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Adsorption of N2 on Mo6 S8 q _Vx clusters (x=0, 1, 2; q=0, ±1) were systematically studied by density functional theory calculations with dispersion corrections. It was found that the N2 can be chemisorbed and undergo non-dissociative activation on single or double metal atoms. The adsorption and activation are influenced by metal types (V or Mo), N2 coordination modes and charge states of the clusters. Particularly, anionic Mo6 S8 - _V2 clusters have remarkable ability to fix and activate N2 . In Mo6 S8 - _V2 , two V atoms prefer to adsorb on two adjacent S-Mo-S hollow sites, leading to the formation of a supported V…V unit. The N2 is bridged side-on coordinated with these two V atoms with high adsorption energy and significant charge transfer. The bond order, bond length and vibration frequency of the adsorbed N2 are close to those of a N-N single bond.
Pre-existing immunities hamper the application of human adenovirus (HAdV) vectors in gene therapy or vaccine development. Fowl adenovirus (FAdV)-based vector might represent an alternative.
An intermediate plasmid containing FAdV-4 fiber genes, pMD-FAV4Fs, was separated from FAdV-4 adenoviral plasmid pKFAV4GFP. ITF3756 in vitro An overlap extension polymerase chain reaction (PCR) was employed for fiber modification in pMD-FAV4Fs, and the modified fibers were restored to generate new adenoviral plasmids through restriction-assembly. FAdV-4 vectors were rescued and amplified in chicken LMH cells. Fluorescence microscopy and flow cytometry were used to evaluate the gene transfer efficiency. The amount of viruses binding to cells was determined by a real-time PCR. A plaque-forming assay and one-step growth curve were used to evaluate virus growth.
Four sites in the CD-, DE-, HI- and IJ-loop of fiber1 knob could tolerate the insertion of exogenous peptide. The insertion of RGD4C peptide in the fiber1 knob significantly promoted FAdV-4 transduction to human adherent cells such as 293, A549 and HEp-2, and the insertion to the IJ-loop demonstrated the best performance. The replacement of the fiber2 knob of FAdV-4 with that of HAdV-35 improved the gene transfer to human suspension cells such as Jurkat, K562 and U937. Fiber-modified FAdV-4 vectors could transduce approximately 80% human cells at an acceptable multiplicity of infection. Enhanced gene transfer mainly resulted from increased virus binding. Fiber modifications did not significantly influence the growth of recombinant FAdV-4 in packaging cells.
As a proof of principle, it was feasible to enhance gene transduction of FAdV-4 vectors to human cells by modifying the fibers.
As a proof of principle, it was feasible to enhance gene transduction of FAdV-4 vectors to human cells by modifying the fibers.
Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined to be level-1 (oxaliplatin, 65 mg/m
; irinotecan, 100 mg/m
; S-1, 80 mg/m
), which has manageable safety and promising anticancer activities.
OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed.
Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
In level 0 (oxaliplatin, 85 mg/m
; irinotecan, 100 mg/m
; S-1, 80 mg/m
), two of five patients experienced DLT. In level-1 (oxaliplatin, 65 mg/m
; irinotecan, 100 mg/m
; S-1, 80 mg/m
), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and-1. ORR was 30% in levels 0 and-1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively.
MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level-1.
MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level -1.In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21,155 newly registered patients and 43,041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from 1 January 2012 to 31 December 2013. Basic statistics compiled for patients newly registered in the 22nd survey was cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world. This article is protected by copyright. All rights reserved.
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