Thomassenbinderup0901

S-1 and pemetrexed (PEM) are key treatments for non-small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S-1 and PEM is similar. Cross-resistance between S-1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment.

This retrospective study included patients with advanced (c-stage III or IV, UICC seventh edition) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS).

A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidence interval [CI] 0.00%-10.1%). Eliglustat Median TTF, PFS, and OS were 65, 84, and 385 days, respectively.

Although there were several limitations in this study, the ORR of S-1 after PEM in patients with nonsquamous (non-SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

Although there were several limitations in this study, the ORR of S-1 after PEM in patients with nonsquamous (non-SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a greatnumber of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism.

Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated μ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state.

Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.

Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.The Mediterranean region possesses a rich diversity of salamanders, which also exhibit a high degree of ecological diversification. It is assumed that the presence of salamanders is dependent on the level of vegetation cover in terrestrial habitats, but the strength of this association is likely to vary among species. In this study, we investigated the patterns of habitat utilization for Mediterranean salamanders based on 589 records of 33 species. We tested the hypothesis that the association between salamander presence and vegetation density varies among genera or reproductive modes (i.e. terrestrial vs aquatic). The results show that vegetation cover has similar influences on terrestrial and aquatic groups but important differences are identified for lotic and lentic aquatic species. Our findings also indicate that the aquatic lotic, terrestrial, and small-body species deviate significantly from that expected from the background range of variation.

Identifying diabetes-susceptible genetic variants will help to provide personalized therapy for the management of type 2 diabetes. Previous studies have reported a genetic risk score (GRS), computed by the sum of nuclear DNA (nDNA) risk alleles, that may predict the future requirement for insulin therapy. Although mitochondrial dysfunction has a close association with insulin resistance (IR), there are few studies investigating whether genetic variants of mitochondrial DNA (mtDNA) will affect the clinical characteristics of type 2 diabetes.

Mitochondrial haplogroups were determined using mtDNA whole genome next generation sequencing and 13 single nucleotide polymorphisms (SNPs) in nDNA susceptibility loci of 13 genes in 604 Taiwanese subjects with type 2 diabetes. A GRS of nDNA was computed by summation of the number of risk alleles. The correlation between the mtDNA haplogroup and the clinical characteristics of type 2 diabetes was assessed by logistic regression analysis. The results were compared with the GRS subgroups for the risk of insulin requirement.

Mitochondrial haplogroups modulate the clinical characteristics of type 2 diabetes, in which patients harboring haplogroup D4, compared with those harboring non-D4 haplotypes, were less prone to require insulin treatment, after adjusting for age, gender, and diabetes duration. However, there was no association between insulin requirement and GRS calculated from nuclear genetic variants.

Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement. The results highlight the role of mitochondria in the management of common metabolic diseases.

Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement. The results highlight the role of mitochondria in the management of common metabolic diseases.