Severe ileitis associated with capecitabine: Two case reports and review of the literature

published_or_final_versio

PD-0458: AFP response as a predictor of clinical outcome after stereotactic body radiotherapy (SBRT) for advanced HCC

POSTER DISCUSSION: YOUNG SCIENTISTS 2: LUNG AND GASTROINTESTINAL TUMOURSpublished_or_final_version2nd ESTRO Forum, Geneva, Switzerland, 19-23 April 2013, In Radiotherapy & Oncology, 2013, v. 106, p. S17

Outcome of neoadjuvant chemoradiation in MRI staged locally advanced rectal cancer: Retrospective analysis of 123 Chinese patients

published_or_final_versio

Enhanced stochastic optimization algorithm for finding effective multi-target therapeutics

<p>Abstract</p> <p>Background</p> <p>For treating a complex disease such as cancer, we need effective means to control the biological network that underlies the disease. However, biological networks are typically robust to external perturbations, making it difficult to beneficially alter the network dynamics by controlling a single target. In fact, multi-target therapeutics is often more effective compared to monotherapies, and combinatory drugs are commonly used these days for treating various diseases. A practical challenge in combination therapy is that the number of possible drug combinations increases exponentially, which makes the prediction of the optimal drug combination a difficult combinatorial optimization problem. Recently, a stochastic optimization algorithm called the Gur Game algorithm was proposed for drug optimization, which was shown to be very efficient in finding potent drug combinations.</p> <p>Results</p> <p>In this paper, we propose a novel stochastic optimization algorithm that can be used for effective optimization of combinatory drugs. The proposed algorithm analyzes how the concentration change of a specific drug affects the overall drug response, thereby making an informed guess on how the concentration should be updated to improve the drug response. We evaluated the performance of the proposed algorithm based on various drug response functions, and compared it with the Gur Game algorithm.</p> <p>Conclusions</p> <p>Numerical experiments clearly show that the proposed algorithm significantly outperforms the original Gur Game algorithm, in terms of reliability and efficiency. This enhanced optimization algorithm can provide an effective framework for identifying potent drug combinations that lead to optimal drug response.</p

Experimental realization of a topological crystalline insulator in SnTe

Topological insulators materialize a topological quantum state of matter where unusual gapless metallic state protected by time-reversal symmetry appears at the edge or surface. Their discovery stimulated the search for new topological states protected by other symmetries, and a recent theory predicted the existence of "topological crystalline insulators" (TCIs) in which the metallic surface states are protected by mirror symmetry of the crystal. However, its experimental verification has not yet been reported. Here we show the first and definitive experimental evidence for the TCI phase in tin telluride (SnTe) which was recently predicted to be a TCI. Our angle-resolved photoemission spectroscopy shows clear signature of a metallic Dirac-cone surface band with its Dirac point slightly away from the edge of the surface Brillouin zone in SnTe. On the other hand, such a gapless surface state is absent in a cousin material lead telluride (PbTe), in line with the theoretical prediction. Our result establishes the presence of a TCI phase, and opens new avenues for exotic topological phenomena.Comment: 11 pages, 3 figure

Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB Activation

BACKGROUND: B1 B cells are believed to be a unique lineage with a distinct developmental pathway, function and activation requirement. How this lineage is genetically determined remained largely obscure. METHODS AND PRINCIPAL FINDINGS: Using the Siglecg-deficient mice with a knockin of green-fluorescent protein encoding sequence, we show here that, although the Siglecg gene is broadly expressed at high levels in all stages and/or lineages of B cells tested and at lower levels in other lineages, its deletion selectively expanded the B1a B cell lineages, including the frequency of the B1 cell progenitor in the bone marrow and the number of B1a cells in the peritoneal cavity, by postnatal expansion. The expansion of B1a B cells in the peritoneal correlated with enhanced activation of NFkappaB and was ablated by an IKK inhibitor. CONCLUSION AND SIGNIFICANCE: Our data revealed a critical role for Siglec G-NFkappaB pathway in regulating B1a B cell lineage. These data lead to a novel model of B1a lineage development that explains a large array of genetic data in this field

Acellular Bone Marrow Extracts Significantly Enhance Engraftment Levels of Human Hematopoietic Stem Cells in Mouse Xeno-Transplantation Models

Hematopoietic stem cells (HSC) derived from cord blood (CB), bone marrow (BM), or mobilized peripheral blood (PBSC) can differentiate into multiple lineages such as lymphoid, myeloid, erythroid cells and platelets. The local microenvironment is critical to the differentiation of HSCs and to the preservation of their phenotype in vivo. This microenvironment comprises a physical support supplied by the organ matrix as well as tissue specific cytokines, chemokines and growth factors. We investigated the effects of acellular bovine bone marrow extracts (BME) on HSC in vitro and in vivo. We observed a significant increase in the number of myeloid and erythroid colonies in CB mononuclear cells (MNC) or CB CD34+ cells cultured in methylcellulose media supplemented with BME. Similarly, in xeno-transplantation experiments, pretreatment with BME during ex-vivo culture of HSCs induced a significant increase in HSC engraftment in vivo. Indeed, we observed both an increase in the number of differentiated myeloid, lymphoid and erythroid cells and an acceleration of engraftment. These results were obtained using CB MNCs, BM MNCs or CD34+ cells, transplanted in immuno-compromised mice (NOD/SCID or NSG). These findings establish the basis for exploring the use of BME in the expansion of CB HSC prior to HSC Transplantation. This study stresses the importance of the mechanical structure and soluble mediators present in the surrounding niche for the proper activity and differentiation of stem cells

Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells

<p>Abstract</p> <p>Background</p> <p>Berberine (BER), the major alkaloidal component of <it>Rhizoma coptidis</it>, has multiple pharmacological effects including inhibition of acetylcholinesterase, reduction of cholesterol and glucose levels, anti-inflammatory, neuroprotective and neurotrophic effects. It has also been demonstrated that BER can reduce the production of beta-amyloid_40/42, which plays a critical and primary role in the pathogenesis of Alzheimer's disease. However, the mechanism by which it accomplishes this remains unclear.</p> <p>Results</p> <p>Here, we report that BER could not only significantly decrease the production of beta-amyloid_40/42and the expression of beta-secretase (BACE), but was also able to activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway in a dose- and time-dependent manner in HEK293 cells stably transfected with APP695 containing the Swedish mutation. We also find that U0126, an antagonist of the ERK1/2 pathway, could abolish (1) the activation activity of BER on the ERK1/2 pathway and (2) the inhibition activity of BER on the production of beta-amyloid_40/42and the expression of BACE.</p> <p>Conclusion</p> <p>Our data indicate that BER decreases the production of beta-amyloid_40/42by inhibiting the expression of BACE via activation of the ERK1/2 pathway.</p

Estrogen Receptor Beta rs1271572 Polymorphism and Invasive Ovarian Carcinoma Risk: Pooled Analysis within the Ovarian Cancer Association Consortium

The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC). All participants were non-Hispanic white women. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR = 1.10; 95%; CI: 1.01–1.21; p = 0.04); the OR was 1.09 (CI: 0.99–1.20; p = 0.07) after excluding data from the center (Hawaii) that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women (OR = 1.35; CI: 1.12–1.62; p = 0.002; p for interaction = 0.02) that remained statistically significant after excluding Hawaii data (OR = 1.34; CI: 1.11–1.61; p = 0.009). No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women