Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer and the 5-year survival rate is only 5%. Several studies have suggested that cancer stem cells (CSCs) are thought to ...be involved in recurrence and metastasis and so it is essential to establish an approach targeting CSCs. Here we have demonstrated that cyclic guanosine monophosphate (cGMP) suppressed CD44 expression and the properties of CSCs in PDAC. Microarray analysis suggested that cGMP inhibited Forkhead box O3 (FOXO3), which is known as a tumor suppressor. Surprisingly, our data demonstrated that FOXO3 is essential for CD44 expression and the properties of CSCs. Our data also indicated that patients with high FOXO3 activation signatures had poor prognoses. This evidence suggested that cGMP induction and FOXO3 inhibition could be ideal candidates for pancreatic CSC.
Nano-layered hybrid compounds composed of a polyfluoroalkyl azobenzene surfactant (abbreviated as C3F-Azo-C6H) and layered inorganic nanosheets undergo three-dimensional morphological changes such as ...reversible shrinkage and expansion of interlayer spaces, and nanosheet sliding by photo-irradiation. Previously, we have investigated the photoreactivity of C3F-Azo-C6H/clay nano-layered hybrids in various microenvironments and found a remarkable enhancement in the photoreactivity for the
cis
-
trans
photo-isomerization reaction (
Φ
cis
-
trans
= 1.9). In this paper, nanosecond and microsecond dynamics of
trans
-C3F-Azo-C6H and its assembly in various microenvironments have been studied by laser flash photolysis to get deeper insight into the extraordinary reactivity of the molecular assembly in the nano-layered microenvironment. In solution, the molecular
trans
-C3F-Azo-C6H exhibited only a depletion of the
trans
-form of azobenzene upon the laser pulse excitation. On the other hand, in the case of the C3F-Azo-C6H/clay hybrid film, the depletion of the
trans
-form was drastically recovered in three steps on nano- and microsecond timescales. This indicates that the once reacted C3F-Azo-C6H molecule (
cis
-C3F-Azo-C6H) was reverted back to the
trans
-form after the laser pulse. It is considered that the excess energy provided by the photo-excitation, which is immediately dissipated to the surrounding media through the intermolecular vibrational modes in solution, is trapped in the nano-layered microenvironment to thermally revert the
cis
-form back to the
trans
-form. Conversely, in the case of
cis
-
trans
isomerization of the C3F-Azo-C6H/clay hybrid film upon photo-irradiation, the reactivity would be much enhanced by the additional contribution of the thermal excess energy efficiently trapped in the nano-layered microenvironment. As compared with the hydrocarbon analogue (C3H-Azo-C6H), the subsequent recovery was very much enhanced in the C3F-Azo-C6H/clay film. The polyfluoroalkyl part of the surfactant layer plays a key role in the retarded dissipation of the excess energy by photo-excitation, which might be coupled with the three-dimensional morphological motion with efficient isomerization reactions.
Trapping of excess energy upon photo-excitation in a polyfluorinated nano-layered microenvironment through step-wise equilibration with the surrounding microenvironment.
We have synthesized a new compound of a benzothiadiazole central core coupled to terminal thienoimide (TI) via vinyl linker, namely, C8-TI-BT. We investigated physical properties of vacuum-deposited ...and spin-coated thin films of C8-TI-BT. Optical properties of C8-TI-BT were different between thin films fabricated by vacuum deposition and spin-coating method. The vacuum-deposited films become more ordered structures by heat treatment. The thin-film transistor (TFT) shows ambipolar semiconducting behavior. We further demonstrated characteristics of electroluminescence (EL) device with the spin-coated C8-TI-BT films.
Aim: To confirm the efficacy of vildagliptin in patients with type 2 diabetes (T2D) by testing the hypothesis that glycosylated haemoglobin (HbA1c) reduction with vildagliptin is superior to that ...with voglibose after 12 weeks of treatment. Methods: In this 12-week, randomized, double-blind, active-controlled, parallel-group study, the efficacy and safety of vildagliptin (50 mg bid, n = 188) was compared with that of voglibose (0.2 mg tid, n = 192) in patients with T2D who were inadequately controlled with diet and exercise. Results: The characteristics of two groups were well matched at baseline. The mean age, body mass index (BMI) and HbA1c were 59.1 years, 24.9 kg/m² and 7.6%, respectively. At baseline, fasting plasma glucose (FPG) and 2-h postprandial glucose (PPG) were 9.01 mmol/l (162.2 mg/dl) and 13.57 mmol/l (244.3 mg/dl), respectively. The adjusted mean change in HbA1c from baseline to endpoint was -0.95 ± 0.04% in the vildagliptin-treated patients and -0.38 ± 0.04% in those receiving voglibose (between-group change = 0.57 ± 0.06%, 95% confidence interval (CI) (-0.68 to -0.46%), p < 0.001), showing that vildagliptin was superior to voglibose. Endpoint HbA1c less-than or equal to 6.5% was achieved in 51% vildagliptin-treated patients compared with 24% patients who were on voglibose (p < 0.001). Vildagliptin also exhibited significantly (p < 0.001) greater reduction compared with voglibose in both FPG 1.34 vs. 0.43 mmol/l (24.1 vs. 7.8 mg/dl) and 2-h PPG 2.86 vs. 1.1 mmol/l (51.5 vs. 19.8 mg/dl). Overall adverse events (AEs) were lower in the vildagliptin-treated patients compared with that in the voglibose-treated patients (61.2 vs. 71.4%), with no incidence of hypoglycaemia and serious adverse events with vildagliptin. Gastrointestinal AEs were significantly lower with vildagliptin compared with that of the voglibose (18.6 vs. 32.8%; p = 0.002). Conclusions: Vildagliptin (50 mg bid) showed superior efficacy and better tolerability compared with voglibose in Japanese patients with T2D.
Purpose: We investigate a novel 4D treatment planning strategy that exploits respiratory motion as an additional degree of freedom. The key idea is to deliver more (less) fluence when the tumor ...target is out‐of‐line (in‐line) with an organ‐at‐risk (OAR). We have developed our weighted‐phase‐correlated (WPC) 4D treatment planning paradigm on a commercial platform (Eclipse, Varian) and designed it for an “open‐gate” delivery, where beam is on throughout the respiratory cycle. Methods: 4DCT data were collected from twenty lung SBRT patients who exhibited >= 5mm tumor motion despite the use of abdominal compression. For each patient, (i)f × θ 3D‐conformal plans were created and corresponding 3D dose distributions were calculated, where θ = number of respiratory phases (10) and f = number of fields (7 – 12) (ii) For each beam, the dose from nine phases was registered to the reference phase (end‐exhale) using a GPU‐based B‐spline deformable registration, NiftyReg. (iv) using dynamic‐penalized‐likelihood optimization, fluence weights were optimized over all dose distributions. This key step ensured that for each motion‐induced state of the anatomy, an optimal fluence would be delivered. (v) A summed fluence map was imported back into Eclipse and an MLC leaf sequence was generated. In order to ensure deliverability, a maximum leaf velocity constraint (v <= 3.5 cm/s) was imposed. Each WPC‐4D plan was compared with the corresponding, clinically‐delivered, ITV‐based plan. Results: In all 20 patients, WPC‐4D plans gave PTV conformity comparable to ITV‐based plans. The percent dose‐sparing (maximum, average) achieved using WPC‐4D compared to ITV‐based planning: Spinal Cord Dmax=(66,20); Esophagus Dmax=(94,29), Heart Dmax=(84,30); Heart Dmean=(82,35); Lung V20=(27,7); Lung Dmean=(27,13). Conclusion: We have developed a novel 4D‐planning solution that exploits rather than trying to mitigate respiratory motion. Initial results indicate that this approach achieves significant dose‐sparing in OARs compared to conventional motion‐management (abdominal compression) + ITV‐based planning. This research was partially supported by Varian Medical Systems, Palo Alto, CA
The objective of this study was to identify clinical and dosimetric factors for the development of radiation pneumonitis (RP) among patients with oesophageal cancer treated with three-dimensional ...radiotherapy without prophylactic nodal irradiation.
125 patients with oesophageal cancer had undergone dose-volume histogram (DVH) metrics and received chemoradiotherapy (CRT). Several clinical and dosimetric factors with regard to the lung were evaluated as predictive factors for the development of symptomatic RP.
26 patients (20.8%) developed symptomatic RP classified as greater than or equal to Grade 2. By univariate analysis, body weight loss, tumour length, Stage IV, response to treatment and all DVH parameters proved to be significant factors for the development of RP (p < 0.05). By multivariate analysis, Stage IV and all dosimetric factors were independent predictive factors for the development of symptomatic RP (p < 0.05). Recursive partitioning analysis indicated that V10 values of 24.8% or more and Stage IV were associated with higher development of RP (odds ratio 6.53).
Our study demonstrated that severe RP was also developed in patients treated with the minimal radiation field. Stage IV and the dosimetric factors were identified as independent predictive factors for symptomatic RP in oesophageal cancer patients treated with CRT without prophylactic nodal irradiation.
The objective of this study was to investigate the therapeutic results of arterial injection therapy via the superficial temporal artery for 134 cases of stages III and IV (M0) oral cavity cancer ...retrospectively, and to clarify the prognostic factors. We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 65 cases from January 1993 to July 2002. Systemic chemotherapy was performed on 26 cases at the same time. We administered intra-arterial chemoradiotherapy by cisplatin with sodium thiosulphate in 69 cases from October 2002 to December 2006. Systemic chemotherapy was performed on 48 cases at the same time. The 3-year local control rate was 68.6% (T2-3: 77.9%; T4: 51.3%), and the 3-year survival rate was 53.9% (stage III: 62.9%; stage IV: 45.3%). Regarding the results of multivariate analysis of survival rates, age (<65), selective intra-arterial infusion, and the use of cisplatin as an agent for intra-arterial infusion were significant factors. The therapeutic results of intra-arterial chemoradiotherapy via the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy by cisplatin with sodium thiosulphate were excellent, so we believe that it will be a new therapy for advanced oral cavity cancer.
SETTING: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality worldwide. While interactions among bacterial pathogens in the respiratory tract have been studied, the impact ...of polybacterial aetiology on mortality has not been fully elucidated.OBJECTIVE:
To investigate the impact of polybacterial aetiology on mortality, prevalence, microbial patterns and clinical characteristics among CAP patients.DESIGN: Retrospective data analysis.RESULTS: Bacterial aetiology was established in 711 (46.0%) of 1544 enrolled hospitalised CAP patients.
Of these, polybacterial aetiology was identified in 89 (12.5%): Streptococcus pneumoniae was the most frequently identified pathogen (n = 55, 61.8%). The most prevalent microbial combination was S. pneumoniae and Haemophilus influenzae (n = 19, 21.3%).
Alcoholism and lack of previous antibiotic therapy were independent predictors of polybacterial aetiology. The proportion of patients with severe pneumonia was significantly higher in the polybacterial aetiology group than in the monobacterial group. Multivariate analysis showed that polybacterial
aetiology was a predictor of 30-day mortality (OR 2.14, 95%CI 1.07-4.24, P = 0.030), independently of severe pneumonia status, pneumonia severity index, chronic obstructive pulmonary disease and inappropriate empirical therapy.CONCLUSION: Polybacterial CAP tends to advance
in severity, and indicates adverse outcomes.
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