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ETHNOPHARMACOLOGICAL RELEVANCE: The sclerotium of Lignosus rhinocerus (Cooke) Ryvarden is used by the local communities in Southeast Asia and China to treat cancer, asthma, fever, and other ailments based on traditional knowledge. The sclerotial water extracts were previously reported to exhibit cytotoxic, apoptotic, and immunomodulatory activities - providing a scientific basis for its use in treating cancer; however, there is still a lack of evidence on its potential anti-angiogenic activity. AIM OF THE STUDY: This study aimed to investigate the toxicity, anti-angiogenic, and anti-tumour activities of the hot-water and cold-water extracts of L. rhinocerus using HCT116 human colorectal carcinoma cells implanted in the chick chorioallantoic membrane (CAM) model. MATERIALS AND METHODS: The toxicity of L. rhinocerus extracts towards the chick embryos was determined 24 h post-treatment. The anti-angiogenic activity of the extracts was then investigated at 0.1-10 µg/embryo (6.7-670 µg/mL) at targeted blood vessels. The anti-tumour effect of selected extracts against the HCT116 human colorectal carcinoma cells xenografted onto the chick embryos was also studied. RESULTS: The cold-water extracts of L. rhinocerus displayed strong in ovo toxicity (LC50: 1.2-37.7 µg/mL) while the hot-water extracts are non-toxic up to 670 µg/mL. Among the extracts, the hot-water extracts demonstrated the highest anti-angiogenic activity with 44.0 ± 17.7% reduction of capillary diameter (relative to the saline-treated control). Moreover, treatment of the HCT116 cells xenografted onto the chick embryos with the hot-water extracts resulted in smaller tumour size and lower number of blood vessels compared to the saline-treated control. CONCLUSIONS: The hot-water extracts of L. rhinocerus sclerotium demonstrated anti-angiogenic and anti-tumour activities but most of the cold-water extracts at similar concentrations were devoid of that. Our findings provide further scientific validation of the medicinal use of the sclerotium in treating cancer and thus, expanding our knowledge on the possible mechanism of its anti-cancer effect apart from direct cytotoxicity, induction of apoptosis and immunomodulation that have been studied thus far.
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Inibidores da Angiogênese , Membrana Corioalantoide , Neoplasias Colorretais , Animais , Embrião de Galinha , Humanos , Células HCT116 , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/toxicidade , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/irrigação sanguínea , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Água/química , Antineoplásicos Fitogênicos/farmacologia , Polyporaceae/químicaRESUMO
A new push-pull aza-BODIPY (AZB-CF3) derivative comprised of dimethylamino groups and trifluoromethyl moieties was successfully synthesized. This derivative exhibited broad absorption in the near-infrared region in the range from 798 to 832 nm. It also exhibited significant near-infrared (NIR) signals in low-polar solvents with emission peaks around 835-940 nm, while non-fluorescence in high-polar environments due to the twisted intramolecular charge transfer (TICT) phenomenon. The nanoprecipitation of this compound with phospholipid-based polyethylene glycol (DSPE-PEG) yielded AZB-CF3@DSPE-PEG nanoparticles (NPs) with a hydrodynamic size of 70 nm. The NPs exhibited good photostability, colloidal stability, biocompatibility, and excellent photothermal (PTT) competence with a conversion efficiency (η) of 44.9%. These NPs were evaluated in vitro and in ovo in a 4T1 breast cancer cell line for NIR light-trigger photothermal therapy. Proven in the chicken egg tumor model, AZB-CF3@DSPE-PEG NPs induced severe vascular damage (â¼40% vascular destruction), showed great anticancer efficacy (â¼75% tumor growth inhibition), and effectively inhibited distant metastasis via photothermal treatment. As such, this PTT-based nanocarrier system could be a potential candidate for a clinical cancer therapy approach.
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BACKGROUND: Salivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton-remodeling-related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial-mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated. METHODS: An analysis of single-cell RNA sequencing (scRNA-seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues. RESULTS: Our analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra-lesional heterogeneity. Cytoskeleton-remodeling-related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA. CONCLUSION: Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.
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Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Análise de Sequência de RNARESUMO
Photothermal therapy is a promising treatment modality in the realm of cancer therapy. Photothermal nanomaterials that absorb and emit in the near-infrared range (750-900 nm) have drawn a lot of attention recently because of the deep penetration of NIR light in biological tissue. Most nanomaterials, however, are produced by encapsulating or altering the surface of a nanoplatform, which has limited loading capacity and long-term storage. Herein, we developed a stable polymer conjugated with aza-BODIPY that self-assembled to form nanoparticles (aza-BODIPY-mPEG) with better hydrophilicity and biocompatibility while retaining the dye's photothermal conversion characteristics. Aza-BODIPY-mPEG with a hydrodynamic size of around 170 nm exhibited great photostability and excellent photothermal therapy in vitro and in ovo. Aza-BODIPY-mPEG exhibits approximately 30% better anti-angiogenesis and antitumor activity against implanted xenograft human HCT116 tumor in the chick embryo compared to parent aza-BODIPY-A, altogether suggesting that aza-BODIPY-mPEG is a promising material for cancer photothermal therapy.
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This study aimed to investigate the epidemiologic, clinical, pathological characteristics, and treatment of patients with Castleman disease (CD) in a single center in China. We retrospectively analyzed the data of 65 Chinese CD patients, divided into unicentric CD (UCD) and multicentric CD (MCD) groups, and also microscopic subtypes as hypervascular (HV), plasmacytic (PC) and Mixed. Based on whether HHV-8 infection existed, MCD was subdivided into HHV-8-associated MCD and idiopathic Castleman disease (iMCD). Detailed epidemiologic, clinicopathological, and treatment data were analyzed and discussed. Of total 65 patients (UCD 33, MCD 32), HV (81.8%) accounted for the most of UCD and total. More females in UCD (60.6%) and more males in MCD (65.6%) were observed. CD occurred in all age groups, most commonly in 40-49 years. The mean age of onset of total was 38.5 years with PC higher than HV (45.5 vs. 35.1 years, P = 0.0413). The median diagnosis delay of MCD was longer than that of UCD (3.00 vs. 1.25 months, P = 0.0436). Abdomen (39.4%) and neck (30.3%) were the most-seen locations of lymphadenopathy in UCD, with neck (65.6%) being predominant in MCD. Mean major diameter of specimens of UCD was greater than MCD (6.4 vs. 3.1 cm, P < 0.0001). These results provided the featured and detailed profile of Castleman disease in Henan province in China with a considerable number of cases, which presented distinct evidence with other studies.
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Hiperplasia do Linfonodo Gigante , Infecções por Herpesviridae , Herpesvirus Humano 8 , Linfadenopatia , Adulto , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/epidemiologia , China , Feminino , Infecções por Herpesviridae/complicações , Humanos , Linfadenopatia/complicações , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Accumulating evidence reveals the significance of long non-coding RNAs (lncRNAs) in various cancers. The current study aimed to evaluate the role of GATA6 antisense RNA 1 (GATA6-AS1) in the epithelial-mesenchymal transition (EMT) and lymph node metastasis (LNM) in GC. GC-related microarray datasets were initially retrieved from the GEO with differentially expressed lncRNAs screened, followed by evaluation of the regulatory relationship between Frizzled 4 (FZD4) and GATA6-AS1. The detailed regulatory mechanism by which GATA6-AS1 influences the Wnt/ß-catenin signaling pathway and GC cell biological behaviors was investigated by treating SGC7901 cells with overexpressed GATA6-AS1, specific antisense oligonucleotide against GATA6-AS1, and lithium chloride (LiCl; activator of the Wnt/ß-catenin signaling pathway). Finally, xenograft nude mice were used to assay tumor growth and LNM in vivo. GATA6-AS1 was poorly expressed, but FZD4 was highly expressed in GC tissues and cells. Elevated GATA6-AS1 reduced FZD4 expression by recruiting enhancer of zeste homolog 2 (EZH2) and trimethylation at lysine 27 of histone H3 (H3K27me3) to the FZD4 promoter region via the inactivated Wnt/ß-catenin signaling pathway, whereby cell invasion, migration, and proliferation, tumor growth, and LNM in nude mice were reduced. Taken together, overexpressed GATA6-AS1 downregulated the expression of FZD4 to inactivate the Wnt/ß-catenin signaling pathway, which ultimately inhibited GC progression.
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PURPOSE: We estimated the expression of nuclear factor kappa B/p65 in non-germinal center B-cell-like subtype diffuse large B-cell lymphoma, to investigate its relationship to clinicopathological features, and to further evaluate its prognostic value and clarify its impact on survival. RESULTS: Among the 49 patients enrolled in this study, 14 (28.6%) had positive p65 expression. The negative p65 group had significantly better survival compared to the positive p65 group in terms of both the 3-year estimated OS (91.2% vs. 39.3%, p = 0.003) and PFS (75.6% vs. 26.5%, p = 0.002). In patients with 4 or more risk factors, p65 was an independent prognostic factor of OS (HR 5.99, 95%CI=1.39-25.75, p=0.016) and PFS (HR 4.01, 95%CI=1.15-14.00, p=0.029). MATERIALS AND METHODS: The expression of the NF-κB/p65 protein was deteremined by immunohistochemistry in 49 non-GCB DLBCL. Survival was assessed by the Kaplan-Meier method and Cox multivariate analysis. The median patient follow-up period was 24 months. CONCLUSIONS: The expression of NF-κB/p65 has prognostic value in high risk non-GCB DLBCL, and it is a suitable target for the development of new therapies.
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Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/química , Fator de Transcrição RelA/análise , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. METHODS: Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. RESULTS: Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043). CONCLUSION: Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation.
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Povo Asiático/genética , Calreticulina/genética , Janus Quinase 2/genética , Mutação , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , China , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico , Adulto JovemRESUMO
Syngnathia is a rare malformation involving soft tissue and/or bony adhesions between the maxilla and mandible. Less than 40 patients have been reported in the literature. Here the authors report a 6-month-old infant diagnosed as syngnathia of the palate and mouth floor combined with cleft palate and funnel chest in the Department of Oral and Maxillofacial Surgery at Henan Provincial People's Hospital in January 2015. The authors discussed and evaluated the diagnostic and treatment difficulties on surgical and anesthetic procedure. There is no standard treatment protocol, but early treatment is necessary to improve airway functions and infant feeding, and to support proper nutrition for the growth of maxillofacial region.
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Anormalidades Múltiplas , Fenda Labial/diagnóstico , Tórax em Funil/diagnóstico , Anormalidades Maxilomandibulares/diagnóstico , Anormalidades da Boca/diagnóstico , Soalho Bucal/anormalidades , Humanos , Lactente , MasculinoRESUMO
This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43-4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05-3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19-0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33-0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neutrófilos/patologia , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Contagem de Linfócitos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Rituximab/administração & dosagem , Análise de Sobrevida , Vincristina/uso terapêuticoRESUMO
The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20 years. The utility of the IPI must be reassessed in the era of immunochemotherapy. Seven risk factors at diagnosis were identified, and a maximum of 7 points were assigned to each patient. Four risk groups were created: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the rituximab era, we performed a retrospective analysis of patients with DLBCL treated with R-CHOP and built an biological markers adjusted IPI with the goal of improving risk stratification.Clinical features from 60 adults with de novo DLBCL diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI remains predictive, but it cannot identify the high-risk subgroup. Compared with the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4 year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is more powerful than the IPI for helping guide treatment planning and interpretation of clinical trials.
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Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Intervalo Livre de Doença , Doxorrubicina , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-myc/análise , Estudos Retrospectivos , Fatores de Risco , Rituximab , Vincristina , Adulto JovemRESUMO
A series of bifunctional molecules with different combinations of macrocyclic polyamine [12]aneN3 and coumarin moieties, 4a/b and 5a/b, were synthesized by a two-step copper(I)-mediated alkyneazide click reactions between 1,3,5-tris(azidomethyl)benzene and Boc-protected N-propynyl-[12]aneN3/7-propynyloxycoumarins. Agarose gel electrophoresis experiments indicated that bifunctional molecules 4b and 5b effectively induced complete plasmid DNA condensation at concentrations up to 40 µM. It was found that the structural variation had a major impact on the condensation behavior of these compounds. The electrostatic interaction involving the [12]aneN3 moiety can be compensated by the binding contribution of the coumarin units during the DNA condensation process. These two types of interaction showed different effects on the reversibility of DNA condensation. Results from studies using dynamic laser scattering, atomic force microscopy, and EB replacement assay further supported the above conclusion. Cytotoxicity assays on bifunctional compounds 4a/b and 5a/b indicated their low cytotoxicity. Results from cellular uptake and cell transfection experiments proved that bifunctional compounds 4b and 5b successfully served as non-viral gene vectors. Furthermore, methyl substituents attached to the coumarin unit (4b and 5b) greatly enhanced their DNA condensation capability and gene transfection. These bifunctional molecules, with the advantages of lower cytotoxicity, good water solubility, and potential structural modification, will have great potential for the development of new non-viral gene delivery agents.
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Cumarínicos/química , DNA/administração & dosagem , Compostos Macrocíclicos/química , Plasmídeos/administração & dosagem , Poliaminas/química , Transfecção , Linhagem Celular Tumoral , Química Click , Cumarínicos/síntese química , DNA/genética , Proteínas de Fluorescência Verde/genética , Humanos , Compostos Macrocíclicos/síntese química , Plasmídeos/genética , Poliaminas/síntese químicaRESUMO
Selective BRAF inhibitors have demonstrated significant clinical benefit in melanoma patients harboring oncogenic BRAF mutations. However, the majority of such patients either exhibit de novo resistance from the beginning of the treatment or acquire resistance and eventually relapse. Despite tremendous progress in understanding the underlying mechanisms of resistance, overcoming resistance to BRAF inhibitors remains an unmet medical need. Constitutive activation of cyclin-dependent kinases (CDK) 4/6 as a result of genetic aberrations including CDKN2A inactivation and CCND1 amplification is common across many cancer types and frequently co-occurs with oncogenic BRAF mutations. Also, cyclin D1 overexpression is a common feature of resistance to BRAF inhibitors. Here we review CDK4/6 as a therapeutic target in BRAF mutant cancers and discuss emerging evidence supporting a critical role of cyclin D1/CDK4/6 axis in de novo and acquired resistance to BRAF inhibitors. Co-targeting CDK4/6 and BRAF could be a more effective therapy to augment clinical response of BRAF inhibitors and overcome resistance in BRAF mutant cancers.
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Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Modelos Biológicos , Mutação , Neoplasias/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
This study aims to investigate the prognostic significance of the MYC protein expression in diffuse large B cell lymphoma (DLBCL) patients treated with RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). A total of 60 patients with DLBCL from 2008 to 2013 were included. Formalin-fixed, paraffin-embedded DLBCL samples were analyzed for MYC protein expression and divided into high or low MYC group. The MYC protein expression and the international prognostic variables were evaluated. The high MYC protein expression predicted a shorter 3-year estimated overall survival (OS) and progression-free survival (PFS) versus the low MYC protein expression (57 % vs. 96 %, P < 0.001 and 50 % vs. 96 %, P = 0.001, respectively). Multivariate analysis confirmed the prognostic significance of the MYC protein expression for both OS (HR, 11.862; 95 % CI, 1.462-96.218; P = 0.021) and PFS (HR, 6.073; 95 % CI, 1.082-34.085; P = 0.040). MYC protein expression with International Prognostic Index (IPI) score distinguished patients into three risk groups with different 3-year OS rates (χ (2) 23.079; P < 0.001) and distinct 3-year PFS rates (χ (2) 15.862; P < 0.001). This study suggests that the MYC protein expression is an important inferior prognostic factor for survival in patients with DLBCL treated with RCHOP. The combinative model with IPI score and MYC protein expression could stratify DLBCL patients into prognostically relevant subgroups more effectively than either the IPI or the MYC alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-myc/biossíntese , Rituximab , Vincristina/administração & dosagemRESUMO
BACKGROUND: To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia. METHODS: A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission. RESULTS: Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RRâ=â1·23; 95% CIâ=â1·07-1·41, pâ=â0.004), EFS (HRâ=â0·64; 95% CIâ=â0·45-0·91, pâ=â0.013), and OS (HRâ=â0·88; 95% CIâ=â0·81-0·95, pâ=â0.02) but not in DFS (HRâ=â0·90; 95% CIâ=â0·80-1·00, pâ=â0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits. CONCLUSION: Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Humanos , Idarubicina/administração & dosagem , Quimioterapia de Indução , Pessoa de Meia-Idade , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
It is generally agreed that adipocytes originate from mesenchymal stem cells in what can be divided into two processes: determination and differentiation. In the past decade, many factors associated with epigenetic signals have been proved to be pivotal for the appropriate timing of adipogenesis progression. A large number of coregulators at critical gene promoters set up specific patterns of DNA methylation, histone acetylation and methylation, and nucleosome rearrangement, that act as an epigenetic code to modulate the correct progress of adipocyte differentiation and adipogenesis during adipogenesis. In this review, we focus on the functions and roles of epigenetic processes in preadipocyte differentiation and adipogenesis.
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Adipócitos/citologia , Adipogenia , Diferenciação Celular , Epigênese Genética , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/fisiologia , Humanos , PPAR gama/genética , Proteína do Retinoblastoma/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/fisiologia , Transcrição GênicaAssuntos
Condromatose Sinovial/diagnóstico , Transtornos da Articulação Temporomandibular/diagnóstico , Diagnóstico Diferencial , Assimetria Facial/diagnóstico , Feminino , Humanos , Côndilo Mandibular/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia Panorâmica , Amplitude de Movimento Articular/fisiologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To observe the outcome of single-lung transplantation (SLT) for end-stage pulmonary parenchymal diseases in combination with pulmonary hypertension (PH). METHODS: From September 2002 to November 2005, there were 22 lung transplantation recipients, suffering from emphysema (10/22), pulmonary fibrosis (10/22), pneumosilicosis (1/22) and vascular leiomyoma (1/22), and all of them were complicated with pulmonary hypertension to different extent. Operative techniques: 10 patients received left-lung transplantations, and 12 patients received right-lung transplantation. In all the patients echocardiography (ECHO) was performed before transplantation, and arterial blood was collected to determine oxygenation index (PaO(2)/FiO(2)). RESULTS: The systolic pulmonary artery pressure (Ppa, syst) was monitored by Swan-Gans catheterization one week post-transplantation, and it was found to have decreased significantly [from (50.00+/-13.00) mm Hg (1 mm Hg=0.133 kPa) to (39.5+/-7.36) mm Hg,P<0.05]. Simultaneously, PaO(2)/FiO(2) was improved [from (241.26+/-79.54) mm Hg to (348.23+/-99.31) mm Hg, P<0.05]. CONCLUSION: Single lung transplantation is an efficient way to deal with end-stage pulmonary parenchymal disease combined with pulmonary hypertension.
Assuntos
Hipertensão Pulmonar/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Adulto , Idoso , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/cirurgia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate monitoring and cares in the intensive care unit (ICU) after lung transplantation. METHODS: From September 2002 to April 2005, there were 18 cases of lung transplant recipients, who had suffered from emphysema (9 cases), pulmonary fibrosis (5 cases), silicosis (1 cases), bronchiectasis (1 case), pulmonary vascular leiomyoma (1 case), ventricular septal defect and Eisenmenger's syndrome (1 case), respectively. Operative procedures included 9 cases with left lung transplantation, 5 right lung transplantation, 1 case right single lung transplantation and ventricular septal defect repair, and 3 cases bilateral lung transplantations. All the patients received mechanical ventilation, immunosuppressive agents, antibacterial prophylaxis, and prevention of reperfusion injury in the ICU after operation. Preoperatively, echocardiography (ECHO), artery blood gas,and oxygenation index (partial pressure of oxygen in artery/fraction of inspired oxygen, PaO(2)/FiO(2)) were observed. RESULTS: The average weaning time from the ventilator was (7.39+/-4.89) days. The average ICU stay time was (9.72+/-8.32) days. The systolic pulmonary artery pressure (Ppa, syst) was monitored with Swan-Ganz catheterization 1 week post transplant, and it was found to have decreased significantly from (48.94+/-14.45) mm Hg (1 mm Hg=0.133 kPa) to (39.59+/-7.45) mm Hg (P<0.05). At the same time, oxygenation index was improved from (263.89+/-82.09) mm Hg to (345.56+/-92.18) mm Hg (P<0.05), partial pressure of carbon dioxide in artery (PaCO(2)) was decreased from (63.29+/-22.56) mm Hg to (38.37+/-9.19) mm Hg (P<0.05). In hospital mortality (HM) was 16.7% (3/18 cases), and an early death was due to severe infection on the 30 th postoperative day in 1 patient and acute rejection on the 15 th postoperative day in another patient, and the other patient died due to pulmonary vein embolism on the 36 th day. Fifteen patients recovered quickly and discharged from the hospital. One patient was followed up for 32 months. CONCLUSION: Lung transplantation remains the only hope for many patients with end stage pulmonary disease. It is important that the lung transplant team possesses a working knowledge of the treatment of common complications, the time of these complications mostly likely to occur and how best to treat them when they do arise, to ensure long-term survival and success.
Assuntos
Transplante de Pulmão , Assistência Perioperatória , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Adulto JovemRESUMO
AIM: To summarize the performing essentials and analyze the characteristics of remote Zeus robot-assisted laparoscopic cholecystectomy. METHODS: Robot-assisted laparoscopic cholecystectomy was performed in 40 patients between May 2004 and July 2005. The operating procedures and a variety of clinical parameters were recorded and analyzed. RESULTS: Forty laparoscopic cholecystectomy procedures were successfully completed with Zeus robotic system. And there were no post-operative complications. Total operating time, system setup time and performing time were 100.3 +/- 18.5 min, 27.7 +/- 8.8 min and 65.6 +/- 18.3 min, respectively. The blood loss and post-operative hospital stay were 30.6 +/- 10.2 mL and 2.8 +/- 0.8 d, respectively. Camera clearing times and time used for operative field adjustment were 1.1+/- 1.0 min and 2.0 +/- 0.8 min, respectively. The operative error was 7.5%. CONCLUSION: Robot-assisted laparoscopic cholecystectomy following the principles of laparoscopic operation has specific performing essentials. It preserves the benefits of minimally invasive surgery and offers enhanced ability of controlling operation field, precise and stable operative manipulations.