Response of lymphocyte subsets and cytokines to Shenyang prescription in Sprague-Dawley rats with tongue squamous cell carcinomas induced by 4NQO

BACKGROUND: The study was designed to investigate immunocompetence in relation to cancer progression in rat and to assess the effect of the traditional Chinese anti-cancer medicine, "Shenyang" prescription, on immunity. METHODS: 4-Nitroquinoline-1-oxide (4NQO) was administered to 80 Sprague-Dawley (SD) rats via the drinking water for up to 36 weeks. Tongue squamous cell carcinoma (SCC) was confirmed by pathological examination in 61 rats. "Shenyang" prescription was administered to subgroups of these rats, and blood samples were taken before and after treatment. Lymphocyte subsets were determined by flow cytometry. Serum Th1 and Th2-type cytokines were assessed by an enzyme-linked immunosorbent assay. RESULTS: As the cancer progressed at the tongue root, the percentage of CD3+CD4+ T lymphocytes and NK cells and the levels of IFN-γ and IL-2 decreased gradually, while the percentage of CD3+CD8+ T lymphocytes and the levels of IL-4 and IL-10 increased. The CD4+/CD8+ ratios were lower in the cancer groups than in the control group. However, after administering "Shenyang" prescription, the levels of CD3+CD4+ T lymphocytes, NK cells, IFN-γ and IL-2 increased, while the CD3+CD8+ T lymphocyte counts and the levels of IL-4 and IL-10 decreased. CONCLUSION: 4NQO-induced lesions were good models for exploring oral cavity carcinogenesis. The rats with 4NQO-induced SCC demonstrated abnormalities in lymphocyte subsets and a shift from Th1-type to Th2-type, which were good models for assessing the effect of anticancer agent on immunity. Oral cancer progression was associated with an aggressive disturbance of immune function. "Shenyang" prescription has the ability to improve the disturbance of immune function

Immunomodulatory role of Keratin 76 in oral and gastric cancer

Keratin 76 (Krt76) is an epithelial differentiation marker that is downregulated in oral squamous cell carcinomas, correlating with poor prognosis. Here the authors show that genetic ablation of Krt76 in a mouse model results in increased susceptibility to carcinogenesis via enhanced accumulation of Tregs

Design and Operation of FACT -- The First G-APD Cherenkov Telescope

The First G-APD Cherenkov Telescope (FACT) is designed to detect cosmic gamma-rays with energies from several hundred GeV up to about 10 TeV using the Imaging Atmospheric Cherenkov Technique. In contrast to former or existing telescopes, the camera of the FACT telescope is comprised of solid-state Geiger-mode Avalanche Photodiodes (G-APD) instead of photomultiplier tubes for photo detection. It is the first full-scale device of its kind employing this new technology. The telescope is operated at the Observatorio del Roque de los Muchachos (La Palma, Canary Islands, Spain) since fall 2011. This paper describes in detail the design, construction and operation of the system, including hardware and software aspects. Technical experiences gained after one year of operation are discussed and conclusions with regard to future projects are drawn.Comment: Corresponding authors: T. Bretz and Q. Weitze

Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. [Results]: We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma. [Conclusions]: In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity.RF and JL received funding from EU FP7 (PREDICT project), EB is a Rosetrees Trust fellow, NM received funding from the Rosetrees Trust, MG is funded by the UK Medical Research Council, IV is funded by Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal, and CS is a senior Cancer Research UK clinical research fellow and is funded by Cancer Research UK, the Rosetrees Trust, EU FP7 (projects PREDICT and RESPONSIFY, ID:259303), the Prostate Cancer Foundation, and the Breast Cancer Research Foundation. This study was supported by researchers at the National Institute for Health Research Biomedical Research Centres at University College London Hospitals and at the Royal Marsden Hospital.Peer Reviewe

Wavelength-shifting materials for the use in RICH detectors - p-terphenyl and tetraphenyl-butadiene revisited

P-terphenyl (PT) and tetraphenyl-butadiene (TPB) in form of thin films have been investigated as possible wavelength shifting material for application in Ring Imaging Cherenkov (RICH) detectors. Films of dierent thickness were evaporated onto borosilicate windows of photomultiplier tubes (PMT) and the quantum eciency of the modified PMTs was determined as a function of wavelength. Gain factors for the number of measured photoelectrons in dependence on the cuto wavelength (energy) for application in Cherenkov counters were established. Using PT, a strong increase in quantum eciency between 200 nm and 300 nm was observed leading to gain factors as high as 1.71 ± 0.11 for a cutoff energy of 6.2 eV. Due to strong absorption in the wavelength range between 300 nm and 400 nm, TPB shows inferior results. No significant thickness dependence was observed for films thicker than 600 nm. Film morphology and wavelength dependent fluorescence was measured to back the results. Simulations encourage the use on flat panel multi-anode photomultipliers