bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of response to platinum (Pt)-based chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Kilari Deepak , Bylow Kathryn A. , Berlin Kathryn E. K. 
Published: March 2017

e575 Background: Aggressive variant PC (AVPC) is a well-described subtype of PC which portends a poor prognosis. Studies have shown an increase in progression-free survival(PFS) when Pt is added to taxane-based treatment in AVPC. Clinical features including visceral metastasis, lytic bone lesions, low PSA, short responses to androgen suppression and high Gleason score at diagnosis predict response to upfront docetaxel (D) and Pt (Aparicio et. al. Clin Cancer Res 2013). Our objective was to study the effect of baseline characteristics on PFS with D+Pt in D-pretreated CRPC. Methods: A retrospective review of D-pretreated mCRPC men who received D (60-75 mg/m2) and carboplatin (C, AUC 4-5) at our institution between 2008- 2015 were included in this analysis. All patients had metastatic CRPC, were heavily pre- treated (median treatments = 4) and received at least one cycle of D+C. Numerical data was analyzed using Student’s T-test; binary data was analyzed with Z-proportions test. Results: 28 patients were identified. The median age was 60 yrs(48-73); median PSA at diagnosis was 21ng/dl(0.3-5000); median PSA at the start of D+C was 115.32 ng/dl( 0.65-1395). The response rate was 60.7% and the median time to response was 1 mo. The median reduction in PSA was 48.13%. The median PFS was 6 mo, and median OS was 10 mo. Common treatment – related side effects included grade 1 fatigue (82.14%), pancytopenia (42.86%), and febrile neutropenia (10.71%). Correlation of baseline characteristics to PFS was evaluated. Short response to ADT < 1 yr (p < 0.05), prior response to D (PFS > 6 months) ( p = 0.037), and presence of visceral mets (p < 0.05) predicted better response to D+C. Age (p = 0.27), Gleason score at diagnosis (p = 0.08), performance status at start of therapy (p = 0.27), PSA at diagnosis (p = 0.35), and PSA at start of D+C (p = 0.420) did not predict response. Conclusions: D+C is effective and safe in D pretreated CRPC. Response to prior D, short response to ADT, and the presence of visceral metastasis predicted response to D+C. These are features of AVPC. Prospective studies to validate our findings and identify molecular characteristics of Pt responders are needed in this heavily pre-treated “real world” patient population.
Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response in castration-resistant patients.
Authors: Thellenberg Karlsson Camilla , Tjon-Kon-Fat Lee-ann , Lundholm Marie , Schröder Mona , Wurdinger Thomas , Widmark Anders , Nilsson Jonas , Wikström Pernilla 
Published: March 2017

e583 Background: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance. Methods: The isolated platelet population of blood samples and QRT-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis directed therapies. The association between biomarker status in platelets (positive vs. negative) and therapy response, progression-free survival (PFS) and overall survival (OS) was examined. Results: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-3 ( KLK3), androgen receptor splice-variant 7 (ARV7), folate hydrolase 1 (FOLH1), and neuropeptide-Y ( NPY) were present within the platelet fraction. Analyzing biomarkers in the chemotherapy group did not add information about PFS, but FOLH1 was associated with short OS (p = 0.00015). In the abiraterone treated cohort, detectable FOLH1 (p = 0.009), KLK3 (p = 0.018), and NPY (p = 0.028) were all associated with short PFS. Patients with biomarker-negative platelets had the best outcome, while FOLH1 and NPY provided independent predictive information regarding PFS and KLK3 (p = 0.001) and FOLH1 (p = 0.002) were associated with short OS. Conclusions: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with high accuracy. Platelet-based analysis of FOLH1, NPY, and KLK3 may be used for treatment stratification of patients scheduled for treatment with abiraterone.
Cell-free DNA as a surrogate marker in patients with CRPCA undergoing taxane-based chemotherapy.
Authors: Haidl Friederike , Kienel Alexandra , Pfister David , Heidenreich Axel 
Published: March 2017

e584 Background: Taxane-based chemotherapy is one of the first-line life prolonging therapeutic approaches in metastatic castration-resistant prostate cancer (mCRPCA). Until now, there is no valid surrogate marker directly reflecting therapeutic response. Prostate specific antigen (PSA) and imaging studies are used to monitor therapy. The aim of this study was to assess whether circulating cell-free DNA (cfDNA) is suitable as a predictive and prognostic marker. Methods: cfDNA was isolated in 74 patients with mCRPCA receiving taxane based chemotherapy. Median serum cfDNA - concentration was correlated with localization of metastasis and tumor burden (bone, lymph node and visceral). In addition we examined the change of cfDNA - concentration under treatment. The median serum cfDNA - concentration at the time of 1st, 5th and 10th cycle of chemotherapy was correlated with PSA response (>80%, >50%, <30% decrease). Results: We identified 21 patients with a PSA decrease >80%, 41 patients with a PSA decrease >50%, 12 patients with a PSA decrease <30 % and 15 patients with a PSA rise during treatment. Median cfDNA concentration in patients with a PSA decrease of >80% was 34.96 ng/ml, in patients with a PSA decrease > 50% 34.96 ng/ml and in patients with a PSA decrease < 30% 38.475 ng/ml. The Median cfDNA concentration in patients with a PSA rise was 31.25 ng/ml. Median cfDNA concentration in patients with lymph node metastasis was 33.78 ng/ml, with bone metastasis < 3 34.24 ng/ml, bone metastasis >3 31.97 ng/ml and with visceral metastasis 34.57 ng/ml. There was no significant correlation between median cfDNA - concentration and type of metastasis (cfDNA vs. PSA bone metastasis <3, P = 0,56938, cfDNA vs. PSA bone metastasis >3 P = 0.472, cfDNA vs. PSA lymph node metastasis P = 0.423). There was no significant change of median cfDNA concentration under treatment ( P > 0.05). Conclusions: Although cfDNA-concentration is a prognostic and predictive marker for survival and therapy response as shown recently, our findings suggest that cfDNA as a surrogate marker is unsuitable.
Polymer-delivered, subcutaneously administered leuprolide acetate provides consistent and prolonged drug delivery in castrate men with advanced prostate cancer.
Authors: Childs Lane , Atkinson Stuart , McLane John A. , Garrett Steve A. 
Published: March 2017

e586 Background: Leuprolide acetate (LA), a LHRH agonist, is standard of care in ADT in prostate cancer and used to suppress serum testosterone (T) to castrate level. Previously, in a head-to-head comparison of long-acting, polymer-delivered, subcutaneously administered LA (SC-LA) and microsphere intramuscularly administered LA depot (IM-LA) in healthy subjects, SC-LA demonstrated extended drug delivery compared to IM-LA, as well as prolonged T suppression. The objective of this study was to evaluate the safety and pharmacokinetics (PK) of SC-LA in orchiectomized, advanced prostate cancer patients to confirm and compare PK results with the head-to-head study. Methods: In this open label, single dose study, male, orchiectomized prostate cancer patients (ages 45-85) received a single dose of 7.5 mg SC-LA (labeled for 1 month dose interval). Blood samples were taken at baseline and at all scheduled visits up to day 56. LA concentration in serum was analyzed with HPLC. PK parameters AUC, Cmax, Tmax (time to Cmax), t1/2 and concentration-time data were evaluated and adverse events (AEs) were assessed. Results: The study was conducted in 8 males with adenocarcinoma of the prostate (mean age = 72.5 y). Following administration, there was an initial rapid absorption phase with maximal concentrations observed at 2-6 hours. Serum LA fell slowly over 4-6 days and remained above 0.1ng/mL, the level associated with T suppression, for a mean of 37 days (range 28-49). Mean Cmax was 26.3 ±12.6 ng/mL with a mean Tmax of 3.79 ±1.39 h. AUC was 999 ±247 ng*h/mL. There were no serious treatment-related AEs and no subjects discontinued the study due to an AE. Conclusions: LA administered as a single, monthly SC dose via polymer delivery in orchiectomized prostate cancer patients showed extended drug delivery and T suppression 3 weeks past the dosing interval, mirroring extended PK in healthy subjects. Taken together, the PK profile of SC-LA demonstrates effective drug release throughout and beyond the labelled dosing interval.
A multivariate index analyte (MIA) assay for differentiating aggressive from nonaggressive prostate cancer.
Authors: Campbell Douglas , Velonas Vicki , Soon Julie T , Wissmueller Sandra , Gillatt David , Walsh Brad 
Published: March 2017

e588 Background: Biomarkers that can assist clinicians and patients to proceed when PSA and /or DRE are equivocal. Such biomarkers should establish both sensitivity and specificity for prostate cancer detection in order to improve go-forward decisions to perform prostate biopsy. Following the successful use of a three-protein marker panel to increase the specificity of prostate cancer detection1 we have now used the same technology to examine whether an MIA assay can assist in differentiating aggressive from non-aggressive cancer in prostate cancer patients. Methods: Samples from patients with either aggressive prostate cancer or non- aggressive prostate cancer were obtained from two sources. The cohort criteria comprised of serum samples where blood was drawn from patients with adenocarcinoma and a PSA greater than or equal to 2ng/mL. All men were Caucasian with the exception of 3 who were African American. Non-aggressive prostate cancer was defined as having a Gleason score of 6 (n = 35) and aggressive prostate cancer was characterized as Gleason score 7 and above (n = 69). Biomarker levels were determined using a plate based ELISA for GPC-12 and a bead-based MIA assay for the other markers. Results: By using biostatistical analysis (Simplicity Bio, Switzerland) two models were identified that were able to differentiate between aggressive and non-aggressive prostate cancer. One consisted of a combination of 5 analytes and the other used 6 analytes. Model 1 containing PSA and GPC-1 plus 4 analytes produced a combined sensitivity of 81% and specificity of 78% (AUC 0.81). The second model comprising of GPC-1 with an additional 4 analytes achieved a sensitivity of 72% with a specificity of 76% (AUC 0.76). Both models had a p value of less than 0.05. By itself PSA was a poor predictor of prostate cancer with a sensitivity of 58% and specificity of 43% (AUC 0.55). Conclusions: The analytes identified by the two statistical models demonstrate potential utility for using the combined markers as a new means of differentiating aggressive prostate cancer from non-aggressive cancer. An additional study to further validate these models is currently being constructed.
Radium-223 in metastatic castration-resistant prostate cancer: Effect of performance score and albumin levels.
Authors: Challapalli Amarnath , Cowley Sue , Griffiths Dorothy , Compton Eleanor , Persad Rajendra , Bahl Amit 
Published: March 2017

e594 Background: Radium-223 (Ra223) is a novel alpha-emitting radiopharmaceutical agent approved for use in patients with metastatic castration resistant prostate cancer (mCRPC) and bone metastases based on ALSYMPCA results. However, its optimal sequencing in the treatment of mCRPC remains unclear. We evaluated the relevance of albumin (A) levels to aid in optimal selection and timing for Ra223 treatment. Methods: Eighty-eight patients had completed treatment with Ra223 from Feb 2014 - Sep 2016. The patients were planned to receive 6 injections at a dose of 55 kBq/kg every 4 weeks. Visual analogue score (VAS) was used to assess pain. The effect of serum alkaline phosphatase (SAP), docetaxel chemotherapy, A levels and performance score (ECOG-PS) on progression free survival (PFS) and overall survival (OS) were evaluated. Results: At baseline (BL) median age was 74.5years; 68% of patients were ECOG-PS-0/1; median VAS was 4.5 & median A level was 34g/dL. 48% had received prior docetaxel. 45 patients (51%) received all the scheduled 6 cycles with significant reduction in the pain scores after 6 cycles compared to the BL score (p < 0.05). The reduction in pain scores was independent of the PSA response and ECOG-PS. A 34% reduction in the SAP levels was seen (p = 0.003). The treatment was well tolerated with no grade 3,4 toxicity. Discontinuation rate was 49% (43/88) due to disease progression. In PS-0/1 patients who completed 6 cycles, PFS & OS were significantly longer compared to those who didn't (7.8vs.4.2& 21vs.7.6 months, respectively). Patients with SAP ≤ 220 U/L & A ≥ 34 g/dL also had significantly prolonged OS (16.2vs.8.6 & 16.1vs.9.5 months, respectively). Patients with PS-2/3 also had significantly longer PFS and OS with completion of 6 cycles and prolonged OS with SAP ≤ 220 U/L, but not with A levels. Conclusions: Ra223 is a safe and effective treatment for mCRPC with bone metastases. Completion of 6 cycles improved outcome. Lower SAP and high A levels significantly prolonged OS in PS-1/2 patients. Whilst the level of SAP can be a reflection of disease activity, monitoring A levels and ensuring that Ra223 is started before A level goes below 34, especially in PS-1/2 patients will aid in the benefit from this treatment in mCRPC.
Effect of chemotherapy on survival for intraductal carcinoma of the prostate (IDC-P) in patients with castration-resistant prostate cancer.
Authors: Yamamoto Akiyuki , Kato Masashi , Tsuzuki Toyonori , Gotoh Momokazu , Matsukawa Yoshihisa , Sassa Naoto , Yamamoto Tokunori 
Published: March 2017

e601 Background: Several studies have reported that intraductal carcinoma of the prostate (IDC-P) was a pathological adverse prognostic factor in patients with prostate cancer; however, there have been no reports regarding the effect of chemotherapy on survival for this group of patients. This study assessed the effect of chemotherapy on survival in patients with IDC-P. Methods: We retrospectively evaluated 150 prostate cancer patients who were initially diagnosed with distant metastases from June 2002 to January 2014 at the authors’ affiliated hospitals. All needle biopsy slides were reviewed by a single genitourinary pathologist according to the 2014 International Society of Urological Pathology (ISUP) grading system. Exclusion criteria were patients with missing data and those receiving local treatment. Seventy-nine patients with castration-resistant prostate cancer (CRPC) were analyzed. Study endpoints included cancer-specific survival after starting chemotherapy and survival duration from diagnosis of CRPC to cancer-related death. Log-rank test and the Cox proportional hazard model were used for statistical analysis. Results: The patients’ median age was 70 years (range 50–85 years). The median serum prostate-specific antigen level at initial diagnosis was 495.0 ng/mL (range 12.6–10,000). IDC-P was found in 62 out of 79 cases. Forty-six patients received docetaxel-based chemotherapy. Patients received a median of seven chemotherapy courses (range 1–55 courses). The cancer-specific survival duration after starting chemotherapy was 16.7 months in patients with IDC-P and 23.4 months in patients without IDC-P (P = 0.068). Chemotherapy could significantly extend survival duration from diagnosis of CRPC in patients with IDC-P (18.4 months vs. 4.4 months, P = 0.001) Conclusions: Although the effect of chemotherapy may be limited in patients with IDC-P, it significantly extended the time from diagnosis of castration-resistant disease to cancer-related death.
Validation of TNM classification for metastatic prostatic cancer treated using primary androgen deprivation therapy.
Authors: Kadono Yoshifumi , Nohara Takahiro , Izumi Kouji , Kitagawa Yasuhide , Hiroyuki Konaka , Mizokami Atsushi , Namiki Mikio , Onozawa Mizuki , Hinotsu Shiro , Akaza Hideyuki 
Published: March 2017

e604 Background: The current tumor–node–metastasis (TNM) classification system has been used for many years. The prognosis of patients with metastatic prostate cancer (mPC) treated using primary androgen deprivation therapy (PADT) was analyzed according to the TNM classification. Methods: A total of 5,618 cases with lymph node metastases only (N1M0), non-regional lymph node metastasis (M1a), bone metastasis (M1b), and distant metastasis (M1c) were selected from the Japanese Study Group of Prostate Cancer database. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) rates were calculated using Kaplan–Meier analysis. The influence of clinical variables on patient prognosis was evaluated using the Cox’s proportional hazard regression model. Results: Regarding age, patients with M1b tumors were significantly older than were those in the other groups. Prostate-specific antigen (PSA) levels tended to increase as the stage progressed. The Gleason score (GS) was significantly higher in the M1a group compared with the other groups. The 5-year OS was 76.0 % in the N1M0, 57.5 % in M1a, 54.0 % in M1b, and 40.0 % in M1c cases. The 5-year CSS was 83.2 % in the N1M0, 69.0 % in M1a, 63.1 % in M1b, and 51.5 % in M1c cases. The 5-year PFS was 38.8 % in the N1M0, 23.0 % in M1a, 23.0 % in M1b, and 16.6 % in M1c cases. OS, CSS, and PFS declined as the stage progressed; however, there were no statistically significant differences between M1a and M1b cases. Among the patients in the M1b group, the 2,445 cases of N0M1b and the 1,607 cases of N1M1b were compared. OS, CSS and PFS were all significantly worse in N1M1b compared with N0M1b. Multivariate analysis revealed that OS and CSS were worse in patients with a GS ≥ 8, and that combined androgen blockade (CAB) treatment provided better OS than non-CAB treatments at any tumor stage. However, OS and CSS were worse in individuals with a PSA > 100 ng/ml only in M1b. Conclusions: Patient prognosis worsened with stage progression. Each PC cell that develops bone or lymphoid metastasis may exhibit different characteristics. CAB is recommended as the primary treatment for mPC.
An Origin for Lattice Expansion in PVP-Protected Small Pd Metal Nanoparticles
Authors: Ohba Tadashi , Kubo Hitoshi , Ohshima Yusuke , Makita Yuichi , Nakamura Noriaki , Uehara Hiromitsu , Takakusagi Satoru , Asakura Kiyotaka 
Published: March 2017

Abstract
Noble metal nanoparticles always show bond length contraction with the decrease in particle size. PVP-protected small Pd metal nanoparticles (MNPs) were reported to have the unique characteristic of expanding Pd-Pd bond lengths with decreases in particle size. To investigate the origin of this phenomenon in more detail, this work examined Pd MNPs supported on SiO2 (Pd MNPs/SiO2) via extended X-ray absorption fine structure (EXAFS) analysis, where the SiO2 support was used to stabilize the MNPs to prevent unexpected aggregation at higher temperatures. EXAFS data showed that each sample had a face-centered cubic (fcc) structure and that the smallest particles had the longest Pd-Pd bonds. Temperature dependent EXAFS measurements also revealed significant static disorder in the bond-elongated Pd MNPs/SiO2 samples. The XAFS spectral features of these bond-elongated Pd MNPs on SiO2 are in good agreement with those for palladium carbide, and we conclude that the lattice expansion in Pd MNPs can be attributed to the formation of palladium carbide.
The perceptions of supervising teachers on the prospective-teacher training: A phenomenographic research
Authors: Koç Sevda , Akran Koray 
Published: March 2017

The main purpose of this research is to identify the perceptions of supervising teachers on prospective- teacher training through phenomenographic method. Phenomenography is a method which determines how the people perceive the events and issues around them and how they explain them by conceptualizing. The working group of the research includes Subject and Classroom teachers working in the central provinces of Siirt and Batman chosen by random sampling. As data collection tool, questions that teachers' personal information take place and a semi-structured interview form including three open-ended questions trying to state the perceptions about prospective- teacher training are prepared and in order to determine the validity of the questionnaire it was submitted to two experts. In accordance with the expert opinions, the interview form has been made ready to apply with necessary corrections. The first question in the interview form is “To me, the prospective- teacher training means…… ” the second one is “The positive sides of prospective- teacher training are……………………. Because……..”, and the third one is “The negative sides of the prospective-teacher training are ……….....Because……”. A period of 20-25 minutes is given to specify the perceptions of teachers on the prospective- teacher training. Teachers’ answers to these questions / opinions have been adopted as the main source of research data. These concepts and statements have been transferred to the computer and as a result of eliminations made in the computer, the remaining concepts and statements are divided into certain categories. Proposals have been made in accordance with the categories obtained.
When is the cayley graph of a semigroup isomorphic to the cayley graph of a group
Authors: Wang Shoufeng 
Published: March 2017

Abstract
It is well known that Cayley graphs of groups are automatically vertex-transitive. A pioneer result of Kelarev and Praeger implies that Cayley graphs of semigroups can be regarded as a source of possibly new vertex-transitive graphs. In this note, we consider the following problem: Is every vertex-transitive Cayley graph of a semigroup isomorphic to a Cayley graph of a group? With the help of the results of Kelarev and Praeger, we show that the vertex-transitive, connected and undirected finite Cayley graphs of semigroups are isomorphic to Cayley graphs of groups, and all finite vertex-transitive Cayley graphs of inverse semigroups are isomorphic to Cayley graphs of groups. Furthermore, some related problems are proposed.
Subcontracting Workshop – GERPAC 2016
Authors: Brandely-Piat Marie-Laure , Bouchoud Lucie 
Published: March 2017

AbstractDrug preparation requires an adequate number of qualified people and premises adapted. Legal requirements for manufacturing drugs are constantly increasing. To face these exigencies, outsourcing preparations between hospital pharmacies or other manufacturers has developed in recent years. Different preparations such as anticancer drugs, parenteral nutritions or other individual or hospital batch preparations can be outsourced.The objective of the workshop was to discuss the following points:– Regulatory aspects– Methodology for the implementation of the outsourcing– Development of the contract between the Contract Giver and the Contract Acceptor– Monitoring of outsourcing in particular by carrying out auditsThese various elements have been discussed theoretically and enriched the workshop with practical experiences of the participants. Subcontracting is an activity well developed and growing. Pharmacists are familiar with regulatory aspects to initiate a new contract, but there is a lack in follow-up and audit over the period of subcontracting. Efforts need to be done to implement regular audit.