ALK-positive lung adenocarcinoma in a patient with rheumatoid arthritis with long-term treatment for organizing pneumonia: A case report.

Rationale: Rheumatoid arthritis (RA) causes inflammation in various organs including the lungs. Pulmonary manifestations include inflammation of the pleura, vasculature, airway, and parenchyma, including interstitial lung disease (ILD). RA-organizing pneumonia (OP) is the third most common cause of RA-ILD.

Synchronous Primary Lung Adenocarcinoma and Hepatocellular Carcinoma Successfully Treated with a Combination of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel.

Chemotherapy for multiple primary malignancies is challenging. We herein report a case of synchronous primary lung adenocarcinoma and hepatocellular carcinoma (HCC). A 72-year-old man was admitted for the evaluation of an abnormal shadow on his lung.

SHOC2 Is a Critical Modulator of Sensitivity to EGFR-TKIs in Non-Small Cell Lung Cancer Cells.

EGFR mutation-positive patients with non-small cell lung cancer (NSCLC) respond well to treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI); however, treatment with EGFR-TKIs is not curative, owing to the presence of residual cancer cells with intrinsic or acquired resistance to this class of drugs. Additional treatment targets that may enhance the efficacy of EGFR-TKIs remain elusive. Using a CRISPR/Cas9-based screen, we identified the leucine-rich repeat scaffold protein SHOC2 as a key modulator of sensitivity to EGFR-TKI treatment.

Analysis of clinical outcomes in elderly patients with impaired swallowing function.

Japan is the world's leading aging society, and increasing medical expenses for elderly people is an urgent issue. Since aspiration pneumonia in elderly people with impaired swallowing function is a huge problem in Japan, their expected long-term clinical course should be clarified. Accordingly, we collected data from 991 elderly (≥75 years old) patients whose swallowing function was evaluated by Kitasato Institute Hospital's speech therapists (January 1, 2010 to December 31, 2017).

Alternative splicing of APOBEC3D generates functional diversity and its role as a DNA mutator.

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) protein family members have cytidine deaminase activity and can induce cytosine to uracil transition in nucleic acid. The main function of APOBEC3 (A3) proteins is to trigger an innate immune response to viral infections. Recent reports have shown that several APOBEC family proteins such as A3B can induce somatic mutations into genomic DNA and thus promote cancer development.

A phase II trial of induction of erlotinib followed by cytotoxic chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer patients.

Background: No consensus has been reached regarding the treatment order and timing of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and cytotoxic chemotherapy administration for EGFR mutation-positive non-small cell lung cancer (NSCLC) patients.

Methods: In this phase II trial, chemotherapy-naïve patients harboring activating EGFR mutations with stage IIIB/IV or post-surgical recurrent non-squamous NSCLC were enrolled. Patients were treated with erlotinib induction at 150 mg/day for 3 months.

[Pulmonary tuberculosis following anti-tumor necrosis factor-α therapy in Crohn's disease:a case report].

Anti-tumor necrosis factor-α (TNF-α) is a principal treatment for Crohn's disease (CD). However, it increases the susceptibility to tuberculosis (TB) infection, and therefore, screening examination prior to treatment initiation is crucial. Here, we report the case of a patient with CD who developed pulmonary TB following anti-TNF-α therapy, despite negative screening.

Erlotinib as second- or third-line treatment in elderly patients with advanced non-small cell lung cancer: Keio Lung Oncology Group Study 001 (KLOG001).

The aim of this study was to assess the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as second- or third-line treatment for elderly Japanese patients with non-small-cell lung cancer (NSCLC). The patients eligible for this phase II trial were aged ≥70 years, had stage III/IV or recurrent NSCLC, and had previously received 1 or 2 chemotherapy regimens that did not include EGFR-TKIs. The patients received erlotinib at a dose of 150 mg/day.

PIGN prevents protein aggregation in the endoplasmic reticulum independently of its function in the GPI synthesis.

Quality control of proteins in the endoplasmic reticulum (ER) is essential for ensuring the integrity of secretory proteins before their release into the extracellular space. Secretory proteins that fail to pass quality control form aggregates. Here we show the PIGN-1/PIGN is required for quality control in Caenorhabditis elegans and in mammalian cells.

Dynamic Transport and Cementation of Skeletal Elements Build Up the Pole-and-Beam Structured Skeleton of Sponges.

Animal bodies are shaped by skeletons, which are built inside the body by biomineralization of condensed mesenchymal cells in vertebrates [1, 2] and echinoderms [3, 4], or outside the body by apical secretion of extracellular matrices by epidermal cell layers in arthropods [5]. In each case, the skeletons' shapes are a direct reflection of the pattern of skeleton-producing cells [6]. Here we report a newly discovered mode of skeleton formation: assembly of sponges' mineralized skeletal elements (spicules) in locations distant from where they were produced.

A Cell-Based High-Throughput Screening for Inducers of Myeloid Differentiation.

Recent progress of genetic studies has dramatically unveiled pathogenesis of acute myeloid leukemia (AML). However, overall survival of AML still remains unsatisfactory, and development of novel therapeutics is required. CCAAT/enhancer binding protein α (C/EBPα) is one of the crucial transcription factors that induce granulocytic differentiation, and its activity is perturbed in human myeloid leukemias.

CCAAT/enhancer binding protein β is dispensable for development of lung adenocarcinoma.

Lung cancer is the leading cause of cancer death worldwide. Although disruption of normal proliferation and differentiation is a vital component of tumorigenesis, the mechanisms of this process in lung cancer are still unclear. A transcription factor, C/EBPβ is a critical regulator of proliferation and/or differentiation in multiple tissues.

A phase II study of biweekly paclitaxel and carboplatin in elderly patients with advanced non-small cell lung cancer.

Purpose: The number of elderly patients with advanced non-small cell lung cancer (NSCLC) is increasing. Although several studies have suggested the benefit of chemotherapy with a platinum doublet for elderly patients with advanced NSCLC, this treatment is still controversial in this age group. To evaluate the efficacy and tolerability of combination chemotherapy with biweekly paclitaxel and carboplatin for elderly patients with advanced NSCLC, we conducted a multicenter, non-randomized, open label, phase II trial.

FOXD1 expression is associated with poor prognosis in non-small cell lung cancer.

Aim: Clinical microarray datasets were analyzed to search for new therapeutic targets and prognostic markers of non-small cell lung cancer (NSCLC).

Materials And Methods: Microarray datasets from 90 lung cancer specimens, were analyzed with focus on the FOXD1 gene. Levels of FOXD1 mRNA were assessed in lung cancer cell lines and these levels were correlated with survival.

Methylation-induced downregulation of TFPI-2 causes TMPRSS4 overexpression and contributes to oncogenesis in a subset of non-small-cell lung carcinoma.

We identified transmembrane protease, serine 4 (TMPRSS4) as a putative, druggable target by screening surgically resected samples from 90 Japanese non-small-cell lung cancer (NSCLC) patients using cDNA microarray. TMPRSS4 has two druggable domains and was upregulated in 94.5% of the lung cancer specimens.

β-catenin contributes to lung tumor development induced by EGFR mutations.

The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of EGFR-mutated lung cancers.

Claudin-1 is a novel target of miR-375 in non-small-cell lung cancer.

Objectives: We previously reported low expression of miR-375 in squamous-cell carcinoma (SCC) and high expression in adenocarcinoma (AC) of the lung. miR-375's target genes and its function in non-small-cell lung cancer (NSCLC) have not been elucidated. Therefore, the present study was designed to identify the targets of miR-375 and to characterize its function in NSCLC.

The efficacy, safety, and pharmacokinetics of biapenem administered thrice daily for the treatment of pneumonia in the elderly.

Biapenem has been widely used to treat bacterial pneumonia; however, there is little information concerning its efficacy and safety in elderly patients. Based on pharmacokinetic-pharmacodynamic theory, administration of biapenem thrice rather than twice daily would be expected to be more effective because of longer time above the minimum inhibitory concentration. In this study, we aimed to evaluate the efficacy, safety, and pharmacokinetics of biapenem (300 mg) administered thrice daily in pneumonic patients aged 65 years or older.