RESUMEN
OBJECTIVE: To investigate the relate of miR-34a/b/c expression with clinical features and prognosis in elderly patients with acute myeloid leukemia (AML). METHODS: 91 elderly patients with AML who consecutively underwent chemotherapy were enrolled in AML group, and 21 patients with non-hematologic malignancies were consider as controls. MiR-34a/b/c expression in bone marrow mononuclear cells (BMMNC) were detected by quantitative polymerase chain reaction (qPCR). All elderly AML patients received the routine induction chemotherapy based on their disease state and risk stratification. The treatment response was assessed. Overall survival (OS) time and event-free survival (EFS) time were recorded. RESULTS: The median miR-34a and miR-34b (all Pï¼0.01) levels in the elderly AML group were lower than those in the control group, while miR-34c level was not different between two groups (Pï¼0.05). MiR-34a high expression correlated with non FLT3-ITD mutation (Pï¼0.05) and lower-risk stage (Pï¼0.05) in elderly AML patients, miR-34b high expression correlated with normal karyotype (NK) (Pï¼0.05), CEBPA double mutation (Pï¼0.01), NPM1 mutation (Pï¼0.05), and WBC count≤10×109/L (Pï¼0.05), while miR-34c expression did not correlate with clinical features of patients (all Pï¼0.05). In addition, the miR-34a high expression correlated with a high CR rate (Pï¼0.05), long EFS (Pï¼0.01) time and OS time (Pï¼0.01) in elderly AML patients, while miR-34b/c expressions not correlated with CR rate, EFS and OS time in patients (all Pï¼0.05). CONCLUSION: The miR-34a/b are low expressed in elderly AML patients, which associates with good clinical manifisfation of patients, and the miR-34a high expression can predict a good prognosis of elderly AML patients to some extent.
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Leucemia Mieloide Aguda , MicroARNs/genética , Anciano , Supervivencia sin Enfermedad , Humanos , Leucemia Mieloide Aguda/genética , Mutación , Nucleofosmina , Pronóstico , Tirosina Quinasa 3 Similar a fmsRESUMEN
BACKGROUND: Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts. RESULTS: To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study. CONCLUSIONS: The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.
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Islas Genómicas , Periquitos/microbiología , Salmonella/clasificación , Secuenciación Completa del Genoma/métodos , Animales , Evolución Molecular , Especiación Genética , Tamaño del Genoma , Genoma Bacteriano , Humanos , Filogenia , Salmonella/genética , Salmonella/patogenicidad , Factores de Virulencia/genéticaRESUMEN
Ovarian cancer is the third most common cancer in the female reproductive organs and epithelial ovarian cancer has the highest lethality of all gynecological cancers. Pomegranate fruit juice (PFJ) has been shown to inhibit the growth of several types of cancer other than ovarian cancer. In this study, we exposed the ovarian cancer cell line A2780 to PFJ and two of its components (ellagic acid and luteolin). MTT and wound healing assays demonstrated that all three treatments suppressed the proliferation and migration of the ovarian cancer cells. In addition, western blotting and ELISA assays showed that the expression levels of MMP2 and MMP9 gradually decreased after treatment with increasing concentrations of ellagic acid and luteolin. To confirm our findings in the in vitro experiments, we used another ovarian cancer cell line, ES-2, in nude mice experiments. All three treatments inhibited tumor growth without obvious side-effects. Furthermore, compared with the control group, the expression levels of MMP2 and MMP9 were depressed. Ellagic acid induced a greater effect than luteolin, suggesting that ellagic acid might be a promising candidate for further preclinical testing for treatment of human ovarian cancer.
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Proliferación Celular/efectos de los fármacos , Ácido Elágico/administración & dosificación , Luteolina/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ácido Elágico/química , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Luteolina/química , Lythraceae/química , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Ratones , Metástasis de la Neoplasia , Neoplasias Ováricas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. METHODS: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. RESULTS: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. CONCLUSION: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.
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4-Butirolactona/análogos & derivados , Antineoplásicos/uso terapéutico , Lignanos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Fitoestrógenos/uso terapéutico , 4-Butirolactona/farmacología , 4-Butirolactona/uso terapéutico , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Lignanos/farmacología , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Ováricas/patología , Fitoestrógenos/farmacología , Carga Tumoral/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Acanthopanax senticosus (previously classified as Eleutherococcus senticosus), commonly known as Ciwujia or Siberian Ginseng, is a traditional Chinese medicine (TCM), widely used for its high medicinal value, such as antifatigue, anti-inflammation, antistress, anti-ulcer and cardiovascular functions, in China, Korea, Japan and Russia. In the past decades, researchers worldwide have conducted systematic investigations on this herb, from chemistry to pharmacology, and a large number of chemical components have been characterized for their significant pharmacological effects. However, reports about the anticancer effects of this plant had been rare until recently, when considerable pharmacological experiments both in vitro and in vivo were conducted to study the anticancer effects of this herb. A. senticosus has been found to have inhibitory effects on malignant tumors, such as those in the lung and liver, suggesting that A. senticosus has potential to be developed as an effective anticancer drug. This paper reviews recent findings on the pharmacological properties of A. senticosus, with a focus on its anticancer effects.
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Antineoplásicos Fitogénicos/uso terapéutico , Cumarinas/farmacología , Cumarinas/uso terapéutico , Dioxoles/farmacología , Dioxoles/uso terapéutico , Eleutherococcus/química , Glucósidos/farmacología , Glucósidos/uso terapéutico , Lignanos/farmacología , Lignanos/uso terapéutico , Fenilpropionatos/farmacología , Fenilpropionatos/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes , Cumarinas/aislamiento & purificación , Dioxoles/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Glucósidos/aislamiento & purificación , Humanos , Factores Inmunológicos/uso terapéutico , Lignanos/aislamiento & purificación , Medicina Tradicional China , Ratones , Fenilpropionatos/aislamiento & purificación , Fitoterapia , RatasRESUMEN
SOX7 as a tumor suppressor belongs to the SOX F gene subfamily and is associated with a variety of human cancers, including breast cancer, but the mechanisms involved are largely unclear. In the current study, we investigated the interactions between SOX7 and AXIN2 in their co-regulation on the Wnt/ß-catenin signal pathway, using clinical specimens and microarray gene expression data from the GEO database, for their roles in breast cancer. We compared the expression levels of SOX7 and other co-expressed genes in the Wnt/ß-catenin pathway and found that the expression of SOX7, SOX17 and SOX18 was all reduced significantly in the breast cancer tissues compared to normal controls. AXIN2 had the highest co-relativity with SOX7 in the Wnt/ß-catenin signaling pathway. Clinicopathological analysis demonstrated that the down-regulated SOX7 was significantly correlated with advanced stages and poorly differentiated breast cancers. Consistent with bioinformatics predictions, SOX7 was correlated positively with AXIN2 and negatively with ß-catenin, suggesting that SOX7 and AXIN2 might play important roles as co-regulators through the Wnt-ß-catenin pathway in the breast tissue to affect the carcinogenesis process. Our results also showed Smad7 as the target of SOX7 and AXIN2 in controlling breast cancer progression through the Wnt/ß-catenin signaling pathway.
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Proteína Axina/metabolismo , Neoplasias de la Mama/patología , Factores de Transcripción SOXF/metabolismo , Transducción de Señal , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Carcinogénesis , Femenino , Perfilación de la Expresión Génica , Humanos , Análisis por MicromatricesRESUMEN
BACKGROUND: Acquisition of exogenous genetic material is a key event in bacterial speciation. It seems reasonable to assume that recombination of the incoming DNA into genome would be more efficient with higher levels of relatedness between the DNA donor and recipient. If so, bacterial speciation would be a smooth process, leading to a continuous spectrum of genomic divergence of bacteria, which, however, is not the case as shown by recent findings. The goal of this study was todetermine if DNA transfer efficiency is correlated with the levels of sequence identity. RESULTS: To compare the relative efficiency of exogenous DNA acquisition among closely related bacteria, we carried out phage-mediated transduction and plasmid-mediated transformation in representative Salmonella strains with different levels of relatedness. We found that the efficiency was remarkably variable even among genetically almost identical bacteria. Although there was a general tendency that more closely related DNA donor-recipient pairs had higher transduction efficiency, transformation efficiency exhibited over a thousand times difference among the closely related Salmonella strains. CONCLUSION: DNA acquisition efficiency is greatly variable among bacteria that have as high as over 99% identical genetic background, suggesting that bacterial speciation involves highly complex processes affected not only by whether beneficial exogenous DNA may exist in the environment but also the "readiness" of the bacteria to accept it.
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ADN/genética , Recombinación Genética , Salmonella/genética , Transducción Genética , ADN/metabolismo , ADN Bacteriano/química , ADN Bacteriano/genética , Especiación Genética , Datos de Secuencia Molecular , Salmonella/metabolismo , Análisis de Secuencia de ADN , Transformación BacterianaRESUMEN
DT104 emerged as a new branch of Salmonella typhimurium with resistance to multiple antimicrobials. To reveal some general genomic features of DT104 for clues of evolutionary events possibly associated with the emergence of this relatively new type of this pathogen, we mapped 11 independent DT104 strains and compared them with non-DT104 S. typhimurium strains. We found that all 11 DT104 strains contained three insertions absent in non-DT104 strains, i.e., the previously reported ST104, ST104B and ST64B. However, SGI-1, a genomic island known to be responsible for DT104 multidrug resistance, was not present in all DT104 strains examined in this study: one DT104 strain did not contain SGI-1 but carried a 144 kb plasmid, suggesting possible evolutionary relationships between the two DNA elements in the development of antimicrobial resistance.
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Genoma Bacteriano/genética , Genómica , Infecciones por Salmonella/microbiología , Salmonella typhimurium/genética , Evolución Biológica , Mapeo Cromosómico , ADN Bacteriano/química , ADN Bacteriano/genética , Desoxirribonucleasas de Localización Especificada Tipo II , Farmacorresistencia Bacteriana Múltiple/genética , Endodesoxirribonucleasas , Reordenamiento Génico , Islas Genómicas/fisiología , Plásmidos/genética , Especificidad de la EspecieRESUMEN
AIM: To construct a prokaryotic plasmid expressing human carboxyles-terases-II (hCE-II ), purify the recombinant protein and investigate the rabbit polyclonal antibody against hCE-II . METHODS: A recombinant plasmid expressing pGEX-4T-1-hCE-II (hCE-II -GST) and pET-32a- hCE-II (hCE-II -His) was constructed and then it was expressed in E.coli BL21 induced by IPTG. The polyclonal antibody was prepared by immunizing the rabbits with the purified recombinant protein. The sensitivity and specificity of the antibody was detected using enzyme -linked immunosorbent assay, immunohistochem ical staining and Western blot analysis. RESULTS: The polyclonal antibody against hCE-II was successfully prepared. Western blot analysis showed that the antibody specifically reacted with the recombinant protein and natural human liver microsomal proteins. Immunohistochemis result demonstrated that the pAb could combine with liver cytoplasm protein but not vascular smooth muscle cell protein. CONCLUSION: The successful preparation of the pAb against hCE-II with high titer and specificity lays a foundation for the investigation of diagnosis kit of liver cancer.