Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study.

Objective: This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice.

Methods: Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240 mg every 2 weeks or 480 mg every 4 weeks.

Periodic cytokinin responses in rhizobium infection and nodule development.

Host plants benefit from legume root nodule symbiosis with nitrogen-fixing bacteria under nitrogen-limiting conditions. In this interaction, the hosts must regulate nodule numbers and distribution patterns to control the degree of symbiosis and maintain root growth functions. The host response to symbiotic bacteria occurs discontinuously but repeatedly at the region behind the tip of the growing roots.

OsSYMRK Plays an Essential Role in AM Symbiosis in Rice (Oryza sativa).

Arbuscular mycorrhizal (AM) fungi establish mutualistic symbiosis with a wide range of terrestrial plants, including rice. However, the mechanisms underlying the initiation of AM symbiosis are yet to be elucidated, particularly in nonleguminous plants. We previously demonstrated that chitin elicitor receptor kinase 1 (OsCERK1), a lysin motif receptor-like kinase essential for chitin-triggered immunity, also plays a key role in AM symbiosis in rice.

Safety and effectiveness of nivolumab in Japanese patients with malignant melanoma: Final analysis of a post-marketing surveillance.

Nivolumab, a monoclonal antibody against human programmed death 1, was approved for the treatment of melanoma in July 2014 in Japan. Because the Japanese phase II studies (ONO-4538-02, ONO-4538-08) enrolled small numbers of melanoma patients, post-marketing surveillance (PMS; JapicCTI-163 272) was conducted to collect safety data in a larger patient population. We report data for melanoma patients who received nivolumab between July 4, 2014 and February 28, 2017.

The in the Promoter Is Important but Not Essential for Infection Thread Formation During Rhizobia Symbiosis.

The establishment of the legume-rhizobia symbiosis, termed the root-nodule symbiosis (RNS), requires elaborate interactions at the molecular level. The host plant-derived transcription factor NODULE INCEPTION (NIN) is known to be crucial for RNS, regulating associated processes such as alteration of root hair morphology, infection thread formation, and cell division during nodulation. This emphasizes the importance of the precise spatiotemporal regulation of expression for the establishment of RNS; however, the detailed role of promoter sequences in this process remains unclear.

Real-world safety and effectiveness of nivolumab in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction cancer that has progressed after chemotherapy: a postmarketing surveillance study.

Background: This postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer.

Methods: This multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab.

Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: Postmarketing surveillance.

Postmarketing surveillance of Japanese patients with unresectable, previously treated, advanced or recurrent non-small-cell lung cancer treated with nivolumab was undertaken during the conditional approval period. The study aim was to evaluate the occurrence of treatment-related adverse events of nivolumab in the real world. Patients were registered between December 2015 and March 2016 at 536 sites.

The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit.

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors.

Real-world safety and effectiveness of nivolumab for recurrent or metastatic head and neck cancer in Japan: a post-marketing surveillance.

Background: On the basis of phase III CheckMate 141 results, nivolumab was approved for recurrent or metastatic head and neck cancer after undergoing platinum-containing chemotherapy in Japan. This post-marketing surveillance aimed to evaluate the safety and effectiveness of nivolumab for head and neck cancer in the real-world setting.

Methods: All patients with head and neck cancer who planned to receive nivolumab were centrally registered.

Endogenous gibberellins affect root nodule symbiosis via transcriptional regulation of NODULE INCEPTION in Lotus japonicus.

Legumes and nitrogen-fixing rhizobial bacteria establish root nodule symbiosis, which is orchestrated by several plant hormones. Exogenous addition of biologically active gibberellic acid (GA) is known to inhibit root nodule symbiosis. However, the precise role of GA has not been elucidated because of the trace amounts of these hormones in plants and the multiple functions of GAs.

Development of an artificial antibody specific for HLA/peptide complex derived from cancer stem-like cell/cancer-initiating cell antigen DNAJB8.

Background: Peptide-vaccination therapy targeting tumour-associated antigens can elicit immune responses, but cannot be used to eliminate large tumour burden. In this study, we developed a therapeutic single-chain variable-fragment (scFv) antibody that recognises the cancer stem-like cell/cancer-initiating cell (CSC/CIC) antigen, DNAJB8.

Methods: We screened scFv clones reacting with HLA-A24:20/DNAJB8-derived peptide (DNAJB8_143) complex using naive scFv phage-display libraries.

Osteosarcoma-initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B.

Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non-responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma-initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC-related genes, and tried to regulate the proliferation of OS by metabolic interference.

In vivo monitoring of plant small GTPase activation using a Förster resonance energy transfer biosensor.

Background: Small GTPases act as molecular switches that regulate various plant responses such as disease resistance, pollen tube growth, root hair development, cell wall patterning and hormone responses. Thus, to monitor their activation status within plant cells is believed to be the key step in understanding their roles.

Results: We have established a plant version of a Förster resonance energy transfer (FRET) probe called Ras and interacting protein chimeric unit (Raichu) that can successfully monitor activation of the rice small GTPase OsRac1 during various defence responses in cells.

Isolation of equine herpesvirus 3 (EHV-3) from equine coital exanthema of two stallions and sero-epidemiology of EHV-3 infection in Japan.

In the spring of 2015, two stallions reared in Farms A and B in Hokkaido in Japan showed symptoms of equine coital exanthema. Equine herpesvirus 3 (EHV-3) was isolated from penis swab samples of both stallions, and the isolates from each stallion in Farms A and B were designated as SS-1 and YS-1 strains, respectively. BamHI restriction profiles of SS-1 and Japanese reference strain Iwate-1 were indistinguishable, but the BamHI-A fragment of YS-1 was larger than those of SS-1 and Iwate-1 by 1.

Crosstalk of Signaling Mechanisms Involved in Host Defense and Symbiosis Against Microorganisms in Rice.

Rice is one of the most important food crops, feeding about half population in the world. Rice pathogens cause enormous damage to rice production worldwide. In plant immunity research, considerable progress has recently been made in our understanding of the molecular mechanisms underlying microbe-associated molecular pattern (MAMP)-triggered immunity.

New insights into the dimerization of small GTPase Rac/ROP guanine nucleotide exchange factors in rice.

Molecular links between receptor-kinases and Rac/ROP family small GTPases mediated by activator guanine nucleotide exchange factors (GEFs) govern diverse biological processes. However, it is unclear how the Rac/ROP GTPases orchestrate such a wide variety of activities. Here, we show that rice OsRacGEF1 forms homodimers, and heterodimers with OsRacGEF2, at the plasma membrane (PM) and the endoplasmic reticulum (ER).

An OsCEBiP/OsCERK1-OsRacGEF1-OsRac1 module is an essential early component of chitin-induced rice immunity.

OsCEBiP, a chitin-binding protein, and OsCERK1, a receptor-like kinase, are plasma membrane (PM) proteins that form a receptor complex essential for fungal chitin-driven immune responses in rice. The signaling events immediately following chitin perception are unclear. Investigating the spatiotemporal regulation of the rice small GTPase OsRac1, we find that chitin induces rapid activation of OsRac1 at the PM.

LGR4 is required for the cell survival of the peripheral mesenchyme at the embryonic stages of nephrogenesis.

In mice, homozygous Lgr4 inactivation results in hypoplastic kidneys. To understand better the role of LGR4 in kidney development, we performed an analysis of kidneys in Lgr4-/- embryos. We stained Lgr4-/- kidneys with anti-WT1 and anti-Cleaved Caspase3 antibodies at E16.

Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats.

Background: Chlorine dioxide (CD) gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.

SWAP70 functions as a Rac/Rop guanine nucleotide-exchange factor in rice.

Rho family small GTPases are involved in diverse signaling processes including immunity, growth, and development. The activity of Rho GTPases is regulated by cycling between guanosine diphosphate (GDP)-bound inactive and guanosine triphosphate (GTP)-bound active forms, in which guanine nucleotide exchange factors (GEFs) predominantly function to promote activation of the GTPases. In animals, most Rho GEFs possess a Dbl (diffuse B-cell lymphoma) homology (DH) domain which functions as a GEF-catalytic domain.

[Municipal housing support for people with mental disabilities to facilitate transition from an institutional to community setting].

Objectives: The study investigated the provision of support by municipalities to assist people with mental disability securing a dwelling in the community.

Methods: In September 2008, a questionnaire was sent to welfare divisions concerned with people having mental disabilities in 1,805 municipalities nationwide. Responses were returned from 1,141 municipalities (recovery rate: 63.

Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3.

We previously reported that Lgr4 has a critical role in the morphogenesis of kidney, but the detailed functions of Lgr4 in kidney development have not been elucidated. In contrast to Lgr4 null mice with 129Ola × C57BL/6J mixed background, C57BL/6J-backcrossed Lgr4 null mice (Lgr4(-/-)) showed the severe phenotype of embryonic lethality and also had dilated tubules in kidneys at E16.5.