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1.
Org Biomol Chem ; 22(9): 1765-1769, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38099597

RESUMEN

We developed a novel thiourea Lewis-base catalyst with phenol moieties for the enantioselective 5-exo-bromolactonization of stilbenecarboxylic acids to afford chiral 3-substituted phthalides. The phenol moieties are crucial for the enantio- and regio-selectivity.

2.
World J Surg ; 41(3): 771-779, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27896403

RESUMEN

OBJECTIVES: There are only a few detailed reports concerning the prognosticators following surgical resection of pulmonary metastases (PMs) from renal cell carcinoma (RCC). We investigated the prognosis of patients with RCC PMs undergoing pulmonary metastasectomy and identified prognostic factors in a multi-institutional retrospective study. METHODS: We retrospectively evaluated 84 patients who underwent resection of PMs from RCC between 1993 and 2014. We assessed the clinicopathological characteristics, focusing on the histological findings of PMs. We classified the histology into three types: pure clear cell carcinoma (N = 68), clear cell carcinoma combined with other histology type (N = 8), and non-clear cell carcinoma (N = 8). We examined the relationship between these histological types and the prognosis of patients with PMs from RCC. RESULTS: Complete resection was achieved in 78 patients (93%). The 5-year overall survival rate after metastasectomy was 59.7%. In multivariate analysis, three factors were found to be independent favorable prognostic factors of overall survival after lung metastasectomy [tumor size <2 cm, hazard ratio (HR) = 0.31, 95% confidence interval (CI) 0.13-0.78, P = 0.012; clear cell type, HR = 0.37, 95% CI 0.16-0.83, P = 0.025; and complete resection, HR = 0.27, 95% CI 0.10-0.78, P = 0.015]. CONCLUSIONS: This study indicates that a histological finding of the clear cell type is a significant favorable prognostic factor in addition to complete resection and a tumor size <2 cm. Histological evaluation of PM lesions is important for predicting survival after metastasectomy.


Asunto(s)
Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Neoplasias Pulmonares/cirugía , Metastasectomía , Neumonectomía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Femenino , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
3.
Kyobu Geka ; 69(7): 521-4, 2016 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-27365064

RESUMEN

The case was 83-year-old man who had complete situs inversus, and was pointed out to have peripheral adenocarcinoma with the size of 1.8 cm at the left upper lobe( S3). Because of severe emphysema and other multiple comorbidities, left S3 segmentectomy with hilar lymph node sampling was performed using video-assisted thoracic surgery (VATS). Preoperatively, the simulation of operation was performed using the 3 dimension computed tomography images of pulmonary arteriovenous and bronchus (3DCTAB). Postoperative course was uneventful. 3DCTAB was thought to be useful in understanding the anatomical location of pulmonary arteriovenous and bronchus directly, and in performing segmentectomy in the case of situs inversus like this.


Asunto(s)
Carcinoma de Células Acinares/complicaciones , Carcinoma de Células Acinares/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Situs Inversus/complicaciones , Situs Inversus/diagnóstico por imagen , Cirugía Torácica Asistida por Video/métodos , Anciano de 80 o más Años , Carcinoma de Células Acinares/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Arteria Pulmonar/diagnóstico por imagen , Venas Pulmonares/diagnóstico por imagen , Radiografía Torácica , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
4.
Nihon Geka Gakkai Zasshi ; 115(6): 352-6, 2014 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-25702519

RESUMEN

In 2010, "A investigating board of the team medical care" started. In 2011, Nurse Practitioner performing a specific medical practice was discussed in the promotion board of the team medical care. In 2012, the trial of Japan Nurse Practitioner (JNP) was started in NHO hospitals, and one JNP assigned to Takasaki General Medical Center. She received on-the-job training in the division of thoracic surgery. Through the thoracic operation, she gradually acquired many surgical maneuvers, such as thoracotomy and closure chest, insertion of thoracic drainage tube and perioperative management. During two years, she engaged many medical practices, including 180 cases of operative assistances, 160 cases of insertion of thoracic drainage tube.


Asunto(s)
Enfermeras Practicantes/estadística & datos numéricos , Grupo de Atención al Paciente , Procedimientos Quirúrgicos Torácicos , Japón
5.
Cancer ; 117(18): 4257-66, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21387273

RESUMEN

BACKGROUND: KRAS and epidermal growth factor receptor (EGFR) mutations are thought to play an important role in the carcinogenesis of lung adenocarcinoma. However, clinicopathological findings of KRAS mutated adenocarcinoma cases have not yet been fully clarified. The authors analyzed the relationship between the KRAS mutation and corresponding clinicopathological findings, focusing on nonmucinous and mucinous bronchioloalveolar elements. METHODS: EGFR and KRAS mutations were detected in DNA samples extracted from 182 surgically resected tissues of lung adenocarcinomas by the Smart Amplification Process. The relations between gene mutation status and clinicopathological features were analyzed. All adenocarcinoma cases were divided into bronchioloalveolar carcinoma (BAC), adenocarcinoma with bronchioloalveolar features, and adenocarcinoma without BAC components (non-BAC). BAC/adenocarcinoma with bronchioloalveolar features tumors were further assessed for the presence of mucinous features. RESULTS: EGFR and KRAS mutations were found in 76 and 30 cases, respectively. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features was found in 22 cases, which included 10 nonmucinous and 12 mucinous tumors. Of 19 cases with mucinous BAC/adenocarcinoma with bronchioloalveolar features, KRAS mutations were detected in 12, but no EGFR mutation was detected. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features had significantly earlier pathological stages and more favorable prognoses than did non-BAC. Mucinous BAC/adenocarcinoma with bronchioloalveolar features showed less smoking history than did nonmucinous BAC/adenocarcinoma with bronchioloalveolar features and non-BAC. Furthermore, transversion type KRAS mutations were more common in non-BAC. CONCLUSIONS: KRAS mutated adenocarcinomas can be divided into BAC/adenocarcinoma with bronchioloalveolar features and non-BAC types. Non-BAC adenocarcinoma is related to smoking history and has a poor prognosis. BAC/adenocarcinoma with bronchioloalveolar features adenocarcinoma, however, has a more favorable prognosis, and mucinous BAC/adenocarcinoma with bronchioloalveolar features has little relationship to smoking history.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Proteínas ras/genética , Adenocarcinoma del Pulmón , Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma Mucinoso/genética , Adolescente , Adulto , Anciano de 80 o más Años , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Fumar/genética
6.
Anticancer Res ; 40(1): 261-269, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892575

RESUMEN

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.


Asunto(s)
Adenoma Pleomórfico/inmunología , Inmunidad , Neoplasias Pulmonares/inmunología , Adenoma Pleomórfico/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico
7.
Anticancer Res ; 39(1): 395-403, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30591486

RESUMEN

BACKGROUND/AIM: The ß2-adrenergic receptor (ß2AR) is highly expressed in various human cancers and has been linked to tumor growth and metastases. Although ß2AR is considered a novel therapeutic target of human neoplasms, the clinicopathological significance of ß2AR expression in patients with pulmonary pleomorphic carcinoma (PPC) remains unclear. The aim of this study was to clarify the prognostic impact of ß2AR in PPC. PATIENTS AND METHODS: One hundred and five Japanese patients with surgically resected PPC were included in the study. The expression levels of ß2AR were assessed by immunohistochemistry in specimens from the resected tumors, and their association with patient survival, as well as with tumor characteristics was investigated. RESULTS: ß2AR was highly expressed in 63% of all patients, irrespective of adenocarcinoma components present. The ß2AR expression was significantly associated with lymph node metastasis, lymphatic permeation and tumor cell proliferation in PPC patients with early-stage disease (stage I or II). A high ß2AR expression was identified as a significant predictor of worse prognosis for PPC patients during early stages of the disease. Multivariate analysis confirmed that ß2AR expression was an independent factor for predicting the overall survival of PPC patients. CONCLUSION: ß2AR can serve as a significant predictor of tumor aggressiveness and poor survival for PPC patients, especially those with early-stage disease.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Pronóstico , Receptores Adrenérgicos beta 2/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Proliferación Celular/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Masculino , Estadificación de Neoplasias
8.
Cancers (Basel) ; 11(11)2019 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-31653009

RESUMEN

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin ß3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

9.
Hum Pathol ; 84: 142-149, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30300664

RESUMEN

Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients with pulmonary pleomorphic carcinoma (PPC) remainsunknown. The aim of this study is to clarify the prognostic impact of these amino acid transporters in PPC. One hundred five patients with surgically resected PPC were assessed by immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index were investigated using specimens of the resected tumors. LAT1 and 4F2hc were highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48% of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58% of patients with a nonadenocarcinoma component (n = 57, P = .18), respectively. A high LAT1 expression was significantly related to advanced disease, lymphatic permeation, tumor cell proliferation, and 4F2hc expression. By multivariate analysis, LAT1 and 4F2hc were identified as significant independent markers for predicting a worse prognosis. LAT1 is highly expressed in PPC, and high LAT1 expression can serve as a significant predictor linked to a worse prognosis in patients with PPC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Cadena Pesada de la Proteína-1 Reguladora de Fusión/biosíntesis , Transportador de Aminoácidos Neutros Grandes 1/biosíntesis , Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico
10.
Am J Transl Res ; 10(10): 3243-3253, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30416665

RESUMEN

OBJECTIVES: Since large cell neuroendocrine carcinoma (LCNEC) is a relatively rare histologic type of primary lung cancer, little is known about the immunological status of patients with LCNEC. We aimed to clarify the expression and prognostic impact of programmed cell death ligand 1 (PD-L1), CD8, CD4, and Forkhead box protein P3 (Foxp3) in LCNEC. METHODS: We retrospectively analyzed PD-L1, CD8, CD4, and Foxp3 expressions in 95 surgically resected LCNEC. PD-L1 positive staining was determined in tumors with more than 1% of tumor cells stained to any intensity, and CD8, CD4, and Foxp3 positivity was determined in tumors with more than 5% of lymphocytes stained. RESULTS: Positive expression of PD-L1, CD8, CD4, and Foxp3 was observed in 70 (74%), 52 (55%), 76 (80%), and 43 (45%) tumors, respectively. The expression of PD-L1 was significantly correlated with positive lymphatic permeation. Positive correlations were mutually observed among tumor infiltrating immune cells. Univariate and multivariate analyses showed that positive pleural invasion and Foxp3 negative expression were independent unfavorable prognostic factors for overall survival (OS). Advanced pathological stage, positive pleural invasion, CD4 negative expression in cancer stroma, and Foxp3 negative expression were identified as independent unfavorable prognostic factors for recurrence free survival (RFS). CONCLUSIONS: Foxp3 positive tumor infiltrating lymphocytes (TILs) were an independent favorable prognostic factor for both OS and RFS, whereas CD4 positive TILs were an independent significant unfavorable prognostic factor for RFS. The high frequency of PD-L1 expression could support the use of anti-programmed cell death 1 antibody in the treatment of LCNEC.

11.
J Glob Oncol ; 2(1): 15-25, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28717678

RESUMEN

PURPOSE: A deletion polymorphism of the Bim gene has been reported to be a prognostic factor for patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors in the Asian population. We investigated the impact of the Bim deletion polymorphism on survival among patients with completely resected NSCLC. PATIENTS AND METHODS: The Bim polymorphism was detected by polymerase chain reaction analysis. We measured overall survival (OS) and recurrence-free survival rates in 411 patients and postrecurrence survival (PRS) in 94 patients who experienced recurrence and received additional anticancer therapy. RESULTS: The Bim deletion polymorphism was detected in 61 patients (14.8%). OS rates were significantly lower for patients with the Bim deletion polymorphism than for those with the wild-type sequence. On multivariable analysis, the Bim deletion polymorphism was identified as an independent prognostic factor for OS (hazard ratio, 1.98; 95% CI, 1.17 to 3.36; P = .011). Among the 94 patients who experienced recurrence and were treated with anticancer therapy, patients with the Bim deletion polymorphism showed significantly poorer PRS than those with the wild-type sequence (median, 9.8 months v 26.9 months, respectively; P < .001). Multivariable analysis revealed that the Bim deletion polymorphism was an independent predictor of PRS (hazard ratio, 3.36; 95% CI, 1.75 to 6.47; P < .001). This trend remained apparent in subgroup analyses stratified by EGFR status, histology, and therapeutic modality. CONCLUSION: The Bim deletion polymorphism is a novel indicator of shortened PRS among patients with recurrent NSCLC treated with anticancer therapy in the Asian population.

12.
Mol Clin Oncol ; 2(2): 187-196, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24649331

RESUMEN

The aim of this study was to investigate the prognosis of pulmonary adenocarcinoma patients following postoperative recurrence, according to epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) gene mutation status and recurrence site. In total 58 adenocarcinoma patients with recurrence following surgical resection were retrospectively evaluated between 2002 and 2011. The patients were divided into groups according to the presence or absence of EGFR and KRAS mutations and the clinicopathological characteristics, recurrence sites and postrecurrence survival were compared. EGFR and KRAS mutations were detected in 26 (45%) and 11 patients (19%), respectively. Initial recurrence was distant in 25 (43%), local in 17 (29%) and both distant and local in 16 cases (28%). In EGFR-mutant (EGFR+) cases, bilateral/contralateral lung recurrence was a frequent finding. EGFR+ cases exhibited significantly better outcomes compared to KRAS+ and EGFR-KRAS- (wild-type) cases. The 2-year post-recurrence survival rates were 81, 18 and 47% in EGFR+, KRAS+ and wild-type cases, respectively. The patients with distant organ recurrence exhibited significantly worse survival compared with those without distant recurrence in wild-type, but not in the EGFR+ cases or the entire cohort. Multivariate analysis revealed that EGFR mutations and a number of recurrent lesions were the only statistically significant independent predictors of postrecurrence prognosis. Our results indicated distinct survival differences in recurrent adenocarcinoma patients according to driver mutations. Patients with EGFR-mutated tumors exhibited increased survival, regardless of recurrence at distant sites, whereas patients with KRAS-mutated adenocarcinoma exhibited poor outcome following postoperative recurrence. Therefore, the assessment of driver mutations is essential for predicting postrecurrence survival following surgical resection.

13.
Oncol Rep ; 28(5): 1727-35, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22922681

RESUMEN

Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Línea Celular Tumoral , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Animales , Técnicas de Cultivo de Célula , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos BALB C , Proteínas de Complejo Poro Nuclear/biosíntesis , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Unión al ARN/biosíntesis , Proteínas de Unión al ARN/genética , Receptores de Lisoesfingolípidos/biosíntesis , Receptores de Lisoesfingolípidos/genética , Receptores de Esfingosina-1-Fosfato , Proteínas de Unión al GTP rab/biosíntesis , Proteínas de Unión al GTP rab/genética , Proteínas de Unión a GTP rab7
14.
Oncol Rep ; 26(5): 1205-11, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21811765

RESUMEN

We examined the correlation between computed tomography (CT) findings and the incidence of epidermal growth factor receptor (EGFR) and KRAS mutations in lung adenocarcinoma. We analyzed the tumors of 136 patients with surgically resected primary lung adenocarcinoma. CT scans were evaluated for the presence of ground grass opacity (GGO), spiculation and the maximum diameter of the tumor was measured. SMart Amplification Process (ver. 2) was used to detect the presence of EGFR and KRAS mutations. EGFR and KRAS mutations were found in 56 (41.1%) and 25 (18.4%) of the 136 cases, respectively. Although no significant association was found between GGO and EGFR mutations (p=0.07), the EGFR mutation occurred more frequently in male patients with GGO than in those without GGO (p=0.04). The KRAS mutation occurred more frequently in patients whose tumor diameter was ≥ 31 mm than in those whose tumor diameter was <30 mm (p=0.003). Evaluation of CT findings may be helpful for determining the presence of EGFR and KRAS mutations, particularly when it is not possible to obtain a tumor specimen.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/genética , Receptores ErbB/genética , Genes ras , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Mutación , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
15.
Oncol Rep ; 25(4): 921-8, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21318227

RESUMEN

Epidermal growth factor receptor (EGFR) gene mutations have been reported to be clinically significant in non-small cell lung cancer (NSCLC). However, because most previous studies focused only on adenocarcinomas, EGFR mutations in other histotypes are poorly investigated. We evaluated the frequency of EGFR gene mutations in squamous cell carcinoma (SCC) and its clinicopathological features. In total, 89 frozen tumor specimens that had been first diagnosed as SCCs, were examined for EGFR mutations in exons 19 and 21 using direct sequencing, PNA-enriched sequencing and SmartAmp2. Additionally, pathological investigation, including immunostaining for p63 and TTF-1, alcian blue staining and EGFR mutation-specific immunohistochemistry in mutation-positive samples was also performed. The frequency of EGFR mutations was 5.6% (5/89); all mutations were deletions in EGFR exon 19. Immunohistological investigation of these samples revealed that two of five were positive for p63 and TTF-1 staining, and showed production of mucin, as evidenced by alcian blue staining. Consequently, three of the samples were considered to be true SCC at final pathological diagnosis, while the remaining two samples were revised to adenosquamous carcinoma and adenocarcinoma. The final frequency of the EGFR mutations in true SCC was 3.4% (3/87). In conclusion, EGFR mutations were found in a small, but significant, number of SCC tumor samples and thus EGFR mutational analysis was useful in the accurate diagnosis of SCC. Our data demonstrate that EGFR mutational analysis should be performed not only in adenocarcinoma, but also in SCC to allow accurate diagnosis and treatment.


Asunto(s)
Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Mutación de Línea Germinal/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo
16.
J Mol Diagn ; 12(2): 257-64, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20093389

RESUMEN

Recent evidence indicates that the presence of epidermal growth factor receptor (EGFR) or KRAS mutations in non-small cell lung cancer (NSCLC) can predict the response of the tumor to gefinitib. However, it is difficult to detect these mutations using formalin-fixed, paraffin-embedded (FFPE) tissues because the fixation process and aging can damage the DNA. In this study, we describe our work in adapting the Smart Amplification Process version 2 (SmartAmp2) to detect EGFR or KRAS mutations in DNA extracted from FFPE tissues. We were able to detect these mutations in 37 (97%) of 38 FFPE lung cancer tissue samples within 60 minutes with the SmartAmp2 assay and to confirm the correlation between EGFR mutations in FFPE tissues and gefitinib responsiveness. All mutations had previously been confirmed in the 38 samples using DNA extracted from frozen tissues. Electrophoresis results indicated that PCR analysis was not reliable for DNA extracted from FFPE tissue when primers with a long amplicon (>300 bp) were used. This study confirms that the SmartAmp2 assay is suitable for use with DNA extracted from FFPE as well as frozen tissues.


Asunto(s)
Receptores ErbB/genética , Formaldehído/química , Neoplasias Pulmonares/genética , Mutación , Técnicas de Amplificación de Ácido Nucleico/métodos , Adhesión en Parafina/métodos , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Antineoplásicos/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Fijadores/química , Gefitinib , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas p21(ras) , Quinazolinas/uso terapéutico , Análisis de Secuencia de ADN/métodos , Fijación del Tejido/métodos
17.
Pathol Int ; 57(12): 765-74, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17988277

RESUMEN

To re-evaluate adenocarcinoma, mixed subtypes (ADMIX) of the lung, a total of 201 cases were classified into three main subgroups according to the most differentiated histological growth pattern; namely bronchioloalveolar carcinoma (BAC)-mixed, which was the most predominant (73.1%), papillary (PAP)-mixed (21.9%), and acinar-mixed (5%). The PAP-mixed was significantly male predominant and had more progressed clinicopathological features. A significant cytological difference was observed among the three subgroups. A tissue microarray was constructed and immunohistochemistry was undertaken using 15 biomarkers. Hierarchical clustering analysis was separately applied to the immunohistochemical results of ADMIX and ADMIX subgroups, and it was found that most acinar-mixed cases were placed in a separate cluster, while the BAC-mixed and PAP-mixed failed to form significant independent clusters. The antibody clustering profile for the acinar-mixed was clearly different from that for the BAC-mixed or PAP-mixed, but the PAP-mixed shared a dendrogram profile with the other two subgroups. Statistically, approximately half of the 15 biomarkers were significant for differentiating between ADMIX subgroups and between different histological growth patterns. In conclusion, ADMIX can be classified into three histopathological subgroups according to the most differentiated growth pattern, of which a PAP growth pattern might indicate more aggressive behavior than that of a BAC growth pattern.


Asunto(s)
Adenocarcinoma/clasificación , Adenocarcinoma/patología , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/análisis , Análisis por Conglomerados , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Matrices Tisulares
18.
Surg Today ; 36(12): 1039-46, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17123130

RESUMEN

PURPOSE: We aimed to identify the key proteins that influence the prognosis of non-small cell lung cancer (NSCLC) using protein expression profiles of previously known prognostic markers. METHODS: Thirty-one cases of Stage II NSCLC with 5-year follow-up data were selected. Tissue microarrays (TMA) and immunohistochemistry were used to make protein expression profiles of 18 previously reported immunohistochemical prognostic markers and their value in NSCLC was statistically re-evaluated by a discriminant analysis. RESULTS: For the discriminant analysis using marker protein expression profiles, we selected three significant markers, TTF-1, RCAS1 and c-MET, to evaluate each patient's 5-year survival. The requested discriminant function was V = -1.08754 x (RCAS1 score) - 0.83174 x (TTF1 score) + 0.55204 x (cMET score) + 5.46972, and V = 0 served as a cut-off point. The correctness for evaluating a patient's 5-year survival by a discriminant analysis was 87.1%. CONCLUSIONS: A discriminant analysis is thus considered to be a useful statistical method for analyzing the protein expression profiles obtained by combined TMA and immunohistochemical techniques using archival NSCLC tissues. However, the sample size and selection of the marker protein depending on the histology greatly influence the results of a NSCLC study.


Asunto(s)
Antígenos de Neoplasias/biosíntesis , Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Unión al ADN/biosíntesis , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas c-met/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Análisis Discriminante , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Japón/epidemiología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Factores de Transcripción
19.
Pathol Int ; 56(4): 217-21, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16634968

RESUMEN

In the lung, acinic cell carcinoma (ACC) is a rare form of tumor. Reported herein is a unique bronchial gland-type tumor diagnosed as well-differentiated ACC that developed in the B9 bronchus of the left lung. Various immunohistochemical and histochemical staining partly satisfied the diagnosis of ACC. Moreover, this tumor contained various sizes of mucous cysts lined by columnar mucous cells, which produced abundant mucin positive for Alcian blue, which is usually present in mucoepidermoid carcinoma. Therefore, the present case is a unique tumor having a broad spectrum of cell differentiation from the terminal duct--acinar unit to the striated duct and excretory duct. This is the first case of unique bronchial gland-type tumor with mixed histological features of ACC and mucoepidermoid carcinoma.


Asunto(s)
Carcinoma de Células Acinares/patología , Carcinoma Broncogénico/patología , Neoplasias Pulmonares/patología , Carcinoma de Células Acinares/metabolismo , Carcinoma Broncogénico/metabolismo , Diferenciación Celular , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Toracoscopía
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