scholarly journals S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

2020 ◽  
Author(s):  
Guiyang Wu ◽  
Chongshan Wu ◽  
Fubo Ye ◽  
Xiongwen Zhu ◽  
Zaiping Chen
Keyword(s):  
Cancer Cell ◽  
Proportional Hazards Model ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Altered Expression ◽  
S100a4 Expression ◽  
The Impact

Abstract Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.

scholarly journals S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

2020 ◽  
Author(s):  
Guiyang Wu ◽  
Chongshan Wu ◽  
Fubo Ye ◽  
Xiongwen Zhu ◽  
Zaiping Chen
Keyword(s):  
Cancer Cell ◽  
Proportional Hazards Model ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Altered Expression ◽  
S100a4 Expression ◽  
The Impact

Abstract Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.

Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Kuan-Ying Lee ◽  
Chung-Yi Li ◽  
Kun-Chia Chang ◽  
Tsung-Hsueh Lu ◽  
Ying-Yeh Chen
Keyword(s):  
Young People ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Birth Registry ◽  
Data Set ◽  
Parental Suicide ◽  
The Impact ◽  
Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-­based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

Post hoc analysis of the CLEAR study in advanced renal cell carcinoma (RCC): Effect of subsequent therapy on survival outcomes in the lenvatinib (LEN) + everolimus (EVE) versus sunitinib (SUN) treatment arms.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4562-4562
Author(s):  
Thomas E. Hutson ◽  
Toni K. Choueiri ◽  
Robert J. Motzer ◽  
Sun Young Rha ◽  
Anna Alyasova ◽  
...  
Keyword(s):  
Median Duration ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Anticancer Therapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Sun ◽  
Post Hoc ◽  
The Impact

4562 Background: The multicenter, open-label, randomized, phase 3 CLEAR study showed that LEN + EVE had a significant PFS benefit (HR 0.65, 95% CI 0.53-0.80, P<0.001) and improved objective response rate (relative risk 1.48, 95% CI 1.26-1.74) vs SUN in the first-line treatment of patients (pts) with advanced RCC. The difference in overall survival (OS) for LEN + EVE vs SUN was not statistically significant (HR 1.15, 95% CI 0.88-1.50) (Motzer R et al. NEJM. 2021). Post hoc subgroup analyses were performed to assess the impact of subsequent therapy on OS. Methods: Pts in the CLEAR study were randomly assigned (1:1:1) to 1 of 3 treatment arms, including LEN 18 mg + EVE 5 mg once daily (QD) and SUN 50 mg QD (4 weeks on then 2 weeks off). These post hoc analyses examined OS by subsequent systemic anticancer medication in the LEN + EVE and SUN arms. Hazard ratios (HR; LEN + EVE vs SUN) were based on stratified (geographic region and MSKCC prognostic risk groups) Cox proportional hazards model. Results: Among 1069 pts with advanced RCC randomized in the CLEAR study, 714 pts were randomly assigned to the LEN + EVE and SUN arms (N=357/each). The median duration of survival follow-up was 27 months in the LEN + EVE arm and 26 months in the SUN arm. Given the shorter median duration of study treatment with SUN (7.8 months) vs LEN + EVE (11.0 months), more pts in the SUN arm received subsequent anticancer therapy during survival follow-up (LEN + EVE, n=167; SUN, n=206). Among pts who received subsequent therapy, pts in the LEN + EVE arm had a longer median time from randomization to initiation of subsequent therapy vs those in the SUN arm (8.0 vs 6.6 months, respectively). OS for the overall population, for pts with no subsequent anticancer therapy, and for pts with no subsequent immunotherapy is shown in the table. In the US population subgroup (LEN + EVE, n=62; SUN, n=61) of the CLEAR study, in which a similar number of pts received subsequent systemic anticancer therapies in the LEN + EVE vs SUN arms (62.9% vs 65.6%, respectively), OS was comparable among the 2 arms (HR 0.95, 95% CI 0.51-1.76). Overall, the safety profile was consistent with the known safety profiles of LEN + EVE and SUN. In both arms, most treatment-emergent deaths were due to progressive disease; there were few treatment-related deaths (<1%, per arm) and no clustering of events. Conclusions: In the CLEAR study, LEN + EVE met the primary endpoint of a significant benefit in PFS vs SUN. The results of these exploratory analyses suggest that subsequent systemic anticancer therapy affected the OS outcome results for LEN + EVE vs SUN in the CLEAR study. Clinical trial information: NCT02811861. [Table: see text]

Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study

2020 ◽  
Author(s):  
I Karaiskos ◽  
G L Daikos ◽  
A Gkoufa ◽  
G Adamis ◽  
A Stefos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Active Agent ◽  
Bloodstream Infections ◽  
National Registry ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Fatal Disease

Abstract Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). Methods A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. Results One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. Conclusions Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Between National Polarization and Local Ideology: The Impact of Partisan Competition on State Medicaid Expansion Decisions

2019 ◽  
Vol 50 (2) ◽  
pp. 237-255 ◽  
Author(s):  
Joshua Meyer-Gutbrod
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Electoral Competition ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Party Competition ◽  
Medicaid Expansion ◽  
Hazards Model ◽  
Partisan Competition ◽  
The Impact

Abstract The U.S. Supreme Court’s decision to grant states the authority to reject Medicaid expansion under the Affordable Care Act without penalty threatened the implementation of this polarized health policy. While many Republican-controlled states followed their national allies and rejected Medicaid expansion, others engaged in bipartisan implementation. Why were some Republican states willing to reject the national partisan agenda and cooperate with Democrats in Washington? I focus on the role of electoral competition within states. I conclude that although electoral competition has been shown to encourage partisan polarization within the states, the combination of intergovernmental implementation and Medicaid expansion’s association with public welfare reverses this dynamic. I employ a Cox proportional-hazards model to examine the impact of state partisan ideology and competition on the likelihood of state Medicaid expansion. I find that strong inter-party competition mitigates the impact of more extreme partisan ideologies, encouraging potentially bipartisan negotiation with the federal administration.

scholarly journals Exploring the determinants of real estate liquidity from an alternative perspective: censored quantile regression in real estate research

2020 ◽  
Vol 90 (7) ◽  
pp. 1057-1086 ◽  
Author(s):  
Marcelo Cajias ◽  
Philipp Freudenreich ◽  
Anna Freudenreich
Keyword(s):  
Real Estate ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Quantile Regressions ◽  
The Real Estate ◽  
Censored Quantile Regression ◽  
The Impact ◽  
German Cities

Abstract In this paper, the liquidity (inverse of time on market) of rental dwellings and its determinants for different liquidity quantiles are examined for the seven largest German cities. The determinants are estimated using censored quantile regressions in order to investigate the impact on very liquid to very illiquid dwellings. As market heterogeneity is not only observed between cities but also within a city, each of the seven cities is considered individually. Micro data for almost 500,000 observations from 2013 to 2017 is used to examine the time on market. Substantial differences in the magnitude and direction of the regression coefficients for the different liquidity quantiles are found. Furthermore, both the magnitude and direction of the impact of an explanatory variable on the liquidity, differ between the cities. To the best of the authors’ knowledge this is the first paper, to apply censored quantile regressions to liquidity analysis of the real estate rental market. The model reveals that the proportionality assumption underlying the Cox proportional hazards model cannot be confirmed for all variables across all cities, but for most of them.

scholarly journals Outcomes of Peritoneal Dialysis Patients and Switching to Hemodialysis: A Competing Risks Analysis

2014 ◽  
Vol 34 (3) ◽  
pp. 289-298 ◽  
Author(s):  
Jernej Pajek ◽  
Alastair J. Hutchison ◽  
Shiv Bhutani ◽  
Paul E.C. Brenchley ◽  
Helen Hurst ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Residual Renal Function ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Adjusted Analysis ◽  
Ultrafiltration Failure ◽  
The Impact ◽  
Technique Failure

BackgroundWe performed a review of a large incident peritoneal dialysis cohort to establish the impact of current practice and that of switching to hemodialysis.MethodsPatients starting peritoneal dialysis between 2004 and 2010 were included and clinical data at start of dialysis recorded. Competing risk analysis and Cox proportional hazards model with time-varying covariate (technique failure) were used.ResultsOf 286 patients (median age 57 years) followed for a median of 24.2 months, 76 were transplanted and 102 died. Outcome probabilities at 3 and 5 years respectively were 0.69 and 0.53 for patient survival (or transplantation) and 0.33 and 0.42 for technique failure. Peritonitis caused technique failure in 42%, but ultrafiltration failure accounted only for 6.3%. Davies comorbidity grade, creatinine and obesity (but not residual renal function or age) predicted technique failure. Due to peritonitis deaths, technique failure was an independent predictor of death hazard. When successful switch to hemodialysis (surviving more than 60 days after technique failure) and its timing were analyzed, no adverse impact on survival in adjusted analysis was found. However, hemodialysis via central venous line was associated with an elevated death hazard as compared to staying on peritoneal dialysis, or hemodialysis through a fistula (adjusted analysis hazard ratio 1.97 (1.02 – 3.80)).ConclusionsOnce the patients survive the first 60 days after technique failure, the switch to hemodialysis does not adversely affect patient outcomes. The nature of vascular access has a significant impact on outcome after peritoneal dialysis failure.

G CSF association with prolonged survival in HIV infected patients with disseminated Mycobacterium avium complex infection

1998 ◽  
Vol 9 (7) ◽  
pp. 394-399 ◽  
Author(s):  
Philip Keiser ◽  
Steven Rademacher ◽  
James Smith ◽  
Daniel Skiest
Keyword(s):  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cd4 Count ◽  
Risk Of Death ◽  
Hazards Model

Summary: Clarithromycin can ameliorate symptoms and improve survival in disseminated Mycobacterium avium complex DMAC infection. Optimal combina tions of this drug with other agents remain unknown. Granulocyte colony stimulating factor G CSF is a cytokine that can improve phagocytosis of M. avium complex in vitro . We aim to determine if G CSF administration is associated with improved survival in patients with DMAC in a retrospective, cohort study. Case records from 1991 to 1995 of 91 patients with DMAC at Parkland Memorial Hospital were reviewed for date of initial DMAC diagnosis, baseline CD4 count, race, sex, antiretroviral use, G CSF use, therapy for DMAC clarithromycin, ethambutol, ciprofloxacin and rifabutin and date of death. Of 91 cases identified, 25 were treated with G CSF and 66 never received this drug. Baseline characteristics were similar in each group including CD4 count 40 cells mm 3 vs 33 cells mm 3, P =0.68 , clarithromycin use 18 patients vs 52 patients, P =0.90 , and antiretroviral use 20 patients vs 42 patients, P =0.21 . Subjects treated with G CSF lived longer than those who did not receive this drug 355 days vs 211 days, P 0.01 . In the subgroup treated with clarithromycin, G CSF was also associated with increased survival 377 days vs 252 days, P 0.01 . Cox proportional hazards model showed a decreased risk of death in patients treated with G CSF RH=0.22, P 0.01 , clarithromycin RH=0.13, P 0.01 and ethambutol RH=0.51, P =0.02 . Ciprofloxacin and rifabutin use did not influence survival. These data support the use of clarithromycin and ethambutol in the treatment of DMAC. Addition of G CSF to a regimen of clarithromycin and ethambutol may increase survival in DMAC and should be studied prospectively.

Clinical outcomes of pancreas cancer patients with peritoneal spread: Results from the chord consortium.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19268-e19268
Author(s):  
Mehrnoosh Pauls ◽  
Abdulaziz AlJassim AlShareef ◽  
Winson Y. Cheung ◽  
Rachel Anne Goodwin ◽  
Brandon M. Meyers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Advanced Pancreatic Cancer ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
The Impact ◽  
Line Chemotherapy

e19268 Background: Prior studies have demonstrated that clonal cells that give rise to pancreatic peritoneal metastases (PM) are geographically and genetically distinct from clonal cells, giving rise to lung and liver metastases. The objective of this study was to assess if there is a distinct difference in prognosis and therapeutic response among patients with pancreatic cancer with (PM compared to the lung/liver. Methods: Using a retrospective cohort design, medical records from adult patients diagnosed with metastatic adenocarcinoma of the pancreas at five Canadian academic cancer centers (2014 - 2019) were reviewed. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and first line chemotherapy were collected. Cox proportional hazards model (MVA) was used to examine the association between peritoneal involvement and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 patients were included. Metastatic sites included peritoneum (n = 170, 14.6%), lung (n = 145, 12.5%) and liver (n = 563, 48.5%). Patients with PM received first-line FOLFIRINOX (FFX, n = 31), Gemcitabine + nab-paclitaxel (G/N, n = 20), Gemcitabine (G, n = 18), and no treatment (n = 97). In univariate analyses, worse ECOG PS was associated with PM (p = 0.002). The majority of patients died (89%), with a median overall survival (OS) of 3 vs 7 months for patients with PM and those without PM (p < 0.001), respectively. The median OS in patient whom receive first-line chemotherapy was 7 months in FFX group (95% CI 1.66-12.33), 6 months in G/N (95% CI 4.54-7.45) and 2 months in G group (95% CI 1.42-2.57). Patients had significantly better OS when treated with FFX or G/N compared to G alone (p = 0.002). Time to treatment failure was significantly shorter among patient treated with G alone compare to patients treated with FFX and G/N (P < 0.005). Conclusions: In the setting of combination chemotherapy for advanced pancreatic cancer, patients with PM continue to have a poor prognosis. This may be due to the impact of PM on PS and the inability to administer palliative chemotherapy. For eligible patients, FFX or G/N results in a higher OS than G monotherapy.

Trends in Treatment of Uterine Serous Cancer in the Medicare Population

2015 ◽  
Vol 25 (6) ◽  
pp. 1023-1030 ◽  
Author(s):  
Jose Alejandro Rauh-Hain ◽  
Sarah C. Connor ◽  
Joel T. Clemmer ◽  
Olivia W. Foley ◽  
Rachel M. Clark ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Serous Carcinoma ◽  
Medicare Population ◽  
Study Population ◽  
Uterine Serous Carcinoma ◽  
The Impact ◽  
Over Time

ObjectiveThe objectives of this study were to evaluate the rates of chemotherapy and radiotherapy delivery in the treatment of uterine serous carcinoma in the Medicare population and to compare clinical outcomes in treated and untreated patients.MethodsThe linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients with a diagnosis of uterine serous carcinoma between 1992 and 2009. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model.ResultsA total of 2188 patients met study eligibility criteria. Stages I, II, III, and IV diseases accounted for 890 (41%), 174 (8%), 470 (21%), and 654 (30%) of the study population, respectively. Chemotherapy, radiotherapy, both, or none, were administered as adjuvant therapy in 635 (29%), 536 (24%), 308 (14%), and 709 (32%) of the study population, respectively. Use of chemotherapy became more frequent over time. Over the study period, and after adjusting for race, time of diagnosis, SEER registry, marital status, stage, age, surgery, lymph node dissection, socioeconomic status, and comorbidity index, there was an association between receipt of radiotherapy alone (hazard ratio [HR], 1.3; 95% CI, 1.04–1.67) and not receiving any treatment (HR, 1.5; 95% CI, 1.2–2.01) and worst survival. Survival was not improved over time.ConclusionAlthough adjuvant chemotherapy and combination treatment with chemotherapy and radiation were associated with improved survival in our model, there was no significant improvement in survival over time.

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