2-b-β can induce apoptosis of primary CML cells and prolong the survival time of CML model mouse, which may be related with the caspase-3 signal pathway related genes and proteins.


Subject(s)
Agaricus , Animals , Apoptosis , Cell Proliferation , Humans , Imatinib Mesylate , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Mice
13.
Journal of Experimental Hematology ; (6): 1162-1166, 2020.
Article in Chinese | WPRIM | ID: wpr-827146

ABSTRACT

OBJECTIVE@#To investigate the curative efficacy of first generation TKI in the treatment of CML-CP combined with vPh and genetic characteristics.@*METHODS@#60 patients with CML-CP combined with vPh from January 2010 to May 2017 in the First Affiliated Hospital of Kunming Medical University were chosen as CML-CP-vPh group, and 107 patients with CML-CP combined with typical Ph chromosome at the same time were chosen as control group. The patients in two groups were treated with imatinib; The curative efficacy, karyotype and FISH signal type were compared between 2 groups, and the factors influencing long-term survival of patients were analyzed by Cox risk model.@*RESULTS@#There was no significant difference in the demographic and hematological baseline data between 2 groups (P>0.05), and there was no significant difference in the incidence of drug-resistance between 2 groups (P>0.05). The incidence of primary drug-resistance and primary hematological drug-resistance in the CML-CP-vPh group were significantly higher than that in control group (P<0.05). There was no significant difference in the accumulative CCyR rate, accumulative MMR rate, OS and EFS between 2 groups (P>0.05). Multivariate Cox model analysis showed that vPh not correlated with OS and EFS of patients with CML-CP (P>0.05). The factors influencing OS in CML-vPh patients included high risk of Sokal scores, peripheral blood basophils proportion ≥10%, BCR-ABL in 3 months after treatment<10%, achieviag CCyR in 6 months after treatment and achieviag MMR in 12 months after treatment (P<0.05). The factors influencing EFS included BCR-ABL<10% in 3 months after treatment and achieving MMR in 12 months after treatment (P<0.05). The regions with high frequency of heterotopic involvement included 12q1, 12q2 [9 cases (15.00%)] and 1p3 [8 cases (13.33%)]. The percentage of 2G2R1Y, 1G1R2F, 1G2R1Y, 2G1R1Y and 1G1R1Y in FISH signal types were 73.33%, 10.00%, 1.67%, 1.67% and 1.67% respectively.@*CONCLUSION@#Patients with CML-CP combined with vPh possess higher primary drug-resistance rate and primary hematological drug-resistance rate for the first generation TKI, while second-generation TKI can efficiently improve long-term survival, its efficacy is similar to efficacy for patients with typical Ph chromosomes. CML-CP combined with vPh does not display special demographic and hematological characteristics. The main involved regions of heterotopic variants include 12q1, 12q2 and 1p3, while 2G2R1Y type is the most common type of FISH signal.


Subject(s)
Fusion Proteins, bcr-abl , Humans , Imatinib Mesylate , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Treatment Outcome
14.
Article in English | WPRIM | ID: wpr-787143

ABSTRACT

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.


Subject(s)
Animals , Brain , Carotid Arteries , Cerebral Infarction , Connexin 43 , Imatinib Mesylate , Ischemia , Learning , Memory , Mice , Motor Activity , Neuroprotection , Phosphotransferases , Reperfusion , Reperfusion Injury , STAT3 Transcription Factor , Transducers , Walking
15.
Braz. J. Pharm. Sci. (Online) ; 56: e18973, 2020. graf
Article in English | LILACS | ID: biblio-1249174

ABSTRACT

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.


Subject(s)
In Vitro Techniques/methods , Efficacy/classification , Imatinib Mesylate/adverse effects , Polyethylene Glycols/analysis , Inhibitory Concentration 50 , MCF-7 Cells/classification , Drug Liberation/drug effects
16.
Braz. J. Pharm. Sci. (Online) ; 56: e18583, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132052

ABSTRACT

Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco's Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 µL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 µg/mL for the three different media


Subject(s)
Determination , Validation Study , Imatinib Mesylate/antagonists & inhibitors , Pharmaceutical Preparations/analysis , Chromatography, Liquid/methods , Acetates/adverse effects , Neoplasms
17.
Hematol., Transfus. Cell Ther. (Impr.) ; 41(4): 329-334, Oct.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1056235

ABSTRACT

ABSTRACT Introduction: The incidence of grade 3-4 anemia was reported to be 3% with imatinib therapy for newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP). However, there are few data regarding the causes and the development of anemia after long-term treatment. This study aimed to evaluate the incidence of anemia after at least two years of imatinib treatment of CML patients in the CP and to identify other contributing causes of anemia in this population. Patients and methods: We performed a retrospective analysis of 97 CML patients in the CP treated with imatinib for at least two years. We analyzed the hemoglobin (Hb) levels of CML patients at diagnosis, upon initiation of treatment with imatinib and after two years of imatinib treatment, and investigated other causes of anemia in this population. Results: Most of the patients presented Hb levels below the normal range (80.4%) after the second year of treatment, 17.9% grade 2 and 1.3% grade 3. In 13 cases (16.7%), anemia was attributed to resistance and in 13 cases (16.7%) the following causes were identified: iron deficiency (n = 5), hypothyroidism (n = 2), vitamin B12 deficiency (n = 3), acquired immune deficiency syndrome (AIDS) (n = 1), pulmonary tuberculosis (n = 1) and renal toxicity (n = 1). In 52 patients (66.6%), there were no other factors contributing to anemia, except imatinib treatment. Conclusion: Regular follow-up is required to identify the causes of anemia not related to CML or imatinib toxicity. The importance of investigating secondary causes of anemia should be emphasized, especially in patients with good adherence to treatment and satisfactory therapeutic response.


Subject(s)
Humans , Male , Female , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Drug-Related Side Effects and Adverse Reactions , Imatinib Mesylate/adverse effects , Imatinib Mesylate/therapeutic use , Anemia
18.
Hematol., Transfus. Cell Ther. (Impr.) ; 41(3): 222-228, July-Sept. 2019. tab, graf, ilus
Article in English | LILACS | ID: biblio-1039921

ABSTRACT

ABSTRACT Objective: To assess clinical outcomes of intolerant, relapsed or refractory patients who could not be treated with new tyrosine kinase inhibitors or experimental therapies. Methods: A retrospective cohort of 90 chronic myeloid leukemia patients in all phases of the disease treated with imatinib mesylate as their first TKI therapy, and with dasatinib or nilotinib as the next line of therapy. We evaluated clinical outcomes of these patients, with special focus on the group that needed more than two therapy lines. Results: Thirty-nine percent of patients were refractory or intolerant to imatinib. An 8-year overall survival rate of the patients who went through three or more lines of treatment was significantly lower, compared to those who were able to maintain imatinib as their first-line therapy (83% and 22%, respectively p < 0.01). Decreased overall survival was associated with advanced-phase disease (p < 0.01), failure to achieve major molecular response in first-line treatment (p < 0.01) and interruption of first-line treatment due to any reason (p = 0.023). Failure in achieving complete cytogenetic response and major molecular response and treatment interruption were associated with the progression to the third-line treatment. Conclusion: The critical outcome observed in relapsed, intolerant or refractory chronic phase CML patients reflects the unmet need for this group of patients without an alternative therapy, such as new drugs or experimental therapies in clinical trials. Broader access to newer treatment possibilities is a crucial asset to improve survival among CML patients, especially those refractory or intolerant to first-line therapies.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Survival Analysis , Imatinib Mesylate , Dasatinib
19.
Hematol., Transfus. Cell Ther. (Impr.) ; 41(2): 106-113, Apr.-June 2019. tab, graf, ilus, mapas
Article in English | LILACS | ID: biblio-1012187

ABSTRACT

ABSTRACT Background: There has been a revolution in the treatment of Chronic Myeloid Leukemia since imatinib's introduction. However, patient adherence has a great impact on the response obtained with medical treatment. This study's objective was to analyze the drug adherence and the factors that influenced it in patients with Chronic Myeloid Leukemia in a referral hospital in the Brazilian Amazon. Method: This was a retrospective study including 120 patients with Chronic Myeloid Leukemia from January 2002 to December 2014. The adherence was estimated by the Proportion of Days Covered and the persistence by Kaplan-Meier analysis. The data was analyzed in Epi Info 7® software and the relationship between the variables was analyzed by Fisher's exact test. A p-value lower than 0.05 was considered significant. Results: Twenty-seven patients (22.5%) were considered non-adherent. There has been irregular medication use and disinterest in the treatment in 20.83% (n = 25), of which 13 were considered non-adherent (p < 0.001). A total of 26.67% (n = 32) abandoned the treatment for a period. Of those, 56.25% (n = 18) were non-adherent (p < 0.001). Distance to the hospital, lack of medication and side-effects were all non-significant to low adherence. At the end of a 360-day follow-up, 44.16% (n = 53) of patients presented a break in persistence, whose average was 255 days. Conclusion: The adherence found in this study was similar to that found in others of its kind. The only factors that negatively influenced the adherence were disinterest and abandonment of treatment, which can reflect the need to individually educate Chronic Myeloid Leukemia patients.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Amazonian Ecosystem , Imatinib Mesylate
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