Search

Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to cancer prognosis. Here we performed a two-stage study of 2647 breast cancer patients to explore the association between SNPs within microRNA binding sites and breast cancer prognosis. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs associated with breast cancer prognosis in another dataset using the TaqMan platform. We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (P

The burden of breast cancer has grown rapidly in China during recent decades. However, the association between tumor markers (CA15-3, CA125, and CEA) and breast cancer survival among certain molecular subtypes is unclear; we described this association in a large, population-based study. We conducted a cohort study including 10,836 women according to the Tianjin Breast Cancer Cases Cohort. Demographic and epidemiologic data were collected by a structured face-to-face questionnaire. Clinico-pathological parameters were abstracted from medical records, and follow-up information was obtained once a year by telephone. The primary endpoints were breast cancer-specific survival (BCSS) and disease-free survival (DFS). We utilized the Cox proportional hazard model to calculate hazard ratios (HRs) and 95% confidence intervals (CI). Among all patients, elevated CA15-3 and CEA exhibited consistently and statistically significant reduced BCSS compared with normal ones (CA15-3: HR 1.54, 95% CI 1.01–2.34; CEA: HR 2.45, 95% CI 1.40–4.30). Similar patterns of association were observed for DFS (CA15-3: HR 2.09, 95% CI 1.44–3.02; CEA: HR 2.71, 95% CI 1.71–4.27). Moreover, in luminal A subtype, high CA15-3 and CEA levels were associated with decreased BCSS (CA15-3: HR 4.47, 95% CI 2.04–9.81; CEA: HR 3.79, 95% CI 1.68–8.55) and DFS (CA15-3: HR 4.06, 95% CI 2.29–7.18, CEA: HR 3.41, 95% CI 1.75–6.64). In basal-like subtype, elevated CEA conferred reduction for BCSS (HR 5.13, 95% CI 1.65–15.9). However, no association was observed between CA125 and breast cancer outcome. Preoperative CA15-3 and CEA levels differ in breast cancer molecular subtypes and yield strong prognostic information in Chinese women with breast cancer. Measuring CA15-3 and CEA levels before surgery may have the potential in predicting breast cancer survival and offering patients’ personalized treatment strategy among luminal A and basal-like subtypes.

Purpose We aim to construct a nomogram to predict breast cancer survival and guide postoperative adjuvant chemotherapy in China. Patients and methods A total of 5,504 breast cancer patients from the Tianjin Breast Cancer Cases Cohort were included. Multivariable Cox regression was used to investigate the factors associated with overall survival (OS) and a nomogram was constructed based on these prognostic factors. The nomogram was internal and external validated and the performance was evaluated by area under the curve (AUC) and calibration curve. The partial score was also constructed and stratified them into low, moderate and high-risk subgroups for death according to the tripartite grouping method. Multivariate Cox regression analysis and the propensity score matching method were respectively used to test the association between adjuvant chemotherapy and OS in different risk subgroups. Results Age, diameter, histological differentiation, lymph node metastasis, estrogen, and progesterone receptor were incorporated into the nomogram and validation results showed this nomogram was well-calibrated to predict the 3-year [AUC =74.1%; 95% confidence interval (CI): 70.1-78.0%] and 5-year overall survival [AUC =72.3%; 95% CI: 69.6-75.1%]. Adjuvant chemotherapy was negatively associated with death in high risk subgroup [Hazard Ratio (HR) = 0.54; 95% CI: 0.37-0.77; P

We employ a nonparametric distribution dynamics approach to examine the long-run trend of particulate matter (PM2.5) air pollution in China. Analysis of the data from 288 Chinese prefectural and above (PAA) level cities over the 2001–2019 period shows evidence of convergence in the estimated long-run distribution of air pollution, which is consistent with Environmental Kuznets Curve hypothesis (EKC). However, presence of strong persistence suggests that convergence process takes considerable time. Conditioning analysis shows that China’s environment policy since 2013 has been successful in driving the air pollution in several cities to converge to a lower level. Furthermore, we uncover a poverty-environment trap in the estimated long-run distribution. Our analysis highlights the need for targeted environmental policies in heterogeneous city clusters in China. Lessons learned from China’s experience can also be useful to policy makers in other developing countries.

Background: Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to the prognosis of cancer. We performed this study to explore the association between SNPs within microRNA binding sites and the prognosis of breast cancer.Methods: We carried out a two-stage study including 2647 breast cancer patients. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs significantly associated with breast cancer prognosis in another dataset using the TaqMan platform. Survival times was calculated, and Kaplan-Meier curves and Cox regression model were used to analyze survival of breast cancer patients with different genotypes.Results: We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (PConclusions: The LRKK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population, and it could be used as a potential prognostic biomarker for breast cancer. Further studies are warranted.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has proven to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD). However, whether podocyte-specific knockin of PTEN protects the kidney against hyperglycemia in vivo remains unknown. The inducible podocyte-specific PTEN knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop- loxP-PTEN mice with podocin-iCreERT2 mice. Diabetes mellitus was induced in mice by intraperitoneal injection of streptozotocin at a dose of 150 mg/kg. In vitro, small interfering RNA and adenovirus interference were used to observe the role of PTEN in HG-treated podocytes. Our data demonstrated that PTEN was markedly reduced in the podocytes of patients with DKD and focal segmental glomerulosclerosis, as well as in those of db/db mice. Interestingly, podocyte-specific knockin of PTEN significantly alleviated albuminuria, mesangial matrix expansion, effacement of podocyte foot processes, and incrassation of glomerular basement membrane in diabetic PPKI mice compared with wild-type diabetic mice, whereas no alteration was observed in the level of blood glucose. The potential renal protection of overexpressed PTEN in podocytes was partly attributed with an improvement in autophagy and motility and the inhibition of apoptosis. Our results showed that podocyte-specific knockin of PTEN protected the kidney against hyperglycemia in vivo , suggesting that targeting PTEN might be a novel and promising therapeutic strategy against DKD.

Purpose We assessed the feasibility and theoretical dosimetric advantages of an injectable hydrogel to increase the space between the head of the pancreas (HOP) and duodenum in a human cadaveric model. Methods and Materials Using 3 human cadaveric specimens, an absorbable radiopaque hydrogel was injected between the HOP and duodenum by way of open laparotomy in 1 case and endoscopic ultrasound (EUS) guidance in 2 cases. The cadavers were subsequently imaged using computed tomography and dissected for histologic confirmation of hydrogel placement. The duodenal dose reduction and planning target volume (PTV) coverage were characterized using pre- and postspacer injection stereotactic body radiation therapy (SBRT) plans for the 2 cadavers with EUS-guided placement, the delivery method that appeared the most clinically desirable. Modeling studies were performed using 60 SBRT plans consisting of 10 previously treated patients with unresectable pancreatic cancer, each with 6 different HOP–duodenum separation distances. The duodenal volume receiving 15 Gy (V15), 20 Gy (V20), and 33 Gy (V33) was assessed for each iteration. Results In the 3 cadaveric studies, an average of 0.9 cm, 1.1 cm, and 0.9 cm HOP–duodenum separation was achieved. In the 2 EUS cases, the V20 decreased from 3.86 cm3 to 0.36 cm3 and 3.75 cm3 to 1.08 cm3 (treatment constraint Conclusions Currently, dose escalation has been limited owing to radiosensitive structures adjacent to the pancreas. We demonstrated the feasibility of hydrogel separation of the HOP and duodenum. Future studies will evaluate the safety and efficacy of this technique with the potential for more effective dose escalation using SBRT or intensity-modulated radiation therapy to improve the outcomes in patients with unresectable pancreatic cancer.

Background To investigate whether women with benign breast disease (BBD) history have higher breast cancer detection rate in screening. Methods We reviewed data for 33 001 female participants in Multi-modality Independent Screening Trial (MIST). Corresponding data for 6823 breast cancer patients were retrieved from the Tianjin Breast Cancer Cases Cohort (TBCCC) and analyzed for comparison. Results The breast cancer detection rate was 2.83‰ among women with BBD history and 3.28‰ in women without. Moreover, the proportion of carcinoma in situ (CIS) was also lower in women with BBD history than women without (7.69 versus 20.31%). In contrast, analysis of TBCCC data revealed a higher proportion of CIS in patients with BBD history (5.05%) than patients without (3.26%). Our data showed that a larger proportion of women with BBD history had undergone previous breast examinations. Additionally, among participants diagnosed with both breast cancer and BBD in MIST, we found a lower proportion of CIS in women with BBD history (11.76%) compared to women without (32.14%). Conclusions Women with BBD history were not found to have higher detection rate in breast cancer screening. Women with BBD history were more likely to be proactive in seeking breast examinations and to have breast cancer be diagnosed in clinic.

Purpose We previously have shown the feasibility of duodenum sparing using a biodegradable hydrogel spacer in pancreatic cancer radiation therapy. In this study, we propose an overlap volume histogram (OVH) prediction model to select patients who might benefit from hydrogel placement and to predict the hydrogel spacing required to achieve clinical constraints. Methods and Materials OVH metrics for the duodenum were collected from the stereotactic body radiation therapy plans of 232 patients with unresectable pancreatic cancer (33 Gy in 5 fractions). OVH metrics L9cc and L3cc were defined as the tumor volume expansion distance at which 9 cm3 and 3 cm3 volumes of the duodenum overlap with tumor. D9cc and D3cc of the duodenum were defined as the dose-volume histogram dose to 9 cm3 and 3 cm3, respectively, of the duodenum. Prediction models were established by linear regression between Lx and Dx, where x = 3 cm3 and 9 cm3. OVH thresholds were obtained for predicting the target spacer thickness. The accuracy of the prediction model was then evaluated using treatment plans on pre–and post–hydrogel injection computed tomography scans from 2 cadaver specimens and 6 patients with previously treated locally advanced pancreatic cancer with simulated spacer. Results Linear regression analysis showed a significant correlation between Lx and Dx (r2 = 0.51 and 0.51 for L3cc-D3cc and L9cc-D9cc, respectively; both P L ˆ 3cc = 7 mm and L ˆ 9cc = 13 mm. The observed planning doses D3cc and D9cc of duodenum from pre–and post–hydrogel injection computed tomography scans of cadaver specimens and clinical patients with simulated spacer using predicted target spacer thickness were within the OVH model prediction range. Conclusion Our model may predict which patients require placement of a hydrogel spacer before stereotactic body radiation therapy to meet predefined dose constraints. Furthermore, by predicting the required target hydrogel thickness, the spacer injection can be better guided to improve efficacy.

Background The purpose of this work is to benchmark RapidPlan against clinical plans for liver Intensity-modulated radiotherapy (IMRT) treatment of patients with special anatomical characteristics, and to investigate the prediction capability of the general model (Model-G) versus our specific model (Model-S). Methods A library consisting of 60 liver cancer patients with IMRT planning was used to set up two models (Model-S, Model-G), using the RapidPlan knowledge-based planning system. Model-S consisted of 30 patients with special anatomical characteristics where the distance from planning target volume (PTV) to the right kidney was less than three centimeters and Model-G was configurated using all 60 patients in this library. Knowledge-based IMRT plans were created for the evaluation group formed of 13 patients similar to those included in Model-S by Model-G, Model-S and manually (M), named RPG-plans, RPS-plans and M-plans, respectively. The differences in the dose-volume histograms (DVHs) were compared, not only between RP-plans and their respective M-plans, but also between RPG-plans and RPS-plans. Results For all 13 patients, RapidPlan could automatically produce clinically acceptable plans. Comparing RP-plans to M-plans, RP-plans improved V95% of PTV and had greater dose sparing in the right kidney. For the normal liver, RPG-plans delivered similar doses, while RPS-plans delivered a higher dose than M-plans. With respect to RapidPlan models, RPS-plans had better conformity index (CI) values and delivered lower doses to the right kidney V20Gy and maximizing point doses to spinal cord, while delivering higher doses to the normal liver. Conclusion The study shows that RapidPlan can create high-quality plans, and our specific model can improve the CI of PTV, resulting in more sparing of OAR in IMRT for individual liver cancer patients.

Background For cervical carcinoma cases, this study aimed to evaluate the quality of intensity-modulated radiation therapy (IMRT) plans optimized by biological constraints. Furthermore, a new integrated strategy in biological planning module was proposed and verified. Methods Twenty patients of advanced stage cervical carcinoma were enrolled in this study. For each patient, dose volume optimization (DVO), biological model optimization (BMO) and integrated strategy optimization (ISO) plans were created using same treatment parameters. Different biological models were also used for organ at risk (OAR) in BMO plans, which include the LKB and Poisson models. Next, BMO plans were compared with their corresponding DVO plans, in order to evaluate BMO plan quality. ISO plans were also compared with DVO and BMO plans, in order to verify the performance of the integrated strategy. Results BMO plans produced slightly inhomogeneity and less coverage of planning target volume (PTV) (V95=96.79, HI = 0.10: p

Purpose: Scatter correction in cone-beam computed tomography (CBCT) has obvious effect on the removal of image noise, the cup artifact and the increase of image contrast. Several methods using a beam blocker for the estimation and subtraction of scatter have been proposed. However, the inconvenience of mechanics and propensity to residual artifacts limited the further evolution of basic and clinical research. Here, we propose a rotating collimator-based approach, in conjunction with reconstruction based on a discrete Radon transform and Tchebichef moments algorithm, to correct scatter-induced artifacts. Methods: A rotating-collimator, comprising round tungsten alloy strips, was mounted on a linear actuator. The rotating-collimator is divided into 6 portions equally. The round strips space is evenly spaced on each portion but staggered between different portions. A step motor connected to the rotating collimator drove the blocker to around x-ray source during the CBCT acquisition. The CBCT reconstruction based on a discrete Radon transform and Tchebichef moments algorithm is performed. Experimental studies using water phantom and Catphan504 were carried out to evaluate the performance of the proposed scheme. Results: The proposed algorithm was tested on both the Monte Carlo simulation and actual experiments with the Catphan504 phantom. From the simulation result, the mean square error of the reconstruction error decreases from 16% to 1.18%, the cupping (τcup) from 14.005% to 0.66%, and the peak signal-to-noise ratio increase from 16.9594 to 31.45. From the actual experiments, the induced visual artifacts are significantly reduced. Conclusion: We conducted an experiment on CBCT imaging system with a rotating collimator to develop and optimize x-ray scatter control and reduction technique. The proposed method is attractive in applications where a high CBCT image quality is critical, for example, dose calculation in adaptive radiation therapy. We want to thank Dr. Lei Xing and Dr. Yong Yang in the Stanford University School of Medicine for this work. This work was jointly supported by NSFC (61471226), Natural Science Foundation for Distinguished Young Scholars of Shandong Province (JQ201516), and China Postdoctoral Science Foundation (2015T80739, 2014M551949).

Purpose: In this study, IMRT optimization based on biological related models were applied in the clinic for cervical carcinoma cases and the results were compared with the traditional physical optimization. Methods: Twenty patients of advanced stage cervical carcinoma were selected in this study. The treatment plan was generated on each patient using both biological and physical optimized model respectively. Additionally, the biological optimization was based on two basic models for bladder and rectum: Poisson (adjustable parameters: alpha/beta, gamma, D50) and Lyman-Kutcher-Burman (adjustable parameters: m, n, D50). And then each optimized biological plan was compared with the corresponding physical plan. During this comparison, all biological and physical parameters, such as NTCP,TCP, target coverage and homogeneous index(HI), were evaluated by paired T-test to verify IMRT plans quality. Results: The NTCP values by biological optimization were lower than the values from corresponding physical optimization. For the bladder and rectum, the detail of NTCP values are 0.144 and 0.178 with p=0.028 for bladder, and 0.108 and 0.186 with p= 7.97E-5 for rectum respectively. The mean dose and V40 of bladder and rectum were comparable, and there was no significant difference between these two optimizations. For PTV, both optimized models achieved similar target coverage and homogeneous index (For example, D98=53.4 Gy and 54.6 Gy from biological optimization and physical optimization respectively with p=2.94E-9), and there were no significant differences in the tumor control probability(TCP) values. Conclusion: IMRT optimization based on biological model did not decrease the plan quality, and could spare bladder and rectum with lower NTCP value much more compared with traditional physical optimization for cervical carcinoma. Our initial experiment demonstrated that the biological optimization could be a potential alternative method to the traditional physical one. We want to thank Dr. Lei Xing and Dr. Yong Yang in the Stanford University School of Medicine for this work. This work was jointly supported by NSFC (61471226), Natural Science Foundation for Distinguished Young Scholars of Shandong Province (JQ201516), and China Postdoctoral Science Foundation (2015T80739, 2014M551949).

Purpose: This study investigated that how the quality of adapted plan was affected by inter-fractional anatomy deformation by using one-step and two-step optimization for on line adaptive radiotherapy (ART) procedure. Methods: 10 lung carcinoma patients were chosen randomly to produce IMRT plan by one-step and two-step algorithms respectively, and the prescribed dose was set as 60 Gy on the planning target volume (PTV) for all patients. To simulate inter-fractional target deformation, four specific cases were created by systematic anatomy variation; including target superior shift 0.5 cm, 0.3cm contraction, 0.3 cm expansion and 45-degree rotation. Based on these four anatomy deformation, adapted plan, regenerated plan and non-adapted plan were created to evaluate quality of adaptation. Adapted plans were generated automatically by using one-step and two-step algorithms respectively to optimize original plans, and regenerated plans were manually created by experience physicists. Non-adapted plans were produced by recalculating the dose distribution based on corresponding original plans. The deviations among these three plans were statistically analyzed by paired T-test. Results: In PTV superior shift case, adapted plans had significantly better PTV coverage by using two-step algorithm compared with one-step one, and meanwhile there was a significant difference of V95 by comparison with adapted and non-adapted plans (p=0.0025). In target contraction deformation, with almost same PTV coverage, the total lung received lower dose using one-step algorithm than two-step algorithm (p=0.0143,0.0126 for V20, Dmean respectively). In other two deformation cases, there were no significant differences observed by both two optimized algorithms. Conclusion: In geometry deformation such as target contraction, with comparable PTV coverage, one-step algorithm gave better OAR sparing than two-step algorithm. Reversely, the adaptation by using two-step algorithm had higher efficiency and accuracy as target occurred position displacement. We want to thank Dr. Lei Xing and Dr. Yong Yang in the Stanford University School of Medicine for this work. This work was jointly supported by NSFC (61471226), Natural Science Foundation for Distinguished Young Scholars of Shandong Province (JQ201516), and China Postdoctoral Science Foundation (2015T80739, 2014M551949).