Tetsuya Mitsudomi

..To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection...

..There was no significant difference in the clinicopathologic characteristics including prognosis of patients with high or low expression of ERBB4. The clinical significance of ERBB4 in lung cancers is negligible...

..The biological significance of such mutations and their relationship with other activated genes in lung cancers are also discussed...

..However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain...

..Through these collaborations among clinicians, basic researchers and pharmaceutical companies, it should be possible to individualize lung cancer treatment to turn this fatal disease into a chronic disorder and, eventually, to cure it...

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..These populations precisely coincide with those populations with higher response rates to TKIs. We and others subsequently confirmed and extended these findings...

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..0247). Epigenetic silencing of RASSF1A is a frequent event in non-small lung cancer and will provide novel opportunities to develop diagnosis and therapy of NSCLC...

..Lung cancer staging system proposed in 2007 adopts detailed tumor size cut-off values. Alternatively, visceral pleural invasion is deemed an important prognosticator, but has not been easily incorporated into the staging system...

..Although the prognoses of patients with resectable lung cancer involving neighboring structures vary, the current tumor-nodes-metastasis (TNM) classification system does not elucidate criteria for tumor subcategorization...

..These results indicate that rs1052133 contributes to the risk of adenocarcinoma of lung...

..The purpose of this study was to clarify in the role of MET activation in lung carcinogenesis...

..023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis...

..However, recent clinical studies revealed that gefitinib or erlotinib are highly effective in the treatment of non-small cell lung cancer with EGFR mutations...

..To evaluate the relationship between the epidermal growth factor receptor (EGFR) mutation status and the effectiveness of gefitinib monotherapy or chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)...

..We speculate that erlotinib, instead of high dose of gefitinib, may be also effective for the treatment of central nervous system (CNS) lesions, as trough serum concentration of erlotinib is nine times higher than that of gefitinib...

..Definitive diagnosis of these nodules, however, is often difficult. We assessed the feasibility of our diagnostic approach for these nodules and estimated the frequency of primary lung cancer occurrence in patients after mastectomy...

..Further evaluation is warranted...

..We examined for EGFR, KRAS or TP53 mutations in a consecutive large cohort of patients with lung adenocarcinoma, and evaluated their prognostic impact...

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..036) and was consistently observed in the analysis among never-drinkers (interaction P = 0.041). These results suggest that ALDH2 Lys/Lys, a null enzyme activity genotype, modifies the impact of smoking on the risk of lung cancer...

..CONCLUSIONS: A secondary T790M mutation of EGFR accounted for half the tumors with acquired resistance to gefitinib in Japanese patients. Other drug-resistant secondary mutations are uncommon in the EGFR gene...

..We evaluated the efficacy of gefitinib monotherapy prospectively in patients with advanced or pretreated non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations...

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..LKB1 gene mutations appear to be frequent in male, smoking patients of Caucasian origin, in contrast to EGFR or HER2 mutations that are frequent in non-smoking, female patients of Asian origin...

..However, selective mediastinal lymph node dissection based on lobe-specific metastases (selective dissection) has often been performed. This study was designed to evaluate the validity of the selective lymph node dissection...

..However its prognostic and predictive implications are not yet established...

..EGFR mutations define a distinct subset of pulmonary adenocarcinoma without KRAS mutations, which is not caused by tobacco carcinogens...

..In this study, we explored their relationship using in vitro models and autopsy specimens...

..Our results clearly show the existence of gene set-definable, intrinsic heterogeneities in lung adenocarcinomas, which seem to be related to both clinical behavior and sensitivity to agents affecting the identified pathways...

..To understand the characteristics of these aggressive tumors, we reviewed the clinicopathological features of small-sized non-small cell lung cancer patients with mediastinal lymph node metastasis resected in our institution...

..In conclusion, our case-control study clearly demonstrated that the impacts of smoking and sex on the risk of EGFRmut NSCLC are different from those for EGFRwt NSCLC. Further epidemiological evaluation is warranted...

..However, some lung adenocarcinomas may express CDX2 strongly: in this case, CK20 also tends to be positive...

..It is ultimately necessary to identify non-tobacco-related carcinogens that cause EGFR mutations for effective prevention of lung cancer...

..Positive association between EGFR mutation and age among never-smokers regardless of sex might indicate that EGFR mutation occurs cumulatively by unidentified internal/external factors other than smoking...

..To examine the impact of 15p25 and 5p15 on lung cancer risk and smoking intensity, we conducted a case-control study in Japanese population. We also examined whether these loci modify the effect of smoking behavior on lung cancer risk...

..This suggests that MGB1 can serve as a differential molecular marker. In practice, prospective examination, using the nine cases with a history of breast cancer, confirmed the usefulness of MGB1 in differential diagnosis...

..CONCLUSIONS: An evaluation of the KRAS mutation, as well as PIK3CA and PTEN expression, might help identify lung cancer patients who are most suitable for gefitinib treatment...

..Results of clustering analyses imply that class II HDAC genes may be regulated by a similar mechanism and deregulated during cancer development...

..In conclusion, the assay is a rapid, sensitive method using paraffin sections of biopsy specimens without a tumor cell-enrichment procedure and is quite useful to select a treatment of choice in clinical practice...

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..We explored the EML4-ALK gene in a relatively large cohort and reviewed the clinicoradiologic background of the patients...

..The data preliminarily suggest treatment with an epithelial growth factor receptor inhibitor may improve survival after bone metastasis...

..A BD placed using a PA approach with suction might be efficient for drainage...

..Taken together, our results show that mutation occurs early in the development of lung adenocarcinoma, and that amplification may be acquired in association with tumor progression...

..These findings warrant future study to clarify how ZD1839 inhibits lung cancer cell growth and to find a useful marker for prediction of sensitivity to this novel and promising agent for the treatment of lung cancers...

..According to this adenocarcinoma-specific nature of EGFR mutation, analysis of EGFR mutations with small cell lung cancers (SCLC) may provide a clue to its histogenesis...

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..We used immunohistochemistry to examine recently developed antibodies specific to major hotspot mutations of L858R and DEL E746-A750...

..Future studies using independent patient cohorts are warranted to confirm the prognostic significance of EGFR mutations in TRU-type adenocarcinoma...

..Carcinoembryonic antigen (CEA) is a tumor marker widely used for nonsmall cell lung cancer (NSCLC). The aim of this study was to evaluate changes in serum CEA levels as a surrogate marker for tumor response to chemotherapy in NSCLC...

..Among patients with non-small-cell lung cancer (NSCLC), those with poor prognosis cannot be distinguished from those with good prognosis...

..However, in patients without these findings, an extrapleural approach could be initially attempted for chest wall resection, because an en-bloc resection had no survival benefit for patients with shallow invasion...

..The elucidation of the particular features of lung cancer unrelated to smoking and the development of new therapeutic modalities may reduce the mortality from lung cancers in the future...

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..This study supported the first study by Sugimura et al (Cancer Epidemiol Biomarkers Prev, 1999; 8: 669-674), that the association of OGG1 Ser326Cys polymorphism was limited for the risk of lung adenocarcinoma...

..This series of experiments highlights the flexibility of cancer cells that have adapted to environmental stresses induced by intensive treatment with TKIs...

..This study was conducted to screen possible cancer sites associated with this polymorphism by a prevalent case-control design...

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..Clarification of the pathways leading to acquired resistance is essential to maximize the efficacy of EGFR-TKI therapy for patients with lung cancer...

..However, its validity has not been established fully. Here we assessed its utilities and drawbacks...

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..Separate analysis of methylation status in positive and negative portions of individual tumors provided an instance of intratumor diversity associated with promoter DNA methylation...

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..Head and neck surgeons should be aware that a particular subset of lung cancers may develop a metastatic solitary nodule in the thyroid, as presented. An effective therapeutic strategy is largely dependent on the differential diagnosis...

..Based on this concept, Phase III clinical trials comparing gefitinib monotherapy with standard platinum-based chemotherapy are currently ongoing for patients with EGFR mutations and lung cancer...

..In this article, we reviewed the advances and current roles of adjuvant chemotherapy in major histology of solid tumors in Japan such as lung, gastric, colorectal and breast cancers...

..In this study, we evaluated the prognostic significance of the number of positive lymph nodes in resected non-small cell lung cancer...

..In this review, we describe the features of KRAS mutations in lung cancer and contrast these with the features of EGFR mutations. Recent strategies to combat lung cancer harboring KRAS mutations are also reviewed...

..This study represents the first report of reduced expression of let-7 and the potential clinical and biological effects of such a microRNA alteration...

..Based on this concept, phaseIII clinical trials comparing gefitinib monotherapy with standard platinum-based chemotherapy in lung cancer patients with EGFR mutations are ongoing...

..This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer...

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..936) and that with light smoking was 2.67 (95% CI 1.00-7.68, P = 0.049). These results suggest that APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms might modify the risk of lung cancer attributable to cigarette smoking exposure...

..These findings further confirm that TRU-type-adenocarcinoma is a distinct adenocarcinoma subset in which a particular molecular pathway is involved...

..01), less frequent RB loss (p <0.05), and preserved expression of p27 (p <0.01). The results supported the TTF-1 lineage marker and suggested that molecular pathogenesis may in part be characterized by cellular lineage...

..Some studies have shown that epidermal growth factor receptor (EGFR) mutations can be heterogeneously distributed in individual tumors. In this study, we re-evaluated the distribution of EGFR mutations within tumors...

..In the present study the current knowledge of EGFR mutations is reviewed, insights from which raise many further questions, and thus suggest new directions for future research...

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..Gefitinib appears to be effective in treating brain metastases in a subgroup of patients. Our data suggested a possible association between the efficacy of gefitinib in the treatment of brain metastases and EGFR mutations...

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..Second, we deal with EGFR mutations, which shows revealing specificities in various aspects. Finally, advances in the expression profiling analysis of both transcriptomes and proteomes of lung cancers are summarized...

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..In this study, we extensively investigated the impact of sex and smoking on the EGFR mutation...

..52 (0.71-3.28) and 0.31 (0.71-1.34), respectively. Although prevalent cases were used, this study suggested that the influence of DPYD T85C posed only a limited risk for the six malignancies...

..However, our in vitro investigation did not explain the response observed in this particular patient. Further investigation is necessary to elucidate the mechanism of tumor sensitivity to EGFR tyrosine kinase inhibitors...

..To evaluate the safety and efficacy of preoperative chemoradiotherapy followed by surgical resection for superior sulcus tumors (SSTs)...

..The association between TP53/TP73 gene polymorphisms and tobacco smoking was evaluated with regard to risk of non-small cell lung cancer (NSCLC)...

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..These results suggest that the phospholipase D(2) gene is a susceptibility locus for colorectal cancer in Japanese individuals, although a functional effect of the 1814C-->T (Thr577Ile) polymorphism was not detected...

..In addition, the presence of a closely related family of beta-tubulins or pseudogenes was thought to hinder accurate evaluation of the beta-tubulin gene...

..Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well...

..In addition, in silico surveys of dbEST database were used for identification of new CT antigens. We identified a novel gene, TES101RP, expressed only in some small cell lung cancers (SCLC) and in testis, as confirmed by RT-PCR analysis...

..Overall, these findings should advance not only our understanding of the biology of lung cancer but also our ability to individualize postoperative therapies based on the predicted outcome...