172 research outputs found
The CLIC Programme: Towards a Staged e+e- Linear Collider Exploring the Terascale : CLIC Conceptual Design Report
This report describes the exploration of fundamental questions in particle
physics at the energy frontier with a future TeV-scale e+e- linear collider
based on the Compact Linear Collider (CLIC) two-beam acceleration technology. A
high-luminosity high-energy e+e- collider allows for the exploration of
Standard Model physics, such as precise measurements of the Higgs, top and
gauge sectors, as well as for a multitude of searches for New Physics, either
through direct discovery or indirectly, via high-precision observables. Given
the current state of knowledge, following the observation of a 125 GeV
Higgs-like particle at the LHC, and pending further LHC results at 8 TeV and 14
TeV, a linear e+e- collider built and operated in centre-of-mass energy stages
from a few-hundred GeV up to a few TeV will be an ideal physics exploration
tool, complementing the LHC. In this document, an overview of the physics
potential of CLIC is given. Two example scenarios are presented for a CLIC
accelerator built in three main stages of 500 GeV, 1.4 (1.5) TeV, and 3 TeV,
together with operating schemes that will make full use of the machine capacity
to explore the physics. The accelerator design, construction, and performance
are presented, as well as the layout and performance of the experiments. The
proposed staging example is accompanied by cost estimates of the accelerator
and detectors and by estimates of operating parameters, such as power
consumption. The resulting physics potential and measurement precisions are
illustrated through detector simulations under realistic beam conditions.Comment: 84 pages, published as CERN Yellow Report
https://cdsweb.cern.ch/record/147522
Targeted therapy against Bcl-2-related proteins in breast cancer cells
INTRODUCTION: Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy. METHODS: Four human breast cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the antitumor effect was assessed in vivo by the success of xenograft transplantation into athymic mice. RESULTS: Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a sequence-specific decrease in protein expression, compared with controls. Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, which was attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to a smaller extent, are major determinants of chemosensitivity in breast cancer cells. CONCLUSION: Targeted therapy against Bcl-2 protein with the use of AS ODNs might enhance the effects of chemotherapy in patients with breast cancer
Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives
The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN®) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-β or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers
Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy
Review article[Abstract] The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy
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