50 research outputs found
Table_S1_Henipavirus zoonosis: outbreaks, animal hosts and potential new emergence.xlsx
Hendra virus (HeV) and Nipah virus (NiV) are biosafety level 4 zoonotic pathogens causing severe and often fatal neurological and respiratory disease. These agents have been recognized by the World Health Organization as top priority pathogens expected to result in severe future outbreaks. HeV has caused sporadic infections in horses and a small number of human cases in Australia since 1994. The NiV Malaysia genotype (NiV-M) was responsible for the 1998–1999 epizootic outbreak in pigs with spillover to humans in Malaysia and Singapore. Since 2001, the NiV Bangladesh genotype (NiV-B) has been the predominant strain leading to outbreaks almost every year in Bangladesh and India, with hundreds of infections in humans. The natural reservoir hosts of HeV and NiV are fruit bats, which carry the viruses without clinical manifestation. The transmission pathways of henipaviruses from bats to humans remain poorly understood. Transmissions are often bridged by an intermediate animal host, which amplifies and spreads the viruses to humans. Horses and pigs are known intermediate hosts for the HeV outbreaks in Australia and NiV-M epidemic in Malaysia and Singapore, respectively. During the NiV-B outbreaks in Bangladesh, following initial spillover thought to be through the consumption of date palm sap, the spread of infection was largely human-to-human transmission. Spillover of NiV-B in recent outbreaks in India is less understood, with the primary route of transmission from bat reservoir to the initial human infection case(s) unknown and no intermediate host established. This review aims to provide a concise update on the epidemiology of henipaviruses covering their previous and current outbreaks with emphasis on the known and potential role of livestock as intermediate hosts in disease transmission. Also included is an up-to-date summary of newly emerging henipa-like viruses and animal hosts. In these contexts we discuss knowledge gaps and new challenges in the field and propose potential future directions.</p
Receiver operating characteristic curves were used to identify the optimal cutoff value of tumor size predicting survival.
<p>(A) cancer-specific survival and (B) recurrence-free survival.</p
Influence of tumor size on oncological outcomes of pathological T3aN0M0 renal cell carcinoma treated by radical nephrectomy
<div><p>Objective</p><p>To evaluate the prognostic significance of tumor size in pathological T3aN0M0 renal cell carcinoma (RCC) treated by radical nephrectomy.</p><p>Materials and methods</p><p>Patients who underwent radical nephrectomy for sporadic RCC with pathological T3aN0M0 RCC at our institution between January 2006 and June 2015 were identified. The entire cohort was divided into two groups according to the cutoff of tumor size obtained from receiver operating characteristic (ROC) curve. Clinicopathological variables were retrospectively collected and compared. Kaplan-Meier analysis and multivariate Cox regression were conducted to evaluate the effect of tumor size on survival outcomes.</p><p>Results</p><p>163 pT3aN0M0 RCC patients were included with a median follow-up period of 31 months. The optimal cutoff for tumor size was 7 cm according to the ROC curve. 90 cases (55.2%) presented tumors which measured 7 cm or less, and 73 cases (44.8%) showed tumor size greater than 7 cm. Patients with larger tumors tended to exhibit higher rates of symptoms and higher Fuhrman grades; they also indicated more necrosis features, and were more likely to invade the collecting system and renal vein. Compared with patients who exhibited tumor size of≤7 cm, those with tumor size>7 cm were associated with shorter estimated five-year cancer-specific survival (CSS, 46.6% versus 75.0%, <i>P</i> = 0.003) and five-year recurrence-free survival (RFS, 35.6% versus 62.7%, <i>P</i> = 0.011). Multivariate Cox analysis revealed that tumor size was retained as an independent factor for CSS (HR = 2.506, 95% CI 1.169–5.373, <i>P</i> = 0.018).</p><p>Conclusions</p><p>The tumor size significantly affected the survival outcomes of pT3aN0M0 RCC treated by radical nephrectomy, and a cutoff size of 7 cm can help enhance the prognostic discrimination. Thus, the tumor size may be considered in the future TNM classification of stage pT3a.</p></div
The Tandem PH Domain-Containing Protein 2 (TAPP2) Regulates Chemokine-Induced Cytoskeletal Reorganization and Malignant B Cell Migration
<div><p>The intracellular signaling processes controlling malignant B cell migration and tissue localization remain largely undefined. Tandem PH domain-containing proteins TAPP1 and TAPP2 are adaptor proteins that specifically bind to phosphatidylinositol-3,4-bisphosphate, or PI(3,4)P2, a product of phosphoinositide 3-kinases (PI3K). While PI3K enzymes have a number of functions in cell biology, including cell migration, the functions of PI(3,4)P2 and its binding proteins are not well understood. Previously we found that TAPP2 is highly expressed in primary leukemic B cells that have strong migratory capacity. Here we find that SDF-1-dependent migration of human malignant B cells requires both PI3K signaling and TAPP2. Migration in a transwell assay is significantly impaired by pan-PI3K and isoform-selective PI3K inhibitors, or by TAPP2 shRNA knockdown (KD). Strikingly, TAPP2 KD in combination with PI3K inhibitor treatment nearly abolished the migration response, suggesting that TAPP2 may contribute some functions independent of the PI3K pathway. In microfluidic chamber cell tracking assays, TAPP2 KD cells show reduction in percentage of migrating cells, migration velocity and directionality. TAPP2 KD led to alterations in chemokine-induced rearrangement of the actin cytoskeleton and failure to form polarized morphology. TAPP2 co-localized with the stable F-actin-binding protein utrophin, with both molecules reciprocally localizing against F-actin accumulated at the leading edge upon SDF-1 stimulation. In TAPP2 KD cells, Rac was over-activated and localized to multiple membrane protrusions, suggesting that TAPP2 may act in concert with utrophin and stable F-actin to spatially restrict Rac activation and reduce formation of multiple membrane protrusions. TAPP2 function in cell migration is also apparent in the more complex context of B cell migration into stromal cell layers – a process that is only partially dependent on PI3K and SDF-1. In summary, this study identified TAPP2 as a novel regulator of malignant B cell migration and a potential therapeutic intervention target.</p> </div
Kaplan–Meier analysis of survival stratified by tumor size with a cutoff of 7 cm.
<p>(A) cancer-specific survival and (B) recurrence-free survival.</p
Univariate and multivariate Cox regression analysis of clinicaopathological variables for cancer-specific survival.
<p>Univariate and multivariate Cox regression analysis of clinicaopathological variables for cancer-specific survival.</p
Clinicopathological characteristics of 163 patients with pT3aN0M0 RCC and subgroup comparison of variables according to the tumor size (cutoff of 7cm).
<p>Clinicopathological characteristics of 163 patients with pT3aN0M0 RCC and subgroup comparison of variables according to the tumor size (cutoff of 7cm).</p
The Association of Platelet Count with Clinicopathological Significance and Prognosis in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis
<div><p>Objective</p><p>Elevated platelet count (PC), a measure of systemic inflammatory response, is inconsistently reported to be associated with poor prognosis in patients with renal cell carcinoma (RCC). We conducted a systematic review and meta-analysis to clarify the significance of PC in RCC prognosis.</p><p>Methods</p><p>PubMed, Embase, and Web of Science databases were searched to identify eligible studies to evaluate the associations of PC with patient survival and clinicopathological features of RCC.</p><p>Results</p><p>We analyzed 25 studies including 11,458 patients in the meta-analysis and categorized the included articles into three groups based on RCC stage. An elevated PC level was associated with poor overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87-2.67, <i>P</i><0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48, <i>P</i><0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI 2.41-10.73, <i>P</i><0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34, <i>P</i><0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, <i>P</i><0.001) for metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, <i>P</i> = 0.038), CSS (HR 3.38, 95% CI 1.86-6.15, <i>P</i><0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, <i>P</i> = 0.002) for clear cell RCC. Furthermore, an elevated PC level was significantly associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, <i>P</i> = 0.001), pathological T stage (OR 3.13, 95% CI 2.60-3.77, <i>P</i><0.001), lymph node metastasis (OR 4.01, 95% CI 2.99-5.37, <i>P</i><0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, <i>P</i><0.001), Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, <i>P</i><0.001), tumor size (OR 4.69, 95% CI 2.78-7.91, <i>P</i><0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI 3.26-9.28, <i>P</i><0.001).</p><p>Conclusion</p><p>An elevated PC level implied poor prognosis in patients with RCC and could serve as a readily available biomarker for managing this disease.</p></div
TAPP2 KD leads to decreased migration speed and directionality in a stable SDF-1 gradient.
<p>NALM-6 cells transduced with control or TAPP2 KD lentivirus were loaded onto a microfluidic chemotaxis device and exposed to a 100 nM SDF-1 gradient (represented with triangles). Time-lapse images were taken and cell movement was analyzed using cell-tracking software. <b>A.</b> Panels show the first and last image from a representative experiment. Migrating cell tracks are marked in blue (migrating toward higher SDF-1 concentration) or red (migrating towards lower SDF-1 concentration). <b>B.</b> Migration tracks of control or TAPP2 KD cells in a 1 hour experiment were normalized to a common origin (0, 0) and plotted to visualize patterns of movement in two dimensions (the chemokine gradient is in the y dimension as indicated). Black tracks represent cells migrating toward the gradient and grey tracks are for cells migrating against the gradient. The solid circles indicate the end of the cell tracks. <b>C.</b> Migration tracks of control or TAPP2 KD cells in a 4 hour experiment were plotted as in C. <b>D.</b> Chemotaxis index of control and TAPP2 KD cells, calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057809#s2" target="_blank">Methods</a>. <b>E.</b> Migration speed of control and TAPP2 KD cells, calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057809#s2" target="_blank">Methods</a>. Data are representative of four independent experiments.</p
Bilateral Synchronous Sporadic Renal Cell Carcinoma: Retroperitoneoscopic Strategies and Intermediate Outcomes of 60 Patients
<div><p>Objective</p><p>To evaluate the presentation, management, pathology, and functional and oncological outcomes of patients undergoing retroperitoneoscopic treatment of bilateral synchronous sporadic RCC at our institution.</p><p>Methods</p><p>We retrospectively evaluated the records of 60 patients with bilateral synchronous sporadic RCC who underwent retroperitoneoscopic treatment at the General Hospital of People's Liberation Army from 2008 to 2014. The estimated glomerular filtration rate was calculated and compared among different surgical procedures. The overall survival and recurrence free survival were assessed based on information from recent follow-up.</p><p>Results</p><p>Fifty-six patients underwent bilateral retroperitoneoscopic surgeries in staged procedures, and four patients underwent bilateral retroperitoneoscopic surgeries in simultaneous procedures. Among the former group of patients, 34 underwent bilateral partial nephrectomy, 12 underwent radical nephrectomy followed by partial nephrectomy, and 10 underwent partial nephrectomy followed by radical nephrectomy. Bilateral partial nephrectomy can better preserve renal function (p = 0.040) and the sequence of partial nephrectomy and radical nephrectomy did not affect functional outcomes (p = 0.790). One patient undergoing simultaneous procedures developed acute renal failure and required temporary hemodialysis. At 3 and 5 years, overall survival rates were 93.0% and 89.4%, and recurrence free survival rates were 90.5% and 81.6%. High nuclear grade (p = 0.014) was related to disease recurrence.</p><p>Conclusions</p><p>Staged bilateral partial nephrectomy was efficient in preserving renal function. The survival of patients with bilateral synchronous sporadic renal tumors was similar to that of patients with unilateral nonmetastatic tumors. Nuclear grade was an independent prognostic factor of disease recurrence.</p></div