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1.
Ann Oncol ; 28(2): 285-291, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28426104

RESUMO

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).


Assuntos
Antraciclinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Antraciclinas/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Taxoides/efeitos adversos , Resultado do Tratamento
2.
Clin. transl. oncol. (Print) ; 17(9): 702-709, sept. 2015. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-140328

RESUMO

Purpose. Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations. Methods/patients. We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy. Results. Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39–75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9 %, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2 %, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS. Conclusions. Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS (AU)


No disponible


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Combinada , Compostos de Platina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Genes erbB-1 , Adenocarcinoma/tratamento farmacológico , Estudos Retrospectivos , Mutagênese , Carboplatina/uso terapêutico , Estimativa de Kaplan-Meier
3.
Clin Transl Oncol ; 17(9): 702-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25990507

RESUMO

PURPOSE: Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations. METHODS/PATIENTS: We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy. RESULTS: Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39-75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9%, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2%, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS. CONCLUSIONS: Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Seguimentos , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Prognóstico , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Gencitabina
4.
Br J Cancer ; 110(8): 2030-9, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24603303

RESUMO

BACKGROUND: ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear. METHODS: One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort. RESULTS: ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients. CONCLUSIONS: ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery.


Assuntos
Sistema ASC de Transporte de Aminoácidos/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor , Metástase Neoplásica/genética
5.
Br J Cancer ; 110(8): 2047-53, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24577055

RESUMO

BACKGROUND: On the basis of our recent findings of oncogenic KRAS-induced interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed the clinicopathological and prognostic significances of IL-8 expression and its relationship to KRAS mutations in lung adenocarcinomas. METHODS: IL-8 expression was examined by quantitative RT-PCR using 136 of surgical specimens from lung adenocarcinoma patients. The association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status and survival was analysed. RESULTS: IL-8 was highly expressed in tumours from elderly patients or smokers and in tumours with pleural involvement or vascular invasion. In a non-smokers' subgroup, IL-8 level positively correlated with age. IL-8 was highly expressed in tumours with KRAS mutations compared with those with EGFR mutations or wild-type EGFR/KRAS. Lung adenocarcinoma patients with high IL-8 showed significantly shorter disease-free survival (DFS) and overall survival (OS) than those with low IL8. DFS and OS were significantly shorter in the patients with mutant KRAS/high IL-8 than in those with wild-type KRAS/low IL-8. Cox regression analyses demonstrated that elevated IL-8 expression correlated with unfavourable prognosis. CONCLUSIONS: Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Interleucina-8/biossíntese , Neoplasias Pulmonares/genética , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8/genética , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas p21(ras)
6.
Oncogene ; 32(34): 4034-42, 2013 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-22964644

RESUMO

KRAS mutations are one of the most common driver mutations in non-small-cell lung cancer (NSCLC) and finding druggable target molecules to inhibit oncogenic KRAS signaling is a significant challenge in NSCLC therapy. We recently identified epiregulin (EREG) as one of several putative transcriptional targets of oncogenic KRAS signaling in both KRAS-mutant NSCLC cells and immortalized bronchial epithelial cells expressing ectopic mutant KRAS. In the current study, we found that EREG is overexpressed in NSCLCs harboring KRAS, BRAF or EGFR mutations compared with NSCLCs with wild-type KRAS/BRAF/EGFR. Small interfering RNAs (siRNAs) targeting mutant KRAS, but not an siRNA targeting wild-type KRAS, significantly reduced EREG expression in KRAS-mutant and EREG-overexpressing NSCLC cell lines. In these cell lines, EREG expression was downregulated by MEK and ERK inhibitors. Importantly, EREG expression significantly correlated with KRAS expression or KRAS copy number in KRAS-mutant NSCLC cell lines. Further expression analysis using 89 NSCLC specimens showed that EREG was predominantly expressed in NSCLCs with pleural involvement, lymphatic permeation or vascular invasion and in KRAS-mutant adenocarcinomas. In addition, multivariate analysis revealed that EREG expression is an independent prognostic marker and EREG overexpression in combination with KRAS mutations was associated with an unfavorable prognosis for lung adenocarcinoma patients. In KRAS-mutant and EREG overexpressing NSCLC cells, siRNA-mediated EREG silencing inhibited anchorage-dependent and -independent growth and induced apoptosis. Our findings suggest that oncogenic KRAS-induced EREG overexpression contributes to an aggressive phenotype and could be a promising therapeutic target in oncogenic KRAS-driven NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Fator de Crescimento Epidérmico/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Idoso , Apoptose/genética , Butadienos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/metabolismo , Epirregulina , Receptores ErbB/genética , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Nitrilas/farmacologia , Fenótipo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Pirazóis/farmacologia , Piridazinas/farmacologia , Interferência de RNA , Proteínas ras/metabolismo
7.
Br J Cancer ; 107(4): 632-8, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22805328

RESUMO

BACKGROUND: The expression of L-type amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression. METHODS: A total of 97 consecutive patients with surgically resected pathological stage I-IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53. RESULTS: L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. L-type amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis. CONCLUSION: L-type amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Intervalo Livre de Doença , Feminino , Proteína-1 Reguladora de Fusão/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico
8.
Int J Immunopathol Pharmacol ; 23(1): 153-64, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20378003

RESUMO

Interactions between CXCL12 and its receptors CXCR4 or CXCR7 are involved in tumor growth and metastasis in various types of human cancer. However, CXCL12 expression and its role in lung cancer are not fully elucidated. Here we examined the expression of CXCL12 in 54 lung cancer cell lines consisting of 23 small cell lung cancers (SCLCs) and 31 non-small cell lung cancers (NSCLCs). CXCL12 was overexpressed in lung cancer cell lines compared to non-malignant human bronchial epithelial cell lines (N = 6). CXCL12 expression was positively but weakly correlated with the expression of CXCR4 or CXCR7. We also examined CXCL12 expression in 89 NSCLC specimens and found that CXCL12 expression was significantly higher in tumor specimens from female patients, non-smokers and adenocarcinoma patients. Small interfering RNAs targeting CXCL12 inhibited cellular proliferation, colony formation and migration of CXCL12-overexpressing lung cancer cells; however, this inhibition did not occur in lung cancer cells that lacked CXCL12. Furthermore, the anti-CXCL12 neutralizing antibody mediated inhibitory effects in three lung cancer cell lines that overexpressed CXCL12, but not in two CXCL12 non-expressing lung cancer cell lines nor two non-malignant bronchial epithelial cell lines. The present study demonstrates that: CXCL12 is concomitantly overexpressed with CXCR4 or CXCR7 in lung cancers; CXCL12 is highly expressed in NSCLCs from females, non-smokers and adenocarcinoma patients; and disruption of CXCL12 inhibits the growth and migration of lung cancer cells. Our findings indicate that CXCL12 is required for tumor growth and provide a rationale for the anti-CXCL12 treatment strategy in lung cancer.


Assuntos
Quimiocina CXCL12/fisiologia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CXCL12/antagonistas & inibidores , Quimiocina CXCL12/genética , Receptores ErbB/fisiologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , RNA Mensageiro/análise , RNA Interferente Pequeno/genética , Receptores CXCR/genética , Receptores CXCR4/genética
9.
Int J Immunopathol Pharmacol ; 22(1): 43-51, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19309551

RESUMO

CXCL12 is a chemokine that binds to a G-protein-coupled receptor (CXCR4). CXCL12 is expressed in various tumors and is considered as playing an important role in tumor growth and invasion. The aim of this study is to investigate the expression of CXCL12 in human malignant mesothelioma (MM), the chemotactic effect of CXCL12 derived from MM, and the expression of CXCR4 in MM tissues in relation to regulatory T cells. CXCL12 expression was examined by immunostaining of tissue specimens from malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPEM). The MM group comprised 6 patients (4 men/2 women, MPM=4, MPEM=2, aged 56.0 +/- 12.4 years) and the control (non-mesothelioma) group also had 6 patients (4 men/2 women aged 65.0 +/- 6.7 years). CXCL12 mRNA expression was also examined by RT-PCR in MPM cell lines (H28, H2052, and H2058), while CXCR4 mRNA expression was examined by in situ hybridization in MPM tissue. CXCL12 was expressed in the cytoplasm of MM cells from all patients, but was not expressed in the control group. H2052 and H2058 cells expressed CXCL12 mRNA, but H28 cells did not. CXCL12 in MM tissue homogenate supernatant had a chemotactic effect on CXCR4-expressing THP-1 cells. CXCR4 mRNA was expressed by a part of LCA+CD3+ Foxp3+CD25+ T cells that were located adjacent to the border of CXCL12-expressing epithelioid MPM. These findings suggest that CXCL12 contributed to tumor-related inflammation by inducing the accumulation of CXCR4-expressing cells with regulatory T cell markers around MM.


Assuntos
Quimiocina CXCL12/análise , Fatores de Transcrição Forkhead/análise , Subunidade alfa de Receptor de Interleucina-2/análise , Mesotelioma/imunologia , Neoplasias Pleurais/imunologia , Receptores CXCR4/análise , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , RNA Mensageiro/análise , Receptores CXCR4/genética
10.
Br J Cancer ; 98(4): 742-8, 2008 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-18253116

RESUMO

The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I-III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; P<0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I-III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
Australas Radiol ; 51 Suppl: B265-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17991081

RESUMO

Pseudomesotheliomatous adenocarcinoma is an uncommon variant of peripheral lung cancer. This condition mimics a malignant mesothelioma in terms of its clinical presentation and its gross and microscopic appearance. An immunohistochemical investigation is important when it is difficult to determine whether diffuse carcinomatous involvement of the pleura is secondary to metastasis, lung cancer, or mesothelioma. We herein report a very rare case of concomitant pseudomesotheliomatous adenocarcinoma, gastric cancer and esophageal cancer.


Assuntos
Adenocarcinoma/diagnóstico , Diagnóstico por Imagem/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Humanos , Masculino
13.
Eur J Gynaecol Oncol ; 27(2): 197-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16620072

RESUMO

Primary peritoneal serous papillary carcinoma (PSPC) is a rare primary peritoneal tumor. Clinically, PSPC usually presents with general abdominal discomfort resulting from variable amounts of ascites. In a state of small amounts of ascites, initial manifestation of massive bilateral pleural effusion is unusual. A 76-year-old female nonsmoker with no asbestos exposure complained of dyspnea during exercise. Chest radiograph showed a massive bilateral pleural effusion. Chest computed tomography (CT) revealed irregular pleural thickening and a small amount of ascites. Abdominopelvic CT revealed nodular thickening of the parietal peritoneum, mesenteric or omental nodules, omental cake, and lymphadenopathy in paraaortic regions. Adenocarcinoma cells were found via cytologic examination in bilateral pleural fluids and ascites. Because the primary site of the adenocarcinoma was not found, a surgical biopsy of the right pleural thickening was performed. The final diagnosis was PSPC. The patient was treated with platinum-based chemotherapy. Physicians should be aware of a possibility of PSPC when the radiographic findings show massive bilateral pleural effusion due to pleural carcinomatosis, with high serum levels of CA125.


Assuntos
Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Derrame Pleural/diagnóstico , Idoso , Antígeno Ca-125/sangue , Feminino , Humanos , Tomografia Computadorizada por Raios X
14.
Br J Cancer ; 93(9): 1029-37, 2005 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-16234815

RESUMO

The transforming growth factor beta (TGFbeta)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFbeta signalling, and RUNX3, which facilitates TGFbeta-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFbeta-related genes are frequently deregulated through aberrant methylation in many human malignancies.


Assuntos
Subunidade alfa 3 de Fator de Ligação ao Core/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Fator de Crescimento Transformador beta/metabolismo , Idoso , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Regulação para Baixo , Feminino , Inativação Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Células Tumorais Cultivadas
15.
Neurosci Lett ; 328(1): 68-70, 2002 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-12123861

RESUMO

This study was designed to examine whether anxious personality, i.e. trait anxiety, influences the autonomic nervous functions in humans without manipulation of experimental stressors. The degrees of state and trait anxiety, blood pressure, heart rate, pupillary light reflex (PLR), and body temperature were measured at the same hour on four different days in 14 healthy college students. A multiple regression analysis showed that trait anxiety predominantly influenced state anxiety and the PLR parameters. A single regression analysis showed that trait anxiety positively correlated to the initial pupillary diameter and the constricted diameter of PLR and negatively to the amplitude of PLR. It was concluded that trait anxiety predicts state anxiety and a smaller amplitude of PLR in humans at rest.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Temperatura Corporal/fisiologia , Frequência Cardíaca/fisiologia , Reflexo Pupilar/fisiologia , Estresse Fisiológico/fisiopatologia , Adulto , Fatores Etários , Doença Crônica , Feminino , Humanos , Valor Preditivo dos Testes , Análise de Regressão
16.
Carcinogenesis ; 22(9): 1355-62, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11532855

RESUMO

8-Hydroxyguanine (8-OHG) is an oxidatively damaged mutagenic base which causes G:C-->T:A transversions in DNA. OGG1 was cloned as a human gene encoding a DNA glycosylase that specifically excises 8-OHG from DNA in vitro. However, it was not clear whether OGG1 protein suppresses G:C-->T:A transversions caused by 8-OHG in human cells in vivo. In the present study we have examined the ability of OGG1 protein to suppress G:C-->T:A transversions caused by 8-OHG in human cells by bacterial suppressor tRNA (supF) forward mutation assay using a shuttle vector DNA, pMY189. Introduction of a single 8-OHG residue at position 159 of the supF gene in plasmid pMY189 resulted in a 130-fold increase in mutation frequency compared with untreated plasmid pMY189 after replication in the NCI-H1299 human lung cancer cell line. G:C-->T:A transversions at position 159 were detected in >90% of the supF mutants from the 8-OHG-containing plasmid. The mutation frequency of the 8-OHG-containing plasmid was significantly reduced by overexpression of OGG1 protein in NCI-H1299 cells and, in particular, the occurrence of G:C-->T:A transversion at position 159 in the supF gene was suppressed. Furthermore, frequencies and spectra of mutations of the untreated pMY189 plasmid did not differ significantly with overexpression of OGG1 protein. These results indicate that OGG1 protein has the ability to suppress G:C-->T:A transversions caused by 8-OHG in human cells in vivo.


Assuntos
Proteínas de Escherichia coli , Guanina/análogos & derivados , Guanina/fisiologia , N-Glicosil Hidrolases/fisiologia , Mutação Puntual , Sequência de Bases , Dano ao DNA , DNA-Formamidopirimidina Glicosilase , Escherichia coli/genética , Genes Supressores , Vetores Genéticos/genética , Guanina/metabolismo , Humanos , Neoplasias Pulmonares/genética , Dados de Sequência Molecular , N-Glicosil Hidrolases/genética , Plasmídeos/genética , RNA de Transferência/genética , Transfecção , Células Tumorais Cultivadas
17.
Genomics ; 72(2): 169-79, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11401430

RESUMO

Here, we report the complete genomic sequence and the characterization of the 311-kb region of 18q21, a candidate tumor suppressor locus containing a region of homozygous deletion in a lung cancer cell line, Ma29. This region contained two known genes, SMAD4 and ME2 (mitochondrial malate oxydoreductase), and two novel genes, D29 (deleted in Ma29 HGMW-approved symbol ELAC1), encoding an evolutionarily conserved protein, and B29 (beside the Ma29 deletion HGMW-approved symbol C18orf3), with no significant homology to any known genes. The deleted DNA segment in Ma29, which was estimated to be 195 kb in size, included all the coding exons of ME2 and D29, but not the coding exons of SMAD4 and B29. The deleted region also included exon 0, a 5'-noncoding exon, of SMAD4, and the expression of SMAD4 was greatly reduced in Ma29 cells. Mutations of SMAD4 and D29 were detected in 1 of 45 lung cancer cell lines examined, while those of ME2 and B29 were not detected, indicating that these four genes are not major targets for 18q21 deletions. The physical and transcriptional map constructed in this study will provide basic information for the identification of a tumor suppressor gene(s) at 18q21 involved in lung carcinogenesis.


Assuntos
Cromossomos Humanos Par 18 , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Proteínas Supressoras de Tumor , Antígenos CD/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Antígenos CD79 , Mapeamento de Sequências Contíguas , DNA de Neoplasias , Proteínas de Ligação a DNA/genética , Deleção de Genes , Expressão Gênica , Humanos , Dados de Sequência Molecular , Mutação , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso/genética , Análise de Sequência de DNA , Proteína Smad4 , Fatores de Transcrição TCF , Transativadores/genética , Fator de Transcrição 4 , Fatores de Transcrição/genética , Transcrição Gênica , Células Tumorais Cultivadas
18.
Neurosci Lett ; 302(2-3): 157-9, 2001 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-11290411

RESUMO

To examine whether the postural balance is influenced by the degree of anxiety, body sway during orthostatic standing while gazing at a visual target was examined in college students. Students, physically and mentally healthy, were divided into two groups according to the degree of state anxiety; high anxiety group (HA) and low anxiety group (LA). A fast Fourier transform analysis of the postural sway in antero-posterior axis showed that frequency components of 0.02-0.21 Hz, reflecting vestibular inputs, were 16% greater and those of 2.02-10.0 Hz, reflecting somatosensory inputs, were 24% smaller in HA. These differences between HA and LA were abolished when the eyes were closed. It is concluded that the interactions of visual inputs with vestibular and somatosensory inputs are influenced by anxiety.


Assuntos
Ansiedade/fisiopatologia , Sistema Nervoso Central/fisiologia , Equilíbrio Postural/fisiologia , Postura/fisiologia , Adolescente , Adulto , Feminino , Humanos , Mecanorreceptores/fisiologia , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Privação Sensorial/fisiologia , Vestíbulo do Labirinto/fisiologia , Percepção Visual/fisiologia
19.
Genes Chromosomes Cancer ; 30(3): 316-21, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11170292

RESUMO

Constitutive activation of the Wnt signaling pathway as a result of genetic alterations of APC, AXIN1, and CTNNB1 has been found in various human cancers, including those of the colon, liver, endometrium, ovary, prostate, and stomach. To investigate the pathogenetic significance of constitutive activation of the Wnt signaling pathway in human lung carcinogenesis, CTNNB1 alterations in exon 3, a region known to represent a mutation hot spot, were screened in 46 lung cancer cell lines and 47 primary lung cancers. Missense mutations causing substitutions of Ser/Thr residues critical for regulation by GSK-3beta were detected in one (2%) of the cell lines, A427, and two (4%) of the surgical specimens. The three lung cancers with CTNNB1 mutations were adenocarcinomas. To explore the prevalence of constitutive activation of the Wnt signaling pathway in human lung cancer, we assessed 15 lung cancer cell lines representing major histological subtypes of lung cancers for constitutive Tcf transcriptional activity (CTTA). CTTA was observed only in the A427 adenocarcinoma cell line, but not in the remaining 14 cell lines. The data indicate that constitutive activation of the Wnt signaling pathway caused by CTNNB1 mutation is involved in the development and/or progression of a subset of lung carcinoma, preferentially in adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Proteínas do Citoesqueleto/genética , Neoplasias Pulmonares/genética , Mutação de Sentido Incorreto/genética , Proteínas Proto-Oncogênicas/genética , Transdução de Sinais/genética , Transativadores , Proteínas de Peixe-Zebra , Adenocarcinoma/enzimologia , Caderinas/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Ativação Enzimática/genética , Quinase 3 da Glicogênio Sintase , Humanos , Neoplasias Pulmonares/enzimologia , Células Tumorais Cultivadas , Proteínas Wnt , beta Catenina
20.
Oncol Rep ; 7(5): 1135-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10948352

RESUMO

We used cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) weekly for salvage chemotherapy in relapsed or refractory small cell lung cancer (SCLC). We reviewed the medical charts of patients between January 1993 and December 1996 at the National Nishi-Gunma Hospital. Twenty patients were treated with salvage chemotherapy. The overall response rate was 55.0%. The median survival time of extensive disease patients from the start of CODE therapy was 23 weeks and the 1-year survival rate was 21.0%. Toxicities were severe, especially in myelosuppression. CODE could be selected as a salvage therapy for chemotherapy- relapsed SCLC cases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Terapia de Salvação , Análise de Sobrevida , Vincristina/administração & dosagem , Vincristina/efeitos adversos
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