Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01.

Background: We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC).

Patients And Methods: Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m on day 1 and irinotecan 50mg/m on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m on day 1 and irinotecan 60mg/m on days 1, 8 and 15 of a 28-day cycle).

Modeling of lung phenotype of Hermansky-Pudlak syndrome type I using patient-specific iPSCs.

Background: Somatic cells differentiated from patient-specific human induced pluripotent stem cells (iPSCs) could be a useful tool in human cell-based disease research. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive genetic disorder characterized by oculocutaneous albinism and a platelet dysfunction. HPS patients often suffer from lethal HPS associated interstitial pneumonia (HPSIP).

Successful treatment of COVID-19-related acute respiratory distress syndrome with a rare blood type: A case report.

Extracorporeal membrane oxygenation is indispensable for critically severe COVID-19 patients. However, it would be inapplicable to patients with a rare blood type or blood transfusion refusal. In that case, severely conservative fluid management with the sacrifice of renal functions and hydrocortisone therapy should be considered for better oxygenation.

Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo.

Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported.

Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology.

Mucociliary clearance is an essential lung function that facilitates the removal of inhaled pathogens and foreign matter unidirectionally from the airway tract and is innately achieved by coordinated ciliary beating of multiciliated cells. Should ciliary function become disturbed, mucus can accumulate in the airway causing subsequent obstruction and potentially recurrent pneumonia. However, it has been difficult to recapitulate unidirectional mucociliary flow using human-derived induced pluripotent stem cells (iPSCs) in vitro and the mechanism governing the flow has not yet been elucidated, hampering the proper humanized airway disease modeling.

A method of generating alveolar organoids using human pluripotent stem cells.

The lung consists of branched structures that are anatomically, developmentally and functionally divided into airway and alveolar regions. Each region contributes to lung-specific functions involving a defense system and gas exchange, and their dysfunction can cause fatal lung diseases. In the alveolar region, the cuboidal alveolar type 2 (AT2) cells account for 90% of the alveolar epithelial cells and serve as the tissue stem cells secreting pulmonary surfactant, and flattened alveolar type I (AT1) cells cover most of the alveolar surface directly contributing to gas exchange adjacent to capillary vessels.

Complete occlusion of right pulmonary artery in Behçet disease.

When a patient with Behçet disease presents with haemoptysis, pulmonary vascular involvement should be considered.

In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids.

It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells.

Long-term expansion of alveolar stem cells derived from human iPS cells in organoids.

The stable expansion of tissue-specific stem cells in vitro has contributed to research on several organs. Alveolar epithelial type II (AT2) cells function as tissue stem cells in the lung, but robust models for studying human AT2 cells are lacking. Here we report a method for the efficient generation and long-term expansion of alveolar organoids (AOs) harboring SFTPC alveolar stem cells derived from human induced pluripotent stem cells (hiPSCs).

Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells.

Multi-ciliated airway cells (MCACs) play a role in mucociliary clearance of the lung. However, the efficient induction of functional MCACs from human pluripotent stem cells has not yet been reported. Using carboxypeptidase M (CPM) as a surface marker of NKX2-1(+)-ventralized anterior foregut endoderm cells (VAFECs), we report a three-dimensional differentiation protocol for generating proximal airway epithelial progenitor cell spheroids from CPM(+) VAFECs.

Retrospective efficacy and safety analyses of erlotinib, pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer.

Objective: Several guidelines recommend erlotinib, pemetrexed, or docetaxel for second-line chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The aim of this study was to retrospectively evaluate the efficacy of erlotinib, pemetrexed, and docetaxel in epidermal growth factor receptor (EGFR) mutation-negative patients with previously treated advanced non-squamous NSCLC.

Materials And Methods: We analyzed the efficacy of these agents in patients with previously treated advanced non-squamous NSCLC who had EGFR wild-type tumors, performance status (PS) of 0, 1, or 2 and received erlotinib, pemetrexed, or docetaxel between December 2007 and September 2011.

Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells.

No methods for isolating induced alveolar epithelial progenitor cells (AEPCs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs), we identified carboxypeptidase M (CPM) as a surface marker of NKX2-1(+) "ventralized" anterior foregut endoderm cells (VAFECs) in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM(+) cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs.

A phase II study of pemetrexed in chemotherapy-naive elderly patients aged ≥ 75 years with advanced non-squamous non-small-cell lung cancer (HANSHIN Oncology Group 003).

Objective: Pemetrexed has relatively mild toxicity and possibly can be administered long term to patients with non-small-cell lung cancer. We conducted a Phase II trial to evaluate the efficacy and safety of pemetrexed in chemotherapy-naïve elderly patients with advanced non-squamous non-small-cell lung cancer.

Methods: In this multicenter Phase II trial, we recruited elderly patients with non-squamous non-small-cell lung cancer.

[A case of lung disease and spondylitis due to Mycobacterium intracellulare in a immunocompetent patient].

A 73-year-old immunocompetent woman was diagnosed with pulmonary nontuberculous mycobacterial (NTM) infection and followed up without treatment. She developed lumbago and consulted a physician. Spinal magnetic resonance imaging (MRI) indicated pyogenic spondylitis and she was admitted to the orthopedics department at our hospital 4 months after developing lumbago.

The clinical characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis.

We herein report the clinical and laboratory characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis (PM/DM). We compared these characteristics with previously published findings. Previous reports and our present cases show that anti-OJ autoantibody-positive interstitial lung disease (ILD) patients with PM/DM lack the manifestations of Raynaud's phenomenon and sclerodactyly and show good prognoses and responses to glucocorticoid therapy.

How sensitive are epidermal growth factor receptor-tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring EGFR gene-sensitive mutations?

Introduction: Epidermal growth factor receptor (EGFR) mutations are found mostly in adenocarcinoma, and rarely in squamous cell carcinoma (SQC). Little is known about SQC harboring EGFR mutations.

Methods: Between April 2006 and October 2010, we investigated the incidence of EGFR activating mutations in SQC of the lung using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method.

Successful treatment of non-small cell lung cancer with gefitinib after severe erlotinib-related hepatotoxicity.

Gefitinib and erlotinib are first-generation small molecular inhibitors of EGFR tyrosine kinase activity. To the best of our knowledge, to date, two reports have stated that patients with NSCLC who develop severe hepatotoxicity secondary to gefitinib treatment can be safely switched to erlotinib. However, the reverse situation has not been reported.

Chemical pneumonitis and acute lung injury caused by inhalation of nickel fumes.

A 50-year-old man with a 30-year occupational history of welding presented with low-grade fever, fatigue and persistent dry cough. Computed tomography (CT) of the chest revealed interlobular septal thickening and bilateral non-segmental patchy ground-glass opacities except in the sub-pleural zone. He revealed that he had inhaled nickel fumes 3 days previously at work.