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1.
ChemSusChem ; 16(19): e202300523, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37728196

RESUMEN

A green and practical method for the electrochemical synthesis of tetrahydroimidazo[1,5-a]quinoxalin-4(5H)-ones through the three-component reaction of quinoxalin-2(1H)-ones, N-arylglycines and paraformaldehyde was reported. In this strategy, EtOH played dual roles (eco-friendly solvent and waste-free pre-catalyst) and the in situ generated ethoxide promoted triple sequential deprotonations.

2.
Chem Commun (Camb) ; 59(94): 14029-14032, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37964611

RESUMEN

With both ferrocene and air as the redox catalysts, for the first time, the low-cost natural ilmenite (FeTiO3) was successfully used for photocatalytic bond formations. Under the assistance of a traceless H-bond, and HCHO as the methylene reagent, a variety of imidazo[1,5-a]quinoxalinones were semi-heterogeneously photosynthesized in high yields with good functional group compatibility.

3.
Ann Hematol ; 91(8): 1235-43, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22373549

RESUMEN

ETV6 is an important hematopoietic regulatory factor and ETV6 gene rearrangement is involved in a wide variety of hematological malignancies. In this study, we sought to investigate the incidence of ETV6-associated fusion genes in B- and T-lineage acute lymphoblastic leukemia (ALL) by multiplex-nested reverse transcription-polymerase chain reaction (RT-PCR) in 176 adult ALL patients. Total RNA was extracted from bone marrow samples of ALL patients including 136 B- and 40 T-lineage ALL, and ETV6 fusion genes were detected by multiplex-nested RT-PCR. Changes of ETV6 fusion gene mRNA transcript levels were examined by real-time RT-PCR. We detected a total of 15 ETV6 gene rearrangements with a positive rate of 8.5%, involving seven ETV6-associated fusion genes in 13 B-ALL (13/136, 9.6%) and 2 T-ALL patients (2/40, 5.0%). ETV6-RUNX1 were observed in six cases (3.4%), ETV6-JAK2 in three cases (1.7%), ETV6-ABL1 in two cases (1.1%), and ETV6-ABL2, ETV6-NCOA2, ETV6-SYK, and PAX5-ETV6 each in one case (0.6%). ETV6-JAK2 was found in both B-ALL and T-ALL patients. Furthermore, real-time quantitative RT-PCR assays showed that the ETV6-RUNX1 mRNA transcript levels decreased during conventional chemotherapy or hematopoietic stem cell transplantation. This study shows that multiplex-nested RT-PCR is an effective and accurate tool to identify ETV6 rearrangements in adult ALL, which provides some clues into the diagnosis and prognosis of ALL but also molecular markers for the detection of minimal residual disease in adult ALL.


Asunto(s)
Mutación , Proteínas de Fusión Oncogénica/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Mutación/fisiología , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proteínas Proto-Oncogénicas c-ets/metabolismo , Proteínas Represoras/metabolismo , Sensibilidad y Especificidad , Translocación Genética/fisiología , Adulto Joven , Proteína ETS de Variante de Translocación 6
4.
Asian Pac J Cancer Prev ; 23(7): 2375-2378, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35901344

RESUMEN

OBJECTIVES: Acute ischemic stroke in cancer patients is uncommon. The study was aimed to identify the relationship of patients' characteristics and the interval time between the diagnosis of stroke and cancer. METHODS: The clinical features of acute ischemic stroke patients with cancer were retrospectively analyzed from May, 2016 to April, 2021. Categorical data was compared between groups using chi-square test. Hematological biomarkers were compared using Mann-Whitney U test. RESULTS: A total of 70 acute ischemic stroke patients with cancer were identified. The median interval time between the diagnosis of acute ischemic stroke and cancer was 53.0 months. Patients with interval < 53.0 months and > 53.0 months were regarded the short interval group and the long interval group, respectively. Between the short and long interval groups, there was no significant differences in respect to sex, age, chemotherapy, hypertension, diabetes, smoking, atrial fibrillation and dyslipidemia. The medians of homocysteine, high-sensitivity C-reactive protein and fibrinogen were also not significantly different between the two different interval groups. D-dimer in the short interval group was higher than that in the long interval group (216 vs. 142 ng/mL, p = 0.037). The long interval group had more surgery for cancer than the short interval group (94.3% vs. 57.1%, p = 0.000). CONCLUSION: In conclusion, in patients with ischemic stroke and cancer, patients with short interval time between the diagnosis of ischemic stroke and cancer had higher D-dimer than patients with long interval time.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Neoplasias , Accidente Cerebrovascular , Biomarcadores , Isquemia Encefálica/diagnóstico , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/etiología , Neoplasias/complicaciones , Neoplasias/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología
5.
World J Clin Cases ; 9(34): 10484-10493, 2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-35004980

RESUMEN

BACKGROUND: Multiple primary malignancies (MPM) are characterized by two or more primary malignancies in the same patient, excluding relapse or metastasis of prior cancer. We aimed to elucidate the clinical features and survival of MPM patients. AIM: To elucidate the clinical features and survival of MPM patients. METHODS: A retrospective study of MPM patients was conducted in our hospital between June 2016 and June 2019. Overall survival (OS) was calculated using the Kaplan-Meier method. The log-rank test was used to compare the survival of different groups. RESULTS: A total of 243 MPM patients were enrolled, including 222 patients with two malignancies and 21 patients with three malignancies. Of patients with two malignancies, 51 (23.0%) had synchronous MPM, and 171 (77.7%) had metachronous MPM. The most common first cancers were breast cancer (33, 14.9%) and colorectal cancer (31, 14.0%). The most common second cancers were non-small cell lung cancer (NSCLC) (66, 29.7%) and gastric cancer (24, 10.8%). There was no survival difference between synchronous and metachronous MPM patients (36.4 vs 35.3 mo, P = 0.809). Patients aged > 65 years at diagnosis of the second cancer had a shorter survival than patients ≤ 65 years (28.4 vs 36.4 mo, P = 0.038). Patients with distant metastasis had worse survival than patients without metastasis (20.4 vs 86.9 mo, P = 0.000). Following multivariate analyses, age > 65 years and distant metastasis were independent adverse prognostic factors for OS. CONCLUSION: During follow-up of a first cancer, the occurrence of a second or more cancers should receive greater attention, especially for common concomitant MPM, to ensure early detection and treatment of the subsequent cancer.

6.
Transl Cancer Res ; 9(12): 7531-7539, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35117353

RESUMEN

BACKGROUND: Esophageal cancer is one of the most common malignant tumors. The role of tumor microenvironment in esophageal cancer is unclear. METHODS: The gene expression profiles and clinical data of 158 patients with esophageal cancer were extracted from The Cancer Genome Atlas database. Immune scores and stromal scores were calculated based on ESTIMATE algorithm. According to different immune/stromal scores, differentially expressed genes (DEGs) were identified. The function enrichment, protein interactions of shared DEGs and their associations with overall survival were analyzed. RESULTS: In regard to the association of the immune/stromal scores and disease stage, pathological type and overall survival, only the stromal scores among the different stages were significantly different (P=0.015). In the high immune and stromal score groups, 603 shared up-regulated genes were found. The related function and pathways included regulation of lymphocyte activation, cytokine binding and chemokine signaling pathway. Protein-protein interaction analysis showed that ITGAM had the most connections, followed by CXCL10 and CCR2. High expression of 11 genes, including MS4A7, TMIGD3, MS4A4A, EVI2A, MS4A6A, FCER1G, AIF1, GNGT2, LCP2, DNAJC5B and RNASE6, were found to be associated with shorter overall survival. CONCLUSIONS: Microenvironment-associated functions and pathways were analyzed in esophageal cancer, and 11 microenvironment-associated genes were correlated to poor prognoses. Further studies on these genes may be helpful to understand the tumor microenvironment and provide new therapies for esophageal cancer.

7.
Transl Cancer Res ; 9(2): 1160-1166, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35117460

RESUMEN

BACKGROUND: Brain metastases significantly reduce the survival of cancer patients. However, detailed researches on the clinical manifestations and prognoses of patients with brain metastases are lacking. The aim of this study was to investigate the clinical features and prognostic factors of cancer patients with brain metastases. METHODS: A retrospective study was conducted on patients with brain metastases who were treated in our hospital between January 2014 and January 2019. Comparison of overall survival (OS) was performed by the Kaplan-Meier method. Multivariate Cox regression models was used to identify prognostic factors for OS. RESULTS: A total of 190 patients with complete data and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 were enrolled. Patients with brain metastases from different primary sites had significantly different survival time (P=0.001). Patients who had a longer survival time included female patients (47.4%) (34 vs. 19 months, P=0.002), those with age <65 years (63.7%) (29 vs. 18 months, P=0.002), with ECOG 0 or 1 (44.2%) (32 vs. 21 months, P=0.005), with ≤3 brain lesions (61.1%) (29 vs. 20 months, P=0.041), and with small molecular targeted therapy (48.4%) (21 vs. 18 months, P=0.006). Furthermore, multivariate analysis revealed that female, age <65 years, ≤3 brain lesions, small molecular targeted therapy were independent favorable prognostic factors of OS. CONCLUSIONS: Female, younger patients with ≤3 brain metastases predicted a better survival. To improve the poor outcomes of these patients, it is necessary to find clinically significant genetic abnormalities and administer the small molecular targeted therapy early in the course of treatment.

8.
Int J Biol Markers ; 33(3): 293-300, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29749758

RESUMEN

PURPOSE: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. METHODS: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan-Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. RESULTS: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.


Asunto(s)
Biomarcadores de Tumor/genética , Colangiocarcinoma/genética , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Colangiocarcinoma/patología , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Transducción de Señal/genética
9.
J Cancer Res Ther ; 14(Supplement): S512-S515, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29970716

RESUMEN

OBJECTIVE: Cancer patients with bone marrow metastases are rare and dismal. The study was to identify the clinical features and prognostic factors in cancer patients with bone marrow metastases. PATIENTS AND METHODS: A total of 30 patients with bone marrow metastases were reviewed between September 2007 and September 2013. Bone marrow metastases were identified by bone marrow aspiration. RESULTS: The median age was 56.5 years (range, 8-85 years). The two most common primary tumor sites were the stomach (7, 23.3%), breast (5, 16.7%). Bone metastases (27, 90.0%) were the most common concurrent metastases. The most common cause for bone marrow aspiration was anemia and thrombocytopenia (10, 33.3%). The median survival time was 3 months (range, 0.5-82 months). Patients with good performance status (n = 19) had a longer median survival time than patients with poor performance status (n = 11) (8 months vs. 1 months, P = 0.041). Patients with primary unknown origin (n = 5) had a significantly shorter overall survival time than patients with known origin (n = 25) (1 month vs. 6 months = 0.010). The median survival time was 9 months in the systemic therapy group (n = 21) and 1 month in the best supportive care group (n = 9) (P = 0.000). CONCLUSION: To make primary origin clear and start systemic antitumor therapy is beneficial for patients with bone marrow metastases.


Asunto(s)
Neoplasias de la Médula Ósea/mortalidad , Neoplasias de la Médula Ósea/secundario , Neoplasias/mortalidad , Neoplasias/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Médula Ósea/terapia , Niño , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 91-96, 2018 Feb.
Artículo en Zh | MEDLINE | ID: mdl-29397824

RESUMEN

OBJECTIVE: To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients. METHODS: Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated. RESULTS: Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 109/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%). CONCLUSION: Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.


Asunto(s)
Leucemia Mieloide Aguda , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/análogos & derivados , Citarabina , Decitabina , Femenino , Humanos , Masculino , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento
11.
Mol Clin Oncol ; 3(4): 859-864, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26171196

RESUMEN

An increasing incidence of hematological malignancies has been observed in children and adults worldwide over the last few decades. Asthma is a common chronic inflammatory disease. The aim of the present meta-analysis was to evaluate the potential association between a history of asthma and the risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL). A literature search was performed through PubMed and the Cochrane Database of Systematic Reviews and the Newcastle-Ottawa Scale was used to evaluate the quality of the selected studies. The I2 index was used to evaluate heterogeneity and the outcome was measured as the odds ratio (OR) by the random-effects model. A total of 16 case-control studies were included. All the studies were of high quality. The OR for ALL was 0.90 [95% confidence interval (CI): 0.68-1.19; P=0.45; I2=79%]. The OR for AML was 0.85 (95% CI: 0.67-1.08; P=0.19; I2=8%). The OR for NHL was 0.91 (95% CI: 0.83-1.00; P=0.05; I2=0%). Asthma was found to be inversely associated with the risk of NHL. A negative trend of association of asthma with ALL and AML was also observed. However, additional large prospective studies are required to confirm these findings.

12.
Oncol Lett ; 8(3): 959-962, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25120641

RESUMEN

Nucleoporin 214 (NUP214), previously termed CAN, is required for cell cycle and nucleocytoplasmic transport. The genetic features and clinical implications of five NUP214-associated fusion genes are described in this review. SET-NUP214 was most frequently observed in T-cell acute lymphoblastic leukemia (T-ALL), concomitant with the elevated expression of HOXA cluster genes. Furthermore, the fusion transcript may be regarded as a potential minimal residual disease marker for SET-NUP214-positive patients. Episomal amplifications of NUP214-ABL1 are specific to T-ALL patients. The NUP214-ABL1 gene is observed in ~6% of T-ALL, in children and adults. Targeted tyrosine kinase inhibitors plus standard chemotherapy appear to present a promising treatment strategy. DEK-NUP214 is formed by the fusion of exon 2 of DEK and exon 6 of NUP214. Achieving molecular negativity of DEK-NUP214 is of great importance for individual management. SQSTM1-NUP214 and NUP214-XKR3 were only identified in one T-ALL patient and one cell line, respectively. The NUP214 fusions have significant diagnostic and therapeutic implications for leukemia patients. Additional NUP214-associated fusions require identification in future studies.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(4): 957-64, 2014 Aug.
Artículo en Zh | MEDLINE | ID: mdl-25130810

RESUMEN

This study was purposed to investigate the clinical features, diagnosis, treatment and prognosis of elderly patients with acute myeloid leukemia (AML) (non-APL). The clinical data of 76 elderly ( ≥ 60 old years) AML (non-APL) patients from January 2000 to January 2010 were analyzed retrospectively. According to treatment methods,the 76 patients were divided into 2 groups: induction chemotherapy group (51 cases) and best supportive treatment group (25 cases). The patients in induction chemotherapy group received the cytarabine-based induction chemotherapy regimens, including DA, MA, HA, IA and CAG; the patients in best supportive treatment group received supportive treatment including hydroxyurea, blood transfusion and so on. The clinical features, diagnosis, treatment and prognosis between 2 groups were compared. The results showed that the median survival times of patients in induction chemotherapy and best supportive treatment groups were 5 (0.2-89) and 3 (0.1-17) months respectively, there was significantly statistical difference in median survival time between 2 groups(P < 0.01) suggesting that the induction chemotherapy obviously prolonged the survival time of elderly CML patients. The 5 patients in induction chemotherapy group survived more than 60 months, one of them survived more than nine years. After the first cycle of chemotherapy, the complete remission (CR) rate of patients was 19.6% (10/51), partial remission (PR) rate was 19.6% (10/51), the overall response rate (ORR) was 39.2%, the mortality of patients in induction remission stage was 13.7% (7/51) in induction chemotherapy group; no 1 case in best supportive treatment group reached to CR. The CR rate of patients by using MA regimen was 44.4% and its ORR was 55.5%, which was higher than that by using DA, HA, IA and CAG regimens. The median chemotherapy cycles were 3 (1-14). The follow-up found that the 3 months-survival rate of patients was 65% and 42%, the 6 month-survival rate of patients was 43% and 21%, the 1 year-survival rate of patients was 29% and 13%, the 5 year-survival rate of patients was 13% and 0% in induction chemotherapy and best supportive treatment groups respectively, showing that the survival of patients in induction chemotherapy group was better than those in best supportive treatment group. A total of 31 of out 51 cases (60.8%) in induction chemotherapy group not response to the first cycle of chemotherapy, the survival time of these patients was not statistically significantly different from that of patients in best supportive treatment group. It is concluded that the induction chemotherapy can significantly improve the prognosis of elderly patients with AML, and prolong their median survival time. The induction remission rate in elderly patients with AML is lower than that of younger patients. The MA regimen is better than DA, HA, IA and CAG, there is individual difference in the elderly patients with AML, If the first cycle of chemotherapy has not reached to CR or PR, the best supportive treatment may be considered. The low toxicity, efficient and well-tolerated chemotherapy regimens may be chosen to prolong the survival time of the elderly patients with AML (non-APL).


Asunto(s)
Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
14.
Leuk Lymphoma ; 54(7): 1521-6, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23210573

RESUMEN

This study aimed to develop a novel multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) assay to accurately and effectively detect 10 common gene rearrangements in adult acute lymphoblastic leukemia (ALL) and to examine the clinicopathologic characteristics and other genetic aberrations of patients with ALL expressing different fusion genes. Our RT-nPCR assay had a positive detection rate of 35.15% (90/256) for the 10 fusion genes. BCR-ABL1, FUS-ERG, MLL-AF4, ETV6-RUNX1, E2A-PBX1, dupMLL, MLL-AF10, MLL-ENL, SET-NUP214 and SIL-TAL1 were detected in 36 (14.06%), 14 (5.47%), 14 (5.47%), four (1.56%), four (1.56%), five (1.95%), four (1.56%), two (0.78%), two (0.78%) and five patients (1.95%), respectively. The RT-nPCR results were further confirmed by split-out PCR, and cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed corresponding translocations and fusions in 63 and 74 cases, respectively. JAK2 and IKZF1 mutations were commonly detected in patients with BCR-ABL1 ALL, and HOX overexpression was highly correlated with MLL fusions and SET-NUP214. This study demonstrates that RT-nPCR is an effective method for identifying 10 gene rearrangements in adult ALL, and it could potentially be developed for diagnostic use and prognostic studies of ALL.


Asunto(s)
Reordenamiento Génico , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Cariotipo Anormal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Fusión Oncogénica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Translocación Genética , Resultado del Tratamiento , Adulto Joven
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(2): 305-10, 2013 Apr.
Artículo en Zh | MEDLINE | ID: mdl-23628021

RESUMEN

The study was aimed to investigate the clinical characteristics of acute myeloid leukemia (AML) with CBFB-MYH11 gene. The clinical data of 12 cases were analyzed retrospectively, including age, clinical characteristics, immunophenotype, treatment protocols and efficacy as well as the prognosis. The results indicated that 12 patients with CBFB-MYH11 were detected in 293 AML patients. The median age of the 12 patients was 32.5 (21 - 57) years old. According to French-American-British (FAB) classification, 66.7% (8/12) patients was diagnosed as M4Eo and 33.3% patients was diagnosed as M4. At new diagnosis, the median WBC count was 19.8×10(9)/L (2.46 - 164.30×10(9)/L). The WBC count > 100×10(9) was found in 16.7% patients (2/12). The complete remission (CR) rate after 1 and 2 cycles of induction chemotherapy were 83.3% and 16.7% respectively, so the total CR rate was 100%. Estimated 5-year relapse-free survival (RFS) and overall survival (OS) were 80% and 83%, respectively. It is concluded that patients with CBFB-MYH11 are usually M4Eo and M4. Patients with this fusion gene are often associated with high frequency of CD33, CD34, CD117, HLA-DR, CD15, CD64 and CD14 expression. Patients with CBFB-MYH11 have a tendency of higher CR rate, longer RFS and OS.


Asunto(s)
Leucemia Mieloide Aguda/genética , Proteínas de Fusión Oncogénica/genética , Adulto , Femenino , Humanos , Inmunofenotipificación , Quimioterapia de Inducción , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/metabolismo , Pronóstico , Estudios Retrospectivos , Adulto Joven
16.
Chin Med J (Engl) ; 126(23): 4552-6, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24286424

RESUMEN

BACKGROUND: Cancer testis antigens (CTAs) are a novel group of tumor associated antigens. Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism, thus enhance the immunogenicity of leukemia cells. However, few researches have ever focused on the questions that whether this immunostimulatory effect of decitabine could induce autologous CTA specific cytotoxic T lymphocytes (CTLs) in vivo, and if so, whether this effect contributes to disease control. In this study, we aimed to show that decitabine could induce specific autologous CTLs against some mouse CTAs in leukemia cells in vitro and in vivo. METHODS: Several mouse CTAs were screened by RT-PCR. CTL specific to one of the CTAs named P1A was detected and sorted by P1A specific dimer by flow cytometry. The activity of specific CTLs was measured by real time RT-PCR. RESULTS: We firstly screened expression of some CTAs in mouse leukemia cells before and after decitabine treatment and found that decitabine treatment did up-regulate expression of many CTAs. Then we measured the CTLs' activity specific to a mouse CTA P1A in vivo and showed that this activity increased after decitabine treatment. Finally, we sorted these in vivo induced P1A specific CTLs by flow cytometry and demonstrated their cytotoxicity against decitabine treated leukemia cells. CONCLUSIONS: Our study showed the autologous immune response induced by decitabine in vivo. And more importantly, we firstly proved that this response may contribute to disease control. We believe that this immunostimulatory effect is another anti-cancer mechanism of decitabine, and this special effect would inspire new applications of decitabine in the field of leukemia treatment in the future.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Azacitidina/análogos & derivados , Linfocitos T Citotóxicos/metabolismo , Animales , Antimetabolitos Antineoplásicos/farmacología , Azacitidina/farmacología , Línea Celular Tumoral , Decitabina , Citometría de Flujo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Linfocitos T Citotóxicos/efectos de los fármacos
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(5): 1142-7, 2013 Oct.
Artículo en Zh | MEDLINE | ID: mdl-24156422

RESUMEN

The aim of this study was to investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL, AML-M6). The clinical features and results of morphologic, immunophenotypic, cytogenetic and molecular biologic detections were retrospectively analyzed in 13 cases of AEL from 305 acute leukemia patients hospitalized between October 2007 and October 2012. The results showed that the expression of erythroid and non-erythroid cells increased at the same time. The myeloid antigens mainly expressed CD13/CD33/CD117/CD34, while the erythroid antigens expressed Gly and CD71. The karyotypic detection indicated that there were 1 case with normal karyotype, 3 cases with simple karyotypic abnormality and 2 cases with complex karyotypic abnormality, the other cases were not detected. The molecular biological detection found that the poor prognosis gene existed in 5 cases [38.5% (5/13)], including 3 cases with MLL-MLL fusion gene, 1 case with MLL mutation, and 1 cases with NRAS gene mutation, the abnormal genes were not detected in remainder 8 cases. After chemotherapy with decitabine, the complete remission (CR) rate achieved 53.5% (7/13), partial remission (DR) rate achieved 15.4% (2/13). Finally, 8 patients received allo-HSCT, the median overall survival (OS) was 20.7 months, 3 year survival rate was 79%, 3 year disease-free survival rate was 78%. It is concluded that the acute erythroleukemia is a rare subtype of AML, which is transformed from MDS and has harmful genes and poor prognosis. Allo-HSCT and treatment with decitabine may enhance the survival rate of AEL.


Asunto(s)
Leucemia Eritroblástica Aguda/diagnóstico , Leucemia Eritroblástica Aguda/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(4): 821-9, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23998567

RESUMEN

This study was aimed to detect the expression of AML1 fusion genes in the patients with adult acute myeloid leukemia (AML) and further to investigate their association with the progression and prognosis of AML. Bone marrow samples were collected from 168 patients with de novo adult AML, and the expression of AML1 ETO, AML1-EVI1, AML1-MDS1, AML1-MTG16, AML1-PRDM16, AML1-LRP16, AML1-CLCA2 and AML1-PRDX4 was analyzed by a novel multiplex nested RT-PCR. Positive samples and minimal residual disease were further examined by real-time fluorescent quantitative PCR. The results showed that the AML1 fusion genes were found in 10.7% (18/168) patients. Among them, AML1-ETO in 12 (7.1%) cases were detected, AML1-EVI1 in 2 cases (1.2%), and AML1-MDS1, AML1-MTG16, AML1-PRDM16, and AML1-CLCA2 in 1 case (0.6%) each were detected. Among the patients with AML1-ETO, 10 patients (10/12, 83.33%) achieved complete remission (CR) after one cycle of chemotherapy, while 2 patients achieved CR after 2 cycles of chemotherapy. The 2 patients with AML1-EVI1 failed to achieve CR after one cycle of chemotherapy. Patients with AML1-MDS1, AML1-MTG16, AML1-PRDM16, or AML1-CACL2 did not achieve CR after one cycle of chemotherapy. It is concluded that AML1 fusion genes are more frequent and can provide the molecular markers for diagnostics and prognosis evaluation of AML and for monitoring MRD.


Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/genética , Proteínas de Fusión Oncogénica/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto Joven
19.
PLoS One ; 8(5): e62924, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23671644

RESUMEN

Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.


Asunto(s)
Azacitidina/análogos & derivados , Antígeno B7-1/metabolismo , Neoplasias Experimentales/tratamiento farmacológico , Linfocitos T Citotóxicos/efectos de los fármacos , Animales , Antimetabolitos Antineoplásicos/farmacología , Azacitidina/farmacología , Antígeno B7-1/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Decitabina , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Células K562 , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Regiones Promotoras Genéticas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Linfocitos T Citotóxicos/metabolismo , Carga Tumoral/efectos de los fármacos , Células U937
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(6): 1370-3, 2012 Dec.
Artículo en Zh | MEDLINE | ID: mdl-23257435

RESUMEN

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL), characterized by great heterogeneity in clinical manifestations and molecular genetics. This study was aimed to explore the clinical significance of applying multiplex PCR to detect BCL2/IGH and BCL6/IGH fusion genes in DLBCL. Multiplex PCR was used to detect bone marrow samples from 80 cases of DLBCL. The results showed that 12 patients (15%) carried BCL2/IGH or BCL6/IGH fusion genes, BCL2/IGH was found in 6 patients (7.5%), and BCL6/IGH in another 6 patients (7.5%). The patients with different molecular markers displayed different clinical features and outcomes. It is concluded that multiple PCR is rapid and accurate method to identify gene abnormalities in DLBCL, but further studying a quantitative or semi-quantitative assay for the expression of fusion genes is needed.


Asunto(s)
Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Adulto Joven
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