Pterin-based small molecule inhibitor capable of binding to the secondary pocket in the active site of ricin-toxin A chain.

The Ricin toxin A chain (RTA), which depurinates an adenine base at a specific region of the ribosome leading to death, has two adjacent specificity pockets in its active site. Based on this structural information, many attempts have been made to develop small-molecule RTA inhibitors that simultaneously block the two pockets. However, no attempt has been successful.

Conformational change in ricin toxin A-Chain: A critical factor for inhibitor binding to the secondary pocket.

Ricin toxin A-chain (RTA), a toxic protein from Ricinus communis, inactivates ribosomes to induce toxicity. The active site of RTA consists of two binding pockets. Many studies have focused on developing RTA inhibitors that can simultaneously bind to these critical pockets; however, almost all the inhibitors developed so far interact with only one pocket.

Prospective observational study of nutritional/immunologic indices as predictive biomarkers for the response to anti-PD-1 drugs in non-small cell lung cancer (ICI-PREDICT study).

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have markedly improved the prognosis of many patients with advanced non-small cell lung cancer (NSCLC). However, the relationship between the patient's nutritional/immunologic status and the outcomes of ICI treatment remains unclear. In previous retrospective studies, we reported that the controlling nutritional status (CONUT) score, skeletal muscle area, and neutrophil-to-lymphocyte ratio were independent predictors of the response of NSCLC patients to anti-PD-1 drugs.

Prognostic impact of the Controlling Nutritional Status score in patients with non-small cell lung cancer treated with pembrolizumab.

Background: Pembrolizumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, has been shown to yield a durable response and significant survival benefit in some non-small cell lung cancer (NSCLC) patients. Recent studies have shown that the Controlling Nutritional Status (CONUT) score, a novel nutritional index, can be useful for predicting the prognosis in some malignancies. However, its usefulness in predicting the clinical outcome of immune-checkpoint inhibitor (ICI) treatment in patients with NSCLC has not been clarified.

Short progression-free survival of ALK inhibitors sensitive to secondary mutations in ALK-positive NSCLC patients.

Background: Most non-small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK-TKI therapies; however, little clinical data exists on the clinical efficacy of ALK-TKI tailored to secondary mutation.

Methods: A retrospective study was conducted to analyze the patterns of ALK-TKI treatment and clinical outcomes, including progression free survival (PFS), of ALK-positive NSCLC patients who received rebiopsy.

Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma.

Background And Purpose: The EGFR, K-ras, EML4-ALK, and BRAF genes are oncogenic drivers of lung adenocarcinoma. We conducted this study to analyze the mutations of these genes in stage I adenocarcinoma.

Methods: The subjects of this retrospective study were 256 patients with resected stage I lung adenocarcinoma.

Preoperative concurrent chemoradiotherapy of S-1/cisplatin for stage III non-small cell lung cancer.

Background: Concurrent chemoradiotherapy using S-1 containing tegafur, an oral 5-FU prodrug, plus cisplatin has been reported to show promising efficacy against locally advanced non-small cell lung cancer with acceptable toxicity. The purpose of this study is to assess the impact of this induction treatment followed by surgery on survival for those patients.

Methods: Potentially resectable locally advanced non-small cell lung cancer patients were eligible.

Increase of bone morphogenetic protein-7 expressing pulmonary resident cells in pneumonectomized rats.

Purpose: Compensatory lung growth (CLG) is recognized in rodents subjected to major pulmonary resection; however, the source of cells constituting regenerated tissues during the CLG is still unknown. We investigated the differentiation of lung resident cells and the participation of bone marrow (BM)-derived cells in the remnant lung of pneumonectomized rats.

Methods: After left pneumonectomy, the right remnant lung of Wistar rats was subjected to morphologic and molecular experiments at several time points.

Mutations of the EGFR and K-ras genes in resected stage I lung adenocarcinoma and their clinical significance.

Purpose: This study retrospectively assessed the mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinical significance in patients with resected stage I adenocarcinomas.

Methods: A total of 354 patients with resected lung adenocarcinomas were included, and 256 patients with stage I disease were analyzed for the prognostic and predictive value of these mutations.

Results: Mutations of EGFR and K-ras genes were detected in 149 (41.

Regression of thymoma associated with a multilocular thymic cyst: report of a case.

A 28-year-old male was diagnosed with acute pericarditis after presenting with acute chest pain, fever and an abnormality in an electrocardiogram. No symptoms suggestive of myasthenia gravis were observed. Although the symptoms were alleviated by antibiotics, computed tomography (CT) showed an anterior mediastinal mass with bilateral pleural effusion.

Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level.

Purpose: Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors.

[Interstitial pneumonitis].

The risk management of interstitial pneumonitis in cancer chemotherapy not only involves an adverse event by an anticancer drug, but there are four steps with the incidence of interstitial pneumonitis: 1 ) the time before chemotherapy treatment, selection of chemotherapy regimens and patients, 2 ) the time chemotherapy treatment is performed, 3 ) the time during following-up, 4 ) the time when interstitial pneumonitis occurs. It is necessary to decrease the risk of interstitial pneumonitis by several steps, cooperating with an entire medical staff.

Signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma: a case report.

We herein report a case of signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma. A 79-year-old female presented with a pulmonary tumor located in the right lower lobe measuring 21 mm in size. A right lower lobectomy was performed.

Expression of an X-family DNA polymerase, pol lambda, in the respiratory epithelium of non-small cell lung cancer patients with habitual smoking.

DNA polymerase lambda, pol lambda, is a eukaryotic member of the X-family DNA polymerases that is involved in two modes of DNA repair, i.e. base excision repair (BER) or non-homologous end joining (NHEJ).

Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients.

Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients.

Upregulation of hypoxia-inducible factor-1alpha mRNA and its clinical significance in non-small cell lung cancer.

Background: Hypoxia-inducible factor 1alpha (HIF-1alpha) is a transcription factor that plays an important role in tumor growth by regulating the energy metabolism and angiogenesis. We herein investigated the mRNA expression level of HIF-1alpha in non-small cell lung cancer (NSCLC) tissues to clarify the impact on the clinical aspects of NSCLC patients.

Experimental Design: HIF-1alpha mRNA derived from either a tumor or an adjacent lung tissue was quantified using quantitative reverse transcription polymerase chain reaction in 66 patients with NSCLC.

Benzo[a]pyrene promotes proliferation of human lung cancer cells by accelerating the epidermal growth factor receptor signaling pathway.

Smoking is an independent prognostic factor of lung adenocarcinoma. Benzo[a]pyrene (B[a]P) is one of the strongest carcinogens and it is present in both the environment and cigarette smoke. In this study, the effect of B[a]P on the proliferative activity of lung adenocarcinoma cells was investigated.

Intratumoral expression of macrophage migration inhibitory factor is correlated with serum C-reactive protein and interleukin-6 in patients with non-small cell lung cancer.

Purpose: To investigate if macrophage migration inhibitory factor (MIF) affects systemic inflammatory response in patients with non-small cell lung cancer (NSCLC), we studied the relationship between intratumoral MIF expression and serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6).

Methods: mRNAs for MIF and beta-actin, and 18S ribosomal RNA derived from tumor-bearing and nontumor-bearing tissues were quantified by a quantitative reverse transcription-polymerase chain reaction in 35 patients with NSCLC. Spearman's test was used to examine the correlation between the quantities of RNAs and the preoperative serum levels of CRP and IL-6 in the corresponding patients.

Schwannoma in the peridiaphragm.

A rare case of benign diaphragmatic schwannoma in a 50-year-old woman is reported. The 8-cm tumor was located in the right diaphragm. This well-circumscribed tumor highly depressed the liver.

Expression of mismatch repair proteins, hMLH1/hMSH2, in non-small cell lung cancer tissues and its clinical significance.

Background: hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system. The purpose of this study is to investigate the expression of hMLH1 and hMSH2 DNA MMR proteins in non-small cell lung cancer (NSCLC) tissue and to elucidate their clinical significance.

Methods: The hMLH1 and hMSH2 protein expression was evaluated by immunohistochemistry for a consecutive series of 113 NSCLC patients.

Never-smoking nonsmall cell lung cancer as a separate entity: clinicopathologic features and survival.

Background: To propose 'never-smoking nonsmall cell lung cancer (NSCLC)' as a separate entity, the clinicopathologic differences of operable NSCLC between never-smoking patients and patients with a history of smoking were investigated.

Methods: The medical records of 1405 patients with primary NSCLC who underwent a complete resection at the study institution from 1974 through 2004 were reviewed for clinicopathologic variables and postoperative survival.

Results: The proportion of never-smoking patients with NSCLC has been significantly increasing over 30 years, from 15.

Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas.

Background: The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas.

Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in lung cancer cells.

Background: It is believed that epithelial-mesenchymal transition (EMT) occurs during the development and progression of cancer; however, the correlation between tobacco smoking and EMT remains to be elucidated.

Methods: Cells from the bronchioloalveolar carcinoma cell line A549 were exposed to benzo(a)pyrene (B[a]P) for 24 weeks, and morphology, proliferative activity, and gene expression profiles were analyzed.

Results: Although no apparent morphologic changes were observed, the B[a]P-exposed A549 cells exhibited enhanced proliferative activity in 1% bovine serum that contained medium, and dramatic changes in expression levels were observed in a large number of genes.