bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of metformin on prostate cancer (PC) outcomes in the E3805 CHAARTED trial.
Authors: Jarrard David Frazier , Chen Yu-Hui , Liu Glenn , Carducci Michael Anthony , Eisenberger Mario A. , Wong Yu-Ning , Hahn Noah M. , Kohli Manish , Cooney Matthew M. , Dreicer Robert , Vogelzang Nicholas J. , Picus Joel , Shevrin Daniel H. , Hussain Maha , Garcia Jorge A. , DiPaola Robert S. , Sweeney Christopher 
Published: March 2017

181 Background: To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods: In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results: A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n = 39) to ADT+D (n = 357) and ADT+Met (n = 29) to ADT alone (n = 363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p = 0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions: In this study, baseline metformin did not improve PC outcomes. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]
Incidence and characterization of antiandrogen withdrawal syndrome (AAWS) after enzalutamide (ENZA) in patients (pts) with metastatic castration-refractory prostate cancer (mCRPC).
Authors: Poole Austin , Gill David Michael , Hahn Andrew W. , Johnson Eric , Carroll Emma , Batten Julia A. , Gupta Sumati , Boucher Kenneth M. , Maughan Benjamin Louis , Agarwal Neeraj 
Published: March 2017

228 Background: AAWS manifested as PSA decline after discontinuation of first generation AAs, like bicalutamide, has been well characterized and reported. Objective of this study was to assess the incidence and characterize AAWS after ENZA in pts with mCRPC. Methods: From a single institution cohort, pts with mCRPC who discontinued ENZA after documented disease progression per PCWG2 criteria were included. AAWS after ENZA was defined as any degree of PSA decline after discontinuation of ENZA. Baseline pts, disease, and treatment characteristics were compared between Òpts with AAWS after ENZAÓ vs. Òpts without AAWS after ENZAÓ treated during the similar time period: median values were compared with the Wilcoxon rank sum test; proportions were compared with FisherÕs Exact test; and the log rank test was used to compare PFS (Table). Results: 5 pts of 72 eligible pts (~7%) experienced AAWS after discontinuation of ENZA. The levels of PSA decline were as follows: 84%, 32%, 17%, 15% and 15%, respectively. Median AAWS response time, until subsequent PSA progression, was 6 weeks. None of the pts, disease or treatment characteristics (such as prior duration of response to ENZA) were different among Òpts with AAWS after ENZAÓ vs. Òpts without AAWS after ENZAÓ. Conclusions: This is the largest study reporting on the incidence and characterization of AAWS after ENZA. AAWS after ENZA is infrequent (~7%), of short duration (6 weeks), and not predicted by pts, disease or treatment related characteristics. Unlike AAWS after first generation AR inhibitors, like bicalutamide, the AAWS after ENZA is not clinically meaningful and should not have any bearing on the eligibility criteria of clinical trials conducted in the post ENZA setting. [Table: see text]
Immune response results of vesigenurtacel-l (HS-410) in combination with BCG from a randomized phase II trial in patients with non-muscle invasive bladder cancer (NMIBC).
Authors: Steinberg Gary D. , Shore Neal D. , Karsh Lawrence Ivan , Bailen James L. , Bivalacqua Trinity J. , Chamie Karim , Cochran James S. , David Richard , Grubb Robert L. , Harb Wael A. , Holzbeierlein Jeffrey M. , Kamat Ashish M. , Trabulsi Edouard John , Walsh William Vincent , Williams Michael Brandon , Wolk Fredrick , Woods Michael , Price Melissa Leigh , Early Brandon , Schreiber Taylor Houghton 
Published: March 2017

319 Background: Vesigenurtacel-L (HS-410) is a vaccine comprised of an allogeneic cell line, selected for high expression from a series of bladder tumor antigens, and transfected with gp96-Ig. Cell-secreted gp96-Ig delivers these cell-derived antigens to a recipient's own antigen presenting cells, activating CD8+ cytotoxic T cells. Here we present the secondary immune outcomes from a randomized Phase 2 trial with HS-410 in combination with BCG in NMIBC. Trial ID NCT02010203. Methods: 78 patients with intermediate- (n=5) or high-risk (n=73) NMIBC who are either BCG-naïve or recurrent, with or without carcinoma in situ (CIS), were enrolled 1:1:1 to one of two doses of HS-410 (either 106 or 107cells/dose) or placebo in combination with 6 weeks of induction BCG, followed by 6 more weeks of HS-410 in the induction phase. Maintenance treatment consisted of 3-weekly treatments at the following timepoints: 3 mo., 6 mo., 12 mo. Concurrently, 16 patients (1 int. risk, 15 high-risk) were enrolled in an open-label monotherapy HS-410 arm for patients who did not receive BCG. The primary endpoint was 1-year RFS. Secondary immune evaluations include ELISPOT, tumor IHC, tumor antigen profiling, flow cytometry, urine cytokine analysis, and T cell receptor sequencing. Results: HS-410 treatment was well tolerated; AE profiles were similar across the treatment arms. HS-410 antigen expression showed prominent overlap with patient tumors. IFNγ ELISPOT assay demonstrated a high baseline response to HS-410; responses to overlapping peptide pools of HS-410 derived antigens defined immune responders (doubling of IFNγ-secreting cells). IHC demonstrated that ~60% of NMIBC patient tumor biopsies were TIL negative at baseline (n=84), but that only ~15% of tumor biopsies were TIL negative post treatment (n=40). Thus, TIL status may be further used to define a responder and non-responder population to HS-410. Conclusions: Vesigenurtacel-L is well-tolerated, and immunologic responses consistent with vaccine mechanism of action may correlate with efficacy and suggest future biomarkers. Vesigenurtacel-L warrants further investigation as a potential treatment for NMIBC. Clinical trial information: NCT02010203.
Therapy for chemopretreated metastatic urothelial cancer (mUC) with the antibody-drug conjugate (ADC) sacituzumab govitecan (IMMU-132).
Authors: Tagawa Scott T. , Ocean Allyson J. , Lam Elaine Tat , Saylor Philip James , Bardia Aditya , Hajdenberg Julio , Morgans Alicia Katherine , Kalinsky Kevin , Galsky Matthew , Faltas Bishoy , Molina Ana M. , Lim Emerson A. , Maliakal Pius , Sharkey Robert M. , Mudenda Boyd , Wegener William A. , Goldenberg David M 
Published: March 2017

327 Background: Patients (pts) with mUC pre-treated with platinum-containing chemotherapy have limited therapeutic options, with checkpoint-inhibitor immunotherapy (IO) responses in a minority of pts. We present an interim update of the safety and activity of sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 ADC, as therapy for chemotherapy-pretreated mUC pts (ClinicalTrials.gov, NCT01631552). Methods: We enrolled 32 pts with mUC and ECOG PS 0-1 who failed ≥ 1 prior standard therapy (median=3; range, 1-5). IMMU-132 was administered at 8 or 10 mg/kg on days 1 and 8 every 21 days, continued until disease progression (PD) or unacceptable toxicity. Response-evaluable pts received ≥ 2 doses, and had ≥ 1 post-baseline response assessment. Results: Twenty-five pts [median age 68 yrs (range: 50-91), 24 males] are currently assessable for safety and response; 23 had prior platinum-containing therapy; 46% had >2 prior therapies; 4 also had IO agents. Sites of metastases included liver (N=4; 16%), lungs (N=7; 28%), bone (N=4; 16%), and lymph nodes (N=16; 64%). Pts received a median of 7 cycles (range, 2-23) of IMMU-132. ORR was 36% (9/25) [1 complete (CR) and 8 partial responses (PR)]; 44% (11/25) had stable disease (SD). Further, pts with 1 line of prior chemotherapy had an ORR of 53.8% (7/13), and 16.7% for those with 2 to 5 prior therapy lines. Median PFS for all patients is 7.2 mos (95% CI, 4.9-10.7); median survival is not reached yet. Of the 4 pts with progression after prior IO, there were 1 PR and 2 SDs with IMMU-132. Duration of response for CR/PR pts is currently 5.1 mos (95% CI, 4.1-12.9) and 10/11 pts (5 with ≥ 20% tumor reduction) had stable disease > 4 mos. Grade 4 neutropenia (16%) lasted < 7 days, and non-hematological grade 3 AEs included fatigue (12%) and hypophosphatemia (8%). No treatment-related deaths were observed. Analysis of Trop-2 expression revealed 1+ to 3+ positive staining in 95% of 19 archival patient specimens. Conclusions: With an ORR of 36% and a median PFS of 7.2 months in a heavily pretreated population, these interim results suggest that IMMU-132 is a promising agent as 2nd line or later therapy for platinum- or IO- pretreated mUC pts. Clinical trial information: NCT01631552.
Flavoperidol as a novel therapeutic agent for bladder cancer.
Authors: Railkar Reema , Sanford Thomas , Krane Spencer , Li Q. Quentin , Agarwal Piyush K. 
Published: March 2017

357 Background: Bladder cancer (CaB) is the 4th most common cancer among men in the US but receives substantially less research resources than many other cancer types. There has been little change to the management of bladder cancer over the past 25 years. Quantitative high throughput screening (qHTS) of representative cancer lines with oncology drugs may identify new treatments or re-purpose already existing therapies for different disease. We utilized this technique to identify new therapies in three primary bladder lines (RT4, T24, and UMUC3) and their metastatic lines (T24T, SLT3 and FL3 for T24 and LUL-2 for UMUC3). Methods: We screened 8 bladder cancer cell lines (including RT4, T24, and UMUC3) against 1,912 oncology drugs using a 48 hour cell proliferation assay with an ATP−based readout to determine activity and potency of compounds in a dose response manner. One of the candidate drugs inhibitory in all cell lines tested is flavopiridol, a pan CDK inhibitor. We further characterized the mechanism of action and in vivo effects of flavopiridol using various cell based assays and mouse xenograft studies. Results: The initial screen identified 95 compounds active in 8 cell lines. The top 50 compounds were further analyzed for molecular size of >200 g/mol and TPSA<90. This identified mitomycin C and 8 novel compounds. Further testing revealed Flavopiridol to be most consistent with qHTS data having IC50 of 100-300nM in all the cell lines tested. Flavopiridol induces G2/M arrest; however, very little apoptosis was seen suggesting a cytostatic rather than a cytotoxic mechanism of flavopiridol action. Flavopiridol showed dose dependent inhibition of migration, invasion and colony formation in all cell lines tested. Xenograft studies in rapidly growing UMUC-3 cells showed slowing of tumor growth but not complete reduction indicating cytostatic mechanism of flavopiridol. Conclusions: A high throughput drug screen can identify novel compounds in bladder cancer. Flavopiridol seems to be a very effective inhibitor both in vitro and in vivo. Physical properties of Flavopiridol are most suited for intravesical use, which may lead to it being an effective inhibitor of CaB in the bladder at higher doses without any/few systemic toxicities.
Evaluation of cabazitaxel's toxicity and tolerance: AC Camargo Cancer Center experience.
Authors: Albuquerque Christiane Silveira Marinho , Rinck Jose A. , Costa Tatiana Vieira , Ferreira Camila Nassif Martins , Dettino Aldo A. , Cunha Ingrid Hariman Fonseca , Calsavara Vinicius Fernando 
Published: March 2017

e566 Background: Cabazitaxel is an approved second-line treatment in metastatic castration-resistant prostate cancer therapy with a significant survival benefit compared to mitoxantrone. There are few data about cabazitaxel's toxicity in patients not selected. Objective: Evaluate the efficacy and toxicity among younger (< 70 years) and older (> 70 years) population. Methods: We selected 62 patients with metastatic castration resistant prostate cancer treated in AC Camargo Cancer Center from January 2011 to July 2015. 58 patients fulfilled the study criteria: diagnosis of adenocarcinoma prostate cancer, at least one session of cabazitaxel, with more than 18 years old. Results: We had in our sample 33 patients less than 70 years and 25 over 70 years. The initial dose of cabazitaxel was 25 mg/m2 in 75.8% of patients < 70 years and 52% in > 70 years patients. The use of granulocytics growing factor was observed in 64% of the older patients and more than 80% of this indication was in primary profilaxis. There were five deaths associated to the treatment, 4 lung infection and 1 kidney failure. The worst grade of adverse event up to 30 days after last administration was grade 2, including hematological and non-hematological events, both with no statistical significance between the groups. However, there was a greater number of febrile neutropenia in elderly people (28% versus 6%) with a statistical significance between < 70 e > 70 years (p 0.031). OS was 13,7 months (IC 9.16 – 18.2) and PFS was 4,6 months (IC 3.43 – 5.73). OS among the two groups was lower in < 70 years reaching 9,3 months (IC 2.06-16.5) versus 22.2 months (IC 4.86-39.50 ), p= 0.073. As well, PFS in < 70 years was 3.8 months (IC 3.26-4.36) versus 4.6 months (IC 2.4-14.1), p = 0.02. Conclusions: Treatment with cabazitaxel is tolerable, with manageable adverse events in a real-world patient population. In our cohort, elderly population (> 70 years) had more febrile neutropenia, suggesting dose reduction in this population, indication of granulocytic growing factor as primary profilaxis, close monitoring, and adequate patient counseling.
Prognostic factors for overall survival in patients with metastatic castration-resistant prostate cancer: Secondary analysis.
Authors: Anampa-Guzman Andrea Carolina , Sulca-Huamani Oliver , Perez-Mendez Rushmely , Mendoza-Soto Gloria , Contreras Chavez Pamela , Aliaga Rolig 
Published: March 2017

e597 Background: The standard treatment for metastatic castration-resistant prostate cancer (MCRPC) is Docetaxel (DTX); however, it has serious adverse effects. It is necessary to know the prognostic factors for overall survival (OS) of patients with MCRPC treated with DTX. The aim of this study was to determine the prognostic factors for OS in patients with MCRPC treated with DTX. Methods: This study is a secondary analysis of the control arms of the clinical trials NTC00273338, NCT00519285 and NCT00988208. 1600 patients aged 18 years or older with MCPRC that received DTX and prednisone were included. Survival curves were estimated by Kaplan-Meier and comparison was done by log-rank test. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model. Results: The median OS time was 14.64 months. The 1-yr-OS and 2-yrs-OS were 86.2% and 28.6%, respectively. Patients with an ECOG score greater than 0 lived significantly less than the rest of patients (p = 0.00). The patients with an alkaline phosphate level (ALP) > 200 had significantly lower OS (p = 0.00). In the multivariate analysis, the factors that influenced OS were ECOG, ALP, HB, LDH and number of metastases. Conclusions: Poor performance status, high alkaline phosphatase level, low hemoglobin level, high LDH and more than 2 metastases were the main prognostic factors in patients with metastatic castration resistant prostate cancer. [Table: see text]
MICROSTRUCTURE HYDRATION PRODUCTS BINDING COMPOSITION OBTAINED IN THE VORTEX JET MILL
Authors: Золотых Сергей , Zolotykh Sergey , Сумской Дмитрий , Sumskoy Dmitriy , Загороднюк Лилия , Zagorodnyuk Liliya , Канева Елена , Kaneva Elena 
Published: March 2017

Zagorodnuk L.H., Sumy D.A., Golden S.V., Kaneva E.V.
MICROSTRUCTURE HYDRATION PRODUCTS BINDING COMPOSITION OBTAINED IN THE VORTEX JET MILL
By electron microscopy to study the microstructure of the cement stone made from Portland cement and activated binders of the compositions in the vortex jet mill. It was found that the open pores of the cement and cementitious compositions prepared using perlite fillers, always filled with tumors, at different stages of collective growth. The microstructure of cementitious compositions has a dense structure by rationally selected composition, effective use of mineral filler - perlite waste, creating additional support for the formation of the internal microstructure of the composite, mechanical activation raw mixture, allowing to obtain composites with desired properties.
A systematic review of Vancouver B2 and B3 periprosthetic femoral fractures
Authors: Khan T. , Grindlay D. , Ollivere B. J. , Scammell B. E. , Manktelow A. R. J. , Pearson R. G. 
Published: March 2017

Aims The aim of this study was to investigate the outcomes of Vancouver type B2 and B3 fractures by performing a systematic review of the methods of surgical treatment which have been reported. Materials and Methods A systematic search was performed in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. For inclusion, studies required a minimum of ten patients with a Vancouver type B2 and/or ten patients with a Vancouver type B3 fracture, a minimum mean follow-up of two years and outcomes which were matched to the type of fracture. Studies were also required to report the rate of re-operation as an outcome measure. The protocol was registered in the PROSPERO database. Results A total of 22 studies were included based on the eligibility criteria, including 343 B2 fractures and 167 B3 fractures. The mean follow-up ranged from 32 months to 74 months. Of 343 Vancouver B2 fractures, the treatment in 298 (86.8%) involved revision arthroplasty and 45 (12.6%) were treated with internal fixation alone. A total of 37 patients (12.4%) treated with revision arthroplasty and six (13.3%) treated by internal fixation only underwent further re-operation. Of 167 Vancouver B3 fractures, the treatment in 160 (95.8%) involved revision arthroplasty and eight (4.8%) were treated with internal fixation without revision. A total of 23 patients (14.4%) treated with revision arthroplasty and two (28.6%) treated only with internal fixation required re-operation. Conclusion A significant proportion, particularly of B2 fractures, were treated without revision of the stem. These were associated with a higher rate of re-operation. The treatment of B3 fractures without revision of the stem resulted in a high rate of re-operation. This demonstrates the importance of careful evaluation and accurate characterisation of the fracture at the time of presentation to ensure the correct management. There is a need for improvement in the reporting of data in case series recording the outcome of the surgical treatment of periprosthetic fractures. We have suggested a minimum dataset to improve the quality of data in studies dealing with these fractures. Cite this article: Bone Joint J 2017;99-B(4 Supple B):17–25.
Assessment of Rock Mass Stability in the Historic Area of Levels IV-V of the “Wieliczka” Salt Mine
Authors: d’Obyrn Kajetan , Hydzik-Wiśniewska Joanna 
Published: March 2017

Abstract
As a result, of more than 700 years of exploitation in the Wieliczka Salt Mine, a network of underground workings spreading over eleven levels was created. All mine workings of significant historic and natural qualities and the majority of functional mine workings designated to be preserved are located on levels I to V. The most precious of them, available to tourists, are located in the central part of the Mine on levels I-III. The Mine is not anticipating to make levels IV, Kołobrzeg and V available for a wider range of visitors, even though there are historically and naturally precious workings in those areas as well. The most valuable of the mine workings come from the eighteenth and nineteenth centuries and were exploited mainly in a bed of fore-shaft salt, Spiza salt and the oldest ones. The characteristic feature of these excavations, distinguish them from the chambers located on the levels I-III, is the room-and-pillar system that had been used there. Mine workings exploited in this system measure up to 100 metres in length, and the unsupported pillars standing between the chambers measuring 4-10 metres in width were remained. The described above levels, including levels of VI-IX are to provide a stable support for the workings located higher up. The remaining part of the mine, with the exception of the function workings, is designated for liquidation by backfilling.
The article presents an assessment of stability of the mine workings, located on levels IV-V, and their impact on the surrounding rock mass and the land surface. The analysis was based on geodetic measurements and numerical calculations for strain state of rock mass surrounding the mine workings, in actual conditions and after partial backfilling, and forecast of the rock stability factor after the end of backfilling. The assessment stability factor in the vicinity of excavations at levels IV-V was based on the results of spatial numerical analysis covering the entire central area of the mine from the surface to level V. Numerical calculations were performed using FLAC programme based on the finite difference method, allowing to observe the mechanisms and processes of destruction and deformation. The calculations were performed for the elastic-plastic medium with the Mohr-Coulomb failure criterium. The choice of this computational model was dictated by a very diverse geological structure of the Wieliczka rock mass and a complex system of excavations.
Standoff detection and classification of bacteria by multispectral laser-induced fluorescence
Authors: Duschek Frank , Fellner Lea , Gebert Florian , Grünewald Karin , Köhntopp Anja , Kraus Marian , Mahnke Peter , Pargmann Carsten , Tomaso Herbert , Walter Arne 
Published: March 2017

Abstract
Biological hazardous substances such as certain fungi and bacteria represent a high risk for the broad public if fallen into wrong hands. Incidents based on bio-agents are commonly considered to have unpredictable and complex consequences for first responders and people. The impact of such an event can be minimized by an early and fast detection of hazards. The presented approach is based on optical standoff detection applying laser-induced fluorescence (LIF) on bacteria. The LIF bio-detector has been designed for outdoor operation at standoff distances from 20 m up to more than 100 m. The detector acquires LIF spectral data for two different excitation wavelengths (280 and 355 nm) which can be used to classify suspicious samples. A correlation analysis and spectral classification by a decision tree is used to discriminate between the measured samples. In order to demonstrate the capabilities of the system, suspensions of the low-risk and non-pathogenic bacteria Bacillus thuringiensis, Bacillus atrophaeus, Bacillus subtilis, Brevibacillus brevis, Micrococcus luteus, Oligella urethralis, Paenibacillus polymyxa and Escherichia coli (K12) have been investigated with the system, resulting in a discrimination accuracy of about 90%.