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1.
Jpn J Clin Oncol ; 53(2): 161-167, 2023 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-36461783

RESUMEN

BACKGROUND: The importance of the stromal components in tumour progression has been discussed widely, but their prognostic role in small size tumours with lepidic components is not fully understood. Applying digital tissue image analysis to whole-slide imaging may enhance the accuracy and reproducibility of pathological assessment. This study aimed to evaluate the prognostic value of tumour components of lung adenocarcinoma by measuring the dimensions of the tumour consisting elements separately, using a machine learning algorithm. METHODS: Between September 2002 and December 2016, 317 patients with surgically resected, pathological stage IA adenocarcinoma with lepidic components were analysed. We assessed the whole tumour area, including the lepidic components, and measured the epithelium, collagen, elastin areas and alveolar air space. We analysed the prognostic impact of each tumour component. RESULTS: The dimensions of the epithelium and collagen areas were independent significant risk factors for recurrence-free survival (hazard ratio, 8.38; 95% confidence interval, 1.14-61.88; P = 0.037, and hazard ratio, 2.58; 95% confidence interval, 1.14-5.83; P = 0.022, respectively). According to the subgroup analysis when combining the epithelium and collagen areas as risk factors, patients with tumours consisting of both large epithelium and collagen areas showed significantly poor prognoses (P = 0.002). CONCLUSIONS: We assessed tumour components using a machine learning algorithm to stratify the post-operative prognosis of surgically resected stage IA adenocarcinomas. This method might guide the selection of patients with a high risk of recurrence.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Pronóstico , Neoplasias Pulmonares/patología , Reproducibilidad de los Resultados , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/patología , Adenocarcinoma/patología , Estadificación de Neoplasias , Estudios Retrospectivos
2.
J Plant Res ; 136(6): 781-786, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37642778

RESUMEN

For almost 50 years, tobacco (Nicotiana tabacum) BY-2 cells have been widely recognized as an important cell line for plant biology. The cell line grows rapidly, can be synchronized to a high degree, and is excellent for imaging; over the years, these features have led to many high-impact discoveries. However, certain other uses of this cell line are virtually unknown. In the early days, I was involved in distributing the cells to laboratories around the world. Many of these scientists wanted to study the cell cycle; however, I also distributed the cells to scientists who were elucidating the mechanism of plant transformation by Agrobacterium tumefaciens. In fact, BY-2 cells played an essential role in the identification and analysis of Vir genes on the Ti plasmid; likewise, the cells were important for discovering the factor that induces the expression of Vir genes. Thus, BY-2 cells were crucial for the development of modern plant biotechnology. Here, I recount the story of how this came to pass and explain why the use of BY-2 cells in this work was never recognized.


Asunto(s)
Agrobacterium tumefaciens , Nicotiana , Nicotiana/genética , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/metabolismo , Línea Celular
3.
Int J Mol Sci ; 24(14)2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37511489

RESUMEN

The circadian rhythm-related genes BHLHE40/DEC1 and BHLHE41/DEC2 have various functions under different cell and tissue conditions. BHLHE41/DEC2 has been reported to be both a cancer-suppressive and an oncogenic gene during cancer development. The effects of BHLHE41/DEC2 on differentiation have been examined using Bhlhe41/Dec2 knockout mice and/or in vitro differentiation models, and research has been conducted using genetic analysis of tumor cells, in vitro analysis of cancer cell lines, and immunohistochemical studies of the clinical samples. We summarize some of these studies, detail several problems, and consider possible reasons for contradictory results and the needs for further research.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Neoplasias Pulmonares , Animales , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Línea Celular , Ritmo Circadiano/fisiología , Neoplasias Pulmonares/genética , Humanos
4.
Int J Clin Oncol ; 26(10): 1840-1846, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34165658

RESUMEN

BACKGROUND: A significant number of non-small cell lung cancer (NSCLC) patients develop osteogenic metastases (OMs) and/or brain metastases (BMs) after surgery, however, routine chest computed tomography (CT) sometimes fails to diagnose these recurrences. We investigated the incidence of BMs and OMs after pulmonary resection and aimed to identify candidates who can benefit from brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in addition to CT. METHODS: We retrospectively reviewed medical records of 1099 NSCLC patients who underwent pulmonary resection between 2002 and 2013. Clinicopathological factors associated with OM and/or BM were investigated using univariate and multivariate analyses. RESULTS: Postoperative recurrence occurred in 344 patients (32.6%). OMs were diagnosed in 56 patients (5.6%) with 93% within 3 years. BMs were identified in 72 patients (6.6%) with 91.1% within 3 years. Multivariate analysis revealed that poorly differentiated tumor and the presence of pathological nodal metastases were significantly associated with postoperative BM (p = 0.037, < 0.001), preoperative serum carcinoembryonic antigen (CEA) level of 5 ng/mL or higher and the presence of pathological nodal metastases were significantly associated with OM (p = 0.034, < 0.001). The prevalence of OM and/or BM in 5 years was as high as 25.9% in patients with pathological nodal metastases. CONCLUSIONS: We identified significant predictive factors of postoperative BM and OM. Under patient selection, the effectiveness of intensive surveillance for the modes of recurrence should be investigated with respect to earlier detection, maintenance of quality of life, and survival outcomes.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugía , Tomografía de Emisión de Positrones , Calidad de Vida , Estudios Retrospectivos
5.
Int J Mol Sci ; 22(21)2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34768959

RESUMEN

Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression. We analyzed BHLHE41 function via in silico and immunohistochemical studies of 177 surgically resected non-small cell lung cancer (NSCLC) samples and 18 early lung squamous cell carcinoma (LUSC) cases. We also examined doxycycline (DOX)-inducible BHLHE41-expressing A549 and H2030 adenocarcinoma cells. BHLHE41 expression was higher in normal lung than in lung adenocarcinoma (LUAD) tissues and was associated with better prognosis for the overall survival (OS) of patients. In total, 15 of 132 LUAD tissues expressed BHLHE41 in normal lung epithelial cells. Staining was mainly observed in adenocarcinoma in situ and the lepidic growth part of invasive cancer tissue. BHLHE41 expression constituted a favorable prognostic factor for OS (p = 0.049) and cause-specific survival (p = 0.042) in patients with LUAD. During early LUSC, 7 of 18 cases expressed BHLHE41, and this expression was inversely correlated with the depth of invasion. DOX suppressed cell proliferation and increased the autophagy protein LC3, while chloroquine enhanced LC3 accumulation and suppressed cell death. In a xenograft model, DOX suppressed tumor growth. Our results indicate that BHLHE41 expression prevents early lung tumor malignant progression by inducing autophagic cell death in NSCLC.


Asunto(s)
Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Células A549 , Adulto , Anciano , Anciano de 80 o más Años , Animales , Muerte Celular Autofágica/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Doxiciclina/farmacología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Surg Today ; 48(6): 640-648, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29383594

RESUMEN

PURPOSE: Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence. METHODS: One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time. RESULTS: ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05). CONCLUSIONS: The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.


Asunto(s)
Colorantes Fluorescentes , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Linfa/diagnóstico por imagen , Vasos Linfáticos/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Bronquios , Femenino , Humanos , Pulmón , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Vasos Linfáticos/patología , Masculino , Mediastino , Persona de Mediana Edad , Neumonectomía
7.
Kyobu Geka ; 69(9): 804-7, 2016 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-27476574

RESUMEN

We reported a case of metastatic lung tumor, which was suspected as being a primary lung cancer because of its accompanying lesion mimicking atypical adenomatous hyperplasia(AAH) based on intraoperative needle biopsy findings. AAH is a preinvasive lesion or marginal lesion of primary lung cancer that is not accompanied by metastatic tumor. However, it needs to be distinguished pathologically from secondary changes of inflammation or fibrosis. In our case, the needle biopsy revealed AAH-like pathological findings, which indicates a primary lung cancer, and the standard lobectomy with lymph node dissection was performed, however, the final diagnosis turned out to be metastatic tumor. The rapidly enlarging tumor led to surrounding obstructive pneumonitis, which may have caused pathological changes mimicking AAH findings. In the case of obstructive pneumonitis, we must be careful to diagnose AAH, in addition to decisions about the surgical procedure especially when based on frozen section diagnosis.


Asunto(s)
Diagnóstico Diferencial , Hiperplasia/diagnóstico , Neoplasias Pulmonares/patología , Biopsia con Aguja , Femenino , Humanos , Hiperplasia/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Persona de Mediana Edad , Neumonectomía , Neoplasias del Recto/patología , Tomografía Computarizada por Rayos X
8.
Respirol Case Rep ; 12(1): e01286, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38269312

RESUMEN

Pleurectomy/decortication for malignant pleural mesothelioma is a relatively recent surgical approach for which there is a dearth of information on complications, especially in the late postoperative period. A 70-year-old man was diagnosed with right epithelioid malignant pleural mesothelioma and underwent pleurectomy/decortication. Computed tomography at 6 months after surgery revealed nodules on the surface of the right lung. These nodules gradually increased in size and were diagnosed as recurrent disease. Immunotherapy was started, but treatment was discontinued a few days after the first course due to pneumonitis. Subsequent oral prednisolone therapy for about 2 months ameliorated pneumonitis, but fistulous pyothorax developed. During attempted transbronchial occlusion of the responsible bronchus, some spigots penetrated the empyema cavity. Open window thoracotomy was performed on the following day. This case suggests that if there is no change in diameter between the proximal and distal parts of the responsible bronchus, transbronchial occlusion should not be chosen.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38945854

RESUMEN

PURPOSE: Regardless of the devastating outcomes of pulmonary resection for metastases from gastric cancer, a handful of patients survive long after pulmonary metastasectomy. This study aimed to identify a good candidate for pulmonary resection for metastases from gastric cancer. METHODS: Between 2005 and 2023, 564 patients underwent pulmonary metastasectomy in our department, of which 12 patients underwent pulmonary resection for metastases from gastric cancer. Variables evaluated were the number and size of metastatic lesions, surgical procedure, disease-free interval (DFI), and the serum carcinoembryonic antigen at pulmonary metastasectomy. RESULTS: The DFI following gastrectomy ≤12.5 months group had a significantly worse overall survival (OS) than the other group (p = 0.005). A comparison between DFI following gastrectomy ≤12.5 months group and DFI following gastrectomy >12.5 months group showed a significant difference in serum carcinoembryonic antigen (CEA) value at pulmonary metastasectomy (p = 0.048). The serum CEA value at pulmonary metastasectomy >5.8 ng/ml group had a significantly worse OS than the other group (p = 0.001). CONCLUSION: Pulmonary metastasectomy can be indicated in some patients with metastasis from gastric cancer who have longer DFI from gastrectomy and lower serum CEA at pulmonary metastasectomy.


Asunto(s)
Antígeno Carcinoembrionario , Gastrectomía , Neoplasias Pulmonares , Metastasectomía , Neumonectomía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/sangre , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/sangre , Metastasectomía/mortalidad , Metastasectomía/efectos adversos , Masculino , Femenino , Neumonectomía/mortalidad , Neumonectomía/efectos adversos , Persona de Mediana Edad , Gastrectomía/mortalidad , Gastrectomía/efectos adversos , Antígeno Carcinoembrionario/sangre , Anciano , Factores de Tiempo , Resultado del Tratamiento , Estudios Retrospectivos , Supervivencia sin Enfermedad , Factores de Riesgo , Estimación de Kaplan-Meier , Adulto , Biomarcadores de Tumor/sangre , Selección de Paciente
10.
Artículo en Inglés | MEDLINE | ID: mdl-38805108

RESUMEN

INTRODUCTION: Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. METHODS: Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. RESULTS: Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2 ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2 ng/ml (n = 28). Patients with postoperative CEA > 6.2 ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. CONCLUSION: The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2 ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

11.
Clin Lung Cancer ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38762395

RESUMEN

BACKGROUND: Although the positive rate of preresection pleural lavage cytology (PLC) is low, it is an important indicator of poor prognosis for non-small-cell lung cancer patients with frequent pleural dissemination (PD) recurrence. Thin-section computed tomography (TSCT) can reveal relationships between a primary tumor and the pleura at 1 to 2 mm intervals, and this is associated with visceral pleural invasion (VPI). However, its association with PLC remains unclear. Therefore, we aimed to improve PLC efficiency and predict PD recurrence by understanding the relationship between PLC and preoperative TSCT findings. PATIENTS AND METHODS: Between January 2014 and December 2018, we reviewed 978 patients with non-small-cell lung cancer who underwent PLC tests during complete resection surgery. Preoperative TSCT findings were evaluated, and factors with the highest specificity (proportion of patients with radiologically to pathologically diagnosed positive PLC) were investigated. We also evaluated their relationships with VPI and PD recurrence. RESULTS: PLC positive was identified in 55 (5.6%) of the 978 patients. The two TSCT findings predicting PLC results, "the absence of pleural findings," ie, tumor not attached to pleura or without pleural tag, and "consolidation-to-tumor ratio ≤0.5", had a specificity of 100% (95% confidence interval: 90.4%-100%); additionally, all cases with these findings were VPI negative and had no PD recurrence. And 24% of the cohort had either of these findings. CONCLUSION: The absence of pleural findings and/or consolidation-to-tumor ratio ≤0.5 of primary tumor on preoperative TSCT can predict PLC negativity with very high probability; therefore, PLC can be omitted for such patients.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38066298

RESUMEN

OBJECTIVES: We investigated the incidence of late recurrence beyond 5 years after pulmonary resection and aimed to identify candidates for long-term surveillance. METHODS: We retrospectively reviewed the medical records of 978 non-small-cell lung cancer patients who underwent pulmonary resection between 2002 and 2015 and survived without recurrence for 5 years. Clinicopathological factors associated with recurrence-free survival beyond 5 years after surgery were investigated using univariate and multivariate analyses. The development of late metachronous malignancies was also investigated. RESULTS: The median follow-up period from 5 years post-surgery was 27 months in the whole cohort. Late recurrence occurred in 37 (3.8%) patients. Late metachronous malignancies were diagnosed in 116 patients (11.9%), including 57 (5.8%) with lung cancer. One-, three-, and five-year recurrence-free survival rates beyond 5 years after surgery were 97.6%, 94.7%, and 94.7%, respectively. The recurrence-free survival of patients with pN1-2 was significantly poorer than that of patients with pN0 disease. Multivariate analysis revealed that adenocarcinoma and pN1-2 status were significantly associated with poor recurrence-free survival beyond 5 years post-surgery (P = 0.009 and 0.007, respectively). CONCLUSIONS: Non-adenocarcinoma histology and pN0 status were significant favorable factors for recurrence-free survival beyond 5 years post-surgery. The efficacies of long-term surveillance for the detection of late recurrence were considered limited for these populations. Twelve percent of the patients experienced late metachronous malignancies after pulmonary resection.

13.
J Thorac Dis ; 15(6): 2916-2925, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37426128

RESUMEN

Background: In the current tumor-node-metastasis (TNM) classification, the clinical T descriptor is defined by solid size (SS) on a computed tomography (CT) slice and the pathological one is done by invasive size (IS) in microscopic evaluations. We sometimes experience discrepancies in diagnosis of both descriptors. A volume analyzing application enables semi-automatic measurement of three-dimensional (3D) parameters in cases where there are discrepancies in diagnosing tumors' solid size and IS. In this study, we aimed to evaluate the association between 3D parameters and pathological invasion in non-solid small-sized lung adenocarcinomas. Methods: We enrolled 246 consecutive patients who underwent pulmonary resection at Shizuoka Cancer Center. Patients with lung adenocarcinomas that were radiologically non-solid, node-negative and sized ≤3 cm were eligible. We used a volume analyzing application to retrospectively measure 3D parameters of max and mean Hounsfield units (HUs) and solid volume (SV). The cut-off value of these parameters for diagnosing invasive adenocarcinoma (IAD) was set by describing receiver operating characteristic (ROC) curves. The correlation of IAD with these parameters was compared to its correlation with the SS. This study was not registered. Results: Of 246 patients with adenocarcinoma, 183 (74.4%) had IADs. In multivariate analyses, the total size (TS) and SS were significantly associated with IAD (P=0.006, 0.001, respectively), whereas 3D parameters including SV were not (P=0.80). In radiological adenocarcinoma (2.1-3.0 cm), SV >300 mm3 diagnosed IAD with a higher sensitivity than that of the SS (0.93 and 0.83, respectively). Conclusions: TS >20 mm and SS >5 mm were well-correlated with IAD. SV measurement may complement the current computed tomographic diagnosis of IAD based on the SS (2.1-3.0 cm).

14.
Anticancer Res ; 43(7): 3003-3013, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37351958

RESUMEN

BACKGROUND/AIM: Dendritic cells (DCs) are difficult to evaluate in lung regional lymph nodes because of region-specific structures, such as abundant trabeculae connecting the medullary and subcapsular sinuses, the latter of which contains few anthracotic macrophages. Therefore, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DCsign)-positive DCs and CD68-positive macrophages are unlikely to show a typical distribution. The present study therefore explored quantitative factors connecting the nodal DC morphology to the patient outcome. MATERIALS AND METHODS: Lymph nodes from 34 non-small-cell lung cancer patients who underwent complete resection were used for immunohistochemical assessments of DCsign and CD68 and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Preoperative patient blood samples were used for the quantitative evaluation of monocytes. RESULTS: The nodal DCs showed a complementary distribution with macrophages, thus few DCs were seen in clusters of macrophages. DCs often presented as a mesh-like rosette that was solitary or connected to a DC cluster. DCs disappeared, and some macrophages were apoptotic when surrounded by cancer cells that have metastasized to lymph nodes. The proportional area of a DC cluster was significantly associated with the histological differentiation of cancer (p=0.013), with a higher ratio tending to lead to a better overall survival (p=0.059), and significantly so in adenocarcinoma (p=0.007). The rosette number was significantly correlated with the smoking index and blood monocyte number (p=0.013 and p=0.005, respectively). CONCLUSION: The nodal DC morphology appears useful as a prognostic factor and may lead to a new phase of clinicopathological studies of solid cancers.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Relevancia Clínica , Macrófagos/metabolismo , Monocitos/patología , Ganglios Linfáticos/patología , Factor de Crecimiento Transformador beta/metabolismo , Células Dendríticas/metabolismo
15.
Case Rep Oncol ; 16(1): 705-710, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37936662

RESUMEN

Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.

16.
Plant Physiol ; 156(4): 2196-206, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21632970

RESUMEN

Understanding the relationship of the size and shape of an organism to the size, shape, and number of its constituent cells is a basic problem in biology; however, numerous studies indicate that the relationship is complex and often nonintuitive. To investigate this problem, we used a system for the inducible expression of genes involved in the G1/S transition of the plant cell cycle and analyzed the outcome on leaf shape. By combining a careful developmental staging with a quantitative analysis of the temporal and spatial response of cell division pattern and leaf shape to these manipulations, we found that changes in cell division frequency occurred much later than the observed changes in leaf shape. These data indicate that altered cell division frequency cannot be causally involved in the observed change of shape. Rather, a shift to a smaller cell size as a result of the genetic manipulations performed correlated with the formation of a smoother leaf perimeter, i.e. appeared to be the primary cellular driver influencing form. These data are discussed in the context of the relationship of cell division, growth, and leaf size and shape.


Asunto(s)
Arabidopsis/citología , Arabidopsis/genética , Ciclo Celular/genética , Tamaño de la Célula , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/anatomía & histología , Hojas de la Planta/citología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , División Celular/genética , Epidermis de la Planta/citología , Epidermis de la Planta/genética , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Factores de Tiempo
17.
Nat Cell Biol ; 7(10): 961-8, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16138083

RESUMEN

Despite the absence of a conspicuous microtubule-organizing centre, microtubules in plant cells at interphase are present in the cell cortex as a well oriented array. A recent report suggests that microtubule nucleation sites for the array are capable of associating with and dissociating from the cortex. Here, we show that nucleation requires extant cortical microtubules, onto which cytosolic gamma-tubulin is recruited. In both living cells and the cell-free system, microtubules are nucleated as branches on the extant cortical microtubules. The branch points contain gamma-tubulin, which is abundant in the cytoplasm, and microtubule nucleation in the cell-free system is prevented by inhibiting gamma-tubulin function with a specific antibody. When isolated plasma membrane with microtubules is exposed to purified neuro-tubulin, no microtubules are nucleated. However, when the membrane is exposed to a cytosolic extract, gamma-tubulin binds microtubules on the membrane, and after a subsequent incubation in neuro-tubulin, microtubules are nucleated on the pre-existing microtubules. We propose that a cytoplasmic gamma-tubulin complex shuttles between the cytoplasm and the side of a cortical microtubule, and has nucleation activity only when bound to the microtubule.


Asunto(s)
Microtúbulos/metabolismo , Nicotiana/metabolismo , Tubulina (Proteína)/metabolismo , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Microtúbulos/ultraestructura , Modelos Biológicos , Nicotiana/citología , Nicotiana/ultraestructura
18.
Biosci Biotechnol Biochem ; 76(3): 447-53, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22451383

RESUMEN

Lachrymatory factor synthase (LFS), an enzyme essential for the synthesis of the onion lachrymatory factor (propanethial S-oxide), was identified in 2002. This was the first reported enzyme involved in the production of thioaldehyde S-oxides via an intra-molecular H(+) substitution reaction, and we therefore attempted to identify the catalytic amino acid residues of LFS as the first step in elucidating the unique catalytic reaction mechanism of this enzyme. A comparison of the LFS cDNA sequences among lachrymatory Allium plants, a deletion analysis and site-directed mutagenesis enabled us to identify two amino acids (Arg71 and Glu88) that were indispensable to the LFS activity. Homology modeling was performed for LFS/23-169 on the basis of the template structure of a pyrabactin resistance 1-like protein (PYL) which had been selected from a BLASTP search on SWISS-MODEL against LFS/23-169. We identified in the modeled structure of LFS a pocket corresponding to the ligand-binding site in PYL, and Arg71 and Glu88 were located in this pocket.


Asunto(s)
Allium/enzimología , Oxidorreductasas Intramoleculares/química , Oxidorreductasas Intramoleculares/metabolismo , Allium/genética , Secuencia de Aminoácidos , Biocatálisis , Clonación Molecular , ADN Complementario/genética , Oxidorreductasas Intramoleculares/genética , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Conformación Proteica , Homología de Secuencia de Aminoácido
19.
Kyobu Geka ; 65(11): 960-3, 2012 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-23023540

RESUMEN

The indication of thoracoscopic excision of mediastinal tumor at our department is benign tumor or noninvasive thymoma diagnosed before surgery. For myasthenia gravis, thoracoscopic extended thymectomy is performed with a bilateral thoracic approach using a laparolift, and this procedure is indicated for cases with complication of thymoma with a tumor size up to 5 cm. We performed thoracoscopic extended thymectomy in 9 myasthenia gravis patients between January and October 2011, and achieved favorable postoperative courses with no development of major complications so far. However,surgery required a long time compared to the conventional extended thymectomy employing median sternotomy, showing that further modification of the surgical procedure and improvement of the surgical skill are necessary. We report the details of thoracoscopic extended thymectomy with a bilateral thoracic approach for 9 myasthenia gravis patients performed at our department.


Asunto(s)
Miastenia Gravis/cirugía , Toracoscopía , Timectomía/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
20.
Respirol Case Rep ; 10(11): e01052, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36303708

RESUMEN

Reports of cervical thymoma with myasthenia gravis are rare. In addition, 99mTc-MIBI (methoxyisobutylisonitrile:sestamibi) scintigraphy is a useful diagnostic examination for enlarged parathyroid tumours; however, there are a few reports of its accumulation in thymoma. Among them, there are no reports of cervical thymomas with 99mTc-MIBI accumulation complicated by myasthenia gravis. In this study, we performed surgery on a patient with preoperative myasthenic crisis accompanied by a cervical thymoma and a parathyroid tumour. Preoperatively, the cervical mass was determined to be a parathyroid tumour and was complicated by myasthenia gravis without thymic tumour. However, a pathological examination revealed that the cervical tumour with 99mTc-MIBI accumulation was a Type B2 thymoma, and a parathyroid tumour was identified in the vicinity. We report a very rare case in which symptoms improved with surgery.

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