Possible differential EGFR-TKI efficacy among exon 19 deletional locations in EGFR-mutant non-small cell lung cancer.

Background: Exon 19 deletion mutations (Del-19s) and the exon 21 L858R point mutation are the most common epidermal growth factor receptor (EGFR) mutations. In Del-19, several subtypes actually exist, consisting of the deletional location with or without amino acid insertion/substitution. Little evidence has been described whether the Del-19 subtype affects EGFR-tyrosine kinase inhibitor (TKI) efficacy.

The safety and efficacy of paclitaxel and carboplatin with or without bevacizumab for treating patients with advanced nonsquamous non-small cell lung cancer with interstitial lung disease.

Purpose: Optimal chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) with interstitial lung disease (ILD) is established for paclitaxel and carboplatin, but is otherwise controversial. Therefore, we assessed the efficacy and safety of paclitaxel and carboplatin with or without bevacizumab for treating these patients.

Methods: We analyzed the outcomes of 21 patients with advanced nonsquamous NSCLC with ILD who received paclitaxel and carboplatin without (paclitaxel-carboplatin group; n = 11) or with bevacizumab (paclitaxel-carboplatin-bevacizumab group; n = 10) between April 2008 and October 2013.

The apoptotic initiator caspase-8: its functional ubiquity and genetic diversity during animal evolution.

The caspases, a family of cysteine proteases, play multiple roles in apoptosis, inflammation, and cellular differentiation. Caspase-8 (Casp8), which was first identified in humans, functions as an initiator caspase in the apoptotic signaling mediated by cell-surface death receptors. To understand the evolution of function in the Casp8 protein family, casp8 orthologs were identified from a comprehensive range of vertebrates and invertebrates, including sponges and cnidarians, and characterized at both the gene and protein levels.

ScreenCap3: Improving prediction of caspase-3 cleavage sites using experimentally verified noncleavage sites.

Because of its wide range of substrates, caspase-3, a main executioner among apoptosis-related caspases, is thought to have many unknown substrates that have remained unidentified. This report describes our predictive method to facilitate the discovery of novel caspase-3 substrates. To develop a more reliable prediction method, we specifically examined improvement of the data quantity and quality of caspase-3 cleavage sites.

Fulminant hepatitis following crizotinib administration for ALK-positive non-small-cell lung carcinoma.

We herein report a case of fatal fulminant hepatitis secondary to crizotinib administration. The patient was 54-year-old female with a history of Hepatitis C infection (not current), dermatomyositis and steroid-induced diabetes mellitus. She was diagnosed with advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement.

Ligand heterogeneity of the cysteine protease binding protein family in the parasitic protist Entamoeba histolytica.

Lysosomal soluble proteins are targeted to endosomes and lysosomes by specific receptors resident in the endoplasmic reticulum and/or the Golgi apparatus. The enteric protozoan parasite Entamoeba histolytica has a novel class of lysosomal targeting receptors, named the cysteine protease binding protein family (CPBF). Among 11 CPBFs (CPBF1-11), ligands for three members, CPBF1, CPBF6 and CPBF8, were previously shown to be cysteine proteases, α- and γ- amylases, and β-hexosaminidase and lysozymes, respectively.

Community-acquired pneumonia caused by carbapenem-resistant Streptococcus pneumoniae: re-examining its prevention and treatment.

A 73-year-old man with no significant past medical history or any history of health care visits was hospitalized for pneumonia. Sputum culture revealed multidrug-resistant Streptococcus pneumoniae, even to carbapenems. The patient was later treated successfully with levofloxacin.

Prognostic value of bronchoalveolar lavage in patients with non-HIV pneumocystis pneumonia.

Objective: Non-HIV patients with pneumocystis pneumonia (PCP) have a poor prognosis. We aimed to evaluate the prognostic factors for in-hospital mortality in terms of the clinical findings, including the results of bronchoalveolar lavage fluid (BALF)-analyses, in non-HIV PCP patients.

Methods: We retrospectively reviewed non-HIV PCP patients diagnosed using bronchoalveolar lavage between April 2006 and July 2012.

Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study.

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.

Weekly administration of paclitaxel and carboplatin with concurrent thoracic radiation in previously untreated elderly patients with locally advanced non-small-cell lung cancer: A case series of 20 patients.

Elderly patients with stage III non-small-cell lung cancer (NSCLC) are frequently underrepresented in clinical trials that evaluate chemoradiotherapy, due to their poor functional status, coexisting illnesses and limited life expectancy. The Japan Clinical Oncology Group 0301 trial (JCOG0301) was the first study to demonstrate that thoracic radiation therapy (TRT) with daily low-dose carboplatin may improve the outcome of elderly patients with stage III NSCLC. However, the efficacy and safety profiles of chemoradiotherapy, including platinum doublets, have not been clearly determined in this patient population.

Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis.

Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma.

GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids.

Background: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation.

Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan.

Background: Secondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown.

Comparison of two transport systems available in Japan (TERUMO kenkiporter II and BBL Port-A-Cul) for maintenance of aerobic and anaerobic bacteria.

The kenkiporter II (KP II) transport system is commonly used in many hospitals in Japan for transporting bacterial specimens to microbiology laboratories. Recently, the BBL Port-A-Cul (PAC) fluid vial became available. However, no reports thus far have compared the effectiveness of these two transport systems.

Bevacizumab plus weekly paclitaxel with or without carboplatin for previously-treated non-squamous non-small cell lung cancer.

Aim: The aim of this retrospective study was to evaluate bevacizumab combined with weekly paclitaxel with and without carboplatin in pre-treated patients with non-squamous non-small cell lung cancer (NSCLC).

Patients And Methods: Between November 2009 and October 2011, 43 pre-treated patients with non-squamous NSCLC received bevacizumab (15 mg/kg, day 1) plus weekly paclitaxel (60-80 mg/m(2), days 1, 8, 15) with carboplatin (area under the curve=4-5, day 1) (n=36), or bevacizumab plus weekly paclitaxel (n=7) alone every four weeks.

Results: The response rate and disease control rates were 48.

Detection of herpes viruses by multiplex and real-time polymerase chain reaction in bronchoalveolar lavage fluid of patients with acute lung injury or acute respiratory distress syndrome.

Background: Human herpes viruses (HHVs) are important pathogens in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Rapid and efficient diagnostic tools are needed to detect HHVs in the lung in ALI/ARDS patients.

Objectives: This study aimed to evaluate the usefulness of multiplex and real-time polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid (BALF) for detecting HHV reactivation in ALI/ARDS patients.

A Japanese case of vertebral sarcoidosis.

We herein report the first Japanese case of vertebral sarcoidosis diagnosed using multiple imaging modalities and a biopsy. CT, MRI and (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) detected multiple vertebral lesions, and a vertebral biopsy guided by the PET findings confirmed the diagnosis of vertebral sarcoidosis. Although the disease was refractory to corticosteroids, treatment with methotrexate (MTX) achieved a good response.

Revisiting amino acid substitution matrices for identifying distantly related proteins.

Motivation: Although many amino acid substitution matrices have been developed, it has not been well understood which is the best for similarity searches, especially for remote homology detection. Therefore, we collected information related to existing matrices, condensed it and derived a novel matrix that can detect more remote homology than ever.

Results: Using principal component analysis with existing matrices and benchmarks, we developed a novel matrix, which we designate as MIQS.

A phase II study of pemetrexed in patients with previously heavily treated non-squamous non-small cell lung cancer (HANSHIN Oncology Group 001).

Purpose: Pemetrexed has shown substantial activity in non-squamous non-small cell lung cancer (NSCLC) and is one of the current standard agents in second-line settings due to its efficacy and favorable tolerability profile. We conducted phase II study to evaluate the safety and efficacy of pemetrexed in Japanese patients with previously heavily treated, advanced non-squamous NSCLC.

Methods: Patients with stage IIIB or IV non-squamous NSCLC, performance status (PS) 0-2, previous two to five regimens of chemotherapy were enrolled and received pemetrexed (500 mg/m(2)) on day 1 every 21 days until disease progression.

Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between T790M mutation-positive and mutation-negative populations.

Background: The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the emergence of T790M predicts a favorable prognosis and indolent progression. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M mutation.

Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids.

Background: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown.

Objective: We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment.

Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria.

CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM.

Cytokeratin 19 fragment predicts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancer harboring EGFR mutation.

Background: EGFR gene mutation is independently associated with a favorable response in non-small-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs), regardless of sex or smoking history. Squamous cell carcinoma patients harboring EGFR mutations show a significantly worse response to EGFR-TKIs compared with adenocarcinoma patients. We hypothesized that the serum cytokeratin 19 fragment (CYFRA 21-1) is associated with the efficacy of EGFR-TKIs in EGFR-mutated NSCLC patients.