bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin C supplementation during chronic variable stress exposure modulates contractile functions of testicular artery and sperm parameters in male Wistar rats
Authors: Salami Shakiru Ademola , Salahdeen Hussein Mofomosara , Moronkola Oyinlola Toluwani , Murtala Babatunde Adekunle , Raji Yinusa 
Published: February 2020

Abstract
Background
Humans are exposed to identifiable multiple environmental stressors. However, there is paucity of studies assessing chronic variable stress (CVS) exposure together with antioxidant supplementation on reproductive function. This study investigates impact of vitamin C supplementation, during CVS exposure on contractile functions of testicular artery and sperm parameters. Twenty pubertal male Wistar rats (150–200 g) were grouped into four of five rats each consisting of control (normal saline), vitamin C treated (7 mg/kg bwt), chronic variable stress (CVS) + vitamin C, and CVS only. Animals were treated respectively for 8 weeks. Serum superoxide dismutase (SOD), catalase, malondialdehyde (MDA) activity, testosterone, and cortisol were assayed. Contractile responses of excised testicular artery to phenylephrine, potassium chloride, acetylcholine, and sodium nitroprusside were determined using Ugo Basile data acquisition system. Sperm parameters and histopathology of the testis were also determined. Statistical significance was taken at p < 0.05

Result
MDA activity was significantly increased in group exposed to chronic variable stress. However, groups supplemented with vitamin C during CVS exposure showed no significant increase. Serum SOD and catalase were enhanced in group exposed to CVS with vitamin C supplementation when compared to group exposed to chronic variable stress only. Chronic variable stress exposure increased serum cortisol level and this was attenuated with vitamin C supplementation. Vitamin C supplementation significantly increased serum testosterone level when compared to CVS only exposed group. Contraction responses of testicular arterial strips to phenylephrine and potassium chloride were attenuated in vitamin C supplemented groups when compared to CVS only exposed group. Vitamin C supplementation during CVS exposure also enhanced relaxation of testicular artery strip to sodium nitroprusside and acetylcholine. Sperm count and percentage motility were significantly reduced in CVS only exposed group when compared vitamin C supplemented group. Sperms cells with abnormal morphology were also significantly increased in chronic variable stress only exposed group when compared to control and vitamin C supplemented groups.

Conclusion
Chronic variable stress adversely impacts contractility of testicular artery, sperm parameters, cortisol, and testosterone level. Vitamin C supplementation modulated these by suppressing MDA and enhancing antioxidant enzyme activity.
Renal resistive index in non-alcoholic fatty liver disease as an indicator of early renal affection
Authors: Mahmoud Hossam El-Din A. , Yousry Wael A. , Saleh Shereen A. , El Badry Mohamed , Hussein Ahmed , Ali Mostafa Hassan , El-Hariri Hazem M. 
Published: February 2020

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is a possible risk factor for chronic kidney disease (CKD). Renal resistive index (RRI) which is a ratio of peak systolic and end diastolic velocity can test arterial stiffness and endothelial renal dysfunction. The aim of the work is to detect the relation between NAFLD and RRI as an indicator of early renal affection and its relation to the disease severity. This study included 150 subjects divided into 3 groups: patients with NASH, simple steatosis, and control group (50 patients each). All patients were subjected to full history taking, clinical examination, laboratory investigations, abdominal ultrasound examination, and RRI measurement.

Results
6.0% of NASH patients had significant fibrosis by NAFLD fibrosis score. RRI was significantly higher in NASH patients with fibrosis (mean = 0.74) than NASH patients without fibrosis (mean = 0.65) and patients with simple steatosis (mean = 0.63). It was the lowest in normal controls (mean = 0.61). There were significant correlations between RRI and age, BMI, serum lipids, liver enzymes, and NAFLD fibrosis score. Multiple linear regression analysis found that age and serum cholesterol were significant independent factors of increased RRI (p < 0.0001). RRI showed low diagnostic performance in differentiation between NASH and simple steatosis using ROC curve.

Conclusion
RRI was significantly higher in NASH patients with and without hepatic fibrosis. RRI correlates significantly with NAFLD fibrosis score. RRI can be used as an indicator of early renal affection in patients with NAFLD.
Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): Five-year results of a randomized phase II trial.
Authors: Ost Piet , Reynders Dries , Decaestecker Karel , Fonteyne Valerie , Lumen Nicolaas , De Bruycker Aurélie , Lambert Bieke , Delrue Louke , Bultijnck Renée , Goetghebeur Els , Villeirs Geert , De Man Kathia , Ameye Filip , Billiet Ignace , Joniau Steven , Vanhaverbeke Friedl , de Meerleer Gert 
Published: February 2020

10 Background: Multiple randomized phase II trials suggest that metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa) improves progression-free survival, but the majority of trials lack longer follow-up. We present the updated 5-year results from the STOMP-trial. Methods: In this multicentre, randomised, phase II study, asymptomatic PCa patients were eligible in case of a biochemical recurrence following primary PCa treatment with curative intent and presenting with up to 3 extracranial on choline PET-CT and a serum testosterone levels > 50 ng/ml. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions. Randomisation was balanced dynamically on two factors: PSA doubling time (≤3 vs. > 3 months) and nodal vs non-nodal metastases. The primary endpoint was androgen deprivation therapy (ADT)-free survival. Castrate resistant prostate cancer-free survival (CRPC) was a secondary endpoint. Tests were performed two-sided; p values less than 0.20 were deemed significant. Results: The 5-year ADT-free survival was 8% for the surveillance group and 34% for the MDT group (Figure 1, hazard ratio 0.57 [80% CI: 0.38-0.84], log-rank p = 0.06). There was no significant difference in effect for the different stratification factors (interaction test). The 5-year CRPC-free survival was 53% for the surveillance group and 76% for the MDT group (hazard ratio 0.62 [80% CI: 0.35−1.09]; log−rank p = 0.27). At a median follow for survival of 5.3 years (IQR 4.3-6.3), the 5-year overall survival was 85%, with 6 out of 14 deaths attributed to prostate cancer. Conclusions: The updated STOMP trial outcomes confirm the earlier reported significant difference in ADT free survival in favor of the MDT group compared to surveillance. Prostate-cancer related mortality is low within the first 5 years of diagnosis of oligorecurrent prostate cancer. Clinical trial information: NCT01558427.
Association of body composition with survival and efficacy of first-line treatment in patients with castration-resistant prostate cancer.
Authors: Joung Jae Young , Pak Sahyun 
Published: February 2020

115 Background: We aimed to investigate the association of body composition with survival and efficacy of first-line treatments in patients with castration-resistant prostate cancer (CRPC). Methods: Records of CRPC patients who were treated with first-line docetaxel or androgen receptor signaling inhibitors (ARSi) between 2005 and 2018 were reviewed. Skeletal muscle index (SMI), visceral fat index, and subcutaneous fat index were evaluated using pretreatment computed tomography images. Results: Of the 230 eligible patients, 144 patients received docetaxel and 86 received ARSi as the first-line treatment for CRPC. SMIhi (based on median value) group had higher prostate-specific antigen (PSA) progression-free survival (median 13.5 vs. 8.3 months, p=0.030), radiologic progression-free survival (14.9 vs. 9.1 months; p<0.001), and overall survival (24.1 vs. 16.9 months, p=0.015) compared than SMIlo group. In multivariable analysis, SMI was independently associated with risk of PSA progression (HR=0.68; 95% CI, 0.50-0.93; p=0.017), radiologic progression (HR=0.54; 95% CI, 0.39-0.75; p=0.001), and overall survival (HR=0.72; 95% CI, 0.52-0.98; p=0.037), regardless of BMI. In docetaxel-treated patients, PSA progression-free survival (13.5 vs. 5.9 months, p=0.016) and radiologic progression-free survival (14.6 vs. 6.7 months, p<0.001) were higher in SMIhi than SMIlo group. However, PSA progression-free survival and radiologic progression-free survival were similar between two groups in ARSi-treated patients. Based on treatment-specific hazards of radiologic progression, patients with SMIlo are more likely to benefit from ARSi compared than docetaxel. Conclusions: High skeletal muscle mass may be associated with reduced risks of disease progression and mortality in patients with CRPC. However, the significance of these relationships is limited in patients treated with docetaxel. These results suggest that skeletal muscle mass may be helpful in treatment selection and predicting treatment response in CRPC. Further prospective studies are warranted.
The impact of the expression of the transcription factor MYBL2 on outcomes of patients with localized and advanced prostate cancer.
Authors: Yoshikawa Yuki , Wang Xin Victoria , Chen Yu-Hui , Mazzu Ying Zhang , Chakraborty Goutam , Jehane Lina E. , Rajanala Sai Harisha , Hirani Rahim , Nandakumar Subhiksha , Stopsack Konrad H. , Lee Gwo-Shu Mary , Davicioni Elai , Liu Glenn , DiPaola Robert S. , Carducci Michael Anthony , Kantoff Philip W. , Sweeney Christopher 
Published: February 2020

149 Background: Patients with metastatic hormone-sensitive prostate cancer (mHSPC) have a variable response to ADT and some benefit from the addition of docetaxel or an androgen signaling pathway inhibitor. We found that loss of the epigenetic regulator KDM5D is associated with more aggressive prostate cancer (PC). We sought to determine whether MYBL2 which is regulated by KDM5D mediates this effect. MYBL2 is a transcription factor which controls key genes (e.g. FOXM1) and increases cell cycle progression and survival. Methods: AR expressing hormone-sensitive cell lines, LNCaP and LAPC4 were used. Motif analysis and CHiPseq of LNCaP with and without siKDM5D was performed and impact of modulation of KDM5D and MYBL2 in both cells on cell survival was assessed. Gene expression profiling (GEP) data assessed MYBL2’s association with KDM5D levels in localized disease (publicly available data) and mHSPC (Decipher whole Affymetrix platform on CHAARTED samples). Results: Silencing KDM5D increased H3K4me3 and increased MYBL2 expression. GEP showed a strong negative correlation between KDM5D and MYBL2 in patients with localized PC (-0.66; TCGA) but not from primary prostate cancer tissue with mHSPC (-0.03; CHAARTED). Cells with low KDM5D and high MYBL2 were androgen independent and more resistant to docetaxel. In TCGA, patients with high MYBL2 had a higher rate of relapse from localized disease. In patients with metastatic disease (CHAARTED) low MYBL2 was associated with a better overall survival (OS) on multivariable analysis when treated with ADT or ADT + docetaxel. Conclusions: Low MYBL2 is associated with a longer OS with ADT alone and ADT and docetaxel independent of clinical variables. Patients with high MYBL2 expression had better OS with ADT plus docetaxel compared with patients with high MYBL2 treated with ADT alone.[Table: see text]
Genomic characteristics associated with clinical activity of rucaparib in patients (pts) with BRCA1 or BRCA2 (BRCA)-mutated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Abida Wassim , Campbell David , Patnaik Akash , Sautois Brieuc , Shapiro Jeremy David , Vogelzang Nicholas J. , Bryce Alan Haruo , McDermott Raymond S. , Ricci Francesco , Rowe Julie Haewon , Zhang Jingsong , Loehr Andrea , Despain Darrin , Dowson Melanie , Golsorkhi Tony , Chowdhury Simon 
Published: February 2020

178 Background: The phase 2 TRITON2 study (NCT02952534) is evaluating the PARP inhibitor rucaparib in pts with mCRPC and a deleterious germline or somatic alteration in BRCA ( BRCA pts) or 1 of 13 other DNA damage repair (DDR) genes. Methods: Eligible pts had progressed on 1–2 lines of androgen receptor-directed therapy and 1 taxane-based chemotherapy. Deleterious DDR gene alterations were identified from central testing of plasma and/or tissue samples by Foundation Medicine or from local testing. Results: As of Jul 2, 2019 (visit cutoff), 98 BRCA pts had received rucaparib; median (range) duration of follow-up was 13.0 (4.1–25.8) mo. Confirmed objective response rate (ORR) in BRCA pts (with investigator-assessed measurable disease) and PSA response rates (in pts with and without measurable disease) are shown in the Table. A biallelic alteration was observed in 81.4% (35/43) of BRCA pts for whom zygosity could be determined, and pts with homozygous BRCA loss (20.4%; 20/98) demonstrated high ORR (66.7% [95% CI, 38.4-88.2]; 10/15) and PSA response rates (75.0% [95% CI, 50.9-91.3]; 15/20). The safety profile in BRCA pts was consistent with the overall TRITON2 pt population. Conclusions: Results from TRITON2 showed antitumor activity with rucaparib in pts with mCRPC and a deleterious BRCA alteration. Responses were observed in patients with germline or somatic alterations in BRCA1 or BRCA2. The activity of rucaparib in these and additional genomic subgroups (e.g., based on zygosity, plasma genomic testing, or co-occurring alterations) will be reported. Clinical trial information: NCT02952534. [Table: see text]
CDK12-mutated prostate cancer (PC): Clinical outcomes to standard therapies and immune checkpoint blockade.
Authors: Schweizer Michael Thomas , Gulati Roman , Brown Landon Carter , McKay Rana R. , Dorff Tanya B. , Kilari Deepak , Vats Pankaj , Patel Vaibhav G. , Oh William K. , Armstrong Andrew J. , Montgomery Robert B. , Alva Ajjai Shivaram 
Published: February 2020

191 Background: Translational studies have shown that CDK12 mutations may delineate an immunoresponsive subgroup of PC, characterized by high neoantigen burden. Given that these mutations may define a clinically relevant PC subgroup, we sought to describe outcomes to both standard drugs and PD1 inhibitors. Methods: Clinical data from consecutive patients with CDK12 mutations were retrospectively collected from 7 centers. Multiple clinical grade sequencing assays were used to assess for CDK12 alterations. Descriptive statistics included PSA50 (≥50% decline in PSA from baseline) and clinical/radiographic progression-free survival (PFS). Results: Of 56 CDK12-mutated PC patients, 27 (48%) had biallelic CDK12 alterations. At diagnosis, 46 (82%) had Gleason grade group 4-5 disease, 52% had T3-T4 disease and 15 (27%) had M1 disease. Median follow up was 8.2 yrs (95% CI: 5.6-11.1) and 53 (95%) developed metastatic disease. Median overall survival (OS) from metastasis was 3.9 years (95% CI: 3.2-5.8). Nineteen patients received an anti-PD1 therapy. PSA50 responses to PD1 blockade were infrequent and overall PFS was short (Table); however, the estimated 9-month PFS was 23%. PFS was higher in chemotherapy naïve patients who received anti-PD1 therapy (P=0.004). Outcomes were similar in monoallelic vs. biallelic CDK12-mutated patients. Conclusions: CDK12-mutations define an aggressive PC subgroup, with a high rate of metastatic disease and short OS. Immune checkpoint inhibitors may be effective in a minority of these patients and exploratory analysis supports using anti-PD1 drugs early.[Table: see text]
Addition of abiraterone to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Model to estimate long-term survival, quality-adjusted survival, and cost-effectiveness.
Authors: Clarke Caroline Sarah , Brawley Christopher D. , Ingleby Fiona Caroline , Gabrio Andrea , Dearnaley David P. , Matheson David , Attard Gerhardt , Rush Hannah L. , Jones Robert J. , Clarke Noel W. , Parmar Mahesh K. B. , Sydes Matthew R. , Hunter Rachael Maree , James Nicholas D. 
Published: February 2020

204 Background: Results from randomised trials show adding abiraterone acetate plus prednisolone (AAP) to standard of care (SOC) improves disease-free and overall survival in men with prostate cancer (PC) starting long-term hormone therapy for first time. Formal assessment is required of whether funding AAP here shows appropriate use of resources. This cost-effectiveness decision model tests if giving AAP to these patients is cost-effective using costs from English National Health Service, the largest nation where STAMPEDE recruited. Methods: Health outcomes and costs were modelled using patient data from AAP comparison of STAMPEDE (recruitment 2011-14). This included 1917 men with high-risk, locally advanced metastatic or recurrent PC starting 1st-line hormone therapy. SOC was hormone therapy for ≥2 years with radiotherapy in pre-selected patients. If allocated to research group, AAP (AA 1000mg/day, P 5mg/day) was added to SOC. The model makes lifetime predictions of survival, costs and quality-adjusted lifeyears (QALYs), with costs and QALYs discounted at 3.5% annually. Sensitivity analyses were performed. Results: The model predicted AAP would extend survival (discounted quality-adjusted survival) by 2.68y (1.46 QALYs) for metastatic patients and 0.30y (0.29 QALYs) for non-metastatic. The cost of AAP means it is not currently cost-effective in this setting, including with Patient Access Scheme costs for AAP and enzalutamide and similar reductions for cabazitaxel and Ra. If AAP’s price reduces after patent expiry as expected (90% reduction on BNF cost), it would be cost-effective in both patient groups, with incremental cost-effectiveness ratios below £10,000 (US$12,665) per QALY. AAP could also dominate in non-metastatic patients (i.e. lower costs and higher QALYs than SOC alone). Conclusions: AAP could be cost-effective for patients with non-metastatic and metastatic disease with expected future pricing and may be cost-saving in the former. Policymakers should encourage license submissions and generic price reductions to facilitate use of AAP given cost-saving potential in addition to improving survival. Clinical trial information: NCT00268476.
REACT: A feasibility study to test the integration of a cancer registry early case ascertainment process via electronic pathology reporting with an online clinical trial matching tool.
Authors: Borno Hala , Duffy Christine , Zhang Sylvia , Loya Zinnia , Golden Todd , Oh Debora , Odisho Anobel Y. , Gomez Scarlett Lin 
Published: February 2020

207 Background: Representation of diverse patient populations in prostate cancer clinical trials is essential to ensure results are applicable to all men. However, underrepresentation among underserved populations remains a critical problem. Population-based cancer registries provide a potential platform to overcome problems with inclusion of diverse patient populations in clinical research when used as a source for recruitment. Methods: Leveraging statewide implementation of early-case ascertainment (ECA) via electronic pathology for cancer case identification, we performed a feasibility study within the Greater Bay Area Cancer Registry to (1) test a process using ECA to identify new cases of advanced prostate cancer for potential enrollment into clinical trials and (2) test the utility of an online clinical trial matching tool to improve matching of underrepresented patients into clinical trials. All study materials were translated into Spanish, and recruiters were Spanish-speaking. Results: A total of 419 cases were identified from 19 reporting facilities through ECA and sent invitation letters; 18 cases were excluded due to physician contraindication, and 68 (16%) declined participation. All enrolled participants (N=54) completed baseline surveys. To date, 40 participants completed follow-up surveys after using the online matching tool. Most participants were White (80%), of higher income (>$150,000; 41%), and college-educated (70%). Thirty-seven percent indicated awareness of cancer clinical trials, 69% stated interest in participating in clinical research, and 72% held a positive attitude towards cancer clinical trials. However, 46% indicated they would not participate in a randomized study. To assess utility of the matching tool, 65% indicated it increased their interest in participating in a clinical trial. Conclusions: ECA needs to ensure sociodemographic data are available to make it useful as a tool for clinical trials. Preliminary results indicate ECA used in combination with an online clinical trial matching tool may serve as an important recruitment vehicle for prostate cancer clinical trials.
Differential expression of PSMA and 18F-fluciclovine transporter genes in metastatic castrate-resistant and treatment-emergent small cell/neuroendocrine prostate cancer.
Authors: Chu Carissa , Alshalalfa Mohammed , Sjöström Martin , Zhao Shuang , Herlemann Annika , Chou Jonathan , Baskin Avi Lefridge , Mahal Brandon Arvin Virgil , Spratt Daniel Eidelberg , Cooperberg Matthew R. , Small Eric Jay , Aggarwal Rahul Raj , Wong Anthony C. , Porten Sima P. , Hope Thomas , Nguyen Paul L. , Schaeffer Edward M. , Carroll Peter , Feng Felix Y 
Published: February 2020

24 Background: 18F-fluciclovine (Axumin) PET/CT imaging is recommended by the NCCN in the setting of biochemical recurrence, while prostate-specific membrane antigen (PSMA) PET/CT is preferred by the EAU. The utility of these methods in the post-androgen deprivation therapy (ADT) setting however, is less defined. Our objective was to compare relative gene expression of the molecular targets of these imaging modalities— fluciclovine transporter genes (LAT1-4, ASCT1-2) and PSMA—in metastatic castrate resistant prostate cancer (mCRPC) and treatment-emergent small cell/neuroendocrine prostate cancer (t-SCNC). Methods: Genome-wide expression profiles of five mCRPC cohorts (Aggarwal, Grasso, Kumar, Beltran, Robinson, et al) were used to characterize relative expression of fluciclovine transporter (LAT1-4, ASC1-2) and PSMA (FOLH1) genes. 3 cohorts (Kumar, Beltran, Aggarwal) were enriched with t-SCNC tumors. The GSE35988 cohort included primary tumors and mCRPC. RNA expression profiling methods were consistent within cohorts. Results: 518 mCRPC specimens were included. In the GSE35988 cohort, PSMA expression was downregulated in mCRPC when compared to primary localized tumors (p=0.01). PSMA expression was further depressed in t-SCNC when compared with mCRPC (p<0.001). Of the fluciclovine transporter genes, LAT1 and LAT4 were overexpressed in mCRPC when compared to primary tumors, while ASC2 was less expressed (p<0.001). LAT1 was further overexpressed in t-SCNC when compared to mCRPC, while LAT2 was less expressed (p<0.001). PSMA expression was negatively correlated with LAT1 (p<0.001) but positively correlated with LAT2 (p=0.006). Other fluciclovine transporters were not correlated. Conclusions: Expression of PSMA and a subset of fluciclovine transporter genes are inversely correlated in mCRPC and t-SCNC. These findings suggest that fluciclovine-based imaging may play a role in castrate resistant states. Clinical comparison between PSMA- and fluciclovine-based imaging modalities in mCRPC and t-SCNC is warranted.