Exploring the supersymmetric U(1)B−L×_{B-L} \times U(1)R_{R} model with dark matter, muon g−2g-2 and Z′Z^\prime mass limits

We study the low scale predictions of supersymmetric standard model extended by $U(1)_{B-L}\times U(1)_{R}$ symmetry, obtained from $SO(10)$ breaking via a left-right supersymmetric model, imposing universal boundary conditions. Two singlet Higgs fields are responsible for the radiative $U(1)_{B-L}\times U(1)_{R}$ symmetry breaking, and a singlet fermion $S$ is introduced to generate neutrino masses through inverse seesaw mechanism. The lightest neutralino or sneutrino emerge as dark matter candidates, with different low scale implications. We find that the composition of the neutralino LSP changes considerably depending on the neutralino LSP mass, from roughly half $U(1)_R$ bino, half MSSM bino, to singlet higgsino, or completely dominated by MSSM higgsino. The sneutrino LSP is statistically much less likely, and when it occurs it is a 50-50 mixture of right-handed sneutrino and the scalar $\tilde S$. Most of the solutions consistent with the relic density constraint survive the XENON 1T exclusion curve for both LSP cases. We compare the two scenarios and investigate parameter space points and find consistency with the muon anomalous magnetic moment only at the edge of $2\sigma$ deviation from the measured value. However, we find that the sneutrino LSP solutions could be ruled out completely by strict reinforcement of the recent $Z^\prime$ mass bounds. We finally discuss collider prospects for testing the model

A Minor (<50%) Signet-Ring Cell Component Associated with Poor Prognosis in Colorectal Cancer Patients: A 26-Year Retrospective Study in China

<div><p>Background</p><p>We performed a retrospective study to determine the cancer-specific survival of colorectal cancer patients with a component of signet-ring cells or mucin comprising < 50% of the tumor mass.</p><p>Methods</p><p>A total of 2454 patients seen in our hospital from 1985 to 2011 were retrospectively studied. The patients were divided into five groups according to type of cancer: signet-ring cell carcinoma (with > 50% signet-ring cell, n = 36), partial signet-ring cell carcinoma (with < 50% signet-ring cell, n = 28), mucinous adenocarcinoma (with > 50% mucin lacking signet-ring cell, n = 267), partial mucinous adenocarcinoma (with < 50% mucin lacking signet-ring cell, n = 145), and classic adenocarcinoma (with absence of either mucin or signet-ring cell, n = 1978).</p><p>Results</p><p>Patients with > 50% or < 50% signet-ring cell had the lowest 5-year survival rates (35.5% and 29.7%, respectively), followed by patients with > 50% mucin (48.8%). Patients who had partial mucinous adenocarcinoma with < 50% mucin and classic adenocarcinoma patients had the highest 5-year survival rates (64.8% and 65.3%, respectively). Stratified and multivariate analysis showed that signet-ring cell carcinoma, partial signet-ring cell carcinoma and mucinous adenocarcinoma were independent predictors of decreased survival (hazard ratio 1.699, <i>P</i> = 0.016; hazard ratio 2.182, <i>P</i> = 0.005; hazard ratio 1.532, <i>P</i> < 0.001; respectively), and partial mucinous adenocarcinoma was not (hazard ratio 1.137, <i>P</i> = 0.431).</p><p>Conclusions</p><p>Patients with a component of signet-ring cells, regardless of the extent, had poor prognoses. Patients with mucinous adenocarcinoma containing >50% mucin had poor prognoses as well, whereas those with < 50% mucin had survival rates similar to those of classic adenocarcinoma patients. Therefore, in clinical practice, patients with a component of signet-ring cells, regardless of the extent, should be given significant clinical attention.</p></div

Clinicopathological characteristics of the five groups.

<p>* results compared with AC. Tx and Nx patients were excluded when performing the chi-square test.</p><p>^#Stage IV patients were excluded when calculating the recurrence rate, SRCC, signet-ring cell carcinoma; PSRCC, partial signet-ring cell carcinoma; MAC, mucinous adenocarcinoma; PMAC, partial mucinous adenocarcinoma; AC, classic adenocarcinoma.</p><p>Clinicopathological characteristics of the five groups.</p

Multivariate analysis using Cox’s model for MAC, PMAC and AC.

<p>CSS, cancer-specific survival. MAC, mucinous adenocarcinoma; PMAC, partial mucinous adenocarcinoma; AC, classic adenocarcinoma.</p><p>Multivariate analysis using Cox’s model for MAC, PMAC and AC.</p

Multivariate analysis using Cox’s model for SRCC, PSRCC and AC.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121944#pone.0121944.t004" target="_blank">Table 4</a> CSS, cancer-specific survival. SRCC, signet-ring cell carcinoma; PSRCC, partial signet-ring cell carcinoma; AC, classic adenocarcinoma.</p><p>Multivariate analysis using Cox’s model for SRCC, PSRCC and AC.</p

Representative histopathological images of different kinds of adenocarcinomas.

<p>(A) Signet-ring cell carcinoma. (B) Signet-ring cells floating in the pools of mucus are demonstrated. Mucinous carcinomas or classic adenocarcinomas with a minor signet-ring cell component were classified as partial signet-ring cell carcinoma. (C) Mucinous adenocarcinomas containing no signet-ring cells were classified as MAC or PMAC based on the proportion of mucin in the tumor. (D) Classic adenocarcinoma without any mucin or signet-ring cells.</p

Stratified analysis of 5-year CSS with age at diagnosis, gender, tumor site and tumor stage in SRCC and PSRCC patients.

<p>CSS, cancer-specific survival. N, data cannot be figured out. SRCC, signet-ring cell carcinoma; PSRCC, partial signet-ring cell carcinoma; AC, classic adenocarcinoma.</p><p>Stratified analysis of 5-year CSS with age at diagnosis, gender, tumor site and tumor stage in SRCC and PSRCC patients.</p

The overall survival of patients in the five groups.

<p>SRCC, signet-ring cell carcinoma; PSRCC, partial signet-ring cell carcinoma; MAC, mucinous adenocarcinoma; PMAC, partial mucinous adenocarcinoma; AC, classic adenocarcinoma.</p

BEX1 Promotes Imatinib-Induced Apoptosis by Binding to and Antagonizing BCL-2

<div><p>An enhanced anti-apoptotic capacity of tumor cells plays an important role in the process of breakpoint cluster region/Abelson tyrosine kinase gene (BCR/ABL)-independent imatinib resistance. We have previously demonstrated that brain expressed X-linked 1 (BEX1) was silenced in secondary imatinib-resistant K562 cells and that re-expression of BEX1 can restore imatinib sensitivity resulting in the induction of apoptosis. However, the mechanism by which BEX1 executes its pro-apoptotic function remains unknown. We identified B-cell lymphoma 2 (BCL-2) as a BEX1-interacting protein using a yeast two-hybrid screen. The interaction between BEX1 and BCL-2 was subsequently confirmed by co-immunoprecipitation assays. Like BCL-2, BEX1 was localized to the mitochondria. The region between 33K and 64Q on BEX1 is important for its localization to the mitochondria and its ability to interact with BCL-2. Additionally, we found that this region is essential for BEX1-regulated imatinib-induced apoptosis. Furthermore, we demonstrated that the interaction between BCL-2 and BEX1 promotes imatinib-induced apoptosis by suppressing the formation of anti-apoptotic BCL-2/BCL-2-associated X protein (BAX) heterodimers. Our results revealed an interaction between BEX1 and BCL-2 and a novel mechanism of imatinib resistance mediated by the BEX1/BCL-2 pathway.</p></div

BEX1 fails to localize to the mitochondria without residues 33K-64Q.

<p>A. Fluorescence of live KR cells expressing BEX1Δ33K-64Q-GFP or an empty vector control (GFP). Cells were visualized for GFP (top), Mitotracker (middle), or merged images (bottom). B, Biochemical fractionation. WCE prepared from KR cells expressing BEX1Δ33K-64Q-GFP or an empty vector control (GFP) were separated into cytoplasmic (top) and mitochondrial (bottom) fractions as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091782#pone-0091782-g002" target="_blank">Figure 2</a> and then immunoblotted for GFP, GAPDH, or COX IV. The bands between 39 kDa and 26 kDa were non-specific signals.</p