Therapies after first-line afatinib in patients with m NSCLC in Japan: retrospective analysis of LUX-Lung 3.

Acquired resistance to EGFR tyrosine kinase inhibitors is inevitable in non-small-cell lung cancer. To inform subsequent treatment decisions, we retrospectively assessed therapies following afatinib in Japanese patients from LUX-Lung 3. LUX-Lung 3 was a randomized, open-label, Phase III study of afatinib versus cisplatin/pemetrexed in treatment-naive patients with mutation-positive (m) advanced lung adenocarcinoma.

Correction to: Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib.

The original article can be found online.

Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib.

Background: This prospective, post-marketing observational study in Japanese patients aimed to evaluate the safety and effectiveness of daily afatinib use in general practice.

Methods: This non-interventional study (NCT02131259) enrolled treatment-naïve and pre-treated patients with inoperable/recurrent EGFR mutation-positive NSCLC, eligible for afatinib treatment as per the afatinib label in Japan. Patients received afatinib at the approved dose (20, 30, 40, or 50 mg/day; physician decision), and were observed following treatment initiation for 52 weeks or until premature discontinuation.

Therapeutic liver reconstitution with murine cells isolated long after death.

Background & Aims: Due to the shortage of donor organs, many patients needing liver transplantation cannot receive one. For some liver diseases, hepatocyte transplantation could be a viable alternative, but donor cells currently are procured from the same sources as whole organs, and thus the supply is severely limited.

Methods: Here, we investigated the possibility of isolating viable hepatocytes for liver cell therapy from the plentiful source of morgue cadavers.

Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice.

Mice that could be highly repopulated with human hepatocytes would have many potential uses in drug development and research applications. The best available model of liver humanization, the uroplasminogen-activator transgenic model, has major practical limitations. To provide a broadly useful hepatic xenorepopulation system, we generated severely immunodeficient, fumarylacetoacetate hydrolase (Fah)-deficient mice.

Thy1-positive mesenchymal cells promote the maturation of CD49f-positive hepatic progenitor cells in the mouse fetal liver.

Previously, we reported a system to enrich mouse fetal hepatic progenitor cells (HPCs) by forming cell aggregates. In this study, we sorted two cell populations, CD49f(+)Thy1(-)CD45(-) cells (CD49f-positive cells) and CD49f(+/-)Thy1(+)CD45(-) cells (Thy1-positive cells), from the cell aggregates using a flow cytometer. CD49f-positive cells stained positive for endodermal specific markers such as alpha-fetoprotein (AFP), albumin (ALB), and cytokeratin 19 (CK19), and are thus thought to be HPCs.

Commitment of bone marrow cells to hepatic stellate cells in mouse.

Background/aims: Recently, several cells found within the liver have been reported to derive from bone marrow (BM). This study sought to examine the commitment of BM cells to hepatic stellate cell (HSC) lineage in mouse liver.

Methods: We transplanted BM cells from green fluorescent protein (GFP) transgenic mice into age-matched C57BL/J mice.

Purification of adult hepatic progenitor cells using green fluorescent protein (GFP)-transgenic mice and fluorescence-activated cell sorting.

Background/aims: Recent advances in stem cell research have revealed that hepatic stem/progenitor cells may play an important role in liver development and regeneration. However, a lack of detectable definitive markers in viable cells has hindered their primary culture from adult livers.

Methods: Enzymatically dissociated liver cells from green fluorescent protein (GFP)-transgenic mice, which express GFP highly in liver endodermal cells, were sorted by GFP expression using a fluorescence-activated cell sorter.

Enrichment of hepatic progenitor cells from adult mouse liver.

Hepatic progenitor cells (HPCs) have been characterized in several drug-treated rodent models and in the fetal liver; however, their properties have not been fully clarified in the normal adult liver, presumably because of their relatively small population and the existence of mature hepatocytes. In an attempt to resolve this issue, we developed a new enrichment system for HPCs using their cell aggregate formation properties. Nonparenchymal cells (NPCs) derived from enzymatically digested liver cells in normal adult mouse liver were treated in a hypoxic 2-hour suspension culture under constant shaking.

Establishment of a highly efficient gene transfer system for mouse fetal hepatic progenitor cells.

Because of a donor shortage problem in liver transplantation, cell transplantation has been anticipated as a useful bridge or substitute therapy, and has necessitated the development of cell sources other than donated organs. Therefore, the use of fetal hepatic progenitor cells (HPCs) is now being focused on. In this study, we intended to establish an efficient ex vivo nonviral gene-transfer system using a newly developed isolation and culture system for mouse fetal HPCs.

Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice.

Background/aims: We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration after partial hepatectomy, using mice transplanted with green fluorescent protein (GFP) positive BM from GFP transgenic mice.

Methods: Partial hepatectomy or sham operation was performed. Lineage marker analysis of GFP positive liver cells was by immunostaining and flow cytometry.