Author
Yasunori Sohara
Bio: Yasunori Sohara is an academic researcher from Jichi Medical University. The author has contributed to research in topics: Lung cancer & Survival rate. The author has an hindex of 22, co-authored 102 publications receiving 6694 citations.
Topics: Lung cancer, Survival rate, Aspergillosis, Pneumonectomy, Empyema
Papers published on a yearly basis
Papers
More filters
••
TL;DR: It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
Abstract: Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC.
4,826 citations
••
TL;DR: A large registry study provides benchmark prognostic statistics for lung cancer, and the present tumor, node, metastasis staging system well characterizes the stage-specific prognoses.
375 citations
••
TL;DR: Findings indicated that the present stages IB and IIA should be merged into the same stage category and the future revision of the TNM staging system should focus on the subdivision of stages I and II.
281 citations
••
TL;DR: The results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.
Abstract: Purpose: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. Experimental Design: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. Results: Seven genes, including aldo-keto reductase family 1, member B10 ( AKR1B10 ), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non–small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs ( P P Conclusion: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers9 NSCLCs and might be involved in tobacco-related carcinogenesis.
269 citations
••
TL;DR: Situations where infection has spread to posterior medisatinum, particularly when it reaches in the level of the carina (descending necrotizing mediastinitis-type I), may not always require aggressive mediastinal drainage.
Abstract: Background: Descending necrotizing mediastinitis resulting from oropharyngeal abscess, is a serious, life-threatening infection. Exisiting strategies for surgical management, such as transcervical mediastinal drainage or aggressive thoracotomic drainage, remain controversial.Methods: Four patients, (three males and one female) were treated for descending necrotizing mediastinitis resulting from oropharyngeal infection. Two had peritonsillar abscesses, while the others experienced dental abscess and submaxillaritis. Descending necrotizing mediastinitis received its classification according to the degree of diffusion of infection diagnosed by computed tomography. Mediastinitis in two cases, (Localized descending necrotizing mediastinitis-Type I), was localized to the upper mediastinal space above the carina. In the others, infection extended to the lower anterior mediastinum (Diffuse descending necrotizing mediastinitis-Type IIA), and to both anterior and posterior lower mediastinum (Diffuse descending necrotizing mediastinitis-Type IIB). The spread of infection to the pleural cavity occurred in three cases.Results: The surgical outcome concerning each of the patients was successful. Radical cervicotomy (unilateral in three patients, bilateral in the other) in conjunction with mechanical ventilation with continuous postoperative positive airway pressure, was performed in all cases. Tracheostomy was established in three patients and pharyngostomy in two. The two descending necrotizing mediastinitis-Type I cases were successfully managed with transcervical mediastinal drainage. The descending necrotizing mediastinitis-Type IIA case received treatment through transcervicotomy and anterior mediastinal drainage through a subxiphoidal incision. The patient with descending necrotizing mediastinitis-Type IIB required posterior mediastinal drainage through a right standard thoracotomy followed by left minimal thoracotomy.Conclusions: The mediastinal infection, the extent of which has been accurately determined by computed tomograms, necessitates radical cervicotomy followed by pleuromediastinal drainage. Situations where infection has spread to posterior mediastinum, particularly when it reaches in the level of the carina (descending necrotizing mediastinitis-type I), may not always require aggressive mediastinal drainage. In comparison, diffuse descending necrotizing mediastinitis-Type IIB demands complete mediastinal drainage with debridement via thoracotomy. Subxiphoidal mediastinal drainage without sternotomy may provide adequate drainage in diffuse descending necrotizing mediastinitis-Type IIA.
218 citations
Cited by
More filters
••
TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Abstract: Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.
6,441 citations
••
John N. Weinstein1, John N. Weinstein2, Eric A. Collisson3, Gordon B. Mills1 +376 more•Institutions (31)
TL;DR: The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA with a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages.
Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
5,294 citations
•
TL;DR: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels as mentioned in this paper.
Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
4,634 citations
••
TL;DR: The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients, and the drug resulted in grade 1 or 2 gastrointestinal side effects.
Abstract: Background Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non–small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. Methods After screening tumor samples from approximately 1500 patients with non–small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. Results Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. Conclusions The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)
4,091 citations
••
TL;DR: This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies.
3,850 citations