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Background: Prostate cancer is a significant clinical issue, particularly for high Gleason score (GS) malignancy patients. Our study aimed to engineer and validate a risk model based on the profiles of high-GS PCa patients for early identification and the prediction of prognosis. Methods: We conducted differential gene expression analysis on patient samples from The Cancer Genome Atlas (TCGA) and enriched our understanding of gene functions. Using the least absolute selection and shrinkage operator (LASSO) regression, we established a risk model and validated it using an independent dataset from the International Cancer Genome Consortium (ICGC). Clinical variables were incorporated into a nomogram to predict overall survival (OS), and machine learning was used to explore the risk factor characteristics’ impact on PCa prognosis. Our prognostic model was confirmed using various databases, including single-cell RNA-sequencing datasets (scRNA-seq), the Cancer Cell Line Encyclopedia (CCLE), PCa cell lines, and tumor tissues. Results: We identified 83 differentially expressed genes (DEGs). Furthermore, WASIR1, KRTAP5-1, TLX1, KIF4A, and IQGAP3 were determined to be significant risk factors for OS and progression-free survival (PFS). Based on these five risk factors, we developed a risk model and nomogram for predicting OS and PFS, with a C-index of 0.823 (95% CI, 0.766–0.881) and a 10-year area under the curve (AUC) value of 0.788 (95% CI, 0.633–0.943). Additionally, the 3-year AUC was 0.759 when validating using ICGC. KRTAP5-1 and WASIR1 were found to be the most influential prognosis factors when using the optimized machine learning model. Finally, the established model was interrelated with immune cell infiltration, and the signals were found to be differentially expressed in PCa cells when using scRNA-seq datasets and tissues. Conclusions: We engineered an original and novel prognostic model based on five gene signatures through TCGA and machine learning, providing new insights into the risk of scarification and survival prediction for PCa patients in clinical practice.

In recent years, the incidence of prostate cancer in China has shown a trend of continuous growth. Prostate cancer has become a urinary malignant tumor that seriously affects the health of men in China. Radical surgery and precision radiotherapy are the main methods of radical treatment for prostate cancer. Standardized diagnosis and treatment via a multidisciplinary team should be the standard practice to improve cure rate. Rapid development in imaging, pathology and molecular gene diagnosis has significantly changed the management of prostate cancer. In radiation oncology, image‐guided intensity modulated radiotherapy has been widely adopted in the treatment of prostate cancer. The comprehensive approach centered with radiotherapy has achieved excellent curative effect while continuously reducing treatment‐related side effects.

Purpose: Our previous study showed that the linear quadratic (LQ) model appeared to be inappropriate for high doses per fraction owing to α/β ratio tending to become higher when the dose per fraction increased. In order to verify this conclusion, we explored the mechanisms for the elevated α/β ratio after hypofractionated radiotherapy. Materials and Methods: We selected two prostate cancer cell lines DU145 and PC3: 1) Draw the cell survival curve to calculate the α/β ratio, and then use biological effective dose (BED) formula to convert fractionated radiation dose into equivalent single hypofractionated radiation dose (calculated values) comparing with that on the survival curve (actual values). 2) Western Blot and laser confocal immunofluorescence were used to detect the expression of γ-H2AX and RAD51 after different fractionated modes of radiation at different time points. Results: 1) When fractionated radiation dose was converted into equivalent single hypofractionated radiation dose, the ability of hypofractionated radiation was overestimated. If a larger α/β ratio is used, the discrepancy tended to become smaller. 2) Compared with fractionated radiation, the results showed that the expression of γ-H2AX was higher after 30min, 6 h and 24h after single hypofractionated radiation. Meanwhile, the expression of RAD51 lasted for 24 hours and the DNA damage still existed in single hypofractionated radiation. 3) The results also showed that the expression of γ-H2AX decreased slightly after 24 hours of fractionated radiation compared with that of 6 hours, and there was no difference in single hypofractionated radiation between 6 hours and 24 hours. Conclusions: The results of this study suggest that after single hypofractionated radiation, the irreparable damage in cells increased (that is, α value increased), and some repairable sublethal damage (β value) was converted into irreparable damage (α value). When α value increased and β value decreased, the ratio increased.

Background The standard management for upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). However, some patients cannot undergo this procedure for several reasons, such as unresectable disease, old age, and multiple comorbidities. Our study explored the potential safety and effectiveness of radiotherapy as a curative treatment for UTUC patients unfit for surgery. Methods The data of patients treated with radiotherapy between December 2017 and November 2019 were retrospectively reviewed. For the literature review, computerized PubMed Medline, Index Medicus, and Web of Science databases and reference lists from the identified publications of interest were used. And "upper-tract urothelial carcinoma" and "radiotherapy" were used as key words in the search. Results We describe 8 patients with UTUC who were treated with radiotherapy. The median follow-up time was 13.5 months (range, 8.6-30.9 months). Local tumor control was achieved in all patients. However, distant metastases were observed in 2 patients with T3-4/N+ status. One patient had T4 status and the other had N2+ status. The patients died of tumor progression at 15.0 and 17.7 months. In addition, the other 6 patients who were still alive had relatively early-stage tumors without nodal involvement. Regarding acute toxicity, according to the CTCAE v5.0, mild side effects were noted, including grade 1 nausea and diarrhea. Four patients developed mild anemia, generally of grade 1-2. One patient experienced grade 3 anemia, but it was manageable and improved with symptomatic support. In addition, no grade 4 acute or late toxicities were observed. No significant long-term impairment of renal function occurred. Conclusions For patients with nonmetastatic UTUC who are not suitable for surgery, radiotherapy is a safe treatment and can achieve good local tumor control.

Red mud is a byproduct of the aluminium industry and is typically considered hazardous waste owing to its high alkali content and resulting environmental pollution. In this work, Bayer process red mud was used to partially replace oil well cement and its influence on the compressive strength of hardened cement pastes was explored under hydrothermal conditions. X-ray diffraction, scanning electron microscopy, nitrogen adsorption and thermal analysis were used to determine the phase composition, microscopic morphology, pore size distribution and bound water content, respectively, of hardened cement pastes to investigate the reasons underlying the observed strength change. The results obtained revealed that red mud can exert pozzolanic activity at addition levels of up to 5%, promote the cement hydration reaction and the production of calcium silicate hydrate (C–S–H), and ultimately increase the strength of hardened cement pastes. Higher red mud contents decreased the degree of cement hydration, which resulted in an increased volume of macropores (d > 50 nm), a decreased volume of mesopores (d = 4·5–50 nm) and a remarkably decreased strength.

Background Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5–3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. Methods The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification. Results Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI 1.59–1.98), 3.46 Gy (95% CI 3.27–3.65), and 4.24 Gy (95% CI 4.10–4.39), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased. Conclusions The LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.

Purpose We identified the risk predictors related to prostate cancer (PCa) metastasis using contemporary data in a community setting. Then, we assessed the performance of indications for bone imaging recommended from the NCCN, AUA and EAU guidelines. Methods Using the Surveillance, Epidemiology, and End Results database (2010–2015), we collected clinicopathological information from PCa patients. The associated risk factors found by multivariate analyses were used to establish forest plots and nomograms for distant metastasis (DM) and bone(s)-only metastasis (BM). We next evaluated the NCCN, AUA and EAU guidelines indications for the discovery of certain subgroups of patients who should receive bone imaging. Results A total of 120,136 patients were eligible for analysis, of which 96.7% had no metastasis. The odds ratios of positive DM and BM results were 13.90 times and 15.87 times higher in patients with a histologic grade group (GG) 5 than in the reference group. The concordance index of the nomograms based on race, age, T/N stage, PSA, GG, percentage of positive scores for predicting DM and BM was 0.942 and 0.928, respectively. Performance of the NCCN, AUA and EAU guidelines was high and relatively similar in terms of sensitivity (93.2–96.9%) and negative predictive value (99.8–99.9%). NCCN guidelines had the highest accuracy, specificity and positive likelihood ratio, while negative likelihood ratio was lowest in AUA guideline. Conclusion Histologic GG 5 was the foremost factor for DM and BM. NCCN-based recommendations may be more rational in clinical practice. Nomograms predicting metastasis demonstrate high accuracy.

Purpose This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations. Methods Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations. Results A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3–4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001). Conclusions Multifocality, T3–4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

Purpose Our purpose was to compare toxicity and biochemical control in postprostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiation therapy. Methods and Materials Patients who had stage pT3-4, positive surgical margins, or rising prostate-specific antigen ≥ 0.2 ng/mL after radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these 2 cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic toxicities between these 2 cohorts. bPFS was estimated by the Kaplan–Meier method and toxicities were compared using the χ2 test. Results Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range, 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs 82.6%; P = .299). However, in patients with a higher Gleason score (8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs 55.7%; P = .049). Toxicity analysis showed no difference in ≥2 acute or late GI or GU toxicities between these 2 cohorts. A total of 48 patients were scored as urinary incontinence before radiation therapy, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, and only 9 (18.8%) patients reported worsening. There was no difference between the 2 cohorts in urinary incontinence either at baseline or at 1-year follow-up. Conclusions Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities and did not increase urinary incontinence.

Existing gated delivery methods adopting predefined intervention thresholds, and better delivery accuracy comes at the expense of lower therapeutic efficiency. So we present a new gating strategy b...

PurposeWe retrospectively analyzed the oncological outcomes of T3 or G3 distal ureteral urothelial carcinoma (DUUC) underwent partial ureterectomy (PU) followed by adjuvant radiotherapy (ART).MethodsFrom January 2008 to September 2019, clinical data from a total of 221 patients with pathologic T3 or G3 who underwent PU or RNU at our hospital were analyzed. 17 patients of them were treated with PU+ART, 72 with PU alone and 132 with radical nephroureterectomy (RNU). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS), metastasis-free survival (MFS), cancer specific survival (CSS) and overall survival (OS).ResultsMedian age and follow-up time were 68 (IQR 62-76) years old and 43 (IQR 28-67) months, respectively. In univariate and multivariable analyses, no lymph node metastasis(LNM) and ART were independent prognostic factors of RFS (p=0.031 and 0.016, respectively). ART significantly improved 5-year RFS compared with the PU alone, (67.6% vs. 39.5%, HR: 2.431, 95%CI 1.210-4.883, p=0.039). There was no statistical difference in 5-year RFS between PU+ART and RNU groups (67.6% vs. 64.4%, HR=1.113, 95%CI 0.457-2.712, p=0.821). Compared with PU alone or RNU, PU+ART demonstrated no statistical difference in 5-year MFS (PU+ART 73.2%, PU 57.2%, RNU69.4%), CSS (70.7%, 55.1%, 76.6%, respectively), and OS (70.7%, 54.1%, 69.2%, respectively).ConclusionsFor distal ureteral urothelial carcinoma patients with T3 or G3, adjuvant radiotherapy could significantly improve recurrence-free survival compared with partial ureterectomy alone. There was no significant difference between survival outcomes of PU+ART and radical nephroureterectomy.

Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

This study investigates the pore structure of oil well cement slurry (OCS) in the suspension–solid transition stage and the effect of the hydrated products on the pore structure via isothermal calorimetry, scanning electron microscopy (SEM), nitrogen adsorption, thermogravimetry (TG), and low-field nuclear magnetic resonance (LF-NMR). The experimental results show that the suspension–solid transition stage of OCS includes a dynamic balance stage and an acceleration stage. The porosity of the fresh cement slurry is approximately 58.09%, and its pore sizes range from 100 nm to 850 nm. In the dynamic balance stage, a small quantity of formed hydrated products between the cement particles cause the OCS macropore structure (>250 nm) to transform into capillary pores (50–250 nm). In the acceleration stage, amorphous calcium silicate hydrate (C–S–H) gel quickly forms in the pores and on the surface of the cement particles, which causes the capillary pores to transform into gel pores (

In cementing operations in oil and natural gas wells, the reduction in hydrostatic pressure of the oil-well cement (OWC) slurry is a serious threat to the quality and safety of the operations. To elucidate the mechanism of hydrostatic pressure transfer in OWC slurries, this study investigates the rules for the hydrostatic pressure transfer of OWC slurries using a hydrostatic pressure testing device. In addition, static gel strength (SGS) analysis, isothermal calorimetry, low-field nuclear magnetic resonance (LF-NMR), environmental scanning electron microscopy (ESEM), and X-ray computed tomography (μ-CT) were used to study the effects of the SGS, hydration rate, pore water, and microstructure on the hydrostatic pressure of OWC slurries. The experimental results show that the trends in the hydrostatic pressure curves of the cement slurries are similar. The hydrostatic pressure and SGS of the cement slurries vary exponentially, while the hydrostatic pressure and free water content vary linearly. Combined with the SGS results, the hydrostatic pressure curves can be divided into two stages. The first stage encompasses the range from the initial hydrostatic pressure to a pressure approximately equal to the hydrostatic pressure of water. From the hydration rate and microstructure results, it can be ascertained that this hydration stage is a dynamic balance stage. The microstructure of the cement slurry will be changed from a dispersed particles state to the gelation state, which increase the SGS of the cement slurry and the bonding ability between the cement particles and the interfaces of the casing and borehole. Part of the gravitational force of the cement particles acts on these interfaces, which reduces the hydrostatic pressure. The hydrostatic pressure in the second stage is less than that of water. This hydration stage is an acceleration stage, and the rapid hydration reactions form a large number of hydration products in the pores, which change the microstructure of the cement slurry from the gelation state to a solid state. The LF-NMR results indicate that the hydration products also reduce the pore size of the cement slurry, which causes the free water in the macropores to become capillary water and gel water. However, in the cement slurry, the hydrostatic pressure is not readily transferred by capillary water and gel water.

The dynamic mechanical properties and fracture mechanism of three types of oil well cement with different formulations were investigated using a Φ50 mm split Hopkinson pressure bar (SHPB) and quasi-static mechanical tests were conducted with a hydraulic universal testing machine. The stress-strain diagram, time-stress diagram, total energy absorption diagram, and the dynamic growth factor (DIF) under different strain rates were obtained. The crack propagation process of the oil well cement under dynamic loading is evaluated using high-speed photography to determine the fracture mechanism. The test results show that the strength of the cement increases under a dynamic impact. The compressive strength of the pure cement increases from 37 MPa to 184.80 MPa under static loading. However, the peak stress of the cement stone strengthened with cellulose fiber is lower under a dynamic load than a static load. Under dynamic loading, the absorption energy is higher for the pure cement stone than for the cem...

Purpose: The aim of the study was to evaluate the feasibility and toxicity of intra-rectal epinephrine during prostatic radiotherapy. Materials and methods: A total of 34 patients with prostate cancer were randomized to receive daily intra-rectal epinephrine (4 mg in 40 mL, n=16) or placebo (40 mL normal saline, n=18) 5 min before daily radiotherapy. Physical examination including systolic blood pressure (SBP) and heart rate (HR) was performed before, 5 min after, and 20 min after intra-rectal use. Toxicities were graded using the Radiation Therapy Oncology Group standard. A two-sided Fisher's exact test was used to compare proportions between groups. A mixed-effects model was used to analyze multiple measurements of SBP and HR. Survival curves were calculated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: All patients completed the protocol treatment and reported no cardiovascular symptoms after intra-rectal administration. There were no differences in SBP and HR between these two groups at any time point (before, 5 min after, and 20 min after epinephrine). At 5 weeks after the start of radiotherapy, the incidence of rectal toxicity≥grade 2 was 27.8% (5/18) for the control group versus 12.5% (2/16) for the epinephrine group, but was not statistically significant (p=0.4). There was no rectal toxicity≥grade 2 in these two groups beyond 2-year follow-up. The 5-year biochemical relapse-free survival was 75.0% and 72.2% for the epinephrine and control group, respectively. Conclusion: Results of this pilot randomized trial have demonstrated that intra-rectal administration of epinephrine is feasible and safe in prostatic radiotherapy. Its radio-protective effect warrants further investigation.

BackgroundIt is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death.MethodsWe identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan–Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems.ResultsWe analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system.ConclusionsThe NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations.

Interventional therapy has been commonly used in liver cancer. However, this modality is not a predominant therapy of pancreatic cancer. Interventional therapy of pancreatic cancer includes radiofrequency ablation (RFA), cryotherapy, microwave ablation (MWA), irreversible electroporation (IRE), high-intensity focused ultrasound (HIFU), transarterial infusion chemotherapy (TIC), and so forth.

As one of the most ominous malignancies, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, owing to its aggressive invasion and metastatic spread. Emerging evidence has demonstrated that Rictor, as a unique component of the mTORC2, plays a role in cell migration, as it is dysregulated in various cancers, including HCC. However, the underlying molecular mechanism has not been well-characterized. Here, evaluation on a tissue-array panel and bioinformatics analysis revealed that Rictor is highly expressed in HCC tissues. Moreover, increased Rictor expression predicts poor survival of HCC patients. Rictor knockdown significantly suppressed cell migration and actin polymerization, thereby leading to decreased nuclear accumulation of MKL1 and subsequent inactivation of SRF/MKL1-dependent gene transcription, i.e. Arp3 and c-Fos. Mechanistically, we identified ABLIM1 as a previously unknown phosphorylation target of Rictor. Rictor interacts with ABLIM1 and regulates its serine phosphorylation in HCC cells. We generated ABLIM1 knockout cell lines of HCC, in which dominant negative mutations of Ser 214 and Ser 431 residues inhibited the ABLIM1-mediated actin polymerization and the MKL1 signaling pathway. Overall, ABLIM1 phosphorylation induced by Rictor plays an important role in controlling actin polymerization in HCC cells.

Based on the decades of studies and commercial experiments, the geo-sequestration of carbon dioxide (CO2) has been the most efficient way to solve the green gas emission problem for the world. As the vital barrier of the sequestration well, the cement shell must be credible and durable until the well is abandoned. To date, some of sequestration projects have operated for many years, however, CO2 leakage has been a major threat in these projects. Although, ordinary Portland cement (OPC) is widely used in these projects, it has been found to be unstable in acidic environments. To assess these potential risks, this study combines cement hydration and carbonation as a coupled reaction to study the cement at an early age. OPC contents are too complex to study, thus, the main phase of C3S in the OPC was assessed in the CO2 environment. The experimental results indicate that the coupled reaction was considerably different from that in a previous study. In regard to the hydration reaction, cement slurry may provide the leakage pathway for sequestered CO2. In addition, the carbonation product is composed of an unstable crystal, which has proved to dissolve during long-lasting experiments.

Purpose In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells. Patients and methods We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Results We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P 0.05). The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P 0.05). Conclusion Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels.

Xiaobin Gu,1 Xianshu Gao,1 Ming Cui,1 Mu Xie,1 Mingwei Ma,1 Shangbin Qin,1 Xiaoying Li,1 Xin Qi,1 Yun Bai,1 Dian Wang2 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China; 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA Objective: This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results: A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7months for RP and EBRT groups, respectively (P20ng/mL were significant risk factors for both CSS and OS. Conclusion: This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged

Yun Bai,1 Xian-shu Gao,1 Shang-bin Qin,1 Jia-yan Chen,1 Meng-meng Su,1 Qing Liu,2 Xiu-bo Qin,2 Ming-wei Ma,1 Bo Zhao,1 Xiao-bin Gu,1 Mu Xie,1 Ming Cui,1 Xin Qi,1 Xiao-ying Li1 1Department of Radiation Oncology, Peking University First Hospital, Beijing, China; 2Department of Medical Imaging, Peking University First Hospital, Beijing, China Purpose: Bulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC. Patients and methods: From December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated. Results: Median follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects .CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P

// Ming Cui 1 , Xian-Shu Gao 1 , Xiaobin Gu 1 , Wei Guo 2 , Xiaoying Li 1 , Mingwei Ma 1 , Shangbin Qin 1 , Xin Qi 1 , Mu Xie 1 , Chuan Peng 1 and Yun Bai 1 1 Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China 2 Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei, China Correspondence to: Xian-Shu Gao, email: doctorgaoxs@126.com Keywords: BRCA2, mutation, prostate cancer, survival, molecular classification Received: January 23, 2017 Accepted: March 21, 2017 Published: March 30, 2017 ABSTRACT The aim of this study was to focus on clinicopathological characteristics and prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 ( BRCA2 ) gene mutation and to offer convincing evidence to consider BRCA2 mutation as a marker of poor prognosis in the molecular classification of PCa. We searched relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library databases to evaluate the differences in the overall survival (OS) and cancer-specific survival (CSS) between BRCA2 mutation carriers and non-carriers in patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers in total from 10 studies in our meta-analysis. The results showed that carrying a BRCA2 mutation was correlated with a reduced CSS and OS when compared with that of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval (CI): 2.10–3.06, P 7), TNM stage (> T3, N1, M1), and risk level than non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor survival outcomes in patients with prostate cancer, especially in those undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.

// Shao-Qian Sun 1, * , Xiaobin Gu 1, * , Xian-Shu Gao 1 , Yi Li 2 , Hongliang Yu 3 , Wei Xiong 4 , Hao Yu 1 , Wen Wang 1 , Yingbo Li 2 , Yingqi Teng 5 , Demin Zhou 2 1 Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China 3 Department of Radiation Oncology, Jiangsu Cancer Hospital Affiliated with Nanjing Medical University, Nanjing, China 4 Tangshan People’s Hospital, Hebei, China 5 Beijing Reciproca Pharmaceutical Co. Ltd., Beijing, China * These authors contributed equally to this work Correspondence to: Xian-Shu Gao, email: 857957241@qq.com Keywords: AKR1C3, radioresistance, ROS, prostaglandinF2α, MAPK Received: March 28, 2016 Accepted: June 09, 2016 Published: June 30, 2016 ABSTRACT Aldo-keto reductase 1C3(AKR1C3) is an enzyme involved in prostaglandins metabolism. Studies suggest that AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer, yet the role of AKR1C3 in prostate cancer cells radiation resistance has not yet been clarified. In our study, we established a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145 and its control cell line (Control). We conducted colony formation assay to determine the role of AKR1C3 in radioresistance and we used its chemical inhibitor to detect whether it can restored the sensitivity of the acquired tumor cells. Flow cytometry assay was carried out to detect IR-induced ROS accumulation. Elisa was adopted to dedect the concentration of PGF2α in the suspension of the cells after 6GY radiation. Western blotting was used to dedect the MAPK and PPAR γ. The results demonstrated that overexpression of AKR1C3 in prostate cancer can result in radioresistance and suppression of AKR1C3 via its chemical inhibitor indocin restored the sensitivity of the acquired tumor cells. According to the flow cytometry assay, ROS was decreased by 80% in DU145-over cells. Also overexpression of AKR1C3 could result in the accumulation of prostaglandin F2α (PGF2α), which can not only promote prostate cancer cell ’s proliferation but also could enhance prostate cancer cells resistance to radiation and activated the MAPK pathway and inhibited the expression of PPARγ. In conclusion, we found that overexpression of AKR1C3 significantly enhanced human prostate cancer cells resistance to radiation through activation of MAPK pathway.

Background The purpose of this study was to develop prognostic nomograms from a cohort of patients with triple-negative breast cancer (TNBC) with histology of infiltrating duct carcinoma (IDC) by correlating their clinical and pathological parameters with the rates of disease-free survival (DFS) and overall survival (OS). Methods We retrospectively analyzed TNBC patients with histology of IDC at our institution between 2009 and 2012. Age, family history, menopausal status, surgery type, T stage, N stage, histological grade, vascular invasion, perineural invasion, cytokeratin 5/6 status, Ki-67 expression, and epithelial cadherin (E-cadherin) status were analyzed. Predictors were used in multivariable logistic regression analysis to develop a nomogram to predict DFS and OS rates. The nomograms were then subjected to internal validation, with external validation of the nomogram for predicting OS using separate cohorts of TNBC patients known from the Cancer Genome Atlas (TCGA) database. Using the concordance index (C-index) with calibration curves, the predictive accuracy and discriminative ability were calculated. Results A total of 242 eligible TNBC patients were included for analysis. The median follow-up time was 70.73 months. Of the patients, 32.6%, 42.6%, and 24.8% had stage I, II, and III disease, respectively. The 3- and 5-year survival rates were 81.0% and 76.5% for DFS, and 86.5% and 81.1%, for OS, respectively. Age, T stage, N stage, and E-cadherin status were found to be risk factors. The nomograms based on those risk factors accurately predicted the 3- and 5-year survival rates. The C-index was 0.798 and 0.821 for DFS and OS, respectively. Besides, the nomogram for OS showed relatively reliable performance in stratifying different risk groups of patients in training and validation cohorts identified from the TCGA database. The C-index reached 0.843. DFS validation was not completed, as there was insufficient data. Conclusions Using clinicopathological information, we produced a prognostic nomogram that accurately predicts the 3- and 5-year DFS and OS for patients with TNBC with histology of IDC. More external confirmation is required.

Understanding the pore structure of oil-well cement slurry during early hydration is key to resolving short-term gas migration in natural gas wells. This study evaluated the three-dimensional microstructure and pore structure of oil-well cement slurry during early hydration using in situ high-resolution X-ray computed tomography and image reconstruction techniques. Experimental results showed that in the initial hydration stage the microstructure of the oil-well cement slurry comprised ‘dispersed particles’. When the hydration rate increased, some hydration products formed between the dispersed particles, and the microstructure of the slurry changed from a ‘dispersed particles’ structure to an ‘agglomerated skeleton’ structure. Furthermore, when the hydration time increased from 180 to 600 min, the porosity of the slurry decreased from 11.46% to 10.14% (a 11.52% decrease), the porosity of pores with volumes of 201 or more voxels reduced from 2.96% to 1.81% (a 38.83% decrease), and the connected porosity decreased from 4.47% to 2.26% (a 49.47% decrease). These results indicate that during early hydration, the formation of hydration products reduces the pore volume and cuts off some connected pores to produce many pores with small volumes. Based on the Kelvin−Laplace equation, the reduction in pore size increases the capillary pressure of the pore solution and shifts the weight of the pore solution acting on the agglomerated skeleton to reduce the hydrostatic pressure of the slurry. This study further proves that the pore structure of oil-well cement slurry is a key factor in reducing hydrostatic pressures and enabling short-term gas migration.

Understanding the effects of cellulose fibre on the nanostructure of and adhesion energy at the cellulose fibre-calcium silicate hydrate (C-S-H) interface is essential for designing high-performance cement-based composites (CBCs). Therefore, the chemical structure of cellulose fibre surface and microstructure of the fibre-cement matrix interface were investigated using X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Molecular dynamics (MD) simulations were used to study the adhesion energy and nanostructure at the cellulose fibre-(C-S-H) interface by comparing crystalline Iβ and amorphous celluloses (AC). The results revealed that the adhesion energy at the AC-(C-S-H) interface was approximately 35% greater than that at Iβ-(C-S-H) interface. Given that the AC configuration was disordered and presented greater deformation than Iβ, the AC-(C-S-H) interface was denser than the Iβ-(C-S-H) interface. Electrostatic interactions between OH groups and Ca2+ ions caused the Ca2+ in C-S-H to migrate towards the interface; the Ca2+ ions exhibit a bridging effect at the interface. Additionally, the OH groups in the cellulose fibre and C-S-H could also interact with each other via hydrogen bonding. The electrostatic and hydrogen bonds increased the interfacial adhesion energy, which was beneficial for improving the performance of cellulose fibre-reinforced CBCs.

H2S corrosion affects the molecular structure collapse of the cement matrix leading to cement cracking scanned by SEM. This research investigates whether C3S and C2S in cement react and undergo phase changes with high concentrations of corrosive H2S examined by XRD, TGA and RS. The products were evaluated to examine their bonds and moieties for H2S corrosion and to compare the molecular structure changes of silicates for further assessment based on 29Si SSNMR results. A lower mass of corrosion products and fewer molecular structure changes were observed in C2S specimens when compared with C3S specimens under H2S corrosion conditions.

This study aims to test whether Cordyceps sinensis (CS), the most expensive Asian nutrient supplement might stimulate growth of prostate cancer cells.Impact of CS on growth of prostate cancer was determined in vivo and in vitro.Firstly, the serum testosterone level was significantly elevated in mice fed CS. Prostate glands were significantly enlarged (weight index 0.53 ± 0.04 mg/g vs. 0.31 ± 0.04 mg/g, P = 0.006). Furthermore, cell viability was increased twofold in the androgen-responsive prostate cancer cell line (VCaP) after CS treatment. This promoting effect disappeared after bicalutamide was added. In addition, serum prostate-specific antigen (PSA) in mice bearing VCaP xenografts was significantly elevated (0.66 ± 0.04 ng/ml vs. 0.26 ± 0.06 ng/ml, P 0.001) after treatment with CS. Finally, VCaP tumors in mice treated with CS grew much faster (479.2 ± 78.74 mmThese results suggest that CS promotes growth of prostate cancer cells by increasing production of testosterone and stimulating the AR-dependent pathway. Additional studies are required to see whether CS is safely consumed by patients with prostate cancer.

The effect of blast furnace slag (BFS) on the mechanical and thermal properties of calcium aluminate cement (CAC) subjected to high temperature was evaluated in this study. The hydrate phase, micromorphology, and porous structure characteristics were determined by differential thermal analysis/thermogravimetry, X-ray diffraction (XRD), scanning electron microscopy, and nitrogen adsorption–desorption. The thermal conductivity of the pastes was evaluated using a thermal conductivity analyzer. The results indicated that with an increase in BFS, the thermal conductivity of CAC–BFS blend samples increases initially and decreases subsequently, and the compressive strength of the CAC–BFS blend samples exhibits the same trend. The addition of 30–40% BFS positively influenced the pore size distribution of cement paste and improved the thermal conductivity (λ) of the CAC-based composites subjected to high temperature, enhancing the mechanical properties of the CAC-based composites. Thermal conductivity also decreases at increased temperatures and correlates with pore structure. The experimental results indicate that the amount of BFS added considerably affects thermal conductivity and compressive strength, and that the optimal amount of BFS can be determined.