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With the advent of immune checkpoint inhibitors (ICIs), a better understanding of tumor microenvironment (TME) is becoming crucial in managing esophageal squamous cell carcinoma (ESCC) patients. We investigated the survival impact of TME status and changes in patients with ESCC who underwent neoadjuvant chemotherapy (NAC) followed by surgery (n = 264). We examined immunohistochemical status (CD4+, CD8+, CD20+, Foxp3+, HLA class-1+, CD204+, and programmed death ligand-1 [PD-L1+]) on 264 pre-NAC and 204 paired post-NAC specimens. Patients were classified by their pre- and post-NAC immune cell status and their changes following NAC. Our findings showed that pre-NAC TME status was not significantly associated with survival outcomes. In contrast, post-NAC TME status, such as low level of T cells, CD4+ T cells, and high PD-L1 combined positive score (CPS), were significantly associated with poor overall survival (OS). Notably, TME changes through NAC exerted significant survival impacts; patients with consistently low levels of T cells, low levels of CD4+ T cells, or high levels of PD-L1 (CPS) had very poor OS (3-year OS: 35.5%, 40.2%, and 33.3%, respectively). Tumor microenvironment changes of consistently low T cells, low CD4+ T cells, and high PD-L1 were independent predictors of poor OS in multivariate Cox hazards analyses, while factors indicating post-NAC status (T cells, CD4+, and PD-L1 [CPS]) alone were not. Therefore, we suggest that the consistently low T/high PD-L1 group could benefit from additional therapies, such as ICIs, and the importance of stratification by the TME, which has recently been recognized.
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Antígeno B7-H1 , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Terapia Neoadyuvante/métodos , Masculino , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/inmunología , Femenino , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Persona de Mediana Edad , Anciano , Antígeno B7-H1/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Pronóstico , Quimioterapia Adyuvante/métodosRESUMEN
The bulk heterojunction structures of organic photovoltaics (OPVs) have been overlooked in their machine learning (ML) approach despite their presumably significant impact on power conversion efficiency (PCE). In this study, we examined the use of atomic force microscopy (AFM) images to construct an ML model for predicting the PCE of polymer : non-fullerene molecular acceptor OPVs. We manually collected experimentally observed AFM images from the literature, applied data curing and performed image analyses (fast Fourier transform, FFT; gray-level co-occurrence matrix, GLCM; histogram analysis, HA) and ML linear regression. The accuracy of the model did not considerably improve even by including AFM data in addition to the chemical structure fingerprints, material properties and process parameters. However, we found that a specific spatial wavelength of FFT (40-65 nm) significantly affects PCE. The GLCM and HA methods, such as homogeneity, correlation and skewness expand the scope of image analysis and artificial intelligence in materials science research fields.
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Objective Phosphate is a fundamental element involved in a number of physiological pathways. A previous study showed abnormal laboratory findings and a higher mortality in hypophosphatemic patients than in normophosphatemic patients with pneumonia. Sporadic cases of pneumonia due to Legionella spp., Streptococcus pneumoniae, and viruses have been reported; however, the significance of hypophosphatemia in patients with pneumonia has not been adequately studied. We determined whether or not hypophosphatemia in patients with community-acquired pneumonia (CAP) was associated with specific pathogens, patient factors, disease severity, and mortality. Method We retrospectively analyzed 600 patients with CAP who were admitted to our hospital between January 1, 2010, and December 31, 2019. Results Hypophosphatemia was found in 72 (12.0%) of the 600 patients. The most frequent causative microbial agents of CAP in patients with hypophosphatemia were S. pneumoniae, Legionella spp., and influenza virus, whereas in severely ill patients with hypophosphatemia, influenza virus was the most common. Legionella spp., diabetes mellitus, and severe pneumonia were the independent factors for hypophosphatemia in the multivariable analysis. An impaired performance status, severe status on admission, interstitial pneumonia, bacteremia, and guideline-discordant therapy were the independent factors associated with mortality in the multivariable analysis. Hypophosphatemia was not significantly associated with mortality but showed a trend towards higher mortality in the multivariable analysis. Conclusion Hypophosphatemia was not associated with the prognosis in patients with CAP. However, the significance of hypophosphatemia for clinicians lies in the laboratory findings that predict abnormal glucose metabolism, Legionella infection, and severe disease.
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Infecciones Comunitarias Adquiridas , Hipofosfatemia , Neumonía , Infecciones Comunitarias Adquiridas/complicaciones , Humanos , Hipofosfatemia/complicaciones , Neumonía/etiología , Estudios Retrospectivos , Streptococcus pneumoniaeRESUMEN
Objective Viral pneumonia is not rare in community-acquired pneumonia (CAP). Mixed or secondary pneumonia (coinfection) can be seen in viral pneumonia; however, its frequency in coronavirus disease 2019 (COVID-19) has only been investigated in a few studies of short duration, and its significance has not been fully elucidated. We investigated the frequency and significance of co-infection in patients with COVID-19 over a 1-year study period. Methods Coinfection was investigated via multiplex polymerase chain reaction (PCR), culture of respiratory samples, rapid diagnostic tests, and paired sera. We used logistic regression analysis to analyze the effect of coinfection on severity at admission and Cox proportional-hazards model analysis to analyze the effect of coinfection on need for high-flow nasal cannula, invasive mandatory ventilation use, and death, respectively. Patients We retrospectively investigated 298 patients who suffered CAP due to severe acute respiratory syndrome coronavirus-2 infection diagnosed by PCR and were admitted to our institution from February 2020 to January 2021. Results Primary viral pneumonia, and mixed viral and bacterial pneumonia, accounted for 90.3% and 9.7%, respectively, of COVID-19-associated CAP, with viral coinfection found in 30.5% of patients with primary viral pneumonia. Influenza virus was the most common (9.4%). Multivariable analysis showed coinfection not to be an independent factor of severity on admission, need for high-flow nasal cannula or invasive mandatory ventilation, and mortality. Conclusion Viral coinfection was common in COVID-19-associated CAP. Severity on admission, need for high-flow oxygen therapy or invasive mandatory ventilation, and mortality were not affected by coinfection.
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COVID-19 , Coinfección , Infecciones Comunitarias Adquiridas , Neumonía Viral , Coinfección/epidemiología , Infecciones Comunitarias Adquiridas/epidemiología , Hospitales , Humanos , Neumonía Viral/epidemiología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
To understand the mechanism underlying metastasis, identification of a mechanism-based and common biomarker for circulating tumour cells (CTCs) in heterogenous breast cancer is needed. SET, an endogenous inhibitor of protein phosphatase 2A, was overexpressed in all subtypes of invasive breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60-70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24 breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I-III breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with lymph node metastasis in patients with stage I-III disease. Our results indicate that SET contributes to breast cancer progression and can act as a potential biomarker of CTCs for the detection of metastasis.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Inhibidores Enzimáticos/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Proteína Fosfatasa 2/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Metástasis Linfática , Células MCF-7 , Proteína Fosfatasa 2/metabolismoRESUMEN
Two patients, a 60-year-old man and 43-year-old woman, presented to our hospital with symptoms of respiratory tract infection. These patients showed imaging findings of multiple small nodules, ground-glass opacities, and consolidations. In case 1, although antibiotics were started, bilateral shadows spread widely, which made us suspect interstitial pneumonia. The condition improved after steroid administration, and there has been no recurrence since completing this treatment. In case 2, the patient recovered rapidly with antibiotics only. In both cases, we performed bronchoalveolar lavage, in which only human rhinovirus infection was detected by multiplex polymerase chain reaction testing, and primary rhinovirus pneumonia was diagnosed.
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Enfermedades Pulmonares Intersticiales , Nódulos Pulmonares Múltiples , Neumonía Viral , Neumonía , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Masculino , Recurrencia Local de Neoplasia , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/tratamiento farmacológico , RhinovirusRESUMEN
OBJECTIVE: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. METHODS: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. RESULTS: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients' symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients' clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. CONCLUSION: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality.
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We experienced a 72-year-old man who developed laboratory-confirmed human coronavirus HKU1 pneumonia. PCR testing for SARS-CoV-2 from a nasopharyngeal specimen was negative twice, and rapid immunochromatographic antibody test (RIAT) using a commercially available kit for IgM and IgG against SARS-CoV-2 showed him turning positive for IgG against SARS-CoV-2. We then performed RIAT in stored serum samples from other patients who suffered laboratory-confirmed human common cold coronaviruses (n = 6) and viruses other than coronavirus (influenza virus, n = 3; rhinovirus, n = 3; metapneumovirus, n = 1; adenovirus, n = 1) admitted until January 2019. Including the present case, four of 7 (57%) showed false-positive RIAT results due to human common cold coronaviruses infection. Two of the 4 patients showed initial negative to subsequent positive RIAT results, indicating seroconversion. RIAT was positive for IgG and IgM in viruses other than coronavirus in 2 (25.0%) and 1 (12.5%) patient. Because of high incidence of false positive RIAT results, cross antigenicity between human common cold coronaviruses and SARS-CoV-2 can be considered. Results of RIAT should be interpreted in light of epidemics of human common cold coronaviruses infection. Prevalence of past SARS-CoV-2 infection may be overestimated due to high incidence of false-positive RIAT results.
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Adjuvant chemotherapy with capecitabine is frequently not completed due to adverse events, including hand-foot syndrome. A higher completion rate of capecitabine by reduction of the side effects may improve disease-free survival and quality of life of affected patients. In the present study, colorectal cancer (CRC) patients were treated with capecitabine (2,500 mg/m2/day), which was taken for five days, followed by an interval of two days (5-days-on/2-days-off schedule). One course lasted three weeks, and eight courses (24 weeks) were administered. The median number of treatment courses was significantly higher in patients in the 5-days-on/2-days-off regimen group compared with that of patients in the retrospectively included conventional regimen group (P=0.0438). The frequency of completion of the scheduled treatment by patients in the 5-days-on/2-days-off regimen group was significantly higher (P=0.0389). The present phase II study suggests that toxicities associated with the 5-days-on/2-days-off regimen are lower compared with those of the conventional regimen, and that the occurrence of adverse events was higher, but less high-grade toxicities were reported. The time to treatment failure was also favorable in the new regimen and it demonstrated good feasibility. In conclusion, the present study demonstrated good feasibility with retained quality of life and acceptable adverse effects (mostly low-grade), and the 5-days-on/2-days-off regimen should be further evaluated in future randomized controlled trials. The present study was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (no. UMIN000012813).
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Two patients, a 76-year-old woman and 66-year-old woman, presented to our hospital with symptoms of lower respiratory tract infection. Both patients showed chest imaging findings of bilateral ground-glass opacities and consolidations. We initially suspected these patients of having influenza-associated pneumonia and cryptogenic organizing pneumonia, respectively, and performed bronchoalveolar lavage, but only human parainfluenza virus-1 infection was detected by multiplex polymerase chain reaction testing. These findings suggest that pneumonia due to human parainfluenza virus-1 should be included in the differential diagnosis of such cases.
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Líquido del Lavado Bronquioalveolar/química , Neumonía en Organización Criptogénica/diagnóstico , Gripe Humana/diagnóstico , Virus de la Parainfluenza 1 Humana/genética , Neumonía Viral/diagnóstico por imagen , ARN Viral/análisis , Infecciones por Respirovirus/diagnóstico por imagen , Anciano , Líquido del Lavado Bronquioalveolar/virología , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Reacción en Cadena de la Polimerasa Multiplex , Neumonía Viral/patología , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa , Infecciones por Respirovirus/patología , Infecciones por Respirovirus/virología , Tomografía Computarizada por Rayos XRESUMEN
A 70-year-old woman was admitted to our hospital for dyspnea and a fever of 2 weeks duration. Chest imaging showed bilateral infiltration, and a rapid diagnostic test for influenza virus, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Legionella spp. was negative. She was intubated and mechanically ventilated and underwent bronchoalveolar lavage. Bronchoalveolar lavage fluid yielded no significant pathogens, and the multiplex polymerase chain reaction test was positive only for human bocavirus. Specific antibodies against significant pathogens were not increased in paired sera, so we diagnosed her with primary human bocavirus pneumonia.
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Bocavirus Humano/aislamiento & purificación , Huésped Inmunocomprometido , Infecciones por Parvoviridae/mortalidad , Infecciones por Parvoviridae/fisiopatología , Neumonía/mortalidad , Neumonía/fisiopatología , Anciano , Resultado Fatal , Femenino , Humanos , Neumonía/virologíaRESUMEN
Objective The clinical characteristics and chest imaging findings of viral pneumonia and several interstitial lung diseases (ILDs) overlap, and viral pneumonia may be underrecognized and misdiagnosed as certain ILDs. To clarify the frequency of viral pneumonia among patients with acute progressive clinical courses that required a differential diagnosis between ILDs and pneumonia, and to determine the most frequent ILDs misdiagnosed in cases of viral pneumonia. Patients and Methods We retrospectively analyzed patients hospitalized from 2010 to 2017 with an acute clinical course (≤30 days) who underwent bronchoalveolar lavage (BAL) for the differential diagnosis of infection and ILDs. We performed a multiplex PCR for respiratory viruses using the patients' preserved BAL fluid. The final diagnosis was made by a multidisciplinary approach and after considering the PCR results. The diagnosis at discharge was compared to the final diagnosis. Results Among the 109 patients, 53 were diagnosed with viral pneumonia. Viral pneumonia and other diseases showed some differences in symptoms and laboratory data; however, the differences were small or overlapped. Viral pneumonia was misdiagnosed on discharge as acute fibrinous organizing pneumonia, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia (AFOP/COP/CEP) (n=22), acute interstitial pneumonia (n=5), connective tissue disease-related ILDs (n=3), unclassifiable interstitial pneumonia (n=2), drug-induced ILD (n=1), and pneumonia (n=20). Conclusion Approximately half of the patients who underwent BAL had viral pneumonia. The most common ILD-related misdiagnoses were AFOP/COP/CEP. Differences in symptoms and laboratory findings between viral pneumonia and other diseases were small, and viral pneumonia should be included in the differential diagnosis when physicians encounter cases in which the abovementioned ILDs are suspected.
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Enfermedades Pulmonares Intersticiales/diagnóstico , Neumonía Viral/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/virología , Neumonía en Organización Criptogénica/diagnóstico , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/diagnóstico , Fibrosis Pulmonar Idiopática/diagnóstico , Masculino , Persona de Mediana Edad , Eosinofilia Pulmonar/diagnóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
A 27-year-old man presented to our hospital with symptoms of lower respiratory tract infection. This patient showed imaging findings of diffuse bronchiolitis, ground-glass opacities, and consolidations. Antibiotics were not effective, and we performed bronchoalveolar lavage, in which only human rhinovirus infection was detected by multiplex PCR testing.
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A 62-year-old man presented to our hospital for the further evaluation and treatment of his back pain, general fatigue, and dyspnea, which had developed 4 days after the 29th administration of nivolumab to treat his lung cancer. Based on his clinical history, elevated serum cardiac enzyme values, and cardiac magnetic resonance (CMR) imaging and myocardial biopsy findings, he was diagnosed with myocarditis induced by nivolumab. Corticosteroid therapy improved his condition, and CMR performed on hospital day 11 also showed remarkable improvement. Although nivolumab-induced myocarditis is rare, cardiologists should consider it when encountering patients treated with such a drug for malignant disease.
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Corticoesteroides/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/fisiopatología , Miocarditis/tratamiento farmacológico , Miocarditis/etiología , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Biopsia , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The anticancer activity of immune checkpoint inhibitors is attracting attention in various clinical sites. Since green tea catechin has cancer-preventive activity in humans, whether green tea catechin supports the role of immune checkpoint inhibitors was studied. We here report that (-)-epigallocatechin gallate (EGCG) inhibited programmed cell death ligand 1 (PD-L1) expression in nonâ»small-cell lung cancer cells, induced by both interferon (IFN)-γ and epidermal growth factor (EGF). The mRNA and protein levels of IFN-γâ»induced PD-L1 were reduced 40â»80% after pretreatment with EGCG and green tea extract (GTE) in A549 cells, via inhibition of JAK2/STAT1 signaling. Similarly, EGF-induced PD-L1 expression was reduced about 37â»50% in EGCG-pretreated Lu99 cells through inhibition of EGF receptor/Akt signaling. Furthermore, 0.3% GTE in drinking water reduced the average number of tumors per mouse from 4.1 ± 0.5 to 2.6 ± 0.4 and the percentage of PD-L1 positive cells from 9.6% to 2.9%, a decrease of 70%, in lung tumors of A/J mice given a single intraperitoneal injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In co-culture experiments using F10-OVA melanoma cells and tumor-specific CD3+ T cells, EGCG reduced PD-L1 mRNA expression about 30% in F10-OVA cells and restored interleukin-2 mRNA expression in tumor-specific CD3+ T cells. The results show that green tea catechin is an immune checkpoint inhibitor.
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Antineoplásicos Fitogénicos/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Catequina/farmacología , Inmunomodulación/efectos de los fármacos , Té/química , Animales , Antineoplásicos Fitogénicos/química , Catequina/química , Línea Celular Tumoral , Modelos Animales de Enfermedad , Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2/TIS21), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach. Expression was increased in the mucous epithelium following H. pylori infection in contrast to its loss in human gastric adenocarcinoma. Indeed, adenoviral transduction of BTG2/TIS21 significantly inhibited Tipα activity in MKN-1 and MGT-40, human and mouse gastric cancer cells, respectively, thereby downregulating tumor necrosis factor-α (TNFα) expression and Erk1/2 phosphorylation by reducing expression of nucleolin, a Tipα receptor. Chromatin immunoprecipitation proved that BTG2/TIS21 inhibited Sp1 expression and its binding to the promoter of the nucleolin gene. In addition, BTG2/TIS21 expression significantly reduced membrane-localized nucleolin expression in cancer cells, and the loss of BTG2/TIS21 expression induced cytoplasmic nucleolin availability in gastric cancer tissues, as evidenced by immunoblotting and immunohistochemistry. Higher expression of BTG2 and lower expression of nucleolin were accompanied with better overall survival of poorly differentiated gastric cancer patients. This is the first report showing that BTG2/TIS21 inhibits nucleolin expression via Sp1 binding, which might be associated with the inhibition of H. pylori-induced carcinogenesis. We suggest that BTG2/TIS21 is a potential inhibitor of nucleolin in the cytoplasm, leading to inhibition of carcinogenesis after H. pylori infection.
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Proteínas Bacterianas/antagonistas & inhibidores , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Inmediatas-Precoces/metabolismo , Fosfoproteínas/genética , Proteínas de Unión al ARN/genética , Neoplasias Gástricas/etiología , Neoplasias Gástricas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Biomarcadores de Tumor , Línea Celular Tumoral , Modelos Animales de Enfermedad , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Proteínas Inmediatas-Precoces/genética , Estimación de Kaplan-Meier , Ratones , Modelos Biológicos , Fosfoproteínas/metabolismo , Pronóstico , Regiones Promotoras Genéticas , Unión Proteica , Proteínas de Unión al ARN/metabolismo , Factor de Transcripción Sp1/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Proteínas Supresoras de Tumor/genética , NucleolinaRESUMEN
Amphiphilic hyaluronic acid (HA) derivatives bearing hydrophobic indocyanine green dye derivatives and hydrophilic poly(ethylene glycol) were synthesized through the use of condensation and copper-catalyzed click cyclization reactions. The amphiphilic HA derivatives dissolved in water and formed self-assemblies in which the near-infrared dyes were tightly packed and arranged to form dimers or H-aggregates. By irradiating an aqueous solution of HA derivatives with near-infrared light, photoacoustic signals were detected along with fluorescence emission. Self-assemblies consisting of HA derivatives could smoothly accumulate in tumor tissues by passive tumor targeting. By utilizing HA derivatives as a contrast agent, tumor sites were clearly visualized by optical imaging as well as by photoacoustic tomography.
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Neoplasias del Colon/patología , Medios de Contraste , Ácido Hialurónico/análogos & derivados , Adyuvantes Inmunológicos/síntesis química , Animales , Línea Celular Tumoral , Colorantes/química , Medios de Contraste/síntesis química , Verde de Indocianina/química , Rayos Infrarrojos , Ratones , Trasplante de Neoplasias , Técnicas Fotoacústicas , Polietilenglicoles/química , TomografíaRESUMEN
PURPOSE: JF1/Ms mice, an inbred strain derived from Japanese wild mice, carry a germline hypomorphic mutation in the endothelin receptor type B gene (Ednrb). We observed that the JF1/Ms mice develop various spontaneous tumors at a high incidence late in life. The aim of this study was to elucidate the mechanism responsible for spontaneous tumors in these mice. Possible relevance of milk-borne mammary tumor virus and gene alterations in Ednrb to tumorigenesis was explored. METHODS: Expression and methylation status of Ednrb were quantitatively analyzed in normal and cancer tissues of mammary gland, liver, submandibular gland as well as in a cultured cell line, MW1, established from a submandibular gland adenocarcinoma. The biological effects of EDNRB were examined in the MW1 cells transfected with wild-type Ednrb. RESULTS: Transcripts of Ednrb were barely detectable, and the promoter region of Ednrb was hypermethylated in tumor tissues and the MW1 cells. In contrast, normal counterpart tissues showed positive expression of Ednrb transcripts and had unmethylated promoter regions. Treatment of the MW1 cells with 5-Aza-dC restored transcription of Ednrb to normal levels. Transfection of the MW1 cells with Ednrb1 (MW1-Ednrb1) resulted in lower growth rates and morphological changes compared with the mock-transfected MW1 cells (MW1-mock1). Furthermore, the MW1-Ednrb1 cells transplanted in syngeneic mice showed a lower proliferation rate than the MW1-mock1 cells. CONCLUSIONS: Germline mutation and subsequent promoter methylation of Ednrb may be relevant to cancer susceptibility in the JF1/Ms mice. These data indicate that Ednrb acts as a tumor suppressor, as reported in human prostate, bladder, and clear cell renal carcinomas.
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Metilación de ADN , Mutación de Línea Germinal , Ratones Endogámicos/genética , Neoplasias Experimentales/genética , Receptor de Endotelina B/genética , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Femenino , Genes Supresores de Tumor , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/patología , Neoplasias Mamarias Experimentales/virología , Virus del Tumor Mamario del Ratón/aislamiento & purificación , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/patología , Neoplasias Experimentales/virología , Regiones Promotoras GenéticasRESUMEN
Bacteria isolated from surgical infections during the period from April 2011 to March 2012 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 785 strains including 31 strains of Candida spp. were isolated from 204 (78.8%) of 259 patients with surgical infections. Five hundred and twenty three strains were isolated from primary infections, and 231 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp. and Staphylococcus spp., in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa, K. pneumoniae, and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Collinsella aerofaciens, Lactobacillus acidophilus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated, followed by P micra and L. acidophilus, in this order. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroidesfragilis was the highest from primary infections, followed by Bilophila wadsworthia, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides vulgatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides caccae, B. thetaiotaomicron, Bacteroides ovatus and B. wadsworthia, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant Staphylococcus aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed. We should carefully follow up B. wadsworthia which was resistant to various antimicrobial agents, and also Bacteroides spp. which was resistant to many ß-lactams.
Asunto(s)
Bacterias/aislamiento & purificación , Infección de la Herida Quirúrgica/microbiología , Bacterias/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Bacteria isolated from surgical infections during the period from April 2010 to March 2011 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 631 strains including 25 strains of Candida spp. were isolated from 170 (81.7%) of 208 patients with surgical infections. Four hundred and twenty two strains were isolated from primary infections, and 184 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus avium was highest, followed by Streptococcus spp. such as Streptococcus anginosus and Staphylococcus spp. such as Staphylococcus aureus, in this order, from primary infections, while Enterococcus spp. such as E. faecalis and E. faecium was highest, followed by Staphylococcus spp. such as S. aureus from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Pseudomonas aeruginosa in this order, and from surgical site infection, E. coli and R aeruginosa were most predominantly isolated, followed by E. cloacae and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rates of Parvimonas micra, Eggerthella lenta, Streptococcus constellatus, Gemella morbillorum, and Collinsella aerofaciens were the highest from primary infections, and the isolation rate from surgical site infection was generally low. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by, Bacteroides fragilis and Bacteroides ovatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides thetaiotaomnicron, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant S. aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed.