Efficacy and adverse events of L-Asparaginase administration as a first-line treatment for feline large-cell gastrointestinal lymphoma.

L-Asparaginase (L-Asp) is often used to induce remission in feline large-cell gastrointestinal lymphoma (LCGIL). However, no study has evaluated the efficacy and adverse events following the initial use of this drug as a first-line treatment in feline LCGIL. We retrospectively reviewed medical records of cats with LCGIL treated with L-Asp to induce remission. This study included 43 cats. The response rate (RR) after the first administration of L-Asp was 37.2% (Complete remission: 7.0%, partial remission: 30.2%). RR was significantly higher in cases with primary gastric lesions (64.3%) than in those with primary intestinal lesions (24.1%) (P=0.018), and it was also higher in cases without anemia (57.1%) than those with anemia (15.0%) (P=0.009). The most common adverse event was hyperammonemia, which occurred in 10 of 12 cases where we could compare plasma ammonia concentrations before and after the first dose of L-Asp. Plasma phosphate concentrations were also significantly increased (P<0.001) within 24 hr after the first dose. Decreased appetite, vomiting, and diarrhea were also observed in five, three, and seven cases, respectively, and Grade 3 or higher gastrointestinal signs were observed as adverse events in three cases. The median overall survival of all cats was 150 days (range, 5-1,065 days), and the median progression-free survival was 104 days (range, 2-978 days). In conclusion, L-Asp was effective to induce remission, and severe adverse events were uncommon in feline LCGIL.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Photocatalytic CO2 reduction sensitized by a special-pair mimic porphyrin connected with a rhenium(i) tricarbonyl complex.

Zn porphyrins with an imidazolyl group at the meso position generate a highly stable porphyrin dimer by complementary coordination from the imidazolyl to the Zn ion in noncoordinating solvents such as chloroform, which mimics the natural special pair in photosynthesis. In this work, we have synthesized an imidazolyl-substituted Zn porphyrin connected with a Re 2,2-bipyridine tricarbonyl complex as a CO2 reduction catalyst via a p-phenylene linker, affording a homodimer with two Re complexes on both sides (ReDRe). The dimeric structure is easily dissociated into the corresponding monomers in coordinating solvents. Therefore, we prepared a mixture containing a heterodimer with the Re carbonyl complex on one side (ReD) by simple mixing with an imidazolyl Zn porphyrin and evaporating the solvent. Using the Grubbs catalyst, the subsequent olefin metathesis reaction of the mixture gave covalently linked porphyrin dimers through the allyloxy side chains, enabling the isolation of the stable hetero- (ReD') and homo-dimers (ReD'Re) with gel permeation chromatography. The Zn porphyrin dimers have intense absorption bands in the visible light region and acted as good photosensitizers in photocatalytic CO2 reduction in a mixture of N,N-dimethylacetamide and triethanolamine (5 : 1 v/v) containing 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole as the electron donor, giving CO with high selectivity and durability. Under irradiation with strong light intensity, the reaction rate in ReD' exceeded that of the previous porphyrin[double bond, length as m-dash]Re complex dyad, ZnP-phen=Re. For instance, after irradiation at 560 nm for 18 h, the turnover number (TONCO) of ReD' reached 2800, whereas the TONCO of ZnP-phen=Re was 170. The high activity in the system using the porphyrin dimer originates from no accumulation of the one-electron reduced species of the porphyrin that inhibit light absorption due to the inner-filter effect.