Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT + serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPSderived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that preevaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.neural stem/progenitor cell | cell transplantation | regenerative medicine | remyelination | axonal regrowth

Molecular targeted therapies have significantly improved the treatment outcome of patients with non-small cell lung cancer (NSCLC) harboring driver gene mutations such as receptor (EGFR) or anaplastic lymphoma kinase (ALK). However, the brain is a frequent site of recurrence, and it significantly deteriorates the prognosis of these patients. Treatment strategies include surgical resection, whole-brain radiation therapy, stereotactic radiotherapy, and drug therapy depending on patient condition. First-generation EGFR/ ALK tyrosine kinase inhibitors (TKI) demonstrates only limited efficacy for intracranial lesions probably because of low penetration through the blood-brain barrier (BBB). However, newly developed TKIs with improved penetration such as osimertinib for EGFR and alectinib, ceritinib, brigatinib, or lorlatinib for ALK have demonstrated significant intracranial activity that should contribute to improved overall survival.Whole-brain radiation therapy used to be a standard of care that confers alleviation of symptom and modest survival benefit. However, it potentially causes neurological and cognitive deficits as a chronic toxicity. With the prolonged survival owing to newer generation drugs, this toxicity is becoming more relevant. Stereotactic radiotherapy is considered when there are three or fewer lesions, and the lesions are <3 cm as local control of tumor is excellent, and neurotoxicity is less. In this review, we discuss the various aspects of brain metastases occurring in NSCLC patients with driver gene mutations. We also propose a treatment algorithm for these patients.

No abstract

No abstract

Background Atezolizumab is a programmed death‐ligand 1 (PD‐L1) targeted monoclonal antibody that inhibits PD‐L1 interacting with its receptors PD‐1 and B7‐1, thereby enhancing anticancer immunity. Some real‐world efficacy and safety studies of anti‐PD‐1 antibody have been previously reported. However, there have been no reports investigating the efficacy of atezolizumab monotherapy in clinical practice which have focused on performance status and previous anti‐PD‐1 antibody treatment. Methods We retrospectively reviewed consecutive advanced NSCLC patients who received atezolizumab monotherapy between April 2018 and February 2019 at eight institutions. A total of 152 patients with NSCLC were enrolled in this study. Results A total of 38 patients (25%) had already been treated with anti‐PD‐1 treatment (nivolumab or pembrolizumab) before atezolizumab. The median OS and TTF was 384 days (12.8 months) (95% confidence interval [CI]: 206–424), and 42 days (1.4 months) (95% CI: 27–56) in all patients, respectively. ECOG PS 0 had significantly longer OS (median OS; not reached, p < 0.0001) and TTF (median TTF; 63 days, p = 0.012) compared with PS 1 or 2–3. Most retreated patients were unable to continue atezolizumab for a longer period, but seven patients (18.4%) were able to continue atezolizumab over four months as an ICI retreatment. Conclusions In previously treated advanced NSCLC patients, atezolizumab monotherapy demonstrated good efficacy and safety regardless of heavily treated patients in real‐world clinical practice, and ECOG PS 0 was a favorable predictive factor. The efficacy of retreatment with atezolizumab was limited but was well tolerated in patients treated with prior anti‐PD‐1 antibody.