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1.
Kyobu Geka ; 76(1): 40-47, 2023 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-36731832

RESUMEN

The Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L trial has recently reported that in small lung cancer, segmentectomy has a higher overall survival rate than lobectomy, increasing the significance of sublobar resection. However, local recurrence is a major concern after sublobar resection, and an insufficient surgical margin is a significant risk factor for locoregional recurrence. Therefore, since 2014, we have performed virtual-assisted lung mapping (VALMAP), a preoperative bronchoscopic multiple-spot dye-marking technique, using indigo carmine as a preoperative localization technique to identify hardly detectable pulmonary nodules and confirm the adequacy of the surgical margin. However, conventional VAL-MAP (VAL-MAP 1.0) faced some chal-lenges. One issue is that approximately 10% marks were invisible and unidentifiable due to patient factors or technical issues. Another problem was that, in some cases requiring large resection depth, VAL-MAP did not lead to successful resection with adequate surgical margin. Thus, we have invented several novel techniques to solve these issues. VAL-MAP dual staining is a technique using indocyanine green (ICG) as well as indigo carmine that has improved the success rate of marking detection during surgery without causing additional complications. VAL-MAP 2.0 is a proximal mapping technique that involves the use of a coil, enabling three-dimensional mapping and making sublobar resection more accurate, particularly for a deeply located tumor.


Asunto(s)
Carmin de Índigo , Neoplasias Pulmonares , Humanos , Márgenes de Escisión , Neumonectomía/métodos , Broncoscopía/métodos , Pulmón/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología
2.
Surg Today ; 52(10): 1497-1503, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35237884

RESUMEN

PURPOSE: It is unknown whether intraoperative needle biopsy (INB) predisposes to the postoperative recurrence of lung cancer and compromises the prognosis of these patients. We conducted this study to identify the effect of INB before lobectomy on the postoperative recurrence rate and prognosis of patients with nonsmall cell lung cancer (NSCLC). METHODS: The subjects of this retrospective study were 953 patients with pathological stage I-III NSCLC who underwent lobectomy between 2001 and 2016. The patients were divided into two groups: the INB group (n = 94) and the non-INB group (n = 859). After propensity score matching (PSM), we compared the postoperative cumulative recurrence rate, recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) between the two groups. RESULTS: After PSM, 94 patient pairs were matched. The cumulative recurrence rate was significantly higher in the INB group than in the non-INB group (P = 0.01). The 5-year RFS rate was significantly lower in the INB group than in non-INB group (48% vs 68%), as were the 5-year DSS (76% vs 92%) and 5-year OS rates (67% vs 84%) (all P < 0.05). CONCLUSIONS: The findings of this analysis suggest that INB before lobectomy may increase the cumulative recurrence rate and worsen the prognosis of patients with resectable NSCLC. Thus, we believe that INB should be avoided unless a lung lesion cannot be diagnosed by another type of biopsy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biopsia con Aguja , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Neumonectomía , Puntaje de Propensión , Estudios Retrospectivos
3.
Biol Pharm Bull ; 44(4): 522-527, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790104

RESUMEN

Methylmercury (MeHg) exposure during pregnancy is a concern because of its potential health risks to fetuses. Intestinal microbiota has important roles in the decomposition and fecal excretion of MeHg. We investigated the effect of nondigestible saccharides on the accumulation and excretion of Hg after MeHg exposure. Female BALB/cByJ mice were fed a basal diet or the same diet supplemented with 5% fructooligosaccharides (FOS) or 2.5% glucomannan. Six weeks after feeding, mice were administered MeHg chloride (4 mg Hg/kg, per os (p.o.)), and urine and feces were collected for 28 d. FOS-fed mice had lower total Hg levels in all tissues (including the brain) compared with that of controls. The glucomannan diet had no effect on tissue Hg levels. No differences in tissue concentrations of inorganic Hg among groups were found. Fecal Hg excretion was markedly higher in FOS-fed mice than that in controls, but urinary Hg excretion was similar. FOS-fed mice had a higher proportion of inorganic Hg in feces than that of controls, with a significant increase in fecal Hg excretion. Analysis of fecal bacterial population showed the relative abundance of Bacteroides in FOS-fed mice to be higher than that in controls. The results suggest that FOS enhanced fecal Hg excretion and decreased tissue Hg levels after MeHg administration, possibly by accelerating MeHg demethylation by intestinal bacteria (the candidate genus Bacteroides). This demethylation also reduces MeHg absorption in the large intestine. In conclusion, daily FOS intake may decrease tissue Hg levels in animals and humans exposed to MeHg.


Asunto(s)
Encéfalo/metabolismo , Suplementos Dietéticos , Mercurio/metabolismo , Compuestos de Metilmercurio/farmacocinética , Oligosacáridos/farmacología , Animales , Bacterias/genética , Bacterias/aislamiento & purificación , Heces/química , Heces/microbiología , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Riñón/metabolismo , Hígado/metabolismo , Mananos/farmacología , Compuestos de Metilmercurio/sangre , Ratones Endogámicos BALB C , ARN Ribosómico 16S
4.
Cancer Sci ; 110(4): 1464-1479, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30737998

RESUMEN

Tumor molecular profiling is becoming a standard of care for patients with cancer, but the optimal platform for cancer sequencing remains undetermined. We established a comprehensive assay, the Todai OncoPanel (TOP), which consists of DNA and RNA hybridization capture-based next-generation sequencing panels. A novel method for target enrichment, named the junction capture method, was developed for the RNA panel to accurately and cost-effectively detect 365 fusion genes as well as aberrantly spliced transcripts. The TOP RNA panel can also measure the expression profiles of an additional 109 genes. The TOP DNA panel was developed to detect single nucleotide variants and insertions/deletions for 464 genes, to calculate tumor mutation burden and microsatellite instability status, and to infer chromosomal copy number. Clinically relevant somatic mutations were identified in 32.2% (59/183) of patients by prospective TOP testing, signifying the clinical utility of TOP for providing personalized medicine to cancer patients.


Asunto(s)
Perfilación de la Expresión Génica , Neoplasias/genética , Transcriptoma , Empalme Alternativo , Biomarcadores de Tumor , Biopsia , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias/diagnóstico , Neoplasias/metabolismo , Proteínas de Fusión Oncogénica/genética , Secuenciación Completa del Genoma
5.
Kyobu Geka ; 68(9): 764-7, 2015 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-26329710

RESUMEN

A 79-year-old female visited a hospital because of high fever and computed tomography(CT)showed a cystic lesion with fluid accumulation in her left lung. She had hemoptysis and left chest pain 3 days after antibiotic therapy was started. Chest CT demonstrated the cystic lesion rupturing and causing hemopneumothorax. Then she was referred to our department and thoracic drainage was performed. However, a week after the drainage, she had hemoptysis and chest pain again, and the left lower lobectomy was performed. Histopathological findings showed the cystic lesion was intrapulmonary bronchogenic cyst. We describe a rare case of the hemopneumothorax due to the hemorrhage in the bronchogenic cyst.

6.
Cancers (Basel) ; 15(7)2023 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-37046632

RESUMEN

Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking technique used in sublobar lung resection of barely palpable lung nodules. This review summarizes the history and outcomes of the VAL-MAP procedure. VAL-MAP was developed in 2012, and long-term outcomes of lung resection using VAL-MAP have recently been verified. Problems associated with conventional VAL-MAP include a prerequisite of post-mapping computed tomography (CT), occasional inability to see dye marks during surgery, and infrequent resection failure due to deep resection margins; various techniques have been developed to address these issues. VAL-MAP using electromagnetic navigation bronchoscopy with on-site adjustment can omit post-mapping CT. The use of indocyanine green in VAL-MAP has increased the success rate of marking detection during surgery without causing additional complications. VAL-MAP 2.0-a three-dimensional mapping technique that involves the intrabronchial placement of a microcoil-has increased the accuracy of sublobar resection, particularly for deeply located tumors. Although these promising new techniques have some limitations, they are beneficial for sublobar lung resection.

7.
J Thorac Dis ; 15(10): 5750-5759, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37969293

RESUMEN

Background and Objective: The use of low-dose computed tomography for screening has improved the detection of early-stage lung cancers. In addition, two large clinical studies have recently reported good outcomes of sublobar resection for early-stage lung cancers, increasing the need for limited resection. However, locoregional recurrence is an important issue in sublobar resection, and R0-resection with sufficient surgical margin is essential to prevent recurrences. This study aimed to investigate the suitable surgical margin distance after sublobar resection of lung cancers with a review of the literature. Methods: We used the PubMed interface to search the Medline database for retrieving literature related to surgical margin after sublobar resection published between 2003 and 2023. Key Content and Findings: Overall, 175 papers were found; of them, we investigated the outcomes of 18 selected papers. The correlation between the actual surgical margin distances and recurrences was evaluated in seven articles. All the articles, except one, indicated that an increased margin distance was associated with survival and a lower risk of locoregional recurrence. Further, a surgical margin of 9-15 mm was reported to be sufficient. The correlation between the margin-tumor ratio (M/T) and recurrences was investigated in six articles, most of which demonstrated that the ratio of <1 would be a remarkable predictor of recurrence or poor survival. Although the correlation between surgical margin and spread through air spaces (STAS) was discussed in four articles, their findings remain debatable. Conclusions: A surgical margin of >10 mm or M/T of ≥1 would be necessary for sublobar resection for STAS-negative early-stage non-small cell lung cancer, although it is difficult to draw a definite conclusion about the appropriate surgical margin because of the characteristics of available literature (mainly retrospective, with different inclusion criteria and surgical margin measurement methods).

8.
J Cardiothorac Surg ; 18(1): 125, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37041583

RESUMEN

BACKGROUND: Pulmonary segmentectomy for a lung with an incomplete interlobar fissure may complicate persistent air leakage. The fissureless technique is often used in lobectomy to prevent persistent air leakage. We herein describe successful use of the fissureless technique for segmentectomy with the aid of a robotic surgical system. CASE PRESENTATION: A 63-year-old man was clinically diagnosed with early-stage lung cancer for which lingular segmentectomy was indicated. A preoperative image revealed a lung with an incomplete fissure. Based on three-dimensional reconstruction imaging, we planned to divide the hilum structures in the order of the pulmonary vein, bronchus, and pulmonary artery and finally resect the lung parenchyma by dividing the intersegmental plane and interlobar fissure. This fissureless technique was successfully conducted using a robotic surgical system. The patient did not develop persistent air leakage and was alive without recurrence 1 year after segmentectomy. CONCLUSIONS: The fissureless technique may be a useful option in segmentectomy for a lung with an incomplete interlobar fissure.


Asunto(s)
Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Persona de Mediana Edad , Neumonectomía/métodos , Neoplasias Pulmonares/cirugía , Pulmón/cirugía , Arteria Pulmonar/cirugía
9.
Respir Med Case Rep ; 42: 101809, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36655007

RESUMEN

A 45-year-old woman with recurrent dyspnea for 40 years was previously diagnosed with bronchial asthma and spasmodic dysphonia. On admission, the patient was diagnosed with expiratory central airway collapse (ECAC) due to expiratory dynamic airway collapse based on radiographic examination, chest computed tomography, and bronchoscopy. After continuous positive airway pressure and temporal airway stenting, surgical tracheobronchoplasty and tracheal membranous portion reinforcement using polypropylene mesh successfully relieved the respiratory symptoms. In patients with airway obstructive disease refractory to conventional therapies, ECAC should be considered.

10.
Gen Thorac Cardiovasc Surg ; 71(5): 313-320, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36495469

RESUMEN

OBJECTIVES: Virtual-assisted lung mapping is a preoperative bronchoscopic multi-spot dye-marking technique used in sublobar lung resection for hardly palpable lung nodules. However, the number of marks required per nodule remains unknown. Therefore, we examined the correlation between the number of intraoperative visible marks and the successful resection rate. METHODS: We retrospectively examined 210 consecutive patients with 256 lesions who underwent virtual-assisted lung mapping during January 2014-December 2020 at our hospital. When a nodule was not resected at the initial attempt, or when a nodule was very close to the cut margin in the resected specimen and required additional resection, we categorized it as unsuccessful resection. We divided 256 lesions into successful and unsuccessful groups and compared the numbers of intraoperative visible marks between the two groups. RESULTS: Of 797 attempted marks, 738 (92.4%) were visible during the surgery. Fourteen (5.4%) of 256 lesions were determined to be unsuccessful according to the study criteria. There was a remarkable difference in the average numbers of intraoperative visible marks between both groups (3 [interquartile range: 2-4] vs. 2 [interquartile range: 1-2.8]; p < 0.01). Multivariable logistic analysis revealed a significant difference in the number of intraoperative visible marks (odds ratio: 0.28, 95% confidence interval: 0.14-0.57; p < 0.001) between both groups. CONCLUSIONS: Successful sublobar lung resection requires three or more intraoperative visible marks established using virtual-assisted lung mapping per lung nodule.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Broncoscopía/métodos , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Pulmón/patología
11.
J Thorac Dis ; 14(4): 1061-1069, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35572865

RESUMEN

Background: Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking procedure to facilitate sublobar lung resection for unidentifiable lung nodules. To increase detectable markings, we performed VAL-MAP using dual staining (VAL-MAP DS) with indocyanine green (ICG) and indigo carmine. This study was designed to evaluate the efficacy and safety of the modified technique. Methods: We retrospectively reviewed the records of patients who underwent VAL-MAP DS. Twenty patients with 27 lesions underwent 72 VAL-MAP DS markings. We investigated the overall detectable marking rate, visible marking rate, successful resection rate, and complications. Results: The overall detectable marking rate, thanks to both ICG and indigo carmine, tended to be higher than the indigo carmine visible marking rate (95.7% vs. 85.5%, P=0.08). The successful resection rate with sufficient margins was 92.0%. There were no adverse events related to the use of ICG. ICG markings of the lungs of patients with a history of smoking more than 50 pack-years tended to be visible, but the staining was too extensive compared with the staining in patients who smoked less or not at all (58.8% vs. 0.0%, P<0.001). Conclusions: VAL-MAP DS is likely be efficacious and safe in enhancing the detectability of markings. This bronchoscopic technique should be considered as one of the optimal preoperative marking methods in thoracic surgery.

12.
Radiol Case Rep ; 17(9): 3107-3110, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35784785

RESUMEN

Acupuncture is an alternative treatment for a variety of diseases, and serious complications are rare. We report a case of transcatheter arterial embolization performed in a patient with a massive hemothorax after acupuncture treatment. A 36-year-old woman with no previous medical history was admitted to our hospital with left back pain and respiratory distress after acupuncture treatment. Contrast-enhanced computed tomography showed a left hemothorax and leakage of contrast medium, which was considered to result from an injury to the second intercostal artery, caused by acupuncture treatment. Transcatheter arterial embolization successfully stopped the bleeding, and the hematoma was thoracoscopically removed. No rebleeding was observed 6 months after treatment.

13.
Sci Rep ; 12(1): 9100, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35650221

RESUMEN

Rapid identification of lung-cancer micro-lesions is becoming increasingly important to improve the outcome of surgery by accurately defining the tumor/normal tissue margins and detecting tiny tumors, especially for patients with low lung function and early-stage cancer. The purpose of this study is to select and validate the best red fluorescent probe for rapid diagnosis of lung cancer by screening a library of 400 red fluorescent probes based on 2-methyl silicon rhodamine (2MeSiR) as the fluorescent scaffold, as well as to identify the target enzymes that activate the selected probe, and to confirm their expression in cancer cells. The selected probe, glutamine-alanine-2-methyl silicon rhodamine (QA-2MeSiR), showed 96.3% sensitivity and 85.2% specificity for visualization of lung cancer in surgically resected specimens within 10 min. In order to further reduce the background fluorescence while retaining the same side-chain structure, we modified QA-2MeSiR to obtain glutamine-alanine-2-methoxy silicon rhodamine (QA-2OMeSiR). This probe rapidly visualized even borderline lesions. Dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase were identified as enzymes mediating the cleavage and consequent fluorescence activation of QA-2OMeSiR, and it was confirmed that both enzymes are expressed in lung cancer. QA-2OMeSiR is a promising candidate for clinical application.


Asunto(s)
Colorantes Fluorescentes , Neoplasias Pulmonares , Alanina , Aminopeptidasas , Dipeptidil Peptidasa 4/metabolismo , Colorantes Fluorescentes/química , Glutamina , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Rodaminas/química , Silicio
14.
Ann Thorac Cardiovasc Surg ; 27(5): 290-296, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-33431760

RESUMEN

PURPOSE: Surgical lung biopsy (SLB) is an important diagnostic tool for interstitial lung disease (ILD), yet the risk factors for SLB are still debatable and long-term outcomes remain unknown. METHODS: We retrospectively reviewed the records of 85 consecutive patients with ILD who underwent SLB by video-assisted thoracic surgery (VATS) from 2008 to 2019. Risk factors for complications and differences of outcomes between idiopathic pulmonary fibrosis (IPF) and other ILDs were examined. RESULTS: All patients who underwent VATS had no mortality or acute exacerbation of ILD within 90 days of SLB. The rate of complication was 9.4%, and there were no statistically significant risk factors for complications. While the IPF group was not significantly different from the non-IPF group with regard to surgical parameters or complications, patients with IPF had significantly higher rates of mortality (50% vs. 9% in 5 years; p <0.001) and readmission due to acute exacerbation (75% vs. 8% in 5 years; p <0.001). CONCLUSION: VATS lung biopsy for ILD can be a safe approach regardless of underlying phenotypes. An accurate diagnosis of IPF via SLB may be beneficial for correct patient management.


Asunto(s)
Biopsia , Enfermedades Pulmonares Intersticiales , Cirugía Torácica Asistida por Video , Biopsia/efectos adversos , Biopsia/métodos , Humanos , Enfermedades Pulmonares Intersticiales/patología , Estudios Retrospectivos , Resultado del Tratamiento
15.
NPJ Precis Oncol ; 5(1): 57, 2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34158601

RESUMEN

Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.

16.
J Thorac Oncol ; 15(6): 948-961, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32036070

RESUMEN

INTRODUCTION: Studies are yet to characterize the differences in molecular profiles of lung adenocarcinoma (LUAD) among divergent ethnic groups. Herein, we conducted comprehensive molecular profiling of LUAD in never or light smokers from Asia to discover novel targetable mutations and prognostic biomarkers of this distinct disease entity. METHODS: We analyzed 996 cases of Japanese LUAD and performed whole-exome sequencing and RNA-seq in 125 cases of Japanese LUAD negative for the driver oncogenes defined by conventional laboratory testing. We also investigated the clinical and pathologic characteristics among the 996 cases. RESULTS: Driver oncogenes were identified in 88 cases (70.4%) with specific hotspot mutations differing from those in The Cancer Genome Atlas study. Two actionable novel fusions of FGFR2 and NRG2α were also identified. Clustering on the basis of mRNA expression profiles, but not genetic mutational ones, could predict patient prognosis. The risk score generated by the expression of a three-gene set was a strong prognostic marker for overall survival and progression-free survival in our cohort, and was further validated using The Cancer Genome Atlas cohort. Among the 996 cases, each driver alteration is distributed across all histologic subtypes. Adenocarcinoma in situ was identified to harbor driver mutations, suggesting that these alterations are early events in the pathogenesis of LUAD. ERBB2 mutations were over-represented in young adults. CONCLUSIONS: This study indicates the value of applying gene expression profiling for predicting the prognosis after a surgical operation, and that the identification of actionable mutations is important for optimizing targeted drugs in Japanese LUAD.


Asunto(s)
Neoplasias Pulmonares , Fumadores , Adenocarcinoma del Pulmón/genética , Asia , Biomarcadores de Tumor/genética , Humanos , Japón/epidemiología , Neoplasias Pulmonares/genética , Mutación , Adulto Joven
17.
Arch Toxicol ; 83(7): 647-52, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19479238

RESUMEN

Previously, we reported that Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced lethality and hepatotoxicity compared to Fischer 344 (F344) rats. Since the testes are one of the most sensitive organs to acute Cd toxicity, we examined possible strain-related differences in Cd-induced testicular toxicity between inbred WI and F344 rats. Rats were treated with a single dose of 0.5, 1.0 or 2.0 mg Cd/kg, as CdCl(2), sc and killed 24 h later. Cd at doses of 1.0 and 2.0 mg/kg induced severe testicular hemorrhage, as assessed by pathological and testis hemoglobin content, in F344 rats, but not WI rats. After Cd treatment (2.0 mg/kg), the testicular Cd content was significantly lower in WI rats than in the F344 rats, indicating a toxiokinetic mechanism for the observed strain difference. Thus, the remarkable resistance to Cd-induced testicular toxicity in WI rats is associated, at least in part, with lower testicular accumulation of Cd. When zinc (Zn; 10 mg/kg, sc) was administered in combination with Cd (2.0 mg/kg) to F344 rats, the Cd-induced increase in testicular hemoglobin content, indicative of hemorrhage, was significantly reduced. Similarly, the testicular Cd content was significantly decreased with Zn co-treatment compared to Cd treatment alone. Thus, it can be concluded that the testicular Cd accumulation partly competes with Zn transport systems and that these systems may play an important role in the strain-related differences in Cd-induced testicular toxicity between WI and F344 rats.


Asunto(s)
Intoxicación por Cadmio/complicaciones , Cadmio/metabolismo , Testículo/metabolismo , Animales , Intoxicación por Cadmio/metabolismo , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Hemoglobinas/análisis , Riñón/metabolismo , Hígado/metabolismo , Masculino , Metalotioneína/análisis , Metalotioneína/metabolismo , Ratas , Ratas Endogámicas F344 , Ratas Wistar , Especificidad de la Especie , Espectrofotometría , Testículo/patología , Zinc/metabolismo , Zinc/farmacología
18.
Medicine (Baltimore) ; 97(7): e9921, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29443771

RESUMEN

RATIONALE: The development of postoperative bronchopleural fistula (BPF) remains a challenge in thoracic surgery. We herein report a case of BPF successfully treated with endoscopic bronchial occlusion under computed tomography (CT) fluoroscopy and virtual bronchoscopic navigation (VBN). PATIENT CONCERNS: A 63-year-old man underwent right upper lobectomy with concomitant S6a subsegmentectomy for lung adenocarcinoma. On postoperative day 24, he complained of shaking chills with high fever. DIAGNOSES: BPF with subsequent pneumonia and empyema. INTERVENTIONS: Despite aggressive surgical interventions for the BPF, air leakage persisted postoperatively. On days 26 and 34 after the final operation, endobronchial occlusions were performed under CT fluoroscopy and VBN. OUTCOMES: The air leaks greatly decreased and the patient was discharged. LESSONS: CT fluoroscopy and VBN can be useful techniques for endobronchial occlusion in the treatment of BPF.


Asunto(s)
Fístula Bronquial/terapia , Broncoscopía/métodos , Fluoroscopía , Enfermedades Pleurales/terapia , Complicaciones Posoperatorias/terapia , Tomografía Computarizada por Rayos X , Adenocarcinoma/cirugía , Fístula Bronquial/diagnóstico por imagen , Fístula Bronquial/etiología , Empiema/etiología , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Enfermedades Pleurales/diagnóstico por imagen , Enfermedades Pleurales/etiología , Neumonectomía/efectos adversos , Neumonía/etiología , Complicaciones Posoperatorias/diagnóstico por imagen
19.
Clin Cancer Res ; 24(20): 5112-5122, 2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-29967253

RESUMEN

Purpose: The advent of next-generation sequencing technologies has enabled the identification of several activating mutations of Erb-B2 receptor tyrosine kinase 2 (ERBB2) among various cancers. However, the significance of infrequent mutations has not been fully investigated. Herein, we comprehensively assessed the functional significance of the ERBB2 mutations in a high-throughput manner.Experimental Design: We evaluated the transforming activities and drug sensitivities of 55 nonsynonymous ERBB2 mutations using the mixed-all-nominated-in-one (MANO) method.Results: G776V, G778_S779insG, and L841V were newly revealed to be activating mutations. Although afatinib, neratinib, and osimertinib were shown to be effective against most of the ERBB2 mutations, only osimertinib demonstrated good efficacy against L755P and L755S mutations, the most common mutations in breast cancer. In contrast, afatinib and neratinib were predicted to be more effective than other inhibitors for the A775_776insYVMA mutation, the most frequent ERBB2 mutation in lung cancer. We surveyed the prevalence of concurrent ERBB2 mutation with gene amplification and found that approximately 30% of ERBB2-amplified urothelial carcinomas simultaneously carried ERBB2 mutations, altering their sensitivity to trastuzumab, an mAb against ERBB2. Furthermore, the MANO method was applied to evaluate the functional significance of 17 compound mutations within ERBB2 reported in the COSMIC database, revealing that compound mutations involving L755S were sensitive to osimertinib but insensitive to afatinib and neratinib.Conclusions: Several ERBB2 mutations showed varying sensitivities to ERBB2-targeted inhibitors. Our comprehensive assessment of ERBB2 mutations offers a fundamental database to help customize therapy for ERBB2-driven cancers.We identified several ERBB2 mutations as activating mutations related to tumorigenesis. In addition, our comprehensive evaluation revealed that several ERBB2 mutations showed varying sensitivities to ERBB2-targeted inhibitors, and thus, the functional significance of each variant should be interpreted precisely to design the best treatment for each patient. Clin Cancer Res; 24(20); 5112-22. ©2018 AACR.


Asunto(s)
Variación Genética , Receptor ErbB-2/genética , Animales , Biomarcadores , Línea Celular Tumoral , Supervivencia Celular/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Ratones , Anotación de Secuencia Molecular , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología
20.
Anal Sci ; 34(5): 583-588, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29743431

RESUMEN

The contents and elution behavior of metals in consumer electronics parts were determined so as to understand their maximum environmental risk. Elements contained most in printed-circuit boards were Cu, Si, Br, Ca, Al, Sn, Pb, Sb, Ba, Fe, Ni, Ti, and Zn; in cathode-ray tube glass were Si, Pb, Ba, Sr, Zn, Zr, Ca, and Sb; in arsenic contained liquid-crystal displays were Si, Ca, Sr, Ba, As, and Fe; and in antimony contained liquid-crystal displays were Si, Ba, Ca, Sb, Sr, Fe, and Sn. The elements eluted most from printed-circuit boards were Zn, Pb, and Cu; from cathode-ray tube glass were Pb, Zn, B, Ba, and Si; and from liquid-crystal displays were B and Si, and the toxic As and Sb. The amount eluted was greatest at acidic pH. It was revealed that officially recommended 6-h-shaking with a pure water test was insufficient to understand the real environmental risk of waste electronics.

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