China's Three Gorges Dam has generated a large riparian zone around the reservoir that has changed the natural fluctuation in water level (FWL) and intensity of anthropogenic disturbance (AD, i.e. ...human activities triggering pollutant input). Knowledge about how riparian soil properties respond to such changes remains limited. The aims of this study were to identify the distribution of soil properties in the riparian zone and to determine which types of factors, local‐scale FWL or regional‐scale AD, have a larger effect on the soil properties. A total of 144 composite soil samples, collected from two riparian areas in four sampling surveys, were investigated. Multivariate regression tree analysis indicated that the variation in soil properties was mainly controlled by FWL (40.1%) compared with the minor role of AD (2.1%). Soil total carbon, total nitrogen and organic matter were mainly affected by AD, whereas FWL had a major influence on soil pH, ammonium and nitrate. Along the elevation gradient (150–175 m), the soil properties were determined mainly by the sampling elevation, accounting for 67.6% of the variation, followed by short‐term (5.6%) and long‐term flooding (3.3%). The 167.5‐m elevation was proposed to be the threshold that divides the riparian zone into two different response zones. Soil below 167.5 m was mainly affected by local‐scale FWL, whereas that above 167.5 m was largely affected by regional‐scale AD. This proposed threshold suggests that riparian soil management around the Three Gorges Reservoir should consider both local‐ and regional‐scale factors and that different approaches and strategies for ecological restoration need to be applied along an elevation gradient.
Highlights
We studied how soil properties respond to fluctuation in water level (FWL) and anthropogenic disturbance (AD).
The relative importance of local‐scale FWL and regional‐scale AD was evaluated quantitatively.
The 167.5‐m elevation divides the riparian zone into two areas that respond differently to local and regional factors.
The variation in riparian soil properties was mainly controlled by local FWL (40.1%) rather than regional AD (2.1%).
Abstract
This work investigated the cytotoxicities of three silver nanoparticles (SNPs) SNP-5, SNP-20 and SNP-50 with different sizes (∼ 5 nm, ∼ 20 nm and ∼ 50 nm) using four human cell models (A549, ...SGC-7901, HepG2 and MCF-7). Endpoints included cell morphology, cell viability, cellular membrane integrity, oxidative stress and cell cycle progression. Observable deleterious effects on the cell morphologies and membrane integrity were induced by SNP-5 and SNP-20. SNPs elevated the ROS levels in cells and arrested the cells at S phase. Apoptosis occurred for 4-9% of the exposed cells. All these cellular responses as well as EC50 values were found to be size-dependent for the tested SNPs. Ultrastructural observations confirmed the presence of SNPs inside cells. Elemental analysis of silver in cells by ICP-MS showed that smaller nanoparticles enter cells more easily than larger ones, which may be the cause of higher toxic effects. The findings may assist in the design of SNP applications and provide insights into their toxicity.
Androgen receptor (AR)-mediated gene expression continues to have a critical role in promoting castration-resistant prostate cancer (CRPC) survival and growth even after androgen deprivation therapy. ...AR cistrome analyses in CRPC cells have identified a large number of AR target genes involved in proliferative and cell cycle-related functions, and hold promise for development of novel therapeutic approaches for CRPC. However, there is little understanding of how these genes function in vivo and what the clinical implications are. We previously reported that secretory leukocyte peptidase inhibitor (SLPI) is regulated by the AR in a ligand-independent manner in CRPC cells and required for CRPC cell proliferation under androgen-deprived conditions. SLPI is a secreted serine protease inhibitor, which is overexpressed in a number of cancers, including lung, breast and ovarian cancer, and involved in tumor progression. However, the oncogenic potential of SLPI in prostate cancer remains unknown. Here we provide the first evidence that SLPI is upregulated in a subset of CRPC cell lines and CRPC patient tumors. In addition, serum SLPI levels are significantly elevated in metastatic CRPC patients compared with hormone naive patients, raising the possibility that this could serve as a biomarker. We demonstrated that SLPI expression has functional significance, as it promotes CRPC cell survival and growth after androgen withdrawal in vivo and in vitro. Last, we demonstrated that the oncogenic effect of SLPI may be due to protection of growth factor progranulin from enzymatic cleavage or suppression of CRPC cell apoptosis independent of anti-protease activity of SLPI. These findings implicate SLPI as a potential biomarker of resistance to AR inhibition and therapeutic target for CRPC treatment.
Extramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment ...strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years.
A systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language.
According to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death.
To date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.
The steady state radial electric field (Er) is calculated by coupling a plasma transport model with the quasi-neutrality constraint and the vorticity equation within the BOUT++ framework. Based on ...the experimentally measured plasma density and temperature profiles in Alcator C-Mod discharges, the effective radial particle and heat diffusivities are inferred from the set of plasma transport equations. The effective diffusivities are then extended into the scrape-off layer (SOL) to calculate the plasma density, temperature and flow profiles across the separatrix into the SOL with the electrostatic sheath boundary conditions (SBC) applied on the divertor plates. Given these diffusivities, the electric field can be calculated self-consistently across the separatrix from the vorticity equation with SBC coupled to the plasma transport equations. The sheath boundary conditions act to generate a large and positive Er in the SOL, which is consistent with experimental measurements. The effect of magnetic particle drifts is shown to play a significant role on local particle transport and Er by inducing a net particle flow in both the edge and SOL regions.
Objectives
To assess the diagnostic performance of conventional and DW-MRI parameters in the detection of residual tumor in locally advanced cervical cancer (LACC) patients treated with neoadjuvant ...chemoradiotherapy (nCRT) and radical surgery
Methods
Between October 2010 and June 2014, 88 patients with histologically documented cervical cancer (FIGO stage IB2–IVA) were prospectively included in the study. Maximum tumor diameters (
max
TD), tumor volume (TV), DWI signal intensity (SI), and ADC
mean
were evaluated at MRI after nCRT. Histology was the reference standard. Treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney,
χ
2
, and Fisher’s exact tests. ROC curves were generated for variables to evaluate diagnostic ability to predict PR and to determine the best cutoff value to predict PR. For each diagnostic test, sensitivity, specificity, and accuracy were calculated.
Results
TV and
max
TD were significantly smaller in the CR than in the PR group (
p
< 0.001;
p
= 0.001) and showed, respectively, sensitivity of 68.8%, specificity of 72.5%, and accuracy of 70.5% and of 47.9, 87.5, and 65.9% in predicting PR. High DWI SI was more frequent in the PR (81.8%) than in the CR group (55.3%) (
p
< 0.009). ADC
mean
was higher in the CR (1.3 × 10
-3
mm
2
/s, range 0.8–1.6 × 10
-3
mm
2
/s) than in the PR group (1.1 × 10
-3
mm
2
/s; range 0.7–1.8 × 10
-3
mm
2
/s) (
p
< 0.018). High DWI SI showed sensitivity, specificity, and accuracy of 81.8, 44.7, and 64.6% in predicting PR. The ADC
mean
measurement increased sensitivity, specificity, and accuracy to 75.0, 76.2, and 75.4%.
Conclusions
Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. The ADC
mean
value ≤ 1.1 × 10
-3
mm
2
/s was the best cutoff to predict PR.
Key Points
• Conventional and DW-MRI is useful for predicting PR after nCRT in LACC.
• The combination of T2 sequences, DW-MRI, and the quantitative measurement of ADC
mean
showed the best results in predicting pathological PR.
• The best cutoff for predicting pathological PR was ADC
mean
value ≤ 1.1 × 10
-3
mm
2
/s.
Objectives
To analyse the role of DW-MRI in early prediction of pathologically-assessed residual disease in locally-advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed ...by radical surgery.
Methods
Between October 2010–June 2014, 108 women with histologically-proven cervical cancer were screened; 88 were included in this study. Tumour volume (TV) and ADC
mean
were measured before (baseline-MRI) and after 2 weeks of chemoradiotherapy (early-MRI). According to histopathology, treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, Wilcoxon and χ2 tests. ROC curves were generated for statistically significant parameters on univariate analysis.
Results
CR and PR were documented in 40 and 48 patients. At baseline-MRI, TV did not differ between groups. At early-MRI, TV was higher in PR than in CR (p=0.001). ΔTV reduction after treatment was lower in PR than in CR (63.6% vs. 81.1%; p=0.001). At baseline-MRI and early-MRI, ADC
mean
did not differ between PR and CR. ROC curve showed best cut-off for predicting pathological PR was ΔTV reduction of 73% with sensitivity, specificity, accuracy, NPV, PPV of 73%, 72.5%, 72.7%, 76%, 69%.
Conclusions
TV evaluated before and early after treatment could predict pathological response in LACC. ADC
mean
did not correlate with treatment outcome.
Key Points
• Early-MRI tumour volume assessment could predict pathological response to nCRT in LACC.
• Best cut-off for predicting pathological PR was ΔTV reduction of 73 %.
• Early-MRI ADC
mean
measurements did not correlate with treatment outcome.
Objective
The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma.
Evidence ...acquisition
A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990–2018) as concerns the years of the publication was considered.
Evidence synthesis
Primary disease: the median 5-year LC was 43.5% (range 19–68%); the median 5-year DFS was 44.5% (range 44–81%); the median 5-year OS was 50.5% (range 27–85%). Recurrent disease: the median 5-year DFS was 64% (range 56–72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3–4) ranged from 0% to 14.3% (median 7.7%).
Conclusion
IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.
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