On the Security of the Schnorr Signature Scheme and DSA against Related-Key Attacks

In the ordinary security model for signature schemes, we consider an adversary that may forge a signature on a new message using only his knowledge of other valid message and signature pairs. To take into account side channel attacks such as tampering or fault-injection attacks, Bellare and Kohno (Eurocrypt 2003) formalized related-key attacks (RKA), where stronger adversaries are considered. In RKA for signature schemes, the adversary can also manipulate the signing key and obtain signatures for the modified key. This paper considers RKA security of two established signature schemes: the Schnorr signature scheme and (a well-known variant of) DSA. First, we show that these signature schemes are secure against a weak notion of RKA. Second, we demonstrate that, on the other hand, neither the Schnorr signature scheme nor DSA achieves the standard notion of RKA security, by showing concrete attacks on these. Lastly, we show that a slight modification of both the Schnorr signature scheme and (the considered variant of) DSA yields fully RKA secure schemes

WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth

ABSTRACT: INTRODUCTION: In breast cancer deregulation of the WNT signaling pathway occurs by autocrine mechanisms. WNT ligands and Frizzled (FZD) receptors are coexpressed in primary breast tumors and cancer cell lines. Moreover, many breast tumors show hypermethylation of secreted Frizzled-related protein 1 (sFRP1)'s promoter region, causing low expression of this WNT antagonist. We have previously shown that the WNT pathway influences proliferation of breast cancer cell lines via activation of canonical signaling and epidermal growth factor receptor (EGFR) transactivation, and that interference with WNT signaling reduces proliferation. Here we examine the role of WNT signaling in breast tumor cell migration and on xenograft outgrowth. METHODS: The breast cancer cell line MDA-MB-231 was used to study WNT signaling. We examined the effects of activating or blocking the WNT pathway on cell motility by treatment with WNT ligands or by ectopic sFPR1 expression, respectively. The ability of sFRP1 expressing MDA-MB-231 cells to grow as xenografts was also tested. Microarray analyses were carried out to identify targets with roles in MDA-MB-231/sFRP1 tumor growth inhibition. RESULTS: We show that WNT stimulates the migratory ability of MDA-MB-231 cells. Furthermore, ectopic expression of sFRP1 in MDA-MB-231 cells blocks canonical WNT signaling and decreases their migratory potential. Moreover, the ability of MDA-MB-231/sFRP1 expressing cells to grow as xenografts in mammary glands and to form lung metastases is dramatically impaired. Microarray analyses led to the identification of two genes, CCND1 and CDKN1A, whose expression level is selectively altered in vivo in sFRP1 expressing tumors. The encoded proteins, Cyclin D1 and p21Cip1 were down- and up-regulated, respectively, in sFRP1 expressing tumors, suggesting that they are downstream mediators of WNT signaling. CONCLUSIONS: Our results show that the WNT pathway influences multiple biological properties of MDA-MB-231 breast cancer cells. WNT stimulates tumor cell motility; conversely sFRP1 mediated WNT pathway blockade reduces motility. Moreover, ectopic sFRP1 expression in MDA-MB-231 cells has a strong negative impact on tumor outgrowth and blocked lung metastases. These results suggest that interference with WNT signaling using sFRP1 to block the ligand-receptor interaction may be a valid therapeutic approach in breast cancer

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

The elements of human cyclin D1 promoter and regulation involved

Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the promoter at different time to get the correct cell cycle switch. Disorder regulation or special extracellular stimuli can result in cell cycle out of control through the promoter activity regulation. Epigenetic modifications such as DNA methylation and histone acetylation may involved in cyclin D1 transcriptional regulation

Significance of prediction of the dorsal landmark using three-dimensional computed tomography during laparoscopic lymph node dissection along the proximal splenic artery in gastric cancer

Objectives: Dissection of the No. 11p lymph nodes is technically challenging because of variations in anatomical landmarks. This study aimed to determine the accuracy and efficacy of predicting the dorsal landmark of No. 11p lymph node using three-dimensional computed tomography simulation. Methods: Laparoscopic gastrectomy with No. 11p lymph node dissection with preoperative simulation using three-dimensional computed tomography was performed in 24 patients at our institution from October 2016 to May 2018. Initially, preoperative three-dimensional computed tomography findings with operative videos in these 24 patients were compared. The dorsal landmark was defined as an anatomical structure behind the splenic artery on preoperative three-dimensional computed tomography and operative videos. The dorsal landmark of No. 11p lymph node was divided into four types: (1) splenic vein type, (2) splenic vein and pancreas type, (3) pancreas type, and (4) unclear type. Then, to investigate the efficacy of three-dimensional computed tomography, we compared the clinical and pathological features and surgical outcomes of nine patients who underwent preoperative three-dimensional computed tomography simulation (three-dimensional computed tomography group) and 23 patients who did not undergo three-dimensional computed tomography simulation from August 2014 to September 2016 (non-three-dimensional computed tomography group). All procedures were performed by one surgeon certified by the Endoscopic Surgical Skill Qualification System in Japan. Results: The concordance rate between three-dimensional computed tomography and operative videos of the dorsal landmark using three-dimensional computed tomography was 79% (19/24). The operative time of No. 11p lymph node dissection was significantly shorter in the three-dimensional computed tomography group than in the non-three-dimensional computed tomography group (7.7 versus 15.8 min, P = 0.044). Conclusion: The accuracy of predicting the dorsal landmark of No. 11p lymph node using three-dimensional computed tomography was extremely high. Preoperative simulation with three-dimensional computed tomography was useful in shortening the operative time of No. 11p lymph node dissection