Yasushi Yatabe

..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...

..More recently, similar marked responses to an ALK inhibitor in patients with ALK fusion lung cancers were demonstrated. In this article, we review such recent advances in lung cancer, focusing on EGFR mutation and ALK fusion....

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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...

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

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

..In this review, we hypothesize a novel scenario for the progression of lung adenocarcinoma, which does not support a linear progression schema...

..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 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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..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...

..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...

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

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

..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...

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

..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...

..The aim of this study was to test whether similar associations would be seen between mRNA expression for the RRM1, ERCC1 and ERCC2 genes and in vitro chemosensitivity in lung cancer...

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

..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...

..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...

..Future studies of transcriptional targets of YAP1 in MPMs may shed light on the molecular mechanisms of MPM development and lead to new therapeutic strategies...

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..The purpose of this analysis was to evaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advanced gastric cancer (AGC) treated with second-line chemotherapy...

..This study aimed to evaluate the efficacy of docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer...

..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 assessed the impact of genetic polymorphisms in the base excision repair (BER) pathway on PC risk among Japanese...

..Interaction between folate consumption, drinking, and ALDH2 genotype was remarkable (three-way interaction, P<0.001). We observed significant interaction among folate, drinking, and ALDH2 genotype in the Japanese population...

..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...

..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...

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..The usefulness of these markers was confirmed using 13 additional pancreatic tumors, prospectively. Although minimal in selection, these markers are helpful in making diagnosis from EUS-FNA specimens of the major pancreatic tumors...

..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...

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..In conclusion, cycleave PCR is practically applicable to KRAS/BRAF genotyping using small amounts of biopsied tumor cells. Care must be taken in the selection of pathological specimens for KRAS/BRAF testing...

..Our results elucidate an ASH1 effector axis in NE-lung cancers that is functionally pivotal in controlling NE features and the alleviation from YAP1-mediated growth inhibition...

..Further evaluation is warranted...

..Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism...

..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...

..We conducted a case-control study to examine the relationship between human leukocyte antigen-A (HLA-A) allele polymorphism and the pathogenesis of cervical neoplasia among Japanese women...

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..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...

..Risk models which include a genetic risk score are possibly useful in distinguishing women at high risk of breast cancer from those at low risk, particularly in the context of targeted prevention...

..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...

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

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..EUS-guided FNA (EUS-FNA) is considered optimal for differentially diagnosing pancreatic masses. However, the sensitivity of EUS-FNA ranges from 65% to 95%, respectively, which requires improvement...

..Although the association with the identified loci was strong, information on its impact in combination with lifestyle factors is limited...

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..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...

..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...

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

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

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

..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...

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

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..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...

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

..Further study would be required to elucidate the precise molecular mechanism for the role of AQP1 in pancreatic fluid secretion from the pancreas in diseases characterized by the impaired ductal fluid secretion such as cystic fibrosis...

..The primary endpoint is response rate. The secondary endpoints include adverse events, progression-free survival and overall survival. The pharmacokinetics of cetuximab will also be evaluated in five patients...

..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...

..This review highlights the diagnostic potential of EUS-FNA, as well as its current indications and contraindications, complications, and techniques...

..In this case, trastuzumab plus lapatinib resulted in durable stable disease, despite the appearance of progression during prior chemotherapy with trastuzumab...

..Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk...

..Together, our findings suggest that reduced expression of POLD4 plays a role in genomic instability in lung cancer...

..We analyzed a consecutive series of gastric MALT lymphomas at our institution regarding treatment, clinical course, and prognosis, with special reference to responsiveness to H. pylori eradication and presence of API2-MALT1...

..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...

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

..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...

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

..Serum biomarkers for the early detection of pancreatic cancer are not currently available. We evaluated the usefulness of a novel serum marker, REG4, in the diagnosis of pancreatic cancer, as compared to carbohydrate antigen (CA) 19-9...

..Secondly, as primary lung adenocarcinomas may express estrogen receptors, MGB1 expression provides further discrimination of the origin of breast cancers...

..PTTG1 is overexpressed in HCC and our results suggest that PTTG1 mRNA expression has prognostic significance for the survival of postoperative patients with HCC...

..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...

..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...

..6%, respectively. All indexes of intraoperative frozen section analysis were superior to imprint cytology. In our experience, multislice frozen section analysis surpasses imprint cytology in intraoperative diagnosis of SLN biopsy...

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..Individual subtypes were clustered among the three dimensions of the components. This implies that salivary gland tumors may be well characterized by using only three components...

..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...

..Taken together, these findings suggest that an increase in COX-2 expression maybe associated with the development of lung cancer and possibly with the acquisition of an invasive and metastatic phenotype...

..Further investigations are needed to clarify the pathogenesis of this disease and to determine the optimal treatment strategy...

..Although the detailed function of CD109 protein is unclear, these results suggest that CD109 expression may play a role in the development of lung squamous cell carcinoma...

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

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

..It remains undetermined whether the nodal papilloma was derived from the papilloma of the mastectomy or if it arose de novo from the breast tissue inclusion of the sentinel node...

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..In these molecular targeted therapies, diagnostic tools to verify the presence of an appropriate molecular target is crucial to the success, and thus the methods and its interpretation are discussed in this review...

..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...

..Combination therapy with cetuximab and IL-2 would thus offer a new potential therapeutic approach for a subset of EGFR-overexpressing gastric cancers...

..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...

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

..The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasonography (EUS)-guided trucut biopsy (TCB) for diagnosis of autoimmune pancreatitis (AIP)...

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..The present study therefore suggests that ASH1 plays a crucial role in lung cancer development and may be an effective therapeutic target in lung cancers with neuroendocrine features...