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1.
BMC Pulm Med ; 24(1): 494, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39379871

RESUMEN

BACKGROUND: We here report the first case of leukemic lung infiltration diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the leukemic cells infiltrated tissues. TBLC is generally considered a superior diagnostic method compared to transbronchial lung forceps biopsy (TBLB) because it utilizes cryotechnology to obtain larger specimens, increasing the likelihood of capturing tissues infiltrated with leukemic cells. CASE PRESENTATION: A 69-year-old male patient with acute myeloid leukemia presented with a fever. His initial chest CT scans revealed consolidative lesions, raising suspicion of fungal infection such as angioinvasive aspergillosis or mucormycosis. TBLC and TBLB were conducted to achieve a precise diagnosis, and eventually, leukemic lung infiltration was identified exclusively in the tissues obtained from TBLC. Two cycles of chemotherapy was administrated to patient, showing improvements in symptoms and chest CT findings. CONCLUSIONS: TBLC has greater potential as a differential diagnostic method for pulmonary lesions than TBLB in leukemia patients facing therapeutic challenges due to its higher diagnostic yield.


Asunto(s)
Leucemia Mieloide Aguda , Tomografía Computarizada por Rayos X , Humanos , Masculino , Anciano , Diagnóstico Diferencial , Biopsia/métodos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/diagnóstico , Pulmón/patología , Pulmón/diagnóstico por imagen , Infiltración Leucémica/diagnóstico , Infiltración Leucémica/patología , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/patología , Broncoscopía/métodos
2.
Transl Lung Cancer Res ; 13(8): 1888-1906, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39263019

RESUMEN

Background: Patients with non-small cell lung cancer (NSCLC) have been shown to exhibit elevated levels of soluble programmed death-ligand 1 (sPD-L1) in the blood, associated with poor survival in NSCLC. The bronchoalveolar lavage fluid (BALF) composition reflects the tumor microenvironment of lung cancer. In this study, we investigated sPD-L1 levels in BALF and its role as a prognostic and predictive marker in patients with stage IV NSCLC. Methods: We prospectively obtained BALF from lung cancer patients who underwent bronchoscopy between January 2020 and September 2022 at Chungnam National University Hospital (CNUH). Finally, 94 NSCLC stage IV patients were included in this study. Soluble PD-L1 levels in BALF were measured using a human PD-L1 Quantikine ELISA kit. Results: The correlation between PD-L1 expression in tumor cells and sPD-L1 in BALF was weakly positive (rho =0.314, P=0.002). The median overall survival (OS) of the low sPD-L1 in BALF group was 16.47 months [95% confidence interval (CI): 11.15-21.79 months], which is significantly longer than 8.87 months (95% CI: 0.0-19.88 months, P=0.001) in the high sPD-L1 in BALF group. In 64 patients treated with or without immune checkpoint inhibitors (ICIs), sPD-L1 in BALF was significantly associated with progression-free survival (PFS) and OS. In the subgroup analysis of 31 patients treated with ICI, the objective response rate (ORR) in the low sPD-L1 BALF group was significantly higher than in high sPD-L1 in BALF group (ORR: 60.9% vs. 12.5%, P=0.02). Conclusions: Soluble PD-L1 in BALF is a potential prognostic indicator for patients with stage IV NSCLC and a predictive marker for ICI treatment response.

3.
PLoS One ; 19(4): e0297344, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38568934

RESUMEN

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Terapia de Reemplazo Renal Continuo , Infecciones por Coronavirus , Coronavirus , Insuficiencia Respiratoria , Humanos , Estudios Retrospectivos , Respiración Artificial , COVID-19/terapia , COVID-19/complicaciones , Pronóstico , Unidades de Cuidados Intensivos , Insuficiencia Multiorgánica/complicaciones , Infecciones por Coronavirus/complicaciones , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/complicaciones , Terapia de Reemplazo Renal
4.
Am J Cancer Res ; 14(1): 97-113, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38323275

RESUMEN

Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is a cathepsin with lysosomal exocysteine protease activity and a central coordinator for the activation of neutrophil-derived serine proteases in the lysosomes of neutrophils. Although the role of CTSC in various cancers, including liver and breast cancers, has recently been reported, its role in non-small cell lung cancer (NSCLC) is largely unknown. This study aimed to investigate the functional role of CTSC in NSCLC and the molecular mechanisms underlying CTSC involvement in disease progression. CTSC overexpression markedly enhanced the growth, motility, and invasiveness of NSCLC cells in vitro and in vivo. CTSC knockdown using shRNA in NSCLC cells reversed the migratory and invasive behavior of NSCLC cells. CTSC also induced epithelial-mesenchymal transition through the Yes-associated protein signaling pathway. In addition, our analyses of clinical samples confirmed that high CTSC expression was associated with lymph node metastasis and recurrence in lung adenocarcinoma. In conclusion, CTSC plays an important role in the progression of NSCLC. Thus, targeting CTSC may be a promising treatment option for patients with NSCLC.

5.
Tuberc Respir Dis (Seoul) ; 87(2): 145-154, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38368903

RESUMEN

The consequences of coronavirus disease 2019 (COVID-19) are particularly severe in older adults with a disproportionate number of severe and fatal outcomes. Therefore, this integrative review aimed to provide a comprehensive overview of the clinical characteristics, management approaches, and prognosis of older patients diagnosed with COVID-19. Common clinical presentations in older patients include fever, cough, and dyspnea. Additionally, preexisting comorbidities, especially diabetes and pulmonary and cardiovascular diseases, were frequently observed and associated with adverse outcomes. Management strategies varied, however, early diagnosis, vigilant monitoring, and multidisciplinary care were identified as key factors for enhancing patient outcomes. Nonetheless, the prognosis remains guarded for older patients, with increased rates of hospitalization, mechanical ventilation, and mortality. However, timely therapeutic interventions, especially antiviral and supportive treatments, have demonstrated some efficacy in mitigating the severe consequences in this age group. In conclusion, while older adults remain highly susceptible to severe outcomes from COVID-19, early intervention, rigorous monitoring, and comprehensive care can play a pivotal role in improving their clinical outcomes.

6.
Thorac Cancer ; 15(8): 672-677, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38352989

RESUMEN

Cancer-associated dermatomyositis (CAD), a paraneoplastic syndrome characterized by dermatomyositis (DM), frequently presents in association with small cell lung cancer (SCLC). Although the advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, their efficacy and safety in patients with concurrent autoimmune diseases (AD) and malignancies remains uncertain. Several studies have suggested the safe administration of ICIs in patients with AD, indicating that successful cancer therapy can alleviate CAD symptoms. Conversely, other studies have raised concerns about the potential for ICIs to exacerbate AD flares or immune-related adverse events (irAEs). A comparative analysis of two cases from our institution emphasizes the variability in ICI responses among SCLC patients with CAD. One patient, previously reported as a case study, exhibited significant clinical improvement in DM symptoms after ICI administration, whereas the other developed severe exfoliative skin changes and experienced an unfavorable prognosis. This variability emphasizes the need for careful patient selection and close monitoring during ICI treatment. We hypothesized that overweight or obese individuals and those with severe initial skin lesions and elevated lactate dehydrogenase levels are more susceptible to developing irAEs following ICI therapy. Therefore, caution is advised when considering immunotherapy in these patients.


Asunto(s)
Antineoplásicos Inmunológicos , Enfermedades Autoinmunes , Dermatomiositis , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Dermatomiositis/complicaciones , Dermatomiositis/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Estudios Retrospectivos , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunoterapia/efectos adversos
8.
Nat Cancer ; 4(2): 290-307, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36550235

RESUMEN

We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA-protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2-4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Carcinoma de Células Escamosas , Neoplasias Pancreáticas , Proteogenómica , Animales , Ratones , Humanos , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Biomarcadores , Neoplasias Pancreáticas
9.
Nat Commun ; 13(1): 6292, 2022 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-36272973

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC. Patients with poor prognosis have high PIGF/VEGF expression and an increased number of PIGF/VEGF receptor-expressing CAFs, associated with enhanced collagen deposition. We also develop a multi-paratopic VEGF decoy receptor (Ate-Grab) by fusing the single-chain Fv of atezolizumab (anti-PD-L1) to VEGF-Grab to target PD-L1-expressing CAFs. Ate-Grab exerts anti-tumor and anti-fibrotic effects in PDAC models via the PD-L1-directed PlGF/VEGF blockade. Furthermore, Ate-Grab synergizes with gemcitabine by relieving desmoplasia. Single-cell RNA sequencing identifies that a CD141+ CAF population is reduced upon Ate-Grab and gemcitabine combination treatment. Overall, our results elucidate the mechanism underlying chemotherapy-induced fibrosis in PDAC and highlight a combinatorial therapeutic strategy for desmoplastic cancers.


Asunto(s)
Antineoplásicos , Fibroblastos Asociados al Cáncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anticuerpos de Cadena Única , Femenino , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Crecimiento Placentario/genética , Factor de Crecimiento Placentario/metabolismo , Anticuerpos de Cadena Única/metabolismo , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/genética , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Antineoplásicos/farmacología , Fibrosis , Neoplasias Pancreáticas
10.
Immune Netw ; 21(4): e31, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34522444

RESUMEN

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45+ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2negative AGC.

11.
Invest Ophthalmol Vis Sci ; 61(13): 22, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33196778

RESUMEN

Purpose: VEGF-Grab is a novel anti-vascular endothelial growth factor (VEGF) candidate drug with higher affinity to both VEGF and placental growth factor (PlGF) compared to aflibercept. We investigated the preclinical efficacy of VEGF-Grab for ophthalmic therapy and compared it to that of aflibercept. Methods: The in vitro anti-VEGF efficacy of VEGF-Grab was determined using VEGF-induced cell proliferation/migration and tube formation assays. The in vivo antiangiogenic efficacy of intravitreal injection of either VEGF-Grab or aflibercept was evaluated using murine models of ocular angiogenesis: mouse oxygen-induced retinopathy (OIR) and rat laser-induced choroidal neovascularization (CNV). The in vivo retinal toxicity in the mouse eye resulting from the injection of either drug was evaluated with light and electron microscopy. Results: VEGF-Grab showed greater inhibition of VEGF-induced cell proliferation/migration than aflibercept, but it showed comparable inhibition of tube formation in vitro. In the in vivo OIR model, VEGF-Grab showed a comparable suppression of retinal neovascularization compared to aflibercept. Additionally, VEGF-Grab showed an efficacy similar to that of aflibercept in terms of CNV inhibition in the laser-induced CNV model. Histology and transmission electron microscopy showed no significant signs of toxicity in the mouse retina at 7 and 30 days following the intravitreal injection of VEGF-Grab or aflibercept. Conclusions: Compared to aflibercept, VEGF-Grab presented comparable in vivo antiangiogenic efficacy and superior in vitro anti-VEGF activity. The retinal safety profiles were comparable for the two drugs. Considering its known higher binding affinity to VEGF and PlGF compared to aflibercept, VEGF-Grab could be a potential candidate drug for neovascular retinal diseases and an alternative to aflibercept.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/efectos adversos , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Inyecciones Intravítreas , Masculino , Ratones , Ratones Endogámicos C57BL , Factor de Crecimiento Placentario/metabolismo , Ratas , Ratas Endogámicas BN , Proteínas Recombinantes de Fusión/efectos adversos , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
Korean J Gastroenterol ; 75(2): 98-102, 2020 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-32098464

RESUMEN

Hepatic hydrothorax is a transudative pleural effusion that complicates advanced liver cirrhosis. Patients refractory to medical treatment plus salt restriction and diuretics are considered to have refractory hepatic hydrothorax and may require transjugular intrahepatic portosystemic shunt (TIPS) or liver transplant. Successful antiviral therapy reduces the incidence of some complications of cirrhosis secondary to HCV infection. We report a case of hepatic hydrothorax in a 55-year-old female patient with HCV cirrhosis, which exhibited a spontaneous decrease in pleural effusion after direct antiviral agent (DAA) therapy. In cases of HCV cirrhosis, DAAs are worth administering before treatment by TIPS or liver transplantation.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hidrotórax/diagnóstico , Esquema de Medicación , Femenino , Hepatitis C Crónica/complicaciones , Humanos , Hidrotórax/complicaciones , Cirrosis Hepática/complicaciones , Persona de Mediana Edad , Respuesta Virológica Sostenida , Tomografía Computarizada por Rayos X
13.
Medicine (Baltimore) ; 99(4): e18928, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31977908

RESUMEN

Computed tomography (CT) is widely used in the pretreatment period of early gastric cancer (EGC). Only few studies have reported low accuracy of CT imaging for T and N staging in patients with EGC. However, owing to the limited number of studies, the value of CT imaging for EGC staging is not well known. Thus, we conducted a retrospective cross-sectional study regarding the associations among submucosal invasion, lymph node metastasis, and CT findings.The medical records of patients with EGC who had surgery or endoscopic resection were reviewed in a single center from January 2011 to December 2016. We evaluated the histological type, invasion depth, and lymph node (LN) metastasis on the basis of two-dimensional CT findings.We enrolled 1544 patients. Submucosal (SM) invasion was related to tumor size, histological type, and wall thickening or enhancement on CT images. Deep SM invasion (>500 µm) was also related to tumor size, poorly differentiated type, and abnormal CT findings (wall thickening, enhancement, and central depression). Among the patients with LN reactive positivity (0.5-1 cm), those who were female and had a tumor invasion of >1000 µm showed a higher prevalence of LN metastasis. The false-negative LN group had a higher prevalence of large tumors (>3 cm), poor differentiation, and SM invasion than the true-negative group.Wall thickening, enhancement, and central depression on CT images might be related to SM invasion. Patients with any positive CT findings needs more attention when performing ESD.


Asunto(s)
Toma de Decisiones , Metástasis Linfática/diagnóstico por imagen , Invasividad Neoplásica/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Estudios Transversales , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Periodo Preoperatorio , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía
14.
Korean J Gastroenterol ; 69(1): 68-73, 2017 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-28135794

RESUMEN

A Morgagni hernia was first described in 1761 by Giovanni Morgagni. In adults, it is accompanied by gastrointestinal- or respiratory-type symptoms. Herein, we report an 84-year-old woman presented to our hospital with nausea and vomiting. After hospitalization, an X-ray revealed a right diaphragmatic hernia. Based on the results of abdominal computed tomography, duodenoscopy, and upper gastrointestinography (gastrografin), we concluded that her symptoms were caused by Morgagni hernia. Our patient underwent laparoscopic surgery, and shortly thereafter, her symptoms resolved.


Asunto(s)
Dispepsia/diagnóstico , Hernias Diafragmáticas Congénitas/diagnóstico , Anciano de 80 o más Años , Diatrizoato de Meglumina/química , Duodenoscopía , Dispepsia/complicaciones , Femenino , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Humanos , Laparoscopía , Náusea/etiología , Tomografía Computarizada por Rayos X , Vómitos/etiología
15.
Korean J Gastroenterol ; 68(5): 265-269, 2016 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-27871163

RESUMEN

Neuroendocrine tumors (NETs) of the esophagus are extremely rare, aggressive and have a poor prognosis. Combined therapy using chemotherapy, radiotherapy and/or surgery appear effective. Here, we present a patient with a complaint of dysphagia who was diagnosed with this rare tumor. Upper gastrointestinal endoscope of a 46-year-old female revealed a localized ulcerative lesion in the middle esophagus. Histologic exam of biopsy specimens indicated a neuroendocrine carcinoma. The tumor cells were arranged in microtubular structures, with small and round cells containing scanty cytoplasm. They were positive for synaptophysin and chromogranin A on immunohistochemical staining. A computed tomography scan showed an esophageal tumor with enlarged superior mediastinal lymph nodes and about 1.2 cm sized liver metastasis, similar to findings in PET-CT scanning. The patient was prescribed chemotherapy consisting of etoposide and cisplatin, which led to regression of disease on follow-up imaging study. She continues under clinical observation. We seek to increase awareness of this exceedingly rare but hazardous disease by sharing our unexpected finding.


Asunto(s)
Carcinoma Neuroendocrino/diagnóstico , Neoplasias Esofágicas/diagnóstico , Antígeno Carcinoembrionario/análisis , Carcinoma Neuroendocrino/terapia , Quimioradioterapia , Cromogranina A/metabolismo , Cisplatino/uso terapéutico , Neoplasias Esofágicas/terapia , Esofagoscopía , Etopósido/uso terapéutico , Femenino , Humanos , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sinaptofisina/metabolismo
16.
Biotechnol Lett ; 38(6): 975-82, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26886192

RESUMEN

OBJECTIVES: To improve the production of 2,3-butanediol (2,3-BD) in Klebsiella pneumoniae, the genes related to the formation of lactic acid, ethanol, and acetic acid were eliminated. RESULTS: Although the cell growth and 2,3-BD production rates of the K. pneumoniae ΔldhA ΔadhE Δpta-ackA strain were lower than those of the wild-type strain, the mutant produced a higher titer of 2,3-BD and a higher yield in batch fermentation: 91 g 2,3-BD/l with a yield of 0.45 g per g glucose and a productivity of 1.62 g/l.h in fed-batch fermentation. The metabolic characteristics of the mutants were consistent with the results of in silico simulation. CONCLUSIONS: K. pneumoniae knockout mutants developed with an aid of in silico investigation could produce higher amounts of 2,3-BD with increased titer, yield, and productivity.


Asunto(s)
Butileno Glicoles/metabolismo , Klebsiella pneumoniae/metabolismo , Ingeniería Metabólica/métodos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Técnicas de Cultivo Celular por Lotes , Simulación por Computador , Fermentación , Regulación Bacteriana de la Expresión Génica , Técnicas de Inactivación de Genes , Klebsiella pneumoniae/genética , Mutación
17.
Biotechnol Prog ; 31(6): 1669-75, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26400837

RESUMEN

A new fermentation process using a mixed sugar medium is proposed in this study for 2,3-butanediol (2,3-BDO) production. The medium contained seven different monosugars known to be present in Nannochloropsis oceanica hydrolysate. The performance of each sugar when existing alone or together with glucose was evaluated. All the sugars except fucose were successfully metabolized for 2,3-BDO production. A 2,3-BDO yield of 0.31g/g was achieved with the mixed sugar medium, which was very close to that with the glucose-only medium. However, the 2,3-BDO productivity (0.28 g L(-1) h(-1) ) was found to be about 30% lower than that with glucose, implying, as expected, the existence of glucose repression on the uptake of other sugars. Strain development is in need to remove such negative effect of glucose for improved process efficiency. Fucose with the lowest uptake rate and no contribution to 2,3-BDO production can be a high value-added byproduct, once recovered and purified.


Asunto(s)
Reactores Biológicos/microbiología , Butileno Glicoles/metabolismo , Glucosa/metabolismo , Klebsiella oxytoca/metabolismo , Butileno Glicoles/análisis , Fermentación , Microalgas
18.
J Biosci Bioeng ; 117(4): 464-70, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24144809

RESUMEN

This study presents a new and effective downstream process to recover 2,3-butanediol (2,3-BD) from fermentation broth which is produced by a recombinant Klebsiella pneumoniae strain. The ldhA-deficient K. pneumoniae strain yielded about 90 g/L of 2,3-BD, along with a number of by-products, such as organic acids and alcohols, in a 65 h fed-batch fermentation. The pH-adjusted cell-free fermentation broth was firstly concentrated until 2,3-BD reached around 500 g/L by vacuum evaporation at 50°C and 50 mbar vacuum pressure. The concentrated solution was further treated using light alcohols, including methanol, ethanol, and isopropanol, for the precipitation of organic acids and inorganic salts. Isopropanol showed the highest removal efficiency, in which 92.5% and 99.8% of organic acids and inorganic salts were precipitated, respectively. At a final step, a vacuum distillation process enabled the recovery of 76.2% of the treated 2,3-BD, with 96.1% purity, indicating that fermentatively produced 2,3-BD is effectively recovered by a simple alcohol precipitation and vacuum distillation.


Asunto(s)
Alcoholes/química , Butileno Glicoles/aislamiento & purificación , Destilación , Fermentación , Ácidos , Técnicas de Cultivo Celular por Lotes , Reactores Biológicos , Butileno Glicoles/química , Butileno Glicoles/metabolismo , Precipitación Química , Eliminación de Gen , Concentración de Iones de Hidrógeno , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/metabolismo , L-Lactato Deshidrogenasa/deficiencia , L-Lactato Deshidrogenasa/genética , Sales (Química) , Vacio
19.
J Biosci Bioeng ; 116(2): 186-92, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23643345

RESUMEN

Fermentative 2,3-butanediol (2,3-BD) production has been receiving increasing interest for its potential as a platform chemical intended for the production of synthetic rubbers, plastics, and solvents. In this study, Klebsiella oxytoca GSC 12206, a 2,3-BD native hyper-producing and nonpathogenic bacterium, was isolated from a cattle farm. Since this isolate produced a significant amount of lactic acid along with 2,3-BD, its mutant deficient in lactic acid formation was constructed by disrupting the ldhA gene which encodes lactate dehydrogenase. The ldhA gene was deleted precisely by using the pKGS plasmid. When compared to the wild-type strain, the mutant deleted with the ldhA gene in glucose fermentation resulted in an increase of 54%, 13%, 60%, and 78% of 2,3-BD titer, productivity, yield, and selectivity, respectively. A fed-batch fermentation by this mutant with intermittent glucose feeding produced 115 g/L of 2,3-BD with an yield and productivity of 0.41 g 2,3-BD per g glucose and 2.27 g/L h, respectively, indicating the usefulness for the industrial production of 2,3-BD.


Asunto(s)
Butileno Glicoles/metabolismo , Klebsiella oxytoca/metabolismo , Animales , Bovinos , Fermentación , Glucosa/metabolismo , Klebsiella oxytoca/genética , Klebsiella oxytoca/aislamiento & purificación , L-Lactato Deshidrogenasa/genética , Ácido Láctico/metabolismo , Ingeniería Metabólica
20.
Enzyme Microb Technol ; 48(6-7): 505-9, 2011 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-22113023

RESUMEN

The enzymatic coproduction of biodiesel and glycerol carbonate by the transesterification of soybean oil was studied using lipase as catalyst in organic solvent. To produce biodiesel and glycerol carbonate simultaneously, experiments were designed sequentially. Enzyme screening, the molar ratio of dimethyl carbonate (DMC) to soybean oil, reaction temperature and solvent effects were investigated. The results of enzyme screening, at 100 g/L Novozym 435 (immobilized Candida antarctica lipase B), biodiesel and glycerol carbonate showed conversions of 58.7% and 50.7%, respectively. The optimal conditions were 60 °C, 100 g/L Novozym 435, 6.0:1 molar ratio with tert-butanol as solvent: 84.9% biodiesel and 92.0% glycerol carbonate production was achieved.


Asunto(s)
Proteínas Bacterianas/metabolismo , Biocombustibles , Formiatos/metabolismo , Proteínas Fúngicas/metabolismo , Glicerol/análogos & derivados , Lipasa/metabolismo , Aceite de Soja/metabolismo , Biocatálisis , Enzimas Inmovilizadas , Esterificación , Glicerol/metabolismo , Solventes , Especificidad por Sustrato , Temperatura , Alcohol terc-Butílico
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