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OBJECTIVES: Although metastatic breast cancer (MBC) is considered incurable, a specific subset of patients exhibits prolonged survival and even achieve a "cure". We retrospectively identified predictive prognostic factors and systemic therapy models to find this group of potentially cured patients. METHODS: Consecutive patients diagnosed with MBC from 1991-2016 in West China Hospital were included. Univariate and multivariate analyses were conducted to assess the association of clinical factors and systemic therapy models with overall survival (OS), breast cancer-specific survival (BCSS) and progression-free survival (PFS). RESULTS: The median OS was 63.4 months. Age, tumor size, lymph node metastasis, histologic grade, molecular subtype, site and number of metastases and metastasis-free interval (MFI) were related to the prognosis of MBC (P < .05). Patients with T1, N0-1, luminal A, bone metastasis, OMBC (oligometastatic breast cancer) or metastasis-free interval (MFI) ≥ 3 years showed the median OS more than 10 years (P < .001). Independent prognostic factors that correlated with OS and BCSS were residence, lymph node metastasis, histologic grade, molecular subtype, and site of metastasis (P < .05). The group of sequential chemo-endocrine therapy (ST) in hormone receptor (HR)-positive MBC patients showed the highest overall response rate (ORR) (P < .05). However, patients who received endocrine therapy (ET) showed the best OS, BCSS and PFS in the first two-line treatment, followed by ST and chemotherapy (CT) (P < .05). CONCLUSIONS: Our study shows the predictive prognostic factors and systemic therapy models to facilitate patients likely to achieve long-term survival.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Metástasis de la Neoplasia , Pronóstico , Receptor ErbB-2/metabolismo , Estudios RetrospectivosRESUMEN
Objectives: To explore the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on lung adenosquamous cell carcinoma (ASC) with EGFR mutation. Methods: Efficacy of EGFR-TKIs in the treatment of advanced or recurrent lung ASC with EGFR mutations was assessed retrospectively in 44 patients. Pooled analysis of 74 patients using EGFR-TKIs, including 30 patients selected from 11 publications, was conducted. Results: In our retrospective research, patients treated with EGFR-TKI in ASC with EGFR mutations had objective response rate (ORR) of 54.5%, disease control rate (DCR) of 79.5%, median progression free survival (mPFS) of 8.8 months, and median overall survival (mOS) of 19.43 months, respectively. A pooled analysis reveals ORR, DCR, mPFS, and mOS are, respectively, 63.4%, 85.9%, 10.00 months, and 21.37 months for ASC patients. In patients with deletions in exon 19 and exon 21 L858R mutations, mPFS (11.0 versus 10.0 months, P=0.771) and mOS (23.67 versus 20.33 months, P=0.973) were similar. Erlotinib or gefitinib-treated patients had an overall survival trend that was superior to that of icotinib-treated patients. Conclusions: ASC harboring EGFR mutations can be treated with EGFR-TKI in a similar manner to Adenocarcinoma (ADC) harboring EGFR mutations. There is still a need for further investigation to identify the separate roles of ASC's two components in treating EGFR.
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E2F transcription factors (E2Fs) are a group of genes that encode a family of transcription factors. They have been identified as being involved in the tumor progression of various cancer types. However, little is known about the expression level, genetic variation, molecular mechanism, and prognostic value and immune infiltration of different E2Fs in HNSCC.In this study, we utilized multiple databases to investigate the mRNA expression level, genetic alteration, and biological function of E2Fs in HNSCC patients. Then, the relationship between E2Fs expression and its association with the occurrence, progress, prognosis, and immune cell infiltration in patients with HNSCC was evaluated. We found that all eight E2Fs were higher expressed in HNSCC tissues than in normal tissues, and the expression levels of E2F1/2/3/4/5/6/8 were also associated with the stage and grade of HNSCC. The abnormal expression of E2F1/2/4/8 in HNSCC patients is related to the clinical outcome. The expression of E2Fs was statistically correlated with the immune cell infiltration in HNSCC and the infiltration of B cells and CD8+ T cells were positively associated with better OS in HNSCC patients. Furthermore, we verified the E2F2 at the tissue level in the validation experiment. Our study may provide novel insights into the choice of immunotherapy targets and potential prognostic biomarkers in HNSCC patients.
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Factores de Transcripción E2F , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Linfocitos T CD8-positivos/inmunología , Regulación Neoplásica de la Expresión Génica , Estadificación de Neoplasias , Linfocitos Infiltrantes de Tumor/inmunologíaRESUMEN
The extracellular matrix (ECM) is a significant constituent of tumors, fulfilling various essential functions such as providing mechanical support, influencing the microenvironment, and serving as a reservoir for signaling molecules. The abundance and degree of cross-linking of ECM components are critical determinants of tissue stiffness. In the process of tumorigenesis, the interaction between ECM and immune cells within the tumor microenvironment (TME) frequently leads to ECM stiffness, thereby disrupting normal mechanotransduction and promoting malignant progression. Therefore, acquiring a thorough comprehension of the dysregulation of ECM within the TME would significantly aid in the identification of potential therapeutic targets for cancer treatment. In this regard, we have compiled a comprehensive summary encompassing the following aspects: (1) the principal components of ECM and their roles in malignant conditions; (2) the intricate interaction between ECM and immune cells within the TME; and (3) the pivotal regulators governing the onco-immune response in ECM.
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Mecanotransducción Celular , Neoplasias , Humanos , Matriz Extracelular , Carcinogénesis , Transformación Celular Neoplásica , Microambiente Tumoral/fisiologíaRESUMEN
The accurate prediction of the status of PLNM preoperatively plays a key role in treatment strategy decisions in early-stage cervical cancer. The aim of this study was to develop and validate a radiomics-based nomogram for the preoperative prediction of pelvic lymph node metastatic status in early-stage cervical cancer. One hundred fifty patients were enrolled in this study. Radiomics features were extracted from T2-weighted MRI imaging (T2WI). Based on the selected features, a support vector machine (SVM) algorithm was used to build the radiomics signature. The radiomics-based nomogram was developed incorporating radiomics signature and clinical risk factors. In the training cohort (AUC = 0.925, accuracy = 81.6%, sensitivity = 70.3%, and specificity = 92.0%) and the testing cohort (AUC = 0.839, accuracy = 74.2%, sensitivity = 65.7%, and specificity = 82.8%), clinical models that combine stromal invasion depth, FIGO stage, and MTD perform poorly. The combined model had the highest AUC in the training cohort (AUC = 0.988, accuracy = 95.9%, sensitivity = 92.0%, and specificity = 100.0%) and the testing cohort (AUC = 0.922, accuracy = 87.1%, sensitivity = 85.7%, and specificity = 88.6%) when compared to the radiomics and clinical models. The study may provide valuable guidance for clinical physicians regarding the treatment strategies for early-stage cervical cancer patients.
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ALK-positive histiocytosis (APH) is a rare and recently described, solitary or generalized, histiocytic proliferative disorder with a characteristic gene translocation involving the fusion of the ALK gene at chromosome 2p23. To date, only 25 cases of APH have been reported. The patient presented with multiple nodules in the lung, liver, gallbladder, pancreas, kidney, and skin rashes, along with recurrent pancreatitis and cholecystitis. The histiocytes from the lesion were positive for CD68 and ALK and negative for S100 and CD1α. A reduced dose of the ALK inhibitor alectinib was administered rather than the standard dose of alectinib or chemotherapy because of recurrent pancreatitis, which has not been previously reported in APH cases. After 18 months of follow-up, the patient was maintained on alectinib, and a partial response (PR) was achieved.
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PURPOSE: To build and evaluate a radiomics-based nomogram that improves the predictive performance of the LVSI in cervical cancer non-invasively before the operation. METHOD: This study involved 149 patients who underwent surgery with cervical cancer from February 2017 to October 2019. Radiomics features were extracted from T2 weighted imaging (T2WI). The radiomic features were selected by logistic regression with the least absolute shrinkage and selection operator (LASSO) penalty in the training cohort. Based on the selected features, support vector machine (SVM) algorithm was used to build the radiomics signature on the training cohort. Incorporating radiomics signature and clinical risk factors, the radiomics-based nomogram was developed. The sensitivity, specificity, accuracy, and area under the curve (AUC) and Receiver operating characteristic (ROC) curve were calculated to assess these models. RESULT: The radiomics model performed much better than the clinical model in both training (AUCs 0.925 vs. 0.786, accuracies 87.5% vs. 70.5%, sensitivities 83.6% vs. 41.7% and specificities 90.9% vs. 94.7%) and testing (AUCs 0.911 vs. 0.706, accuracies 84.0% vs. 71.3%, sensitivities 81.1% vs. 43.4% and specificities 86.4% vs. 95.0%). The combined model based on the radiomics signature and tumor stage, tumor infiltration depth and tumor pathology yielded the best performance (training cohort, AUC = 0.943, accuracies 89.5%, sensitivities 85.4% and specificities 92.9%; testing cohort, AUC = 0.923, accuracies 84.6%, sensitivities 84.0% and specificities 85.1%). CONCLUSION: Radiomics-based nomogram was a useful tool for predicting LVSI of cervical cancer. This would aid the selection of the optimal therapeutic strategy and clinical decision-making for individuals.
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Narrow-band-gap III-V semiconductor nanowires (NWs) with a suitable band structure and strong light-trapping ability are ideal for high-efficiency low-cost solar water-splitting systems. However, due to their nanoscale dimension, they suffer more severe corrosion by the electrolyte solution than the thin-film counterparts. Thus, short-term durability is the major obstacle for using these NWs for practical water-splitting applications. Here, we demonstrated for the first time that a thin layer (â¼7 nm thick) of compact TiO2 deposited by atomic layer deposition can provide robust protection to III-V NWs. The protected GaAs NWs maintain 91.4% of its photoluminescence intensity after 14 months of storage in ambient atmosphere, which suggests the TiO2 layer is pinhole-free. Working as a photocathode for water splitting, they exhibited a 45% larger photocurrent density compared with unprotected counterparts and a high Faraday efficiency of 91% and can also maintain a record-long highly stable performance among narrow-band-gap III-V NW photoelectrodes; after 67 h photoelectrochemical stability test reaction in a strong acid electrolyte solution (pH = 1), they show no apparent indication of corrosion, which is in stark contrast to the unprotected NWs that fully failed after 35 h. These findings provide an effective way to enhance both stability and performance of III-V NW-based photoelectrodes, which are highly important for practical applications in solar-energy-based water-splitting systems.
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Transparent conducting oxides (TCOs) are ubiquitous in modern consumer electronics. SnO2 is an earth abundant, cheaper alternative to In2O3 as a TCO. However, its performance in terms of mobilities and conductivities lags behind that of In2O3. On the basis of the recent discovery of mobility and conductivity enhancements in In2O3 from resonant dopants, we use a combination of state-of-the-art hybrid density functional theory calculations, high resolution photoelectron spectroscopy, and semiconductor statistics modeling to understand what is the optimal dopant to maximize performance of SnO2-based TCOs. We demonstrate that Ta is the optimal dopant for high performance SnO2, as it is a resonant dopant which is readily incorporated into SnO2 with the Ta 5d states sitting â¼1.4 eV above the conduction band minimum. Experimentally, the band edge electron effective mass of Ta doped SnO2 was shown to be 0.23m 0, compared to 0.29m 0 seen with conventional Sb doping, explaining its ability to yield higher mobilities and conductivities.
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An Al2O3 thin film has been grown by vapor deposition using different Al precursors. The most commonly used precursor is trimethylaluminum, which is highly reactive and pyrophoric. In the purpose of searching for a more ideal Al source, the non-pyrophoric aluminum tri-sec-butoxide ([Al(OsBu)3], ATSB) was introduced as a novel precursor for atomic layer deposition (ALD). After demonstrating the deposition of Al2O3 via chemical vapor deposition (CVD) and 'pulsed CVD' routes, the use of ATSB in an atomic layer deposition (ALD)-like process was investigated and optimized to achieve self-limiting growth. The films were characterized using spectral reflectance, ellipsometry and UV-Vis before their composition was studied. The growth rate of Al2O3 via the ALD-like process was consistently 0.12 nm/cycle on glass, silicon and quartz substrates under the optimized conditions. Scanning electron microscopy and transmission electron microscopy images of the ALD-deposited Al2O3 films deposited on complex nanostructures demonstrated the conformity, uniformity and good thickness control of these films, suggesting a potential of being used as the protection layer in photoelectrochemical water splitting.
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Contrast-enhanced computed tomography (CECT) has been extensively used in the restaging and assessment of treatment response for diffuse large B-cell lymphoma (DLBCL). However, CECT does not provide information regarding the specific functionality of lesions. A patient (56 years old, female) was previously admitted to the present institution, with bilateral cervical masses. Following numerous cycles of chemotherapy, a stable disease status was confirmed using CECT. In conjunction with CECT imaging results, contrast-enhanced ultrasound (CEUS) demonstrated important semi-functional information regarding blood perfusion, during the revision of treatment assessment. 18F-fluoro-2-deoxyglucose (FDG)-positron emission tomography-computed tomography imaging demonstrated no increase in FDG uptake of the same tumor lesion, consistent with the results of CEUS. CEUS exhibited the potential to present complementary results to CECT, in the therapeutic assessment of DLBCL, which, to the best of our knowledge, has not previously been reported.
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We obtained a full-length cDNA fragment encoding human O(6)-methylguanine-DNA-methyltransferase (MGMT) from the liver tissue of a patient with cholelithiasis by RT-PCR and confirmed by DNA sequencing. The polycistronic retrovirus vector G1Na-MGMT-Neo(r)-IRES-MDR1 was constructed and verified by restriction endonuclease analysis and DNA sequencing. The vector was transfected into packaging cells GP+E86 and PA317 by the LipofectAMINE method. Cord blood CD34+ cells were transfected with the supernatant of retrovirus containing human MGMT and MDR1cDNA under stimulation of hematopoietic growth factors. PCR, RT-PCR, Southern Blot, Western Blot, FACS and MTT analyses showed that dual drug resistance genes have been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The transgene cord blood CD34+ cells conferred 5.8-6.3-fold stronger resistance to P-glycoprotein effluxed drugs and 5-fold to BCNU than untransduced cells. The polycistronic retrovirus vector mediated transfer of two different types of drug resistance genes into human cord blood CD34+ cells and co-expression provided an experimental foundation for improving combination chemotherapy tolerance in clinical practice.
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Antineoplásicos/toxicidad , Genes MDR , Genes , Virus Helper/genética , Células Madre Hematopoyéticas/citología , O(6)-Metilguanina-ADN Metiltransferasa/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antígenos CD/sangre , Antígenos CD34/sangre , Carmustina/toxicidad , ADN Complementario , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Sangre Fetal/citología , Citometría de Flujo , Vectores Genéticos , Factores de Crecimiento de Célula Hematopoyética/farmacología , Humanos , Células K562 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Vincristina/toxicidadRESUMEN
OBJECTIVE: To investigate the exact kinetics of donor chimerism (DC), outcome of mixed chimerism (MC) and prognostic role of chimerism in the evaluation of engraftment, disease relapse, GVHD and long term survival after nonmyeloablative stem cell transplantation (NST). METHODS: 18 patients who received HLA compatible NST were evaluated. Peripheral blood and bone marrow were collected before and after transplantation at different time. DNA was extracted using QIAmp blood mini kit. Nine different STR markers were co-amplified in a single reaction by commercial AmpF/STR profiler plus PCR amplification kit. Separation of the PCR products and fluorescence detection were performed with ABI prism 310 genetic analyzer with capillary electrophoresis. Genescan and genotype software were used for size calling and quantification of peak areas. The formula to calculate donor chimerism values was based on different allelic distribution types between the donor and recipient. RESULTS: (1) Serial STR-PCR analysis revealed that donor chimerism became dominant (DC > 60%) by day 8; it preceded the detection of hematologic engraftment by an average of 4 days. It was also shown that chronic myeloid leukemia (CML) patients frequently had more delayed donor engraftment as compared with patients of acute leukemia or nonmalignant hematological diseases because the pretransplantation immune status of these two kinds of patients was different. (2) After NST, chimeric status had a process of conversion from the mixed chimerism (MC) to full donor chimerism (FDC). (3) The incidence of graft versus host disease (GVHD) of FDC group was higher than that of MC group (90.0% vs 62.5%). The average time between establishment of FDC and appearance of GVHD was 9 days. (4) Full donor chimerism and stable mixed chimerism with a high level of donor cells were compatible with disease free survival. On the contrary, progressive decrease of donor chimerism value was always followed by hematological relapse or graft rejection. CONCLUSIONS: Sequencial and quantitative detection of donor chimerism may be of great value to study the kinetics of engraftment of NST, to evaluate the status of engraftment, to predict the outcome and prognosis of patients posttransplant and to guide implementation of therapy at an early stage.
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Trasplante de Células Madre Hematopoyéticas , Quimera por Trasplante , Adolescente , Adulto , Ciclosporina/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Hematopoyesis , Humanos , Masculino , Persona de Mediana Edad , Secuencias Repetidas en TándemRESUMEN
To elucidate the effect of established primary bone marrow stromal layers on the gene transduction of human hematopoietic stem/progenitor cells (HSC/HPC), mononuclear cells (MNC) from adult bone marrow were isolated by centrifugation on Ficoll-Hypaque gradients and plated in stromal culture medium. The cells were incubated until passage 4 to establish primary stromal layers. The HSC/HPC prestimulated by cytokines were transduced by retroviral supernatant containing mdr1 gene in presence of irradiated stroma-contact support. Transduced cells were plated in a colony-forming unit assay with and without vincristine (VCR) to assess the efficiency of transduction. Individual colonies were also analyzed by polymerase chain reaction (PCR) for the presence of provirus. The results showed that the mixed adherent cell layers were formed when adult bone marrow stromal cells were incubated for four to six weeks, mainly being composed of fibroblasts. In the presence of stroma-contact support, the average of gene transduction efficiency in marrow-derived progenitors increased 2.1 to 3.3 folds measured by colony-forming assay and/or PCR, significantly higher than those without support of stroma. It is concluded that the presence of bone marrow stroma support in combination with cytokine facilitates augmenting the extent of retroviral-mediated gene transduction.
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Células de la Médula Ósea/fisiología , Células Madre Hematopoyéticas/metabolismo , Transducción Genética , Genes MDR , Humanos , Retroviridae/genética , Células del Estroma/fisiologíaRESUMEN
BACKGROUND & OBJECTIVE: This study was designed to seek an efficient and safe method for transfer of genes of large size. METHODS: The retroviral vector containing different kinds drug resistance genes-class 1 aldehyde dehydrogenase (ALDH1) and multidrug resistance gene (MDR1) was linearized by the restriction enzyme NdeI digestion, and introduced into the packaging PA317 cells by electroporation. Selection was performed by vincristine (VCR) and 4-hydroperoxycyclophosphamide(4-HC) to obtain ALDH1 and MDR1 stably expressing cells. The integration of provirus, transcription and translation of foreign genes were confirmed by Southern blot, reverse transcription(RT)-PCR and flow cytometry, respectively. The safety of this delivery system was verified by testing helper virus(envelop gene) using nested PCR. RESULTS: Both ALDH1 and MDR1 were successfully transduced into PA317 cells by electroporation. Stable integration of foreign genes in host cells genome was determined by Southern hybridization blot. The transcription of ALDH1 and MDR1 was demonstrated by RT-PCR. The overexpression of P-glycoprotein encoded by the downstream gene MDR1 with approximately a 4-fold increase in 98% cells was analyzed by flow cytometry. No helper virus can be detected by nested PCR assay. CONCLUSION: These results implicate that the introduction and overexpression of both ALDH1 and MDR1 genes in vitro is attainable by a simple and convenient electroporation method, with the character of safety and high efficiency.
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Aldehído Deshidrogenasa/genética , Electroporación , Técnicas de Transferencia de Gen , Genes MDR , Isoenzimas/genética , Familia de Aldehído Deshidrogenasa 1 , Citometría de Flujo , Genes env , Retinal-Deshidrogenasa , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cells lines in vitro, this study tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. Results showed that a retroviral vector was used to transduce full-length human ALDH1 cDNA into human hematopoietic cell line K562 that was then tested for resistance to 4-hydroxycyclophosphamide (4-HC), an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced K562 cells (50% inhibition concentration, IC50 = 10 micro mol/L). These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.
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Aldehído Deshidrogenasa/genética , Antineoplásicos Alquilantes/farmacología , Supervivencia Celular/efectos de los fármacos , Ciclofosfamida/análogos & derivados , Ciclofosfamida/farmacología , Células K562/efectos de los fármacos , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Regulación Enzimológica de la Expresión Génica , Vectores Genéticos/genética , Humanos , Concentración 50 Inhibidora , Células K562/enzimología , Células K562/metabolismo , Retroviridae/genética , TransfecciónRESUMEN
BACKGROUND & OBJECTIVE: Drug resistance is a major factor in chemotherapeutic failure of leukemia. Multidrug resistant cell lines are the good models for investigating the mechanisms and reversal of acquired drug resistance. This study was designed to explore the multidrug resistance (MDR) mechanisms in cell line HL-60/VCR. METHODS: Flow cytometry and a panel of antibodies were used to analyze the expression of MDR proteins (P-gp, MRP, LRP, BCRP, GST-pi) and apoptosis-modulating proteins (bcl-2, bcl-x, bax, bad) in MDR cell line HL-60/VCR and drug sensitive cell line HL-60. RESULTS: The expression levels of MDR proteins (P-gp, MRP, BCRP, GST-pi) were (18.62, 1.19, 1.50, 1.32-flod) higher in HL-60/VCR than in HL-60, while the expression of LRP level was similar. The levels of apoptosis-modulating proteins(bcl-2, bcl-x, bad) were (2.48, 1.25, 1.08-fold) higher in HL-60/VCR than in HL-60, while the pro-apoptosis protein bax contrarily decreased in HL-60/VCR. CONCLUSION: Various MDR mechanisms were involved in multi-drug resistance HL-60/VCR cell line, which including increasing expression of drug-resistance protein (P-gp, MRP, BCRP, and GST-pi); the apoptosis-modulating proteins (bcl-2, bcl-x, bax, and bad) might take part in the mechanism of drug resistance.
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Antineoplásicos Fitogénicos/farmacología , Resistencia a Múltiples Medicamentos/fisiología , Proteínas de Neoplasias , Células Tumorales Cultivadas/metabolismo , Vincristina/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/biosíntesis , Proteínas Portadoras/biosíntesis , Ensayos de Selección de Medicamentos Antitumorales , Gutatión-S-Transferasa pi , Glutatión Transferasa/biosíntesis , Células HL-60 , Humanos , Isoenzimas/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Células Tumorales Cultivadas/efectos de los fármacos , Proteína X Asociada a bcl-2 , Proteína Letal Asociada a bcl , Proteína bcl-XRESUMEN
OBJECTIVE: To explore the efficiency and toxicity of non-myeloablative stem cell transplantation (NAST) for hematological disease. METHODS: Seventeen patients, including 3 acute myeloid leukemia, 6 chronic myelogenous leukemia, 4 severe aplastic anemia, 2 non-Hodgkin's lymphoma, 1 multiple myeloma and 1 myelodysplastic syndromes received NAST from HLA-identical sibling donors. Peripheral blood stem cells were mobilized by G-CSF 300 microg/12 hours x 5 d. (2.15 -10.01) x 10(6) CD(34)(+) cells/kg were transplanted. A non-myeloablative conditioning regimen included fludarabine 30 mg.m(-2).d(-1) x 6 d;busulfan 4 mg.kg(-1).d(-1) x 2 d or cyclophosphamide 50 mg.kg(-1).d(-1) x 2 d and antilymphocytic globulin 12 approximately 15 mg.kg(-1).d(-1) x 4 d. Cyclosporin A was used to prevent graft versus host disease (GVHD) alone and no G-CSF was administered after NAST. RESULT: Hematopoiesis reconstitution resumed on day 8 to day 19 (average of day 13). Severe mucositis was absent. Hepatic venoocclusive disease did not occur. Infectious complications were rare. Acute and chronic GVHD each occurred in 5 patients. Idiopathic pneumonia was developed in 5 patients. In the follow-up duration of 120 to 425 days, 16 of the 17 cases had a stable mixed or complete chimerical states. Fourteen of 17 patients are alive. CONCLUSION: NAST is an effective therapy in the treatment of hematological diseases with less complications, less blood transfusion and lower cost.