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Cognitive decline is a common health problem among breast cancer patients and understanding trajectories of cognitive change following among breast cancer survivors is an important public health goal. We conducted a longitudinal study to investigate the cognitive function changes from 18 month to 3 years after breast cancer diagnosis among participants of the Shanghai Breast cancer survivor study, a population-based cohort study of breast cancer survivors. In our study, we completed cognitive function evaluation for 1,300 breast cancer survivors at the 18th month's survey and 1,059 at 36th month's survey, respectively, using a battery of cognitive function measurements. We found the scores in attention and executive function, immediate memory and delayed memory significantly improved from 18 to 36 months after breast cancer diagnosis. The improvements appeared in breast cancer survivors receiving treatments (i.e., surgery, radiotherapy, tamoxifen, or chemotherapy combined with or without tamoxifen), but not in those who received neither chemotherapy nor tamoxifen treatment. The results indicate that cognitive functions, particularly immediate verbal episodic memory, and delayed memory significantly improved among breast cancer survivors from 18 to 36 months after cancer diagnosis. In general, comorbidity was inversely associated with the improvements.

Background: Gastric cancer remains a major health issue and a leading cause of death worldwide. This study presented a long-term survival data of gastric cancer registered in Shanghai of China from 1972-2003, with aims to describe the trends as well as the age, sex, stage and tumor sites specific characteristics., Methods: The main source of information on cancer cases was the notification card sending to the registry. The residential status of cancer cases was confirmed by home-visits. The methods of follow-up have been a mixture of both active and passive ones., Results: We observed an increased trend of survival probability during the last decades. Patients diagnosed during 1972-1976 had a 5-years relative survival rate at 12% for males and 11% for females, respectively, which had dramatically increased to 30% for male and 32% for female patients respectively during the period of 2002-2003. Among the patients diagnosed in 2002-2003, the overall survival probability declined with patient's age at the time of diagnosis. The lowest survival rate was observed among the oldest group, with the median survival time of 0.8 years. Patients diagnosed with stage I had a higher relative survival rate. Patients with cardia cancer had the worst prognosis, with the 5-year relative survival rate of 29%., Conclusions: The survival probability of patients with gastric cancer in Shanghai has improved significantly during the last decades. Age, stage and site of tumor have an impact on prognosis.

The objective of this study was to evaluate the utility of a complement-dependent C3d assay to risk stratify donor-specific antibodies (DSA) in a multicenter cohort of kidney recipients presenting with new-onset clinical dysfunction. A total of 106 subjects with evidence of DSA at a mean period of 5.3 ± 5.0 years posttransplant underwent testing using C3d reagents. C3d positivity was strongly associated with both the peak and sum IgG DSA MFI, with 98.3% (n = 57/58) of strongly reactive sera (peak MFI > 10 000) eliciting a positive signal. Patients with C3d+ DSA had a higher creatinine (P = .03), more significant graft fibrosis (P = .035), and a faster rate of graft loss posttest compared to those with C3d- DSA (P = .05). Subanalysis of patients with low-moderate level DSA confirmed the inferior outcome associated with C3d positivity. Despite the prognostic value of C3d as a stand-alone test, the assay did not provide independent risk prediction after incorporation of graft fibrosis in a multivariate model (P = .94). Overall, C3d offered limited discriminatory value for strong DSA with peak IgG MFI > 10 000 and in patients where histologic data is available, but its utilization may be considered in those with low-moderate level DSA and where an allograft biopsy is not accessible.

BackgroundLarge social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort.MethodsWomen from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed.ResultsThere were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only.ConclusionsIn a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society.

Background: The simplified thrombo-inflammatory score (sTIPS) has recently emerged as a novel prognostic score. Hence, we investigated the prognostic value of sTIPS for predicting long-term mortality in patients with heart failure (HF). Methods: A total of 3741 patients were analyzed in this study. The sTIPS was calculated based on the white blood cell count (WBC) and the mean platelet volume to platelet count (MPV/PC) ratio at admission. The mean follow-up time was 22.75 months. Multivariable Cox regression analyses were used to investigate the associations between the sTIPS and all-cause mortality (ACM). Results: In the whole study population, multivariate Cox regression analysis showed that patients in both the sTIPS 2 and sTIPS 1 groups had significantly increased risk of ACM as compared with patients in the sTIPS 0 group (hazard ratio [HR]=1.706, 95% confidence interval [CI]: 1.405– 2.072, P< 0.001 and HR = 1.431, 95% CI 1.270– 1.612, P< 0.001). The same significant trend was observed in heart failure with preserved ejection fraction (HFpEF) patients (sTIPS1 vs sTIPS0: HR = 1.366, 95% CI 1.100– 1.697, P = 0.005; sTIPS2 vs sTIPS0: HR = 1.995, 95% CI 1.460– 2.725, P< 0.001). However, only sTIPS 1 group had a significantly increased the risk of ACM compared to the sTIPS 0 group among patients with HFmrEF (sTIPS1 vs sTIPS0: HR = 1.648, 95% CI 1.238– 2.194, P = 0.001) and HFrEF (sTIPS1 vs sTIPS0: HR = 1.322, 95% CI 1.021– 1.712, P = 0.035). Conclusion: sTIPS is useful in predicting risk for long-term mortality in patients with HF. [ABSTRACT FROM AUTHOR]

Background: As a member of the Krüppel-like factor (KLFs) family, Krüppel-like factor 6 (KLF6) plays a critical role in regulating key cellular functions. Presently, scholars have proved the important role of KLF6 in the tumorigenesis of certain cancers through a large number of experiments. However, gaps still remain in our knowledge of the role of KLF6 in pancreatic cancer (PAAD). Therefore, this paper mainly investigates the role of KLF6 in the progression of pancreatic cancer. Methods: The expression pattern of KLF6 in pancreatic cancer was explored in pancreatic cancer tissues and cell lines. Then, we investigated the prognostic value of KLF6 in pancreatic cancer by immunohistochemical assays. Next, Cell Counting Kit-8 (CCK8) and clone information assays were employed to explore the proliferation of PAAD affected by KLF6. The metastasis and epithelial-mesenchymal transition (EMT) abilities affected by KLF6 were identified through transwell invasion as well as migration assays and western blots. Finally, the TRRUST tool was used to analyze the potential targeted genes of KLF6. The results were verified by Quantificational Real-time Polymerase Chain Reaction (qRT-PCR), western blot and rescue assays. Results: KLF6 expresses lowly in pancreatic cancer compared to corresponding normal tissues and relates to poor survival times. Overexpression of KLF6 inhibits the proliferation, metastasis, and EMT progression in pancreatic cancer cells. Further studies suggest that KLF6 could upregulate ATF3 in PAAD. Conclusions: Our results suggest that KLF6 can be a useful factor in predicting the prognosis of PAAD patients and that it inhibits the progression of pancreatic cancer by upregulating activating transcription factor 3 (ATF3). [ABSTRACT FROM AUTHOR]

Background: Given that age, international normalized ratio (INR), total bilirubin, and creatinine are reported to be independent risk factors for predicting outcome in patients with coronary artery disease (CAD), it is possible that the age–bilirubin–INR–creatinine (ABIC) score might be a potential prognostic model for patients with CAD. Methods: A total of 6046 CAD patients after percutaneous coronary intervention (PCI) from the retrospective cohort study (Identifier: ChiCTR-ORC-16010153) were evaluated finally. The primary outcome long-term mortality and secondary endpoints mainly major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded. Multivariate Cox regression models were used to determine risk factors for mortality and MACCEs. Results: The ABIC score was significantly higher in the death group than in the survival group. After adjusting for other CAD risk factors, the ABIC score was identified to be an independent risk factor for long-term mortality by multivariate Cox analysis. When in the high ABIC group, the incidence of all-cause mortality would increased 1.7 times (adjusted HR=1.729 (1.347– 2.218), P< 0.001), and 1.5 times for cardiac death (adjusted HR=1.482 (1.126– 1.951), P=0.005). Conclusion: The present study indicated that ABIC score≥ 7.985 predicts high long-term mortality and cardiac death risk for PCI patients. The ABIC score might be a potential prognostic model for patients with PCI. [ABSTRACT FROM AUTHOR]

Cardiovascular failure is one of the most relevant causes of death in pulmonary hypertension (PH). With progressive increases of right ventricular (RV) afterload in PH patients, both RV and left ventricular (LV) function impair and RV–LV dyssynchrony develop in parallel. We aimed to analyze the balance between the left and right ventricular deformation to assess the outcome of patients with pulmonary hypertension by means of speckle tracking echocardiography. In this prospective study, 54 patients with invasively diagnosed pulmonary hypertension, and 26 healthy volunteers were included and underwent a broad panel of noninvasive assessment including 2D-echocardiography, 2D speckle tracking, 6-minute walking test and BNP. Patients were followed up for 338.7 ± 131.1 (range 60 to 572) days. There were significant differences in |LVGLS/RVFLS-1| and |LASc/RASc-1| between PH patients and the control group. During the follow up, 13 patients experienced MACEs, which included 7 patients with cardiac death and 6 patients with re-admitted hospital due to right ventricular dysfunction. In the multivariate Cox model analysis, |LVGLS/RVFLS-1| remained independent prognosis of markers (HR = 4.03). Our study findings show that |LVGLS/RVFLS-1| is of high clinical and prognostic relevance in pulmonary hypertension patients and reveal the importance of the balance between the left and right ventricular deformation. [ABSTRACT FROM AUTHOR]

Background: Little is known about the prognostic advantage of sex for pulmonary adenocarcinoma among Chinese patients. In this study, we aimed to investigate the true sex differences in prognosis by adjusting for confounders and to explore whether the differences were time‐varying. Methods: We identified 4438 lung adenocarcinoma patients who underwent surgery at a regional Cancer Center of China from 2008 to 2016, retrospectively. Sex, age group, smoking history, year of diagnosis and pathological stage were collected. Time‐dependent Cox regression models with inverse probability of treatment weighting (IPTW) based on propensity score were used to assess the effect of sex and account for confounders. Landmark analyses were conducted to assess survival before, and after, five years. Results: Of these patients, 1761 (39.7%) were men and 2677 (60.3%) were women. Median follow‐up time was 52.6 months. After IPTW adjustment, women were found to have significantly better survival than men varying with time in both crude and IPTW models (hazard ratio [HR] [t] = 0.453*1.015t, where t is the length of time from treatment and its unit is month, p < 0.001). Women had significantly better survival than men within 0–5 years after surgery (HR = 0.763, 95% CI: 0.649–0.897, p = 0.001), whereas there was no difference after five years (HR = 1.135, 95% CI: 0.803–1.605, p = 0.472). In subgroup analysis, women in the 61–71+ age group, in the more than 20 year packs group, pathological stage 0–IB group, and 2013–2016 diagnosis period group revealed the same prognostic pattern. Conclusions: Compared with men, women had better survival after surgical resection of lung adenocarcinoma, especially those who were older and nonsmokers or heavy‐smokers and were pathological stage 0–IB in early years, while the advantage for women diminished with time. [ABSTRACT FROM AUTHOR]

Our study aimed to explore the intercorrelations of brachial‐ankle pulse wave velocity (baPWV), ankle‐brachial index (ABI), ambulatory arterial stiffness index (AASI), 24‐hour mean pulse pressure (24‐h PP), and augmentation index (AIx, AIx@75, the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49‐65) years and 50.5 (35.5‐84.1) ml/min/1.73 m2, respectively. In Pearson correlation analysis, baPWV was significantly associated with 24‐h PP (r =.531, p <.001), AIx@75 (r =.306, p <.001). Additionally, 24‐h PP was associated with AASI (r =.507, p <.001) and AIx@75 (r =.217, p =.019). During follow‐up for a median of 25 months, 26.5% (n = 31) of patients had a composite outcome; of these, 10 initiated dialysis, 17 had 40% eGFR loss, and 4 died. Increased AASI, 24‐h PP, and baPWV were associated with poor renal outcomes in a univariate Cox analysis. After adjusting for age, sex, MAP, eGFR, and 24 hours proteinuria, 1‐SD increase in AASI and 24‐h PP was associated with renal outcomes. The ROC analysis yielded the largest area under the curve (AUC) of 0.727 (95% CI: 0.624 to 0.831; p <.001) for 24 ‐h PP. When the Youden's index was at its maximum, the 24‐h PP value was 52 mmHg. In conclusion, 24‐h PP, baPWV, and AIx@75 were linked well to one another. Arterial stiffness is a target for delaying the decline in kidney function. The use of 24‐h PP as an arterial stiffness marker should be valued in CKD clinical practice. [ABSTRACT FROM AUTHOR]

MicroRNA-155 is over-expressed in many human cancers, but researches on its association with malignant oesophageal squamous cell carcinoma (ESCC) are limited. The aim of the present study was to evaluate the potential value of miR-155 as a biomarker for ESCC diagnosis and prognosis. In this study, we found that miR-155 was significantly increased in ESCC tissues compared with the paired adjacent tissues and healthy normal controls (p <.001), according to qRT-PCR, which suggested that miR-155 might act as an oncogene in ESCC. In addition, clinical features such as the depth of tumour invasion, tumour size, and TNM stage were all proved to impact the expression of miR-155 (p <.01). Then, ROC curve analysis, reaching an AUC of 0.870, and a sensitivity and specificity of 83.5% and 77.5%, respectively, revealed that miR-155 was a predictive factor for ESCC. As well, high expression of miR-155 was associated with poor overall survival of the patients (log-rank test, p =.004), according to Kaplan-Meier analysis. MiR-155 might be an independent predictor for overall survival in ESCC patients, manifested by Cox regression analysis (HR = 16.94, 95%CI = 3.33–86.12, p =.001). Taken together, miR-155 could be an independent diagnostic and prognostic biomarker for ESCC. [ABSTRACT FROM AUTHOR]

The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapeutic drugs leads to a poor prognosis in gastric cancer (GC). The present study aimed to assess the association between pituitary homeobox paired homeodomain transcription 1 (PITX1) expression and the sensitivity of GC cells to the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP). In the present study, the gastric cancer cell lines GES-1, AGS, BGC-823, MCG-803 and SGC-7901 were used. The expression of PITX1 was determined via reverse transcription-quantitative polymerase chain reaction in GC cell lines. AGS and BGC-823 cells, which exhibit a decreased PITX1 expression, were transfected with a PITX1 cDNA construct and its control vector. MCG-803 and SGC-7901 cells, which exhibit an increased PITX1 expression, were transfected with siRNA against PITX1 and its control scramble sequence. A Cell Counting kit-8 assay was performed to determine the impact of PITX1 expression on the sensitivity of GC cells to 5-FU and CDDP. The Cancer Genome Atlas database was used to analyze the expression of PITX1 with GC prognosis in the Asian population and to assess the potential mechanism of PITX1 in 5-FU and CDDP resistance. The results revealed that the overexpression of PIXT1 increased the sensitivity of GC cells to 5-FU/CDDP. The combination of 5-FU/CDDP and PITX1 overexpression also reduced the proliferation of GC cells. Additionally, PIXT1 knockdown decreased the sensitivity of GC cells to 5-FU/CDDP. TCGA data revealed that a lower expression of PITX1 is exhibited in Asian GC patients than in normal individuals. GC patients with a lower expression of PITX1 had a poor prognosis. The expression of PITX1 affected the sensitivity of GC cells to 5-FU/CDDP, indicating that PITX1 may increase the efficacy of treatment in GC patients. [ABSTRACT FROM AUTHOR]

Background: Oral cancer is a serious problem owing to its poor prognosis and destruction of patients' eating ability as well as facial appearance. Epidemiological studies can provide aetiological clues for prevention. The prevalence of oral cancer in densely populated cities in eastern China is unclear. The aim of the study is to analyse the incidence rates of oral cancer in Shanghai over the period 2003-2012 and estimate the temporal trends.Methods: Cases of oral cancer were retrieved from the Shanghai Cancer Registry system in the Shanghai Municipal Center for Disease Control & Prevention for the years 2003 to 2012. Information on the corresponding population was obtained from the Shanghai Municipal Bureau of Public Security. Age-standardised incidence rates were directly calculated according to the world standard population. An annual percent change model was employed to analyse the temporal trends of cancer incidence.Results: A total of 3860 oral cancer cases were reported, representing 0.69% of all malignancies in Shanghai during the 10-year study period. The mean age at diagnosis was 64 years. The age-standardised incidence rate was 1.34 per 100,000 person-years, with a male-to-female ratio of 1.41. Annually, the incidence rates increased by 3.83 and 2.54% for men and women, respectively. The increase was most noticeable in males aged 45-64 years.Conclusion: In Shanghai, the oral cancer incidence is relatively low. However, it is continuously increasing, especially among middle-aged males. This finding urges further investigations on the risk factors of oral cancer in this population, especially on changes in living patterns, such as the smoking, drinking, and dietary habits. [ABSTRACT FROM AUTHOR]

Background: Very little is known about the effect of modifiable lifestyle factors on outcomes of triple-negative breast cancer. We examined this association in a population-based prospective cohort study of patients with triple-negative breast cancer.Methods: A total of 518 women with confirmed triple-negative breast cancer, recruited by the Shanghai Breast Cancer Survival Study, completed 6-, 18-, 36-, and 60-month postdiagnosis surveys. We applied Cox proportional hazard models to evaluate the associations.Results: The mean age at diagnosis was 53.4 (standard deviation = 10.6) years old. After a median follow-up of 9.1 years (range: 0.6-11.8), 128 deaths and 112 recurrences were documented. Exercise during the first 60 months postdiagnosis was inversely associated with total mortality and recurrence/disease-specific mortality with adjusted hazard ratios (HRs) of 0.67 (95% confidence interval [CI] = 0.46, 0.96) and 0.58 (95% CI = 0.39, 0.86), respectively. Women with higher exercise-metabolic equivalent scores (≥7.6 metabolic equivalent-hours/week) and longer duration of exercise (≥2.5 hours/week) had lower risk of total and recurrence/disease-specific mortality than did nonexercisers. Compared with nontea drinkers, survival was better among women who were regular tea drinkers during the first 60 months for all cause (HR = 0.57, 95% CI = 0.34, 0.93) and recurrence/disease-specific mortality (HR = 0.54, 95% CI = 0.31, 0.96). There was no dose-response pattern for tea consumption. No interactions were observed for body mass index, menopausal status, and comorbidity.Conclusions: These findings show that postdiagnosis exercise and tea intake were associated with improved survival among women with triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Due to subtle symptoms and the absence of effective early screening methods, most of epithelial ovarian cancer patients are diagnosed in the late stage, when current treatment strategies are not so satisfactory. To date, ovarian cancer is still the leading cause of gynecological malignancy deaths in women. The formation of massive ascites is one of the important characteristics of epithelial ovarian carcinoma in the late stage. Cancer cells, existing in ascites in the form of spheroids, play an important role in metastasis and recurrence of the malignancy. Alpha5/beta1 integrin has been found to participate in the formation of epithelial ovarian cancer multicellular spheroids in vitro. But if we want to choose alpha5- and beta1-integrin subunits as treatment targets, we must specifically block the two subunits in cancer cells, because these two subunits are very important for the physiological activities in normal cells. Based on the knowledge mentioned above, we present hypotheses that we can inhibit specifically the expression of alpha5/beta1 integrin in cancer cells with the help of complementary replication defective adenovirus. As a result, the formation of cancer cells spheroids in ascites might be interfered with and the treatment effects and prognosis of epithelial ovarian cancer might be improved. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a devastating disease with dismal prognosis. Large population-based evidence on its survival rate and influence factors is lacking in China. Objective: This study aimed to depict the demographic factors, tumor characteristics, incidence rate and survival rate of pancreatic cancer cases in urban China. Methods: The demographic factors, tumor characteristics were collected for all the pancreatic cancer cases identified during 2004 to 2009 from the Shanghai Cancer Registry. The survival time was ascertained through linkage of the Shanghai Cancer Registry and the Shanghai Vital Statistics Registry. The deadline of death certificates was the end of December 2012. Kaplan-Meier method and Cox proportional-hazards regression model were used to explore the survival rate and influence factors. Results: 11,672 new pancreatic cancer cases were identified among Shanghai residency during 2004 to 2009. The crude incidence rate of pancreatic cancer was increasing from 12.80/100,000 in 2004 to 15.66/100,000 in 2009, while the standardized incidence rate was about 6.70/100,000 and didn't change a lot. The overall 5-year survival rate was 4.1% and the median survival time was 3.9 (95% Confidence Interval (CI) 3.8–4.0) months. Subjects had received surgical resection had improved survival (HR  = 0.742, 95% CI: 0.634–0.868) than its counterparts. In adjusted multivariable Cox proportional-hazard models, factors associated with poor survival included older age at diagnosis (age > = 70 years: hazard ratio (HR)  = 1.827, 95% CI: 1.614–2.067), male sex (HR  = 1.155, 95% CI: 1.041–1.281), distant disease at diagnosis (HR =  1.257, 95% CI: 1.061–1.488), positive lymph node (HR  = 1.236, 95% CI: 1.085–1.408), tumor stage (Stage IV HR  = 2.817, 95% CI: 2.029–3.909). Conclusion: The age-adjusted incidence rate was stable and overall survival rate was low among pancreatic cancer patients of Shanghai residency. Early detection and improved treatment strategies are needed to improve prognosis for this deadly disease. [ABSTRACT FROM AUTHOR]

Objectives: Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer.Methods: A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM.Results: The DES model's predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64-0.85 and final actual: 0.74; 95% CI 0.6-0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data.Conclusions: Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes. [ABSTRACT FROM AUTHOR]

DEAD-Box Helicase 5(DDX5), also known as P68, is one of the founding members of the DEAD-Box helicase superfamily and it plays a key role in RNA metabolism. Several studies have reported that DDX5 is involved in many types of tumors through abnormal expression, but the detailed mechanism of DDX5 in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we demonstrate that the level of DDX5 is a negative prognostic factor for ESCC. The obtained results indicated that decreased expression of DDX5 inhibits ESCC cell proliferation and metastasis. Further experiments suggested that CDK2, Cyclin D1 and Vimentin were downregulated, while E-cadherin was upregulated after DDX5 was knocked down. In addition, DDX5 was positively correlated with the expression of BIP, phospho-eIF2α, phospho-PERK and P62, suggesting that knockdown of DDX5 can inhibit endoplasmic reticulum(ER) stress and promote the recovery of autophagy flux. Therefore, this study demonstrates that the downregulation of DDX5 in ESSC correlates to lower malignancy and presents a novel target for the development of new treatment strategies. • The level of DDX5 is a negative prognostic factor for esophageal squamous cell carcinomas. • Decreased expression of DDX5 inhibited tumor proliferation and metastasis in vivo and in vitro. • DDX5 regulates CDK2, Cyclin D1, Vimentin and E-cadherin in esophageal squamous cell carcinoma. • Knockdown DDX5 can inhibit endoplasmic reticulum stress and promoting the recovery of autophagy. [ABSTRACT FROM AUTHOR]

Abstract: A multi-center population-based study in Shanghai, China was performed to explore the implications for the management of pancreatic cancer by comparing diagnosis and survival rates. Novel imaging modalities including MRI (13.9%), PET/CT (1.8%), and EUS (5.6%) were not widely used in our population. Only 39.7% of cases were histologically verified (surgery with histologic diagnosis 31.0%, cytological diagnosis 8.7%, surgery without histologic diagnosis 12.1%, and clinical diagnosis 48.2%). Overall, 30.0% of patients underwent curative-intent operation, and only 9.8% of patients received comprehensive treatment. The prognosis of pancreatic cancer patients was significantly better for patients who were treated in high-volume centers than in low-volume centers. We propose that more effort should be put on novel diagnostic modalities, histological confirmation, and comprehensive treatment in China. Multidisciplinary teams specialized in pancreatic cancer therapy in high-volume centers are urgently needed. [Copyright &y& Elsevier]

Abstract: POTE ankyrin domain family, member H (POTEH) belongs to POTE family, which expresses in many cancers. In this study, methylation status of POTEH promoter and its correlation with clinicopathological parameters were evaluated in glioma tissues and cells. Bisulfite sequencing PCR was carried out to investigate the promoter methylation status of POTEH in tumor of 96 glioma patients and glioma cells U251, SF767, and SF126. The effect of promoter hypomethylation on protein expression was evaluated by immunohistochemistry. POTEH was hypomethylated in 81.3% gliomas and none in normal brain tissues, and correlated significantly with its protein expression. But there was no remarkable relationship between sex, age, advanced tumor grade and POTEH hypomethylation. With the grade progressing, POTEH protein expression was enhanced. The correlation between POTEH hypomethylation, protein expression and overall survival was statistically significant. In POTEH hypomethylation group, patients with POTEH high expression had shorter overall survival than those with low expression. Hypomethylation of POTEH promoter in gliomas accounted for POTEH protein overexpression and poor outcome in a subset of patients. Detection of these epigenetic changes in tumors may provide information regarding prognosis. [Copyright &y& Elsevier]