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1.
Breast Cancer Res Treat ; 185(2): 371-380, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32975708

RESUMEN

PURPOSE: Resistance to paclitaxel remains a major challenge in treating breast cancer. Our preclinical study suggested that TEKT4 germline variations in breast cancer are associated with paclitaxel resistance and increase vinorelbine sensitivity. This clinical trial compared the efficacy of paclitaxel and vinorelbine in breast cancer neoadjuvant chemotherapy. METHODS: In this open-label, single-center, phase II trial, female patients with human epidermal growth factor receptor 2 (HER2)-negative, stage IIB-IIIC breast cancer harboring TEKT4 germline variations were randomly assigned to the paclitaxel plus epirubicin (PE) or vinorelbine plus epirubicin (NE). The primary endpoint was the pathologic complete response (pCR) rate, and the secondary endpoints were the objective response rate (ORR) and safety. Targeted sequencing of a panel comprising 484 breast-related genes was performed to identify pCR-associated somatic mutations in each group. RESULTS: 91 Patients were assigned to PE (46 patients) or NE (45 patients). NE numerically increased the pCR rate (22.2% versus 8.7%, P = 0.074). The ORRs for NE and PE were 82.2% and 76.1%, respectively. Interestingly, NE (15.4%) showed a significantly higher pCR rate than PE (0%) in the hormone receptor (HR)-positive subgroup (P = 0.044). Both regimens were well tolerated, with grade 3 and 4 toxicities reported at the expected levels. The biomarker analysis showed that UNC13D mutation predicted the pCR rate in NE (P = 0.011). CONCLUSIONS: Although the primary endpoint was not met, NE might bring clinical benefit to HR-positive patients or patients simultaneously carrying UNC13D mutations.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Epirrubicina , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Humanos , Proteínas de la Membrana , Paclitaxel/efectos adversos , Receptor ErbB-2/genética , Trastuzumab/uso terapéutico , Resultado del Tratamiento , Vinorelbina/uso terapéutico
2.
Mol Cancer ; 19(1): 87, 2020 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-32393270

RESUMEN

BACKGROUND: Estrogen receptor-positive (ER+) breast cancers represent approximately two-thirds of all breast cancers and have a sustained risk of late disease recurrence. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown significant efficacy in ER+ breast cancer. However, their effects are still limited by drug resistance. In this study, we aim to explore the role of long noncoding RNA TROJAN in ER+ breast cancer. METHODS: The expression level of TROJAN in breast cancer tissue and cell lines was determined by quantitative real-time PCR. In vitro and in vivo assays as well as patient derived organoid were preformed to explore the phenotype of TROJAN in ER+ breast cancer. The TROJAN-NKRF-CDK2 axis were screened and validated by RNA pull-down, mass spectrometry, RNA immunoprecipitation, microarray, dual-luciferase reporter and chromatin immunoprecipitation assays. RESULTS: Herein, we showed that TROJAN was highly expressed in ER+ breast cancer. TROJAN promoted cell proliferation and resistance to a CDK4/6 inhibitor and was associated with poor survival in ER+ breast cancer. TROJAN can bind to NKRF and inhibit its interaction with RELA, upregulating the expression of CDK2. The inhibition of TROJAN abolished the activity of CDK2, reversing the resistance to CDK4/6 inhibitor. A TROJAN antisense oligonucleotide sensitized breast cancer cells and organoid to the CDK4/6 inhibitor palbociclib both in vitro and in vivo. CONCLUSIONS: TROJAN promotes ER+ breast cancer proliferation and is a potential target for reversing CDK4/6 inhibitor resistance.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Resistencia a Antineoplásicos , ARN Largo no Codificante/genética , Receptores de Estrógenos/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proliferación Celular , Quinasa 2 Dependiente de la Ciclina/metabolismo , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Piperazinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
3.
J Pharmacol Sci ; 143(3): 238-241, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32265105

RESUMEN

Resveratrol has been extensively studied as the anti-cancer agent. A variety of resveratrol analogues have been developed with structural modification to improve its bioactivity. In this work, resveratrol analogues, compound 1-4, were designed and synthesized with the Stille-Heck reaction. These results showed compound 1-4 had better anticancer effect than that of parent resveratrol. Especially compound 1 ((E)-4,4'-(ethene-1,2-diyl)bis(3-methylphenol)) displayed the excellent cytotoxicity and high selectivity. The mechanism research indicated compound 1 inhibited cell proliferation by binary paths of cell cycle arrest in S phase regulated by cyclin A1/A2 and apoptosis induction mediated by Bax/Bcl2 in a prooxidant manner.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Neoplasias/patología , Resveratrol/análogos & derivados , Resveratrol/farmacología , Apoptosis/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células HeLa , Humanos , Células MCF-7 , Fenómenos Químicos Orgánicos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Resveratrol/síntesis química , Resveratrol/química , Relación Estructura-Actividad , Proteína X Asociada a bcl-2/metabolismo
4.
Biochim Biophys Acta Rev Cancer ; 1879(5): 189143, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936517

RESUMEN

Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as "genomic junk" to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including long interspersed element-1 (LINE-1), Alus, and long terminal repeat (LTR) elements, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.

5.
FEMS Microbiol Lett ; 3712024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38740525

RESUMEN

Enterococcus raffinosus, named by Collins et al. in 1989, is a cocci-shaped bacterium that typically appears in pairs or short chains. As a Gram-positive and non-motile bacterium, it grows at 10°C-45°C, exhibiting negative peroxidase activity [1]. It is a normal flora in the oropharynx and gastrointestinal tract of domestic cats [2] and can also be isolated from human rectal swabs [3], it belongs to the same genus Enterococcus as Enterococcus faecalis and Enterococcus faecium. Enterococcus faecalis and Enterococcus faecium constitute 90% of clinically isolated strains. However, the incidence of other enterococci, excluding E. faecalis and E. faecium, is on the rise [4]. In this case report, a patient with pediatric urinary tract infections caused by E. raffinosus was presented, and a summary of relevant literature was provided.


Asunto(s)
Antibacterianos , Enterococcus , Infecciones por Bacterias Grampositivas , Infecciones Urinarias , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enterococcus/efectos de los fármacos , Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Masculino , Remisión Espontánea , Niño
6.
Cell Res ; 34(1): 58-75, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38168642

RESUMEN

Triple-negative breast cancer (TNBC) is an aggressive disease characterized by remarkable intratumor heterogeneity (ITH), which poses therapeutic challenges. However, the clinical relevance and key determinant of ITH in TNBC are poorly understood. Here, we comprehensively characterized ITH levels using multi-omics data across our center's cohort (n = 260), The Cancer Genome Atlas cohort (n = 134), and four immunotherapy-treated cohorts (n = 109). Our results revealed that high ITH was associated with poor patient survival and immunotherapy resistance. Importantly, we identified zinc finger protein 689 (ZNF689) deficiency as a crucial determinant of ITH formation. Mechanistically, the ZNF689-TRIM28 complex was found to directly bind to the promoter of long interspersed element-1 (LINE-1), inducing H3K9me3-mediated transcriptional silencing. ZNF689 deficiency reactivated LINE-1 retrotransposition to exacerbate genomic instability, which fostered ITH. Single-cell RNA sequencing, spatially resolved transcriptomics and flow cytometry analysis confirmed that ZNF689 deficiency-induced ITH inhibited antigen presentation and T-cell activation, conferring immunotherapy resistance. Pharmacological inhibition of LINE-1 significantly reduced ITH, enhanced antitumor immunity, and eventually sensitized ZNF689-deficient tumors to immunotherapy in vivo. Consistently, ZNF689 expression positively correlated with favorable prognosis and immunotherapy response in clinical samples. Altogether, our study uncovers a previously unrecognized mechanism underlying ZNF689 deficiency-induced ITH and suggests LINE-1 inhibition combined with immunotherapy as a novel treatment strategy for TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Inmunoterapia , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapia , Factores de Transcripción/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Resistencia a Antineoplásicos/genética
7.
Nat Chem ; 16(1): 122-131, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37710046

RESUMEN

Biomarker discovery is essential for the understanding, diagnosis, targeted therapy and prognosis assessment of malignant diseases. However, it remains a huge challenge due to the lack of sensitive methods to identify disease-specific rare molecules. Here we present MORAC, molecular recognition based on affinity and catalysis, which enables the effective identification of candidate biomarkers with low abundance. MORAC relies on a class of DNAzymes, each cleaving a sole RNA linkage embedded in their DNA chain upon specifically sensing a complex system with no prior knowledge of the system's molecular content. We show that signal amplification from catalysis ensures the DNAzymes high sensitivity (for target probing); meanwhile, a simple RNA-to-DNA mutation can shut down their RNA cleavage ability and turn them into a pure affinity tool (for target pulldown). Using MORAC, we identify previously unknown, low-abundance candidate biomarkers with clear clinical value, including apolipoprotein L6 in breast cancer and seryl-tRNA synthetase 1 in polyps preceding colon cancer.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , ADN Catalítico/genética , ADN , ARN , Biomarcadores
8.
Int J Cancer ; 132(5): 1098-104, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22930255

RESUMEN

Survivin and livin are two members of the inhibitor of apoptosis gene family, which have been found to be expressed in many human cancer tissues. But their expression could not be detected in normal adult tissue. The aim of our study was to evaluate the diagnostic role of survivin and livin mRNA expression in the bronchial aspirates of patients with lung cancer. Seventy lung cancer patients and 26 benign lung disease patients participated in our study. The bronchial aspirates (bronchial wash or bronchoalveolar lavage fluids) obtained during bronchoscopy. Survivin and livin mRNA were determined by reverse transcriptase-polymerase chain reaction. Receiver operating characteristic (ROC) curve was used to analyze diagnostic performance of the two markers. Survivin and livin mRNA levels in patients with lung cancer were significantly higher than in those with benign lung disease (p < 0.001 and p = 0.001, respectively). In lung cancer patients, specimens taken from cancerous bronchi had significantly higher levels of survivin and livin mRNA than specimens from the mirror side bronchi in the same patients (p < 0.001 and p = 0.001, respectively). The best cutoff values of survivin and livin were selected according to ROC curves. The survivin mRNA expression in bronchial aspirates had sensitivity and specificity of 83 and 96% for diagnosis of lung cancer. Livin mRNA detection in bronchial aspirates showed 63% sensitivity and 92% specificity. Our findings suggest that survivin and livin mRNA detection in bronchial aspirates may be valuable diagnostic marker for the early diagnosis of lung cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores de Tumor/genética , Proteínas Inhibidoras de la Apoptosis/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , ARN Mensajero/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Bronquios/metabolismo , Líquido del Lavado Bronquioalveolar/química , Broncoscopía/métodos , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , ARN Mensajero/metabolismo , Survivin
9.
Tumour Biol ; 33(5): 1803-10, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22696161

RESUMEN

Survivin and X-linked inhibitor of apoptosis (XIAP) are two inhibitors of apoptosis that are expressed highly in most malignancies and may be diagnostic markers of cancer. The aim of this study was to assess the diagnostic value of survivin and XIAP as tumor markers in malignant pleural effusion. Ninety-eight consecutive patients (including 56 malignant effusions and 42 benign effusions) with pleural effusion were enrolled in the study. Levels of survivin and XIAP mRNA in pleural fluid were measured by reverse transcription polymerase chain reaction. Carcinoembryonic antigen (CEA) was also detected simultaneously. Results showed that levels of survivin and XIAP mRNA were significantly higher in malignant than in benign effusion (P < 0.001 and P = 0.002, respectively). In the diagnosis of malignant pleural effusion, survivin achieved the highest sensitivity (89.3 %) and specificity (95.2 %), as compared with XIAP (66.1 % sensitivity and 85.7 % specificity), or CEA (71.4 % sensitivity and 80.9 % specificity). The combination of survivin and CEA reached 94.6 % sensitivity, with 90.5 % specificity, whereas the combined analysis of survivin and XIAP yielded the highest specificity (95.2 %) and a very good sensitivity (91.1 %). In conclusion, survivin mRNA assay is a useful tumor marker for discriminating malignant from benign pleural effusion. XIAP may be a good candidate for molecular detection of malignant effusion. The combination of survivin and CEA, or XIAP, can increase diagnostic performance.


Asunto(s)
Proteínas Inhibidoras de la Apoptosis/metabolismo , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/diagnóstico , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor , Antígeno Carcinoembrionario/metabolismo , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Masculino , Persona de Mediana Edad , Derrame Pleural/etiología , Derrame Pleural Maligno/química , Derrame Pleural Maligno/etiología , Curva ROC , Survivin , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Adulto Joven
10.
Front Psychol ; 13: 941943, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35898976

RESUMEN

Teachers' work engagement is considered an essential component in instruction. Accordingly, the emphasis should be over physical and mental predictors of this construct. In this line, this study investigates the relationship between Chinese English as a Foreign Language (EFL) teachers' individual self-efficacy, collective efficacy, and work engagement. To this end, 300 Chinese instructors (males = 96, females = 204) from different colleges and universities participated in this study. The questionnaires were distributed among teachers with different educational levels and experiences. Linear multiple regression was used as a measure for data analysis. The findings showed the significant correlations between teachers' work engagement, self-efficacy, and collective efficacy. Comparing the predictability power, teachers' self-efficacy (B = 0.57) proved to have a higher index compared to their index of collective efficacy competence (B = 0.22). This study concluded that self-efficacious teachers and teachers who believe in collective efficacy are more engaged in the EFL contexts. Moreover, the study has some pedagogical implications and suggestions for different teacher educators, administrators, and advisors.

11.
Public Transp ; 14(1): 191-261, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-38625193

RESUMEN

Network-based systems are at the core of our everyday life. Whether it is electronic networking, electricity grids or transportation, users expect the networks to function properly and provide a feeling of safety and security. However, there may be disturbances. In this paper, we consider disturbances in the context of public transportation. The focus in this respect is on public transport planning and operations. To classify and cope with disturbances, one can find many ideas, including robustness, resilience, vulnerability, disruption mitigation or delay management. We survey related streams of literature and put them into perspective. As a major insight we show that different strands of literature exist that may benefit from becoming better connected and intertwined. Together with recent advances in information technology and solution methods, more integrated problem settings incorporating robustness and disturbances can play a major role in future planning and operations.

12.
Aging (Albany NY) ; 14(18): 7328-7347, 2022 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-36178365

RESUMEN

There is considerable heterogeneity in the genomic drivers of lung adenocarcinoma, which has a dismal prognosis. Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model. According to the risk score, a Kaplan-Meier cumulative curve was plotted to evaluate the prognostic value. Furthermore, a nomogram was established to predict the three-year and five-year survival of patients with LUAD based on their prognostic characteristics. Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001). The Kaplan-Meier cumulative curve showed that low-risk patients had significantly better overall (P<0.0001). The validation dataset GSE68465 further confirmed the nomogram's robust ability to assess the prognosis of LUAD patients. A prognosis model of autophagy-related genes based on a LUAD dataset was constructed and exhibited diagnostic value in the prognosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3 and ITGB1 in LUAD cell lines. Two key autophagy-related genes have been suggested as prognostic markers for lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/patología , Autofagia/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Pronóstico , Modelos de Riesgos Proporcionales
13.
Cell Res ; 32(5): 477-490, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35105939

RESUMEN

Metabolic reprogramming is a hallmark of cancer. However, systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC. Combining with previously established transcriptomic and genomic data of the same cohort, we conducted a comprehensive analysis linking TNBC metabolome to genomics. Our study classified TNBCs into three distinct metabolomic subgroups: C1, characterized by the enrichment of ceramides and fatty acids; C2, featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer; and C3, having the lowest level of metabolic dysregulation. Based on this newly developed metabolomic dataset, we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets. The transcriptomic luminal androgen receptor (LAR) subtype overlapped with metabolomic C1 subtype. Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate (S1P), an intermediate of the ceramide pathway, is a promising therapy for LAR tumors. Moreover, the transcriptomic basal-like immune-suppressed (BLIS) subtype contained two prognostic metabolomic subgroups (C2 and C3), which could be distinguished through machine-learning methods. We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors. Together, our study reveals the clinical significance of TNBC metabolomics, which can not only optimize the transcriptomic subtyping system, but also suggest novel therapeutic targets. This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Biomarcadores de Tumor/genética , Humanos , Metabolómica , Medicina de Precisión , Transcriptoma , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología
14.
Mitochondrial DNA B Resour ; 6(3): 1253-1255, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33829100

RESUMEN

Phaius hainanensis C. Z. Tang et S. J. Cheng is a species with extremely small populations and is endemic to China. Genetic data of this orchid species is minimal. With the aim to identify appropriate chloroplast markers for the use in conservation biology studies, the plastome of P. hainanenisis was assembled. The plastome of P. hainanensis is 158,314 bp in length and contains a large single copy region of 86,700 bp in length, a small single copy region of 18,452 bp, and a pair of inverted repeats of 26,581 bp. The annotation predicted 114 unique genes, including 80 protein-coding, 30 tRNAs, and four rRNAs. Seventeen genes contained a single intron and two genes (clpP and ycf3) have two introns. The GC content of P. hainanensis is 36.9%. Phylogenetic analysis indicated P. hainanensis is closely related to P. tancarvilleae, and it also supported that Phaius and Calanthe are sister groups. The plastome data reported in this study will contribute to further studies of phylogeny and conservation of Phaius species.

15.
Medicine (Baltimore) ; 100(14): e25375, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832123

RESUMEN

RATIONALE: Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare congenital malformation in neonates that results in severe respiratory distress and pulmonary hypertension. ACD/MPV is caused by mutations in the FOXF1 gene. Herein, a new case of a girl with ACD/MPV carrying a novel pathogenic variant of FOXF1 was reported. PATIENT CONCERNS: A 3-month-old Chinese girl was admitted to the hospital presenting a complaint of cyanosis for 10 days and respiratory distress for 2 days. The history of foreign body inhalation was denied. DIAGNOSES: Blood routine, liver and kidney function, electrolytes, type B natriuretic peptide, electrocardiogram, cardiac computed tomography (CT), and echocardiography were done after admission. Dysplasia of the alveolar and the left upper pulmonary vein was displayed through cardiac CT. Echocardiography showed atrial septal defect, tricuspid valve malformation, and pulmonary hypertension. Sequence analysis of FOXF1 from genomic deoxyribonucleic acid (DNA) revealed that the patient was heterozygous for a novel missense variant (c.418 C>T, p.Pro140Gly). Furthermore, genetic analysis of both parents confirmed the de novo occurrence of the variant. Conservation analysis showed that the locus was highly conserved across species. Then, ACD/MPV was a clinical diagnosis. INTERVENTIONS: After admission, nasal catheter oxygen inhalation, cefazoxime sodium, furosemide diuretic, milrinone lactate, and Bosentan were given to the patient. OUTCOMES: After 6 days of hospitalization, the patient's condition did not improved, the parents gave up treatment and discharged. The patient died half a month after discharge. LESSONS: ACD/MPV is a rare congenital malformation with a poor prognosis. A new de novo mutation of FOXF1 was found in our case. Non-invasive methods such as DNA sequencing and FOXF1 analysis are helpful in the clinical diagnosis of ACD/MPV especially in early infants with respiratory distress and pulmonary hypertension.


Asunto(s)
Factores de Transcripción Forkhead/genética , Síndrome de Circulación Fetal Persistente/diagnóstico , Síndrome de Circulación Fetal Persistente/genética , Alveolos Pulmonares/anomalías , Venas Pulmonares/anomalías , Ecocardiografía/métodos , Resultado Fatal , Femenino , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/genética , Heterocigoto , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/genética , Lactante , Mutación Missense , Terapia por Inhalación de Oxígeno/métodos , Síndrome de Circulación Fetal Persistente/tratamiento farmacológico , Análisis de Secuencia/métodos , Insuficiencia del Tratamiento , Válvula Tricúspide/anomalías , Válvula Tricúspide/diagnóstico por imagen
16.
Oncogene ; 40(12): 2323-2334, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33654196

RESUMEN

Progression of triple-negative breast cancer (TNBC) constitutes a major unresolved clinical challenge, and effective targeted therapies are lacking. Because microtubule dynamics play pivotal roles in breast cancer metastasis, we performed RNA sequencing on 245 samples from TNBC patients to characterize the landscape of microtubule-associated proteins (MAPs). Here, our transcriptome analyses revealed that low expression of one MAP, tektin4, indicated poor patient outcomes. Tektin4 loss led to a marked increase in TNBC migration, invasion, and metastasis and a decrease in microtubule stability. Mechanistically, we identified a novel microtubule-associated complex containing tektin4 and histone deacetylase 6 (HDAC6). Tektin4 loss increased the interaction between HDAC6 and α-tubulin, thus decreasing microtubule stability through HDAC6-mediated tubulin deacetylation. Significantly, we found that tektin4 loss sensitized TNBC cells, xenograft models, and patient-derived organoid models to the HDAC6-selective inhibitor ACY1215. Furthermore, tektin4 expression levels were positively correlated with microtubule stability levels in clinical samples. Together, our findings uncover a metastasis suppressor function of tektin4 and support clinical development of HDAC6 inhibition as a new therapeutic strategy for tektin4-deficient TNBC patients.


Asunto(s)
Histona Desacetilasa 6/genética , Inhibidores de Histona Desacetilasas/farmacología , Proteínas de Microtúbulos/genética , Neoplasias de la Mama Triple Negativas/genética , Tubulina (Proteína)/genética , Acetilación/efectos de los fármacos , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Xenoinjertos , Humanos , Ácidos Hidroxámicos/farmacología , Ratones , Metástasis de la Neoplasia , Pirimidinas/farmacología , Análisis de Secuencia de ARN , Neoplasias de la Mama Triple Negativas/patología , Secuenciación del Exoma
17.
Jpn J Clin Oncol ; 40(4): 327-35, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20056675

RESUMEN

OBJECTIVE: Survivin and livin, which are members of the inhibitor of apoptosis protein family, regulate both programmed cell death and proliferation. Second mitochondria-derived activator of caspase is thought to regulate apoptosis by antagonizing inhibitor of apoptosis protein. These gene expressions are regarded as prognostic markers in some malignancies. However, result in previous studies of the association of these gene expressions with prognosis of patients with non-small cell lung cancer remains contradictory. METHODS: Survivin, livin and second mitochondria-derived activator of caspase mRNA was detected by semi-quantitative reverse transcriptase-polymerase chain reaction in surgical resected tumor specimen from 66 non-small cell lung patients who received adjuvant platinum-based chemotherapy. RESULTS: Results showed that patients with survivin high expression had significantly shorter tumor-free survival (P = 0.012) and overall survival (P = 0.007) than those with survivin low expression. There was a significant association of second mitochondria-derived activator of caspase high expression in non-small cell lung cancer tissue with longer tumor-free survival (P = 0.021) and overall survival (P = 0.0013). However, livin mRNA expression level had no impact on the tumor-free survival and overall survival of the patients. In multivariate analyses, survivin mRNA high expression (P = 0.033 and P = 0.024) and advanced pathologic stage (P = 0.009 and P = 0.008) were the factors which independently predicted a worse tumor-free survival and overall survival. CONCLUSIONS: Our data suggest that assessment of survivin and second mitochondria-derived activator of caspase mRNA expression may be useful for predicting survival in non-small cell lung cancer patients receiving platinum-based chemotherapy after surgical resection and can provide valuable information for deciding better therapy strategy.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Proteínas Asociadas a Microtúbulos/biosíntesis , Proteínas Mitocondriales/biosíntesis , Adulto , Anciano , Proteínas Reguladoras de la Apoptosis , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioterapia Adyuvante , Femenino , Expresión Génica , Humanos , Proteínas Inhibidoras de la Apoptosis , Péptidos y Proteínas de Señalización Intracelular/genética , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Proteínas Mitocondriales/genética , Neumonectomía , Pronóstico , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Survivin
18.
Respirology ; 15(3): 501-9, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20210890

RESUMEN

BACKGROUND AND OBJECTIVE: Survivin and X-linked inhibitor of apoptosis protein (XIAP) in vitro mediate cancer cell survival and chemoresistance. Second mitochondria-derived activator of caspases (Smac), an antagonist of XIAP, has been shown in vitro to increase chemosensitivity. This study examined the prognostic value of survivin, XIAP and Smac in advanced non-small-cell lung cancer (NSCLC) patients treated with cisplatin-containing chemotherapy. METHODS: Semi-quantitative RT-PCR was used to measure survivin, XIAP and Smac mRNA expression in transbronchial biopsy tumour specimens from 72 patients with advanced NSCLC before commencing chemotherapy. Outcome measures were response to chemotherapy, progression-free survival (PFS) and overall survival (OS). RESULTS: Low expression of survivin was associated with good response to chemotherapy (P = 0.028). No association was found between XIAP and Smac expression levels and response to chemotherapy (P = 0.224 and P = 0.088, respectively). Patients with low survivin expression or high Smac expression had significantly longer PFS (P = 0.012 and P = 0.029, respectively) and OS (P = 0.007 and P = 0.031, respectively) compared with patients with high expression of survivin or low expression of Smac. XIAP expression was not correlated with PFS or OS. Additionally, PFS and OS in patients with performance status of 0 or 1 and stage IIIB were significantly longer than PFS and OS in patients with performance status (PS) of 2 and stage IV disease. Multivariate Cox regression analyses demonstrated that survivin and clinical stage were independent predictors for PFS and OS. Smac was an independent prognostic factor for OS, but not for PFS. CONCLUSIONS: Our findings suggest that the expression levels of survivin and Smac, but not XIAP, predict the survival of patients with advanced NSCLC treated with chemotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Mitocondriales/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Adulto , Anciano , Antineoplásicos/uso terapéutico , Proteínas Reguladoras de la Apoptosis , Biopsia , Bronquios/metabolismo , Bronquios/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Inhibidoras de la Apoptosis , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/metabolismo , Análisis de Regresión , Estudios Retrospectivos , Survivin , Resultado del Tratamiento
19.
Front Pediatr ; 8: 524, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33014928

RESUMEN

Introduction: Congenital descending aorta-right atrial tunnel is a rare congenital heart defect. Herein, a new case successfully treated by transcatheter closure using a new type of ventricular septal defect occluder from the aortic side was reported. Case Presentation: An 11-month-old Chinese girl presenting with a cardiac murmur was suspected with partial anomalous pulmonary venous connection as assessed by echocardiography. Descending aorta-right atrial tunnel was confirmed by computed tomography angiography and cardiac catheterization. Subsequently, transcatheter closure was performed successfully using a new type of ventricular septal defect occluder from the aortic side. The cardiac murmur disappeared after the intervention, and echocardiography did not reveal any abnormal flow inside the right atrium. At 6 months, the patient had no murmur, and no residual shunt was found using the echocardiogram. Conclusion: Descending aorta-right atrial tunnel is a rare anomaly. Transcatheter closure was successful in our case. Long-term follow-up is needed to assess any progressive growth of the residual tunnel.

20.
Mitochondrial DNA B Resour ; 5(3): 3612-3613, 2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33367030

RESUMEN

Paphiopedilum spicerianum (H. G. Reichenbach) Pfitzer is an endangered and threatened orchid species in China. The genetic and molecular data of this orchid species is deficient. With the aim to identify appropriate chloroplast markers for the use in a conservation biology study, the complete chloroplast genome of P. spicerianum was reported. We found that the chloroplast genome of P. spicerianum is 157,292 bp in length, containing a large single-copy region of 87,252 bp, a small single-copy region of 1828 bp, and a pair of inverted repeats of 34,106 bp. Genome annotation predicted 105 unique genes, including 71 protein-coding genes, 30 tRNAs, and four rRNAs. Fourteen genes contained one intron and two genes (clpP and ycf3) had two introns. The GC content of the P. spicerianum was 35.8%. Phylogenetic analysis indicated P. spicerianum was closely related to P. purpuratum.

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