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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(More)
BACKGROUND After initial response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM). To achieve longer survival, control of CNS metastases is important, but therapeutic options are limited for LM after(More)
Blood coagulation capacity increases with age in healthy individuals. Through extensive longitudinal analyses of human factor IX gene expression in transgenic mice, two essential age-regulatory elements, AE5' and AE3', have been identified. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5', a(More)
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(More)
A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)1 approximately 3-(maleic acid 4 approximately 7/anhydride 1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential amino groups (alpha-amino of Ala-1, epsilon-amino of(More)
The aim of this study was to detect the epidermal growth factor receptor (EGFR)-activating mutations and other oncogene alterations in patients with non-small-cell lung cancers (NSCLC) who experienced a treatment failure in response to EGFR-tyrosine kinase inhibitors (TKIs) with a next generation sequencer. Fifteen patients with advanced NSCLC previously(More)
PURPOSE The aim of our study was to investigate the efficacy and safety of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 patients with epidermal growth factor receptor (EGFR) wild-type or unknown advanced non-squamous non-small cell lung cancer (NSCLC). METHODS Pemetrexed was administered at 500(More)
The organ specificity and pharmacokinetics of SMANCS, poly (maleic acid-styrene)-conjugated neocarzinostatin (NCS), were investigated in rats. The drug activity accumulated primarily in the regional lymph nodes after subcutaneous injection. After intravenous injection, the drug was found in the kidney, lymph nodes, and bladder in very high concentrations,(More)
A highly lymphotropic derivative of a proteinaceous antitumor agent, Neocarzinostatin, was prepared by chemical conjugation of a water-soluble synthetic poly(maleic acid)-styrene oligomer. The derivative of 2.5 X 10(4) dalton exhibited a strong antitumor activity against AH109A and DBLA-6 as well as antimetastatic activity against metastatic AH109A with(More)
BACKGROUND Efficacies of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) rechallenge have been demonstrated in EGFR-mutant non-small cell lung cancer (NSCLC). However, their efficacies were only moderate. Some preclinical studies suggested synergistic effects of bevacizumab to EGFR-TKI in TKI-resistant models. METHODS We(More)