Citations

In recent years, the emerging electronic cigarette (e-cigarette) marketplace has shown great development prospects all over the world. Reddit, one of the most popular forums in the world, has a very large user group and thus great influence. This study aims to gain a systematic understanding of e-cigarette flavors based on data collected from Reddit. Flavor popularity, mixing, characteristics, trends, and brands are analyzed. Fruit flavors were mentioned the most (n = 15,720) among all the posts and were among the most popular flavors (n = 2902) used in mixed blends. Strawberry and vanilla flavors were the most popular for e-juice mixing. The number of posts discussing e-cigarette flavors has increased sharply since 2014. Mt. Baker Vapor and Hangen were the most popular brands discussed among users. Information posted on Reddit about e-cigarette flavors reflected consumers’ interest in a variety of flavors. Our findings suggest that Reddit could be used for data mining and analysis of e-cigarette-related content. Understanding how e-cigarette consumers’ view and utilize flavors within their vaping experience and how producers and marketers use social media to promote flavors and sell products could provide valuable information for regulatory decision-makers.

Abstract Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1680–91. ©2015 AACR.

Key PointsThe NF-κB subunits p52 and RelB increase IRF4 promoter activity and expression in PTCL cells. A positive feedback loop involving CD30, NF-κB, and IRF4 drives PTCL cell proliferation and can be blocked by NF-κB inhibitors.

BackgroundGiven the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of epratuzumab (anti‐CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B‐lymphoblastic leukemia (B‐ALL) and early bone marrow relapse.ProcedureTherapy consisted of three established blocks of re‐induction chemotherapy. Epratuzumab (360 mg/m2/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re‐induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone.ResultsCR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without epratuzumab. Rates of MRD negativity (<0.01%) were 31% in B1 (P = 0.4128) and 39% in B2 patients (P = 0.1731), compared to 25% in historical controls. The addition of epratuzumab was well tolerated, with a similar toxicity profile to that observed with the re‐induction chemotherapy platform regimen alone.ConclusionsEpratuzumab was well tolerated in combination with re‐induction chemotherapy. While CR2 rates were not improved compared to historical controls treated with chemotherapy alone, there was a non‐significant trend towards improvement in MRD response with the addition of epratuzumab (twice weekly for eight doses) to re‐induction chemotherapy. Pediatr Blood Cancer 2015;62:1171–1175. © 2015 Wiley Periodicals, Inc.

Context and Objective:Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management.Design and Patients:Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene.Results:Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors.Conclusion:Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.

AbstractIn tissue engineering, development of an osteoconductive construct that integrates with host tissue remains a challenge. In this work, the effect of bone‐like minerals on maturation of pre‐osteoblast cells was investigated using polymer‐mineral scaffolds composed of poly(propylene fumarate)‐co‐poly(caprolactone) (PPF‐co‐PCL) and nano‐sized hydroxyapatite (HA). The HA of varying concentrations was added to an injectable formulation of PPF‐co‐PCL and the change in thermal and mechanical properties of the scaffolds was evaluated. No change in onset of degradation temperature was observed due to the addition of HA, however compressive and tensile moduli of copolymer changed significantly when HA amounts were increased in composite formulation. The change in mechanical properties of copolymer was found to correlate well to HA concentration in the constructs. Electron microscopy revealed mineral nucleation and a change in surface morphology and the presence of calcium and phosphate on surfaces was confirmed using energy dispersive X‐ray analysis. To characterize the effect of mineral on attachment and maturation of pre‐osteoblasts, W20‐17 cells were seeded on HA/copolymer composites. We demonstrated that cells attached more to the surface of HA containing copolymers and their proliferation rate was significantly increased. Thus, these findings suggest that HA/PPF‐co‐PCL composite scaffolds are capable of inducing maturation of pre‐osteoblasts and have the potential for use as scaffold in bone tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2549–2557, 2015.

Abstract The Polycomb repressive complex 2 (PRC2) is important for maintenance of stem cell pluripotency and suppression of cell differentiation by promoting histone H3 lysine 27 trimethylation (H3K27me3) and transcriptional repression of differentiation regulatory genes. Here we show that the tumor suppressor protein BRCA1 interacts with EZH2 and other components of PRC2 in mouse embryonic stem (ES) and human breast cancer cells. The BRCA1-binding region in EZH2 overlaps with the non-coding RNA (ncRNA)-binding domain, and BRCA1 expression inhibits the binding of EZH2 to the HOTAIR ncRNA. Decreased expression of BRCA1 causes EZH2 re-targeting genome wide and elevates H3K27me3 levels at PRC2 target loci in both mouse ES and human breast cancer cells. BRCA1 deficiency blocks ES cell differentiation and enhances breast cancer migration and invasion in an EZH2-dependent manner. These results reveal that BRCA1 is a key negative modulator of PRC2 and that loss of BRCA1 inhibits ES cell differentiation and enhances cancer aggressive phenotypes via augmented PRC2 function. Citation Format: Xianzhou Zeng, Shuai Chen, Lan Wang, Haojie Huang. BRCA1 is a negative modulator of the PRC2 complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5358. doi:10.1158/1538-7445.AM2013-5358

Abstract Classic hyperacute rejection is dependent on the activation of the terminal components of complement. Recently, xenoantibodies with limited abilities to activate the classical pathway of complement in vitro have been implicated in the acute vascular rejection of xenografts. It is unclear how these Abs affect their pathogenic activities in vivo. In this study, we demonstrate the ability of an anti-Gal-α1,3Gal (Gal) IgG1, with modest complement-activating abilities in vitro, to induce xenograft rejection. This rejection was dependent on the activation of complement, on FcγR-mediated interactions, and on the presence of NK cells. Inhibition of any one of these factors resulted in the abrogation of IgG1-mediated rejection. In contrast, an anti-Gal IgG3 mAb induced classic, hyperacute rejection that was solely dependent on complement activation. Our observations implicate two types of IgG-mediated rejection; one that is dependent on complement activation, and a second that is uniquely dependent on complement, FcγR, and NK cells.

Abstract We have shown previously that Wiskott-Aldrich syndrome protein (WASP) activation at the site of T cell-APC interaction is a two-step process, with recruitment dependent on the proline-rich domain and activation dependent on binding of Cdc42-GTP to the GTPase binding domain. Here, we show that WASP recruitment occurs through binding to the C-terminal Src homology 3 domain of Nck. In contrast, WASP activation requires Vav-1. In Vav-1-deficient T cells, WASP recruitment proceeds normally, but localized activation of Cdc42 and WASP is disrupted. The recruitment and activation of WASP are coordinated by tyrosine-phosphorylated Src homology 2 domain-containing leukocyte protein of 76 kDa, which functions as a scaffold, bringing Nck and WASP into proximity with Vav-1 and Cdc42-GTP. Taken together, these findings reconstruct the signaling pathway leading from TCR ligation to localized WASP activation.

Significance Tumor cells adapt to hypoxia by modulating energy production and utilization. Endocytosis is an energy-consuming process that is suppressed during hypoxia. Our studies show that Dynamin 2 (DNM2), a key component of endocytic machinery, is transcriptionally suppressed by HIF-1. Genetic and pharmacological inactivation of DNM2 stabilized HIF-1α and HIF-2α. Furthermore, miR-199a, which is encoded from the opposite strand of DNM2 , exerts reciprocal negative regulation upon HIF-1α and HIF-2α. Overexpression of miR-199a decreased HIF-1α and HIF-2α, cell migration, and metastasis. These findings establish a regulatory loop between endocytic pathway and hypoxic response in tumor cells.