20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Epidemiological study of scorpion stings in Saudi Arabia between 1993 and 1997

This investigation evaluated the epidemiological aspects of scorpion stings in different areas of Saudi Arabia. A total of 72,168 cases of scorpion stings recorded in Ministry of Health Medical Centers in 11 selected areas of Saudi Arabia were analyzed based on area, age, sex, time of sting, sting site, treatment outcome, time of year, and scorpion species. Stings occurred throughout the year; the highest frequency was in June (15.08%), the lowest in February (2.52%). Most patients were male (61.8%); the majority of which were more than 15 years old (65.4%). Nocturnal envenomation (47.74%) was more common than diurnal (43.91%); most stings were in exposed limbs (90.95%), mainly in the lower limbs (63%). Most envenomings were mild (74.48%) and all evolved to cure, except for one death. Envenomation was characterized by local pain, erythema, headache, vomiting, and anxiety. This study found that the Leiurus quinquestriatus (Ehrenberg 1828), Androctonus crassicauda (Olivier 1807), and Apistobuthus pterygocercus (Finnegan 1807) were responsible for most of the stings, indicating their medical importance in Saudi Arabia. The study shows low threat to life despite the high number of stings; this is a result of the availability of medical facilities and the multi-center antivenom use in different areas of Saudi Arabia

Seasonal changes in metabolism of the lizard, Lacerta vivippara,

Acute oxygen consumption determinations for both adults and sub-adults of L. vivipara were made over the temperature range 5-30°C during summer and winter. During winter dormancy, both adults and sub-adults were found to have a metabolic rate lower than the metabolic rate of summer animals at each experimental temperature. This reduction of oxygen consumption in winter lizards can be interpreted as an "inverse compensation" (Precept's Type 5 pattern of response). It is concluded that this adjustment can reduce energy costs during the winter period and is a pre-requisite for survival during winter dormancy

<it>Walterinnesia aegyptia </it>venom combined with silica nanoparticles enhances the functioning of normal lymphocytes through PI3K/AKT, NFκB and ERK signaling

Abstract Background The toxicity of snake venom varies over time in some species. The venom of newborn and small juvenile snakes appears to be more potent than adults of the same species, and a bite from a snake that has not fed recently, such as one that has just emerged from hibernation, is more dangerous than one that has recently fed due to the larger volume of venom injected. Therefore, the potency of a snake's venom is typically determined using the LD50 or IC50 tests. In the present study, we evaluated the anti-tumor potential of snake venom from Walterinnesia aegyptia (WEV) on the human breast carcinoma cell line MDA-MB-231, as well as its effect on the normal mice peripheral blood mononuclear cells (PBMCs). Results This venom was used alone (WEV) or in combination with silica nanoparticles (WEV+NP). The IC50 values of WEV alone and WEV+NP in the MDA-MB-231 cells were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal human PBMCs. To investigate the in vivo effects of this venom further, three groups of mice were used (15 mice in each group): Group I was the control, Group II was subcutaneously injected with WEV, and Group III was injected with WEV+NP. Using flow cytometry and western blot analysis, we found that the blood lymphocytes of WEV-injected mice exhibited a significant increase in actin polymerization and cytoskeletal rearrangement in response to CXCL12 through the activation of AKT, NF-κB and ERK. These lymphocytes also showed a significant increase in their proliferative capacity in response to mitogen stimulation compared with those isolated from the control mice (P Conclusion Our data reveal the unique biological effects of WEV, and we demonstrated that its combination with nanoparticles strongly enhanced these biological effects.</p

Spam filtering email classification (SFECM) using gain and graph mining algorithm

This paper proposes a hybrid solution of spam email classifier using context based email classification model as main algorithm complimented by information gain calculation to increase spam classification accuracy. Proposed solution consists of three stages email pre-processing, feature extraction and email classification. Research has found that LingerIG spam filter is highly effective at separating spam emails from cluster of homogenous work emails. Also experiment result proved the accuracy of spam filtering is 100% as recorded by the team of developers at University of Sydney. The study has shown that implementing the spam filter in the context -based email classification model is feasible. Experiment of the study has confirmed that spam filtering aspect of context-based classification model can be improved

Cellular and Molecular Mechanisms Underlie the Anti-Tumor Activities Exerted by <em>Walterinnesia aegyptia</em> Venom Combined with Silica Nanoparticles against Multiple Myeloma Cancer Cell Types

<div><p>Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from <em>Walterinnesia aegyptia</em> (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC₅₀ values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, Bcl_XL and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and the underlying mechanisms against myeloma cancer cells.</p> </div