Current ramp-up with reduced central solenoid (CS) flux consumption in JT-60SA has been investigated using an integrated modeling code suite (TOPICS) with a turbulent model (CDBM). The plasma current ...can be ramped-up from 0.6 MA to 2.1 MA with no additional CS flux consumption if the plasma current is overdriven by neutral-beam-driven and bootstrap current. A time duration required for the current ramp-up without CS flux consumption becomes as long as 150 s in the scenario we have examined. In order to achieve a current overdrive condition from 0.6 MA, the current drive by a lower energy neutral beam (85 keV) is effective. A higher energy neutral beam (500 keV) cannot be used in this early phase with a low central electron density (~2 × 1019 m−3) due to large shine through loss, while it can be effectively used in the later phase. Therefore, the main current driver should be switched from the lower energy neutral beam to the higher energy neutral beam during the current ramp-up phase. As a result of an intensive auxiliary heating, plasma beta (the ratio of the plasma pressure to the magnetic pressure) becomes high. Ideal MHD instabilities of such high beta plasmas have been investigated using a linear ideal MHD stability analysis code (MARG2D). External kink modes which might affect the core plasma can be stabilized during the current ramp-up if there is a perfectly conducting wall at the location of the stabilizing plate and the vacuum vessel of JT-60SA and the plasma has a broader pressure profile with the H-mode pedestal and the internal transport barrier.
We provide the first evidence demonstrating that single-nucleotide polymorphisms in macrophage function-related genes may predict prognosis in locoregional gastric cancer patients. Our results also ...suggest that the immune-related component of tumor for progression may be dictated not only by the malignant epithelial component but also by the genetic predisposition of host in gastric cancer.
Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups.
This study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing.
The univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort hazard ratio (HR) 2.43; P = 0.015 but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001).
Our study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.
According to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 ...expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma.
This was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH–), and HER2-positive (IHC2+/ISH+ or 3+).
In total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n = 410; HER2-low, n = 154, and HER2-positive, n = 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.59-0.89; P = 0.002. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR = 1.01, 95% CI 0.82-1.23; P = 0.843).
Patients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group’s prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required.
•HER2-low G/GEJ adenocarcinoma had intermediate clinicopathological features than the HER2-negative and HER2-positive groups.•The HER2-low group’s prognosis was worse than that of the HER2-positive group but similar to that of the HER2-negative group.•Personalized targeted therapy for the right target is required to improve the prognosis of these patients further.
Plasma current start-up and ramp-up using the lower hybrid wave (LHW) were investigated on the TST-2 spherical tokamak. The LHW was launched by a dielectric-loaded waveguide array (grill) antenna. ...The antenna-plasma coupling of this antenna deteriorates as the input power exceeds several kW. This deterioration is believed to be caused by the density depletion due to the ponderomotive force. This conjecture was confirmed by the measurement of density reduction and the result of a non-linear full wave numerical calculation based on the finite element method (FEM). The plasma current was started and ramped up to 10 kA using this antenna. The ability of this grill antenna to excite the LHW with different n = ck /ω was used to identify the most favourable n spectrum for plasma current ramp-up. It was found that effective current drive can be achieved by the LHW with n less than 6. However, even in this case, the energetic electrons which account for a large fraction of the driven current, are lost rapidly because the poloidal field generated by this level of plasma current is not sufficient to confine high energy electrons.
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