bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial in progress: Pamiparib, an investigational PARP inhibitor, in patients with metastatic castration-resistant prostate cancer and a circulating tumor cell homologous recombination deficiency (HRD) phenotype or BRCA defects.
Authors: Chowdhury Simon , Mateo Joaquin , Gross Mitchell , Armstrong Andrew J. , Cruz-Correa Marcia , Piulats Josep M. , Blay Jean-Yves , Rivas Delcia , Quintero Luis , Castro Henry , Nkobena Andong , Raponi Mitch , Pelham Robert , Landers Mark Andrew , Montgomery Robert B. 
Published: March 2019

TPS328 Background: Men with metastatic castration-resistant prostate cancer (mCRPC) who have a BRCA1/2 mutation ( BRCA1/2mut) or mutations in other HRD genes have a poor prognosis. The EPIC liquid biopsy test is a novel assay that can identify circulating tumor cells (CTC) with HRD associated phenotypes. Preliminary studies have shown that these men may respond to treatment with a PARP inhibitor. Pamiparib is an investigational PARP1/2 inhibitor that has shown brain penetration and potent PARP–DNA complex trapping in nonclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib was generally well tolerated and showed preliminary antitumor activity; 60 mg orally twice daily (BID) was established as the recommended investigational dose. Methods: This open-label, global, phase 2 study (NCT03712930) will evaluate antitumor activity and safety of pamiparib in mCRPC pts with CTC-HRD, assessed by the EPIC CTC-HRD assay, or deleterious germline/somatic BRCA1/2mut status. Patients must have progressed on/after ≥1 androgen receptor-targeted therapy, have received ≥1 taxane-based therapy, and have prostate-specific antigen (PSA) progression per PCWG3 criteria. Four cohorts of patients will receive pamiparib 60 mg BID in 28-day cycles. Cohort 1 will include ~50 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with measurable metastatic disease; Cohort 2 will include ~30 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with bone-only disease; Cohorts 3 & 4 will include ~20 pts with CTC-HRD-/unknown + BRCA1/2mut mCRPC with measurable metastatic disease (Cohort 3), or bone-only disease (Cohort 4). Disease status will be assessed every 8 wks for 24 wks, then every 12 wks; PSA levels will be tested every 4 wks. Co-primary endpoints are radiographic ORR assessed by IRC (pts with measurable disease) and confirmed PSA response rate per PCWG3 criteria (pts +/- measurable disease). Secondary endpoints include ORR, time to PSA response/progression, duration of PSA response, time to symptomatic skeletal event, radiographic progression-free survival, overall survival, and safety. Clinical trial information: NCT03712930.
A phase II study of onvansertib (PCM-075) in combination with abiraterone and prednisone in patients with metastatic castration-resistant prostate cancer.
Authors: Einstein David Johnson , Choudhury Atish Dipankar , Saylor Philip James , Werner Lillian , Erlander Mark G. , Ridinger Maya , Bubley Glenn 
Published: March 2019

TPS336 Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a leading cause of cancer-related deaths worldwide. Although abiraterone (abi) in either the castration-sensitive or castration-resistant setting increases survival, resistance is universal and limits the efficacy of subsequent hormonal therapies. Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase that regulates mitotic functions and promotes the progression of cells through mitosis, and it is highly upregulated in prostate cancer following castration. PLK1 inhibition enhances the efficacy of abi in cell line models as well as patient-derived tumor xenografts via several mechanisms. Onvansertib (PCM-075; Trovagene, Inc.) is the first orally available PLK1-specific inhibitor. In phase 1 testing, onvansertib demonstrated a manageable safety profile, with transient hematologic effects as its most prominent, yet reversible, toxicity. Methods: The goal of this phase 2 study (NCT03414034) is to observe the effects of onvansertib in combination with abi + prednisone on disease control, as assessed by prostate-specific antigen (PSA) decline or stabilization after 12 weeks of study treatment, in subjects with mCRPC and early resistance to abi. Patients will be enrolled at time of PSA progression while on standard abi. A completed 3-patient safety lead-in phase tested the safety of the combination of onvansertib with abi, and the accruing expansion phase will treat 29 more patients with onvansertib (24 mg/m2 orally on days 1-5 of a 21-day cycle) plus abi (administered orally and continuously once daily with prednisone) until time of radiographic or symptomatic progression. With 32 patients, there will be 90% power to detect a change in disease-control rate from 10% (null) to 30% (alternative). Based on a Simon’s two-stage optimal design, the study will terminate early if < 2 of the first 13 patients achieve disease control. Exploratory analyses include evaluations of predictive genomic biomarkers in circulating tumor cells and circulating tumor DNA, including alterations of oncogenes and tumor suppressors implicated in PLK1 sensitivity within preclinical models. Clinical trial information: NCT03414034.
A randomized phase II study comparing cabazitaxel/prednisone to cabazitaxel alone in docetaxel-pretreated men with metastatic castration resistant prostate cancer (mCRPC): The CABACARE trial.
Authors: Buonerba Carlo , Grillone Francesco , Rossetti Sabrina , Livi Lorenzo , Scartozzi Mario , Tagliaferri Pierosandro , Bruzzese Dario , Scafuri Luca , Riccio Vittorio , Costabile Ferdinando , Bosso Davide , Iaccarino Simona , Facchini Gaetano , Carrano Simone , Izzo Michela , Caraglia Michele , De Placido Sabino , di Lorenzo Giuseppe 
Published: March 2019

TPS345 Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients (Pts). Whether daily PDN may significantly contribute to CAB efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are scarce. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect CAB clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE (EudraCT 2016-005251-25) is a randomized, phase II, open label, multi-center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective (non-inferiority HR = 1.4). Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events . The influence of AR-V7 and RB status measured in circulating epithelial cells at baseline on CAB activity will also be evaluated. A total of 35 Italian centers have started / will start recruiting pts in the CABACARE trial. Of the 220 pts required by the trial design, 43 pts have been enrolled since 30th Nov , 2017 until 2nd Oct, 2018 in 10 different Italian Institutions. Clinical trial information: 2016-005251-25.
Metacure: Multi-arm multimodality therapy for very high risk localized and low volume metastatic prostatic adenocarcinoma.
Authors: Teo Min Yuen , Taplin Mary-Ellen , Eastham James Andrew , Benoliel Hannah , Kibel Adam S. , McBride Sean Matthew , Nguyen Paul L. , Gopalan Anuradha , Lis Rosina , Scher Howard I. 
Published: March 2019

TPS349 Background: Therapeutic advances in the management of metastatic castration-resistant prostate cancer (mCRPC) have not been matched in non-castrate states. A key obstacle is the traditional paradigm in which therapies with significant benefit in mCRPC are then studied in patients (pts) with localized, rising PSA or early metastatic disease using time-to-event (TTE) outcomes (e.g. biochemical recurrence, radiographic progression or death). These trials are costly, lengthy and often give inconclusive results that do not change practice nor provide a methodology to rank regimens based on efficacy. A new strategy is needed that gives a rapid efficacy readout and prioritizes approaches for large-scale testing. Methods: Metacure is a multi-arm, multi-stage randomized Phase 2 trial in which novel systemic therapies are studied in the context of a multimodality approach, which includes radical prostatectomy + pelvic and retroperitoneal lymph node dissection, if applicable, stereotactic radiotherapy (RT) to osseous metastases, and an option for adjuvant RT based on risk factors. The arms include combinations of ADT + apalutamide +/- abiraterone acetate and prednisone. Non-castrate prostate cancer pts with high probability of relapse or death from disease ranging from very high risk localized to low-volume metastatic disease are eligible. The primary endpoint is pathologic complete response and minimal residual disease. The secondary endpoint is undetectable PSA with non-castrate levels of testosterone. Both are binary endpoints that circumvent interpretations of the clinical relevance of TTE outcomes, providing a read-out of success or failure in a shorter time frame with fewer pts. The uniform entry criteria and continuous randomization enables ranking and prioritization of the strategies evaluated for further development in large-scale trials so that only the most effective ones move forward. This multicenter trial is managed by the Prostate Cancer Clinical Trials Consortium, funded by Janssen and is currently open and actively accruing. Future plans include opening a cohort of pts with aggressive non-castrate disease harboring DNA damage repair alterations. Clinical trial information: NCT03436654.
A phase I-II study to evaluate safety and efficacy of the combination of niraparib plus cabozantinib in patients with advanced kidney/urothelial carcinoma.
Authors: Font Pous Albert , Climent Duran Miguel Angel , Duran Ignacio , Mellado Begona , Paramio Jesus , Real Francisco X. , Ramirez Jose Luis , Sanz Juan Luis , Castellano Daniel E. 
Published: March 2019

TPS501 Background: Niraparib (N) is an orally selective poly(ADP-ribose) polymerase (PARP)-1/-2 inhibitor approved for maintenance treatment of patients (pt) with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after complete or partial response to platinum-based chemotherapy (CT). Cabozantinib (C) is a tyrosine kinase (TK) inhibitor with activity against TKs including VEGFR2, MET and AXL, approved on kidney cancer pt after TK failure, that has demonstrated clinical activity in heavily pretreated, advanced UC pt. c-Met receptor TK is activated in urothelial carcinoma (UC) cells. c-Met activity can decrease response to PARP inhibitors, whereas treatment with c-Met inhibitors renders cells more sensitive to PARP inhibition. UC pt with tumors overexpressing c-Met may benefit from the combination of c-Met and PARP inhibitors. This multicenter, open-label phase (ph) I-II study is to explore the maximum-tolerated dose (MTD) of N + C combination in pt with advanced genitourinary malignancies (UC and kidney cancer) follow by a preliminary efficacy of the combination in advanced UC. Methods: Eligible pt have confirmed histopathology of UC or clear cell renal cell carcinoma, advanced or metastatic disease, age ≥18 years, ECOG PS ≤1, progressive disease after platinum-based CT, measurable lesions, no prior therapy with PARP or c-Met inhibitors and adequate bone marrow, liver and renal functions. The ph I portion is enrolling ≈24 pt to identify the MTD proposed to use in a ph II (RP2D). Pt will receive N and C p.o. once daily in 28-day cycles: Dose level 1 (DL1) N/C 100/20 mg; DL2 200/20 mg; DL3 200/40 mg; DL4 200/60 mg. Pt will be accrued to each dose level in cohorts of 6 pt until the MTD is achieved (the highest dose at which ≤1 out of 6 pt experience a dose-limiting toxicity [DLT]). DLT will be evaluated during the first 2 cycles. The ph 2 portion will enroll 51 UC pt to receive the RP2D. Tumor response will be assessed per RECIST v1.1. Endpoints of the ph 2 are 6-month PFS (primary), overall response rate, disease control rate, duration of response, PFS and OS. Tissue and plasma sample will be collected for translational study. Clinical trial information: NCT03425201.
CANTATA: Randomized, international, double-blind study of CB-839 plus cabozantinib versus cabozantinib plus placebo in patients with metastatic renal cell carcinoma.
Authors: Tannir Nizar M. , Agarwal Neeraj , Dawson Nancy Ann , Motzer Robert J. , Jacobs Carmel Maree , Choueiri Toni K. , Hrom John Stewart , Geynisman Daniel M. , Davis Nancy B. , Figlin Robert A. , O'Keeffe Mary Kathleen , Parikh Jigarkumar R. , Vaena Daniel A. , Liu Ping-Yu , O'Keeffe Bridget , Tran Xuan , Escudier Bernard 
Published: March 2019

TPS682 Background: Glutamine metabolism is upregulated in renal cell carcinoma (RCC) and important for RCC tumor cell proliferation and survival. CB-839 is a first-in-clinic, potent, oral inhibitor of the mitochondrial enzyme glutaminase (GLS), which controls a critical step in tumor cell metabolism of glutamine. CB-839 demonstrated synergistic anti-tumor activity when combined with cabozantinib, a VEGFR2/MET/AXL inhibitor, in preclinical RCC models. In a phase 1 study cohort, CB-839 plus cabozantinib as 2L+ therapy showed encouraging safety and efficacy results, with 50% overall response rate (ORR; RECIST v1.1) and 100% disease control rate in 10 patients with clear cell advanced/metastatic RCC (mRCC). A randomized, double-blind study comparing CB-839 plus cabozantinib vs. cabozantinib plus placebo has been initiated in patients with clear cell mRCC. Methods: In this ongoing international, randomized, double-blind, multi-center study, enrollment is planned for ~300 patients with clear cell mRCC. To be eligible, patients should have received 1-2 prior lines of systemic therapy for mRCC including ≥1 anti-angiogenic therapy or the combination of nivolumab + ipilimumab, have KPS ≥70%, measurable disease (RECIST v1.1), and no prior cabozantinib (or other MET inhibitor). Patients are randomized 1:1 to receive either CB-839 (800 mg twice daily per oral [PO] route) plus cabozantinib (60 mg daily PO) or cabozantinib plus placebo in 28-day cycles until disease progression or unacceptable toxicity. Patients are stratified by prior PD-1/PD-L1 inhibitor therapy and by IMDC prognostic risk group (favorable vs. intermediate vs. poor). The primary endpoint is progression-free survival (PFS) per RECIST v1.1, determined by blinded independent radiology review. Secondary endpoints are investigator-assessed PFS and overall survival. Safety, response per RECIST, and quality of life are also assessed. Findings of this randomized, international clinical trial will inform the efficacy and safety profile of CB-839, a first-in-clinic metabolic inhibitor, in combination with cabozantinib in patients with mRCC. Clinical trial information: NCT03428217.
An Integrative Review of the Barriers to Indigenous Peoples Participation in Biobanking and Genomic Research
Authors: Aramoana Jaclyn , Koea Jonathan ,   on behalf of the CommNETS Collaboration
Published: March 2019

PURPOSE This investigation was undertaken to define the barriers to Indigenous peoples participating in biobanking and genomic research. METHODS A literature review was conducted to identify studies reporting on the experience of Indigenous peoples with biobanking, tissue banking, and genomic research. Studies pertaining to organ transplantation or blood donation for transfusion were excluded. The databases searched were MEDLINE, EMBASE, PubMed, Web of Science, and Google Scholar, with all literature available until the search date of June 1, 2018, included. The reference lists of all included papers, as well as related review articles, were manually searched to identify additional relevant studies. An inductive approach was used to identify common themes. RESULTS Seventeen publications discussed the experiences of New Zealand Māori (n = 2), Aboriginal and Torres Strait Islanders (n = 3), Native Hawaiian (n = 4), Native Alaskan (n = 2), American First Nation (n = 2), or multiple ethnicities (n = 4). Across all Indigenous peoples, four themes emerged: land, ancestors, culture, and bodily substances are powerfully interconnected and can act on each other; tissue and blood can provide important information (both Western and traditional) about a person; the ownership of specimens—custodians, trustees, or guardians; and the beneficence of the researchers and research team. CONCLUSION Indigenous communities, like Western populations, are concerned with issues pertaining to handling, treatment, and ownership of tissue as well as knowledge gained from specimen analysis. Unlike many Western populations, Indigenous communities have retained a strong sense of cultural connection to ancestors and traditional lands and view biologic specimens as inseparable from these things.
Two Incompletes
Authors: Schestag Thomas 
Published: March 2019

Abstract
This essay gathers two contributions to conferences or panels delivered in 2015 and 2016. The liminal figure relating both incompletes is the Sammler, as discussed in two texts by Walter Benjamin: “Eduard Fuchs, der Sammler und der Historiker” (“Eduard Fuchs: Collector and Historian”) and “Ich packe meine Bibliothek aus: Eine Rede über das Sammeln” (“Unpacking My Library: A Talk about Collecting”).
Spotlight on zebrafish: the next wave of translational research
Authors: Patton E. Elizabeth , Tobin David M. 
Published: March 2019

ABSTRACT
Five years after the launch of the Disease Models & Mechanisms (DMM) Special Issue on zebrafish as a disease model, the field has progressed significantly. Zebrafish have been used to precisely model human genetic variants, to unpick the mechanisms of metabolic and other diseases, to study infection, inflammation and cancer, and to develop and test new therapeutic approaches. In this Editorial, we highlight recent research published in DMM that uses zebrafish to develop new experimental tools and to provide new insight into disease mechanism and therapy. The broad spectrum of subjects and approaches covered in these articles underscores the versatility of zebrafish in translational research. Further, it highlights the zebrafish community's ethos of creativity and collaboration in translating basic biological research into clinically relevant advances affecting how we understand and treat human disease.
Effects of Exercise on Stress-induced Attenuation of Vaccination Responses in Mice
Authors: SUN YI , PENCE BRANDT D. , WANG SELENA SHIYUE , WOODS JEFFREY A. 
Published: March 2019

ABSTRACT
Studies suggest that exercise can improve vaccination responses in humans. Chronic stress can lead to immunosuppression, and there may be a role for exercise in augmenting immune responses.

Purpose
To investigate the effects of acute eccentric exercise (ECC) and voluntary wheel exercise training (VWR) on antibody and cell-mediated immune responses to vaccination in chronically stressed mice. We hypothesized that both ECC and VWR would attenuate chronic stress-induced reductions in vaccination responses.

Methods
Mice were randomized into four groups: control (CON), stress (S)-ECC, S-VWR, and S-sedentary (SED). Stressed groups received chronic restraint stress for 6 h·d−1, 5 d·wk−1 for 3 wk. After the first week of stress, S-ECC were exercised at 17 m·min−1 speed at −20% grade for 45 min on a treadmill and then intramuscularly injected with 100 μg of ovalbumin (OVA) and 200 μg of alum adjuvant. All other groups were also vaccinated at this time. Stress-VWR mice voluntarily ran on a wheel for the entire experiment. Plasma was collected before, and at 1, 2, and 4 wk postvaccination. Enzyme-linked immunosorbent assay was performed to analyze anti-OVA IgG and IgM antibodies. After 3 wk of chronic stress, all mice were injected with OVA into the ear to determine the delayed-type hypersensitivity.

Results
We found that chronic restraint stress significantly reduced body weight and caused adrenal hypertrophy. We also found both S-ECC and S-VWR groups had significantly elevated anti-OVA IgG (P < 0.05), whereas no significant differences between the two exercise groups. Neither S-ECC nor S-VWR altered anti-OVA IgM or delayed-type hypersensitivity responses compared with S-SED group.

Conclusions
Acute eccentric exercise and voluntary exercise training alleviated the chronic stress-induced anti-OVA IgG reductions in vaccination responses.
Quality of Life of asthmatic children and their caregivers
Authors: Ibrahim Nahla Khamis , Alhainiah Maha , Khayat Maie , Abulaban Orjwan , Almaghrabi Sarah , Filmban Osama 
Published: March 2019

Objectives: To assess Quality of Life (QOL), and its associated factors between asthmatic children and their caregivers, and determine the correlation between QOL of patients and caregivers, at King Abdulaziz University Hospital (KAUH), Jeddah.
Methods: A cross-sectional study was conducted among eligible participants who attended Pediatric Pulmonology Outpatient Clinic of KAUH, during 2016/2017. A data collection sheet was used. The standardized Arabic version of Pediatric Asthma Quality of Life Questionnaire (PAQLQ) for children aged 7 - 17 years was completed. The caregiver who accompanied the child fulfilled the Pediatric Asthma Caregiver’s Quality of Life Questionnaire (PACQLQ). Descriptive and inferential analyses were performed.
Results: QOL scores were reduced among asthmatic children who had other type of allergy, or a family history of allergies. Uncontrolled management of asthma presented by frequent waking-up at night, frequent wheezes, visiting Emergency Rooms (ER), or hospital admission was associated with poor QOL of both asthmatic children and their caregivers. There is a positive correlation between child symptoms domain of PAQLQ and emotional domain of PACQLQ of their caregivers.
Conclusion: Uncontrolled asthma was associated with poor QOL of asthmatic child and caregivers. Better management of asthma is recommended to improve their QOL.
How to cite this:Ibrahim NK, Alhainiah M, Khayat M, Abulaban O, Almaghrabi S, Felmban O. Quality of Life of asthmatic children and their caregivers. Pak J Med Sci. 2019;35(2):521-526. doi: https://doi.org/10.12669/pjms.35.2.686
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.