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1.
Gan To Kagaku Ryoho ; 48(8): 1057-1060, 2021 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-34404076

RESUMO

The patient was a 66-year-old male who had undergone an operation for lung cancer and solitary brain metastases. Follow- up PET-CT after 1 year detected FDG accumulation in the stomach. We performed esophagogastroscopy and found an approximately 20 mm-sized Type 2 tumor on the greater curvature of the upper stomach. A pathological diagnosis of lung adenocarcinoma metastasis in the stomach was made. Laparoscopic surgery was performed on the metastatic lesion to prevent bleeding and perforation, and resection was achieved with minimal invasion. The current development of chemotherapy, including immunotherapy, has contributed to the improved prognosis of cancer patients, including those with lung metastasis in the stomach. Considering these backgrounds, preventive surgical resection under laparoscopy may be an effective approach for improving prognosis and preventing acute life-threatening adverse events. We report this case along with a literature review.


Assuntos
Laparoscopia , Neoplasias Pulmonares , Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
2.
Gan To Kagaku Ryoho ; 48(7): 959-962, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267036

RESUMO

An 86-year-old man was referred to our hospital with pulmonary tuberculosis developed during postoperative chemotherapy for gastric cancer. We initiated treatment with an anti-tuberculosis drug. Following confirmation of the effectiveness of this regimen, we combined the treatment with anti-cancer drugs. Tuberculosis treatment was completed without any drug interactions or serious side effects due to multidrug administration. For cancer patients who developed tuberculosis, combination treatment requires careful observation; however, it is a treatment option that can control both diseases.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Tuberculose Pulmonar , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antituberculosos/efeitos adversos , Humanos , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tuberculose Pulmonar/tratamento farmacológico
3.
Commun Biol ; 4(1): 820, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188173

RESUMO

Host lipid metabolism and viral responses are intimately connected. However, the process by which the acquired immune systems adapts lipid metabolism to meet demands, and whether or not the metabolic rewiring confers a selective advantage to host immunity, remains unclear. Here we show that viral infection attenuates the expression of genes related to lipid metabolism in murine CD4+ T cells, which in turn increases the expression of antiviral genes. Inhibition of the fatty acid synthesis pathway substantially increases the basal expression of antiviral genes via the spontaneous production of type I interferon (IFN). Using a combination of CRISPR/Cas9-mediated genome editing technology and a global lipidomics analysis, we found that the decrease in monounsaturated fatty acid caused by genetic deletion of Scd2 in mice was crucial for the induction of an antiviral response through activation of the cGAS-STING pathway. These findings demonstrate the important relationship between fatty acid biosynthesis and type I IFN responses that enhances the antiviral response.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Ácidos Graxos Monoinsaturados/metabolismo , Interferon Tipo I/farmacologia , Proteínas de Membrana/fisiologia , Nucleotidiltransferases/fisiologia , Estearoil-CoA Dessaturase/fisiologia , Viroses/imunologia , Animais , Interações Hospedeiro-Patógeno , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transdução de Sinais , Viroses/metabolismo
4.
Sci Rep ; 11(1): 13526, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188146

RESUMO

Tumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (-) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p < 0.01). These results suggest that radiomics with machine-learning helped to develop a favorable model of STAS (+) NSCLC, which might be useful for the proper selection of candidates who should undergo sublobar resection.

5.
Auris Nasus Larynx ; 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34140215

RESUMO

OBJECTIVE: To compare the prevalence of middle ear malformations between patients with and without congenital external auditory canal stenosis (CEACS) and to investigate the outcomes of tympanoplasty and/or canalplasty in terms of tympanic membrane (TM) size and external auditory canal (EAC) stenosis in patients with middle ear malformation. METHODS: Twenty-five patients who underwent primary tympanoplasty and/or canalplasty for middle ear malformation at a tertiary academic medical center were retrospectively reviewed. CEACS was defined as an EAC diameter of 4 mm or less. Intraoperative findings, including irregularity of the ossicles, facial nerve, or chorda tympani; size of the TM and EAC on computed tomography; and pre- and postoperative hearing level, were collected. RESULTS: We included 7 and 18 patients with and without CEACS, respectively. The malleus handle defect, anterior deviation of the chorda tympani, and small TM (≤7 mm) (p-values 0.015, <0.001, and 0.003, respectively; Fisher's exact test) had significantly higher prevalence in patients with CEACS than in those without. The mean postoperative air-bone gap (ABG) in patients with CEACS was not significantly different from that in patients with normal-sized EAC (20.6 dB and 19.5 dB, respectively; p-value, 0.121; Mann-Whitney U test). No difference was observed in mean postoperative ABG between patients with small TM and those with normal-sized TM (19.2 dB and 20.0 dB, respectively; p-value, 0.469; Mann-Whitney U test). CONCLUSION: Patients with CEACS were more likely to have malleus handle defect, anterior deviation of the chorda tympani, and small TM than those without CEACS. Hearing outcome of patients with CEACS and a malformed malleus and/or incus might be equivalent to that of patients without CEACS following tympanoplasty and/or canalplasty, regardless of the EAC or TM size.

6.
Int J Mol Sci ; 22(10)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065754

RESUMO

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward Pfr → Po transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse Po → Pfr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm-1. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.


Assuntos
Biliverdina/química , Cianobactérias/genética , Fotorreceptores Microbianos/química , Fitocromo/química , Substituição de Aminoácidos , Biliverdina/genética , Sítios de Ligação , Cianobactérias/metabolismo , Eletrônica , Cinética , Processos Fotoquímicos , Fotorreceptores Microbianos/genética , Fitocromo/genética , Engenharia de Proteínas , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Análise Espectral , Análise Espectral Raman , Tempo , Fatores de Tempo
7.
Gen Thorac Cardiovasc Surg ; 69(10): 1421-1431, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33999348

RESUMO

OBJECTIVES: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. METHODS: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. RESULTS: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years. CONCLUSIONS: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended.


Assuntos
Transplante de Pulmão , Óxido Nítrico , Administração por Inalação , Humanos , Japão , Resultado do Tratamento
8.
Intern Med ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34024848

RESUMO

Hemolytic anemia is a rarely occurring manifestation of native valve infective endocarditis. We herein report an afebrile patient with hemolytic anemia caused by Cardiobacterium hominis endocarditis. A 60-year-old Japanese man had a history of aortic root replacement and the gradual onset of general fatigue. He had hemolytic anemia. Blood cultures detected C. hominis. A transthoracic echocardiogram showed aortic valve vegetation and periannular abscess with perforation of the non-coronary cusp. Intravascular hemolysis recovered after antimicrobial therapy, surgical removal of the vegetation and abscess, and aortic valve replacement. Subacute endocarditis should be considered if patients develop hemolytic anemia with signs of chronic inflammation without a fever.

9.
Respir Investig ; 59(4): 559-563, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33883090

RESUMO

Bronchiolitis obliterans syndrome (BOS) occurring after hematopoietic stem cell transplantation (HSCT) for hematologic malignancies is a progressive and refractory disease, and lung transplantation (LTx) seems to be the only promising treatment. We report two cases of BOS after HSCT, which showed distinct clinical courses and were successfully treated with LTx. The respiratory symptoms and function of the two patients progressively deteriorated to a critical level during the waiting period. In one patient, recurrent and intractable pneumothoraxes consistent with thoracic air-leak syndrome (TALS) occurred, which were associated with pleuroparenchymal fibroelastosis. TALS could accelerate clinical deterioration, thus permitting a shorter waiting period for LTx.

10.
Am J Emerg Med ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33895041

RESUMO

Hyperosmolar hyperglycemic syndrome is a life-threatening diabetic emergency that manifests as altered mental status. An otherwise healthy 40-year-old man presented to our emergency department with headache and severe hypertension. Brain magnetic resonance imaging showed evidence of posterior reversible encephalopathy syndrome, a usually reversible neurological syndrome characterized by subcortical vasogenic oedema. This first reported case details posterior reversible encephalopathy syndrome concurrent with hyperosmolar hyperglycemic syndrome. Prompt diagnosis and management were essential to avoid non-reversible consequences.

11.
Gen Thorac Cardiovasc Surg ; 69(8): 1214-1221, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33754238

RESUMO

OBJECTIVE: The innovation of novel systemic chemo/immunotherapy for metastatic head and neck cancer might contribute to prognostic improvement. We aimed to clarify the recent characteristics and outcomes of pulmonary metastasectomy for head and neck cancer. METHODS: Twenty-five patients who underwent pulmonary metastasectomy from January 2011 to December 2016 were included. The clinicopathological factors and survival were assessed by retrospective chart reviews. RESULTS: The median follow-up period was 39 months (range, 7-94 months). The median age was 66 years (range, 20-89 years), and 23 males were included. The primary tumor locations were as follows: pharynx (n = 12), nasal/paranasal cavity (n = 5), larynx (n = 4), and others (n = 4). The 5-year overall survival rate was 49%. In the univariate analysis, a history of local recurrence before pulmonary metastasis was an independent predictor of a poor prognosis. In 90% of patients with recurrence after pulmonary metastasectomy, the site of recurrence was the lung. Eight patients achieved long-term survival without any evidence of recurrence (median: 45 months). Molecular targeting chemotherapy and immune-checkpoint inhibitors were used in five patients with systemic recurrence after pulmonary metastasectomy, leading to preferable survival. CONCLUSIONS: In the current era of advances in systemic chemotherapy and immunotherapy, surgical indication has not changed for resectable pulmonary metastases and selected patients can still benefit from pulmonary metastasectomy. Further investigation is needed to clarify the significance of systemic therapy in patients with pulmonary metastasis of head and neck cancer.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Metastasectomia , Idoso , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia/cirurgia , Pneumonectomia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
Int J Cancer ; 148(12): 3008-3018, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33533494

RESUMO

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF-associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF-associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Histona-Lisina N-Metiltransferase/genética , Fibrose Pulmonar Idiopática/genética , Fator 2 Relacionado a NF-E2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma de Células Escamosas/etiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Epigênese Genética , Exoma , Feminino , Amplificação de Genes , Estudos de Associação Genética , Testes Genéticos , Humanos , Fibrose Pulmonar Idiopática/complicações , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de Sequência de DNA , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética
13.
J Infect Chemother ; 27(5): 766-769, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33402304

RESUMO

To date, only 26 cases of Mycobacterium wolinskyi infections have been reported in humans. We herein report a first case of prosthetic valve endocarditis due to this organism after cardiovascular surgery. An 82-year-old man presented with repeat episodes of syncope and fever after aortic valve replacement, mitral valve replacement, left atrial appendage closure, and pulmonary vein isolation. Blood cultures maintained in aerobic bottles were repeatedly positive after 90-100 hours, and Gallium scan revealed abnormal accumulations in the sternum and left testis. While colonies formed by culturing the fluid of the parasternal area and blood cultures revealed gram-positive rods, we could not analyze the colony using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF). M. wolinskyi was finally identified on 16S rRNA, hsp65, and rpoB gene sequencing. We treated the patient with multiple antimycobacterial drugs, i.e., amikacin, imipenem, and clarithromycin for 6 weeks, which was changed to oral ciprofloxacin and minocycline for 12 months. This case highlights the need to consider rapidly growing mycobacteria, including M. wolinskyi, if chronic fever persists from weeks to months after surgery, the blood culture is positive, and the organism is not identified. In addition, sequencing the 16S rRNA, hsp65, and rpoB genes is essential for diagnosis.


Assuntos
Endocardite Bacteriana , Endocardite , Próteses Valvulares Cardíacas , Idoso de 80 Anos ou mais , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Masculino , Mycobacteriaceae/genética , RNA Ribossômico 16S/genética
14.
Gen Thorac Cardiovasc Surg ; 69(5): 843-849, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33389593

RESUMO

OBJECTIVE: Intrathoracic negative-pressure wound therapy (NPWT) has been introduced as a novel therapeutic device for the management of empyema. NPWT is expected to reduce the empyema cavity more rapidly than standard treatments; however, no objective analysis of the function of NPWT has yet been conducted. The study objective was to evaluate the efficacy of NPWT in the management of thoracic empyema. METHODS: Ten patients with stage II or III thoracic empyema treated with NPWT were retrospectively analyzed. The volume of the empyema cavity was measured, and the volume change after the administration of NPWT was calculated. A comparison with the institutional historical controls was also performed. RESULTS: The patients had initially undergone fenestration of the chest wall for empyema, and eight had bronchopleural fistula and required procedures to close the fistula. The mean duration of NPWT was 71.1 days (4-190 days). The mean volume of the empyema cavity decreased from 230.2 ml (42.8-788.4 ml) to 78.5 ml (5.2-185.3 ml) by applying NPWT (P = 0.02), and the mean % decrease was 58.7% (0-87.9%). Ultimately, the empyema cavity was able to be cleaned in nine, including seven who were cured by subsequent thoracoplasty and two who were cured without thoracoplasty. The current study group had a tendency toward an early cure with less chest wall destruction, a less hospital stay after open window thoracotomy compared to historical control. CONCLUSIONS: NPWT enables the effective volume reduction and cleaning of the empyema cavity and achieves an early cure and reduced destruction of the chest wall.


Assuntos
Fístula Brônquica , Empiema Pleural , Tratamento de Ferimentos com Pressão Negativa , Fístula do Sistema Respiratório , Fístula Brônquica/terapia , Empiema Pleural/terapia , Humanos , Estudos Retrospectivos
15.
Surg Today ; 51(3): 415-421, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32804303

RESUMO

PURPOSE: The sampling and accurate diagnosis of lymph nodes during the clinical history of lung cancer are essential for selecting the appropriate treatment strategies. This study aims to evaluate the feasibility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with previously treated lung cancer. METHODS: Patients who underwent EBUS-TBNA after treatment for lung cancer were retrospectively reviewed. We classified the patients into two groups; Group 1 (G1): Indicated to have a recurrence of new lesions after radical surgery or chemo/radiotherapy with a curative intent; and Group 2 (G2): Indicated to have residual tumor cells after undergoing primary treatment for chemo/radiotherapy or re-staging after induction therapy prior to surgery. RESULTS: Seventy previously treated lung cancer cases (G1, n = 52; G2, n = 18) were enrolled. Thirty-two cases (61.5%) had recurrent disease in G1, and 9 cases (50.0%) had nodal metastasis in G2. The diagnostic accuracy was 95.2% in G1 and 88.9% in G2. Twenty-four cases were examined for epidermal growth factor receptor (EGFR) mutations, and 9 (37.5%) cases had mutations, including two cases with a T790M mutation. Furthermore, in one case, a re-biopsy revealed that the initial adenocarcinoma had transformed into small cell lung cancer. CONCLUSION: Performing EBUS-TBNA during lung cancer treatment showed a high diagnostic yield. Samples obtained by EBUS-TBNA were helpful in determining when to perform repeat biomarker testing as well as for making pathological re-evaluations.


Assuntos
Adenocarcinoma/diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Receptores ErbB , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Estudos Retrospectivos , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/terapia
16.
Gen Thorac Cardiovasc Surg ; 69(2): 274-281, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32734427

RESUMO

PURPOSE: The aim of this study was to evaluate the ability of fluorine-18-fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG-PET/CT) to predict the WHO malignancy grade, initial staging, and invasive potential of thymic epithelial tumors. METHODS: We retrospectively reviewed the medical records of 56 patients with thymic epithelial tumors who were evaluated by PET/CT before surgery and underwent surgical resection. We analyzed the relationship of the maximum standardized uptake value (SUVmax) with the WHO histological classification, tumor invasion, TNM classification, and the Masaoka-Koga classification. RESULTS: There were differences of SUVmax of the FDG-PET between thymic carcinoma (9.09 ± 3.34) and thymoma (4.86 ± 2.45; p < 0.01), thymic carcinoma (9.09 ± 3.34) and high-grade thymoma (6.01 ± 2.78; p < 0.01), and high-grade thymoma (6.01 ± 2.78) and low-grade thymoma (4.06 ± 1.86; p < 0.01). The cut-off value for the SUVmax was 7.40 and 5.40, and the sensitivity/specificity for predicting the histologic subtype of each group was 0.72/0.79 and 0.61/0.85, respectively. According to T classification, SUVmax was significantly higher in T3 (8.31 ± 2.57) than in T1a (4.45 ± 2.06; p < 0.01). Regarding Masaoka-Koga classification and WHO histological classification, a significantly higher SUVmax was detected in patients with stage III and IV disease than in those with stage I and II diseases (p < 0.01). The cut-off value for SUVmax was 5.40 in Masaoka-Koga stage and 5.60 in the WHO classification; the sensitivity/specificity for predicting the histologic subtype was 0.85/0.80 and 0.89/0.78, respectively. CONCLUSIONS: FDG-PET is a useful tool to predict aggressiveness of thymic epithelial tumors.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , Fluordesoxiglucose F18 , Humanos , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/cirurgia
17.
Mucosal Immunol ; 14(2): 342-356, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32690871

RESUMO

A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by cells implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), but its contributions to COPD are unknown. To address this gap, ADAM15 levels were measured in samples from cigarette smoke (CS)-versus air-exposed wild-type (WT) mice. CS-induced COPD-like disease was compared in CS-exposed WT, Adam15-/-, and Adam15 bone marrow chimeric mice. CS exposure increased Adam15 expression in lung macrophages and CD8+ T cells and to a lesser extent in airway epithelial cells in WT mice. CS-exposed Adam15-/- mice had greater emphysema, small airway fibrosis, and lung inflammation (macrophages and CD8+ T cells) than WT mice. Adam15 bone marrow chimera studies revealed that Adam15 deficiency in leukocytes led to exaggerated pulmonary inflammation and COPD-like disease in mice. Adam15 deficiency in CD8+ T cells was required for the exaggerated pulmonary inflammation and COPD-like disease in CS-exposed Adam15-/- mice (as assessed by genetically deleting CD8+ T cells in Adam15-/- mice). Adam15 deficiency increased pulmonary inflammation by rendering CD8+ T cells and macrophages resistant to CS-induced activation of the mitochondrial apoptosis pathway by preserving mTOR signaling and intracellular Mcl-1 levels in these cells. These results strongly link ADAM15 deficiency to the pathogenesis of COPD.

18.
J Clin Pharm Ther ; 46(2): 515-518, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33037823

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The removal rates of tacrolimus (TAC) and mycophenolic acid (MPA) by simultaneous plasma exchange (PE) and continuous hemodiafiltration (CHDF) are not clear. CASE SUMMARY: We evaluated the removal rates of TAC and MPA by PE and CHDF started simultaneously 5 hours after administration in a lung transplant patient. TAC was not removed. MPA was transferred into the PE effluent, but the total amount in the effluent was only 1% of the dosage. WHAT IS NEW AND CONCLUSION: TAC and MPA were less likely to be removed by PE and CHDF initiated 5 hours after administration.

20.
RNA ; 27(2): 163-173, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33177188

RESUMO

Small interfering RNAs (siRNAs) can be utilized not only as functional biological research tools but also as therapeutic agents. For the clinical use of siRNA as drugs, various chemical modifications have been used to improve the activity of siRNA drugs, and further chemical modifications are expected to improve the utility of siRNA therapeutics. As the 5' nucleobase of the guide strand affects the interaction between an siRNA and AGO2 and target cleavage activity, structural optimization of this specific position may be a useful strategy for improving siRNA activity. Here, using the in silico model of the complex between human AGO2 MID domain and nucleoside monophosphates, we screened and synthesized an original adenine-derived analog, 6-(3-(2-carboxyethyl)phenyl)purine (6-mCEPh-purine), that fits better than the natural nucleotide bases into the MID domain of AGO2. Introduction of the 6-mCEPh-purine analog at the 5'-end of the siRNA guide strand significantly enhanced target knockdown activity in both cultured cell lines and in vivo animal models. Our findings can help expand strategies for rationally optimizing siRNA activity via chemical modifications of nucleotide bases.


Assuntos
Adenina/farmacologia , Proteínas Argonauta/genética , Interferência de RNA/efeitos dos fármacos , RNA de Cadeia Dupla/genética , RNA Interferente Pequeno/agonistas , Complexo de Inativação Induzido por RNA/agonistas , Adenina/análogos & derivados , Adenina/síntese química , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Animais , Apolipoproteína B-100/antagonistas & inibidores , Apolipoproteína B-100/sangue , Apolipoproteína B-100/química , Apolipoproteína B-100/genética , Proteínas Argonauta/metabolismo , Pareamento de Bases , Sequência de Bases , Sítios de Ligação , Colesterol/sangue , Células HeLa , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Masculino , Metilação , Camundongos , Camundongos Knockout , Modelos Moleculares , Ligação Proteica , RNA de Cadeia Dupla/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Complexo de Inativação Induzido por RNA/genética , Complexo de Inativação Induzido por RNA/metabolismo , Uridina Monofosfato/química , Uridina Monofosfato/metabolismo
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