Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty / 中华创伤杂志(英文版)

PURPOSE@#Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.@*METHODS@#The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3.@*RESULTS@#For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738.@*CONCLUSION@#It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Is there a clinical pathological correlation of colorectal adenocarcinoma with the immunohistochemical expression of opn and abcb5? / Há correlação clínicopatológica do adenocarcinoma colorretal com a expressão imunoistoquímica do opn e abcb5?

ABSTRACT Background: Studies with biomarkers in TMA (tissue microarray) have been showing important results regarding its expression in colon cancer. Aim: Correlate the expression profile of the OPN and ABCB5 biomarkers with the epidemiological and clinicopathological characteristics of the patients, the impact on the progression of the disease and the death. Method: A total of 122 CRC patients who underwent surgical resection, immunomarking and their relationship with progression and death events were evaluated. Result: The average age was 61.9 (±13.4) years. The cases were distributed in 42 (35.9%) in the ascending/transverse colon, 31 (26.5%) in the sigmoid, 27 in the rectum (23.1%), 17 (14.5%) in the descending colon. Most patients had advanced disease (stages III and IV) in 74 cases (60.9%). There was a predominance of moderately differentiated tumors in 101 samples (82.8%); despite this, the poorly differentiated subtype proved to be an independent risk factor for death in 70%. Metastasis to the liver proved to be an independent risk factor for death in 75% (18/24), as well as patients with primary rectal tumors in 81.5% (22/27). Conclusion: The immunohistochemical expression of the OPN and ABCB5 markers was not associated with epidemiological and clinicopathological characteristics. Regarding the progression of disease and death, it was not possible to observe a correspondence relationship with the evaluated markers.

RESUMO Racional: Estudos com biomarcadores com TMA (tissue microarray) vêm demostrando resultados importantes em relação à expressão de biomarcadores em câncer de cólon. Objetivo: Correlacionar o perfil de expressão dos biomarcadores OPN e ABCB5 com as características epidemiológicas e clinicopatológicas dos pacientes, o impacto na progressão de doença e no evento óbito. Método: Foram avaliados 122 pacientes de CCR submetidos à ressecção cirúrgica e à imunomarcação e relação com os eventos progressão e óbito. Resultado: A média de idade encontrada foi de 61,9 (±13,4) anos. Os casos distribuíram-se em 42 (35,9%) no cólon ascendente/transverso, 31 (26,5%) no sigmoide, 27 no reto (23,1%), 17 (14,5%) no cólon descendente. A maioria dos pacientes apresentou doença avançada (estadio III e IV) em 74 casos (60,9%). Houve predomínio de tumor moderadamente diferenciado em 101 amostras (82,8%); apesar disso, o subtipo pouco diferenciado mostrou-se como fator de risco independente para óbito em 70% dos casos. Metástase para o fígado mostrou-se fator de risco independente para óbito em 75% dos casos (18/24), assim como pacientes com tumores primários de reto em 81,5% (22/27). Conclusão: A expressão imunoistoquímica dos marcadores OPN e ABCB5 não apresentou associação com as características epidemiológicas e clinicopatológicas. Em relação à progressão de doença e evento óbito, não se conseguiu observar relação de correspondência com os marcadores avaliados.

P-glycoprotein expression in oral lichen planus

Abstract: Oral lichen planus (OLP) is a stress induced inflammatory condition with malignant potency. The mdr1 (multidrug resistance) is a stress gene overexpressed in cancerous conditions and its translated form, the p-glycoprotein efflux transporter is usually overexpressed with chemotherapy, leading to chemoresistance. OLP, a lesion with carcinogenic potency, is broadly classified into the asymptomatic reticular form and the aggressive erosive form. The objective of the study was to verify the expression level of p-glycoprotein in antifungal-treated and untreated reticular OLP, in untreated erosive OLP and erosive OLP patients treated with corticosteroid. Semi-quantitative reverse transcriptase polymerase chain reaction (SQ-RTPCR) and ELISA were performed on biopsy tissue samples to evaluate the mdr1 mRNA and protein expression of p-glycoprotein, respectively. The present study shows for the first time that mdr1 mRNA as well as its translated form p-glycoprotein are overexpressed in OLP subjects compared to healthy individuals. This overexpression is significantly higher in erosive than in reticular OLP patients, further confirming that the erosive form has higher risk for multidrug resistance. A higher expression is also observed in corticosteroid-treated erosive cases than similar untreated ones. The gradation of expression is in conformity with severity of the disease.

Relación entre la expresión de Glicoproteína P y los hallazgos de la centellografía con Tc-99m MIBI en pacientes con cáncer mamario avanzado / Relation between P-glycoprotein expression and scintigraphic findings with Tc-99m MIBI in advanced breast cancer patients

En un estudio previo encontramos que el grado de captación tumoral pre-tratamiento de Tc-99m MIBI, un sustrato de transporte de la Glicoproteína P (Pgp), se correlaciona con la respuesta clínica a la quimioterapia basada en antraciclinas en pacientes con cáncer mamario avanzado (CMA). El objetivo del presente estudio fue determinar la relación entre la expresión tumoral de Pgp, el grado de captación tumoral de MIBI y la respuesta clínica a la quimioterapia en pacientes con CMA. Se estudiaron 27 lesiones correspondientes a 26 pacientes. La expresión de Pgp fue investigada previamente a la quimioterapia mediante inmunocitoquímica. Las imágenes centellográficas fueron realizadas dentro de la semana previa a la quimioterapia, 10 minutos (fase temprana) y 60 minutos (fase tardía) después de la inyección de 740-1110 MBq de Tc-99m MIBI. La captación lesional fue cuantificada mediante tasa de conteo tumor/fondo en las fases precoz (T/Fp) y tardía (T/Ft) del estudio. Ambos índices fueron superiores (p< 0.05) en las lesiones Pgp negativas (n=21) que en las Pgp positivas (n=6). Además, fueron más elevados en las lesiones respondedoras que en las no respondedoras (T/Fp 2.2 vs 1.4; T/Ft 1.8 vs 1.4; p< 0.05). Todas las lesiones con un índice T/Fp mayor de 1.5 respondieron a la quimioterapia. No se encontró asociación significativa entre la expresión de Pgp y la respuesta a la quimioterapia. Concluimos que la centellografía con MIBI puede predecir el fenotipo MDR1 y la respuesta a la quimioterapia basada en adriamicina en pacientes con CMA. El nivel de expresión de Pgp no sería útil para predecir dicha respuesta.