tbuckley/cabot-search huggingface dataset:
Abstract 2067: Attacking prostate cancer with a prodrug-doped cellular Trojan horse
Authors: Nathaniel Brennen, Oren Levy, Edward Han, David Marc Rosen, Juliet Musabeyezu, Helia Safaee, Sudhir Ranganath, Jessica Ngai, Martina Heinelt, Sandrine Billett, Neil Bhowmick, Samuel Denmeade, Jeffrey Karp, John Isaacs
Journal: Cancer Research (2016)

Abstract Prostate cancer is the second leading cause of cancer-related deaths in American men. Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. Human mesenchymal stem cells (MSCs) are excellent candidates for cell-based drug delivery since they display tropism towards cancer sites and clinical studies have demonstrated that hundreds of millions of allogeneic human MSCs can be safely administered intravenously without adverse effects in a variety of pathological settings. Furthermore, we have previously documented that MSCs can be detected in radical prostatectomy tissue from men with prostate cancer. In this proof-of-concept study, human MSCs were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) encapsulating the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-loaded MPs were successfully internalized by MSCs without impacting MSC viability, followed by sustained release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs is selectively toxic to the PSA-secreting prostate cancer cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when co-inoculated with CWR22 prostate cancer xenografts, suggesting that cell-based delivery of G114 does not compromise potency of the prodrug in vitro or in vivo. We envision that this MSC-based platform may be developed into an effective, systemic ‘Trojan Horse’ therapy for the targeted delivery of therapeutic agents to sites of metastatic prostate cancer. Citation Format: Nathaniel Brennen, Oren Levy, Edward Han, David Marc Rosen, Juliet Musabeyezu, Helia Safaee, Sudhir Ranganath, Jessica Ngai, Martina Heinelt, Sandrine Billett, Neil Bhowmick, Samuel Denmeade, Jeffrey Karp, John Isaacs. Attacking prostate cancer with a prodrug-doped cellular Trojan horse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2067.
Prognostic Factors For Overall Survival In Elderly Patients With Relapsed Acute Myeloid Leukemia – Retrospective Study On Behalf Of The East German Study Group For Hematology and Oncology (OSHO)
Authors: Thomas Heinicke, Rainer Krahl, Christian Jakob, Christoph Kahl, Hans-Heinrich Wolf, Ute Kreibich, Frank Rothmann, Detlev Hähling, Manfred Schulze, Ulrich Wedding, Ute Hegenbart, Carsten Hirt, Norma Peter, Hans-Heinrich Wolf, Bernhard Opitz, Antje Schulze, Christian Junghanss, Andreas Hochhaus, Thomas Fischer, Dietger Niederwieser, Haifa Kathrin Al-Ali
Journal: Blood (2013)
Abstract 4821: The WEE1 inhibitor AZD-1775 has synergic activity with trabectedin or lurbinectedin in ovarian cancer cells
Authors: Sarah Uboldi, Laura Carrassa, Roberta Frapolli, Paolo Ubezio, Eugenio Erba, Maurizio D’Incalci
Journal: Cancer Research (2016)

Abstract AZD-1775 is a small molecule that selectively inhibits the tyrosine kinase WEE1, with a reported antineoplastic activity in ovarian cancer. WEE1 is a tyrosine kinase key regulator of DNA damage surveillance pathways that controls G2/M transition and ensures faithful DNA replication. WEE1 is required during normal S phase to avoid deleterious DNA breakage and prevent loss of genome integrity in the absence of exogenous DNA damage. Trabectedin is a drug approved in 2007 by EMA and 2015 by FDA for the treatment of soft tissue sarcomas and in 2009 by EMA for the treatment of ovarian cancer patients, who have relapsed after 6 months from Platinum-based therapy, in combination with pegylated liposomal doxorubicin. Lurbinectedin (PM01183) is a trabectedin analog with a similar mechanism of action and, according to ongoing clinical investigations, less toxic and thus suitable for combinations of potential clinical interest. Since both trabectedin and lurbinectedin cause a G2/M block and AZD-1775 is able to inhibit the WEE1 activity with consequent disruption of G2/M checkpoint, we hypothesized that the combined treatment with AZD-1775 could be synergistic in ovarian cancer cells. The sensitivity of the ovarian cancer cell lines OVCAR-5, A2780 and IGROV-1 to trabectedin, lurbinectedin and AZD-1775 alone or in combination (72h of continous treatment) was evaluated by a cell proliferation assay. The cytotoxic effect induced by the simultaneous administration of trabectedin with AZD-1775 or lurbinectedin with AZD-1775 was evaluated by a combination index analysis. The results obtained showed that the combination trabectedin with AZD-1775 or lurbinectedin with AZD-1775 is synergic in all the ovarian cancer cell lines analyzed (Combination Index &amp;lt;1). The combination lurbinectedin with AZD-1775 seems to be better than trabectedin with AZD-1775, in OVCAR5 cell line. The analysis of cell cycle and apoptosis are in progress in order to investigate the mechanism of the observed synergism. These positive results prompted us to study these combinations in vivo, in ovarian cancer xenografts derived from the cell lines used for the in vitro studies. If the synergism observed in vitro will be confirmed in vivo, there will be a strong rationale to test these combinations in ovarian cancer patients. Citation Format: Sarah Uboldi, Laura Carrassa, Roberta Frapolli, Paolo Ubezio, Eugenio Erba, Maurizio D’Incalci. The WEE1 inhibitor AZD-1775 has synergic activity with trabectedin or lurbinectedin in ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4821.
Confirmatory factor analysis to evaluate construct validity of the Brief Pain Inventory (BPI).
Authors: T. M. Atkinson, L. Sit, T. R. Mendoza, M. Fruscione, D. Lavene, M. Shaw, W. Breitbart, B. Rosenfeld, C. S. Cleeland, E. M. Basch
Journal: Journal of Clinical Oncology (2010)

e19505 Background: The Brief Pain Inventory (BPI) is a frequently used instrument designed to assess the patient-reported outcome of pain. Prior exploratory factor analysis study results have suggested a two-factor (i.e., pain intensity and pain interference) structure for this instrument; however, since the BPI was developed with an a priori hypothesis of the relationship amongst its items, it follows that investigations of construct validity should utilize confirmatory factor analysis (CFA). The purpose of this work is to establish the construct validity of the BPI using a CFA framework and demonstrate factorial invariance using a range of demographic variables. Methods: A retrospective CFA was completed in a sample of individuals diagnosed with cancer and HIV/AIDS (N = 364; 63% Male; Age 21-92, M = 51.78) who had been administered the BPI during routine palliative care. A baseline one-factor model was compared against two-factor and three-factor models (i.e., pain intensity, activity interference, and affective interference) that were developed based on the hypothetical design of the instrument. Results: Root mean squared error of approximation (0.075), comparative fit index (0.953), and change in chi-square, given the corresponding change in degrees of freedom (χ2(2) = 9.53, p < .05) values for the three-factor model were statistically superior when compared to the one- and two- factor models. This three-factor structure was found to be invariant across disease types, age, and ethnicity groups. Conclusions: The results of this study provide evidence to support a three-factor representation of the BPI. Further analysis using data from a large multicenter study in patients with cancer is under way to further validate these results. Such findings will provide clinical trialists, pharmaceutical sponsors, and regulators with confidence in the potential three dimensional representation of this instrument when considering its inclusion in clinical research. No significant financial relationships to disclose.
Abstract 3932: Values of single nucleotide polymorphisms identified from genome-wide association studies on risk prediction, risk reclassification, and population-based screening of breast-cancer
Authors: Yubei Huang, Fengju Song, Kexin Chen
Journal: Cancer Research (2016)

Abstract Background: With an increasing number of single nucleotide polymorphisms (SNPs) being identified from genome-wide association studies (GWAS), it's important to examine whether these SNPs have values in public health. And it's also unclear how to select the targeted SNPs valuable for population-based screening from numerous GWAS-identified SNPs. Methods: Based on the fraction of the genetic risk explained by a SNP, the area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, and net reclassification improvement were used to select targeted SNPs and to evaluate the values of genetic risk score (GRS) with targeted SNPs on risk prediction, risk reclassification, and effects of population-based screening among 2 million simulated Chinese women aged 35-69 years. Results: A total of 11 targeted SNPs from 23 GWAS-identified SNPs would be valuable for population-based screening of breast cancer among Chinese women. After incorporating GRS with targeted SNPs into traditional risk predication based on established risk factors (ERF) of breast cancer, the AUC significantly improved from 65.5% to 67.5% (P&amp;lt;0.001). Additional 25.5% (P&amp;lt;0.001) population would be correctly reclassified into cases or controls. If screening targeted at top 25% high-risk women, screening-detected cancer would significantly increase 4.2% (49.2% vs 45.0%, P&amp;lt;0.001) for screening strategy included GRS and ERF in risk assessment before screening compared with that only included ERF in risk assessment. Conclusion: GRS based on targeted GWAS-identified SNPs could significantly improve the risk prediction, risk reclassification, and the effects of population-based screening. Further real-world studies are needed to validate this method and these results. Citation Format: Yubei Huang, Fengju Song, Kexin Chen. Values of single nucleotide polymorphisms identified from genome-wide association studies on risk prediction, risk reclassification, and population-based screening of breast-cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3932.
Abstract 1028: A mouse model of allelic loss of the core autophagy gene BECN1 in ovarian cancer
Authors: Joe R. Delaney, Chandni Patel, Dwayne G. Stupack
Journal: Cancer Research (2016)

Abstract Autophagy, a process of protein and organelle recycling, can both suppress and promote tumors. Gliomas, KRAS mutant, and BRAF driven tumor models require functional autophagy for maximal tumorigenicity and/or tumor progression. Inhibition of autophagy is able to eliminate many human cancer cell lines. However, allelic loss of the autophagy gene BECN1 is present in the majority of ovarian cancers, and BECN1 loss incurs early tumorigenesis in mouse models free of other oncogenic stimuli. Recent sequencing efforts and analyses, depending on the study, have both supported and refuted the relevance of BECN1 allelic loss in ovarian and breast cancers. To directly address the role of BECN1 allelic loss in ovarian cancer, we crossed BECN1 heterozygous knockout dams with MISIIR-TAg sires. In this model, the MISIIR promoter induces expression of large T antigen specifically in the ovarian and fallopian epithelium, inhibiting p53 activity and driving ovarian cancers in a manner befitting its human analogue. Here we present our pre-publication findings relating to the oncogenesis and progression of this murine BECN1 allelic loss model of ovarian cancer. We compare the in vivo murine results to those of in vitro human cell line models of beclin depletion, which exhibit higher basal dsDNA break repair signaling, mitochondrial stress, and reactive oxygen species generation. Citation Format: Joe R. Delaney, Chandni Patel, Dwayne G. Stupack. A mouse model of allelic loss of the core autophagy gene BECN1 in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1028.
Risk of metachronous contralateral testicular germ cell tumor (met-TGCT) among 7,248 Norwegian patients (1953-2007).
Authors: K. E. Andreassen, T. Grotmol, M. Cvancarova, T. B. Johannesen, S. D. Fossa
Journal: Journal of Clinical Oncology (2010)

1579 Background: The aims were to identify the overall incidence and risk of developing a met-TGCT, and compare the risk between patients treated before and after 1980 (cisplatinum-based chemotherapy became available for newly diagnosed TGCT patients in Norway). Our hypothesis was that the risk of TCGT would be reduced for patients diagnosed after 1980, at least for subgroups of patients, due to a protective effect of cisplatinum. Methods: The study included 7,248 men with unilateral TGCT (seminoma: 3,999, nonseminoma: 3,249) recorded in the Cancer Registry of Norway. Allowing for competing risk, 10- and 20-year cumulative incidence (cum. inc.) and adjusted hazard ratios (HR) were estimated for different subgroups, and the diagnostic periods 1953-1979 (I) and 1980-2007 (II). After 1980, 20-25% of all men (1987) with initially localized TGCT, and nearly all men (570) with metastatic TGCT, received cisplatinum. Results: 175 men were diagnosed with met-TGCT. Period I: 38 met-TGCT, 10- and 20-year cumulative incidence 1.3% (0.9-1.9) and 1.9% (1.4-2.6). Period II: 137 met-TGCT, 10- and 20-year cumulative incidence 2.7% (2.2-3.2) and 3.9% (3.3-4.7). Conclusions: Comparing the two periods, there has been a two-fold increase in the incidence of unilateral TGCT, and the cumulative incidence of met-TGCT has doubled. Increasing age reduced the risk in both periods, but more so in period I. In period II, the risk of met-TGCT was halved for patients with metastatic disease compared to patients with localized disease, whereas the protective effect of extent of disease lacked significance for period I. These findings support our hypothesis that cisplatinum reduced the risk of TGCT for patients diagnosed after 1980, at least for those with metastatic TGCT. First TGCC: 1953-1979 1980-2007 10-year cum.inc. Comp.risk reg. 10-year cum.inc. Comp.risk reg. % 95%CI HR 95%CI % 95%CI HR 95%CI Age < 30 years 2.7 1.6-4.2 Ref 3.7 2.8-4.7 Ref ≥30 years 0.7 0.4-1.3 0.2 0.1-0.4 2.0 1.5-2.6 0.5 0.3-0.7 Histology Seminoma 1.2 0.7-2.0 Ref 1.5 0.8-2.6 Ref Nonseminoma 2.8 2.2-3.6 0.8 0.4-1.8 2.5 1.9-3.3 0.9 0.6-1.2 Extent of disease Localized 1.3 0.8-2.1 Ref 3.2 2.6-4.0 Ref Metastatic 1.4 0.7-2.6 0.7 0.3-1.4 1.6 1.0-2.4 0.5 0.3-0.8 No significant financial relationships to disclose.
Vaccination of chimpanzees with a multicomponent DNA-protein prime-boost regimen provides an enhanced recovery following heterologous HCV challenge.
Authors: J Heeney, J Drexhage, B Verstrepen, C Rollier, G Mares, D Jacobs, E Depla, G Maertens, C Brinster, A Fournillier, E Verschoor, G Inchauspe
Journal: Hepatology (2001)
Abstract 4777: The role of BAG3 in human leukemia cells’ response to the experimental anticancer drug laromustine
Authors: Kevin P. Rice, Amanda J. Loya, Kayla M. Gross
Journal: Cancer Research (2016)

Abstract The experimental anticancer drug laromustine, which demonstrates moderate clinical efficacy against acute myelogenous leukemia and glioblastoma multiforme, yields two reactive electrophiles in situ. Therapeutic cytotoxicity is principally due to a 2-chloroethylating species that can cause lethal DNA crosslinks. However, the second electrophile, methyl isocyanate, triggers acute toxicity in cultured cancer cells and synergizes with the cogenerated 2-chloroethylating activity. The mechanism by which laromustine kills cancer cells likely includes apoptosis. We measured changes in transcription for 88 genes relating to this cell death pathway cultured human promyelocytic (HL-60) cells using quantitative real-time reverse transcriptase PCR. Cultured cells were treated with drug for six hours before harvesting mRNA for analysis. Of these genes, the expression of BAG3, whose encoded protein is also known as CAIR-1 or Bis, was increased by more than 300 fold in cells exposed to laromustine. By forming a complex with heat shock protein 70 (Hsp70), it is thought that BAG3 promotes anti-apoptotic activity by interfering with protein chaperones and release of cytochrome-c. We are also examining effects on the entire transcriptome upon treatment with laromustine using GeneChip Microarrays. Finally, we have created a stable BAG3 knockdown cell line using an shRNA construct via lentiviral transfection. Substantial differences in laromustine-induced cytotoxicity in differing BAG3 backgrounds would suggest a mechanistic role in a cell's defense against laromustine and possibly an improved clinical approach. Citation Format: Kevin P. Rice, Amanda J. Loya, Kayla M. Gross. The role of BAG3 in human leukemia cells’ response to the experimental anticancer drug laromustine. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4777.
THE SIGNIFICANCE OF DUCTULAR CELLS AND MYOFIBROBLASTS IN GRAFT FIBROSIS AFTER PEDIATRIC LIVER TRANSPLANTATION
Authors: Annette S. Gouw, Jan J. Doff, Marian Bulthuis, Rene Scheenstra, Henkjan J. Verkade, Paul M. Peeters, Marius C. van den Heuvel
Journal: Hepatology (2010)
Can we use structural lesions seen on MRI of the sacroiliac joints reliably for the classification of patients according to the ASAS axial spondyloarthritis criteria? Data from the DESIR cohort
Authors: Pauline A C Bakker, Rosaline van den Berg, Gregory Lenczner, Fabrice Thévenin, Monique Reijnierse, Pascal Claudepierre, Daniel Wendling, Maxime Dougados, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2016)

Investigating the utility of adding structural lesions seen on MRI of the sacroiliac joints to the imaging criterion of the Assessment of SpondyloArthritis (ASAS) axial SpondyloArthritis (axSpA) criteria and the utility of replacement of radiographic sacroiliitis by structural lesions on MRI.Two well-calibrated readers scored MRI STIR (inflammation, MRI-SI), MRI T1-w images (structural lesions, MRI-SI-s) and radiographs of the sacroiliac joints (X-SI) of patients in the DEvenir des Spondyloarthrites Indifférenciées Récentes cohort (inflammatory back pain: ≥3 months, <3 years, age <50). A third reader adjudicated MRI-SI and X-SI discrepancies. Previously proposed cut-offs for a positive MRI-SI-s were used (based on <5% prevalence among no-SpA patients): erosions (E) ≥3, fatty lesions (FL) ≥3, E/FL ≥5. Patients were classified according to the ASAS axSpA criteria using the various definitions of MRI-SI-s.Of the 582 patients included in this analysis, 418 fulfilled the ASAS axSpA criteria, of which 127 patients were modified New York (mNY) positive and 134 and 75 were MRI-SI-s positive (E/FL≥5) for readers 1 and 2, respectively. Agreement between mNY and MRI-SI-s (E/FL≥5) was moderate (reader 1: κ: 0.39; reader 2: κ: 0.44). Using the E/FL≥5 cut-off instead of mNY classification did not change in 478 (82.1%) and 469 (80.6%) patients for readers 1 and 2, respectively. Twelve (reader 1) or ten (reader 2) patients would not be classified as axSpA if only MRI-SI-s was performed (in the scenario of replacement of mNY), while three (reader 1) or six (reader 2) patients would be additionally classified as axSpA in both scenarios (replacement of mNY and addition of MRI-SI-s). Similar results were seen for the other cut-offs (E≥3, FL≥3).Structural lesions on MRI can be used reliably either as an addition to or as a substitute for radiographs in the ASAS axSpA classification of patients in our cohort of patients with short symptom duration.
The Pentostatin, Cyclophosphamide, and Rituximab Regimen (PCR) Is Highly Active and Well Tolerated Regardless of Patient Age, Creatinine Clearance, and Performance Status: Analysis of a Multi-Center Phase II Trial.
Authors: Tait D. Shanafelt, John C. Byrd, Susan M. Geyer, Debra Bowen, Betsy LaPlant, Clive S. Zent, Timothy G. Call, Neil E. Kay
Journal: Blood (2006)
Continuity of Care and Health Care Utilization in Older Adults With Dementia in Fee-for-Service Medicare
Authors: Halima Amjad, Donald Carmichael, Andrea M. Austin, Chiang-Hua Chang, Julie P. W. Bynum
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Poor continuity of care may contribute to high health care spending and adverse patient outcomes in dementia. <h3>Objective</h3> To examine the association between medical clinician continuity and health care utilization, testing, and spending in older adults with dementia. <h3>Design, Setting, and Participants</h3> This was a study of an observational retrospective cohort from the 2012 national sample in fee-for-service Medicare, conducted from July to December 2015, using inverse probability weighted analysis. A total of 1 416 369 continuously enrolled, community-dwelling, fee-for-service Medicare beneficiaries 65 years or older with a claims-based dementia diagnosis and at least 4 ambulatory visits in 2012 were included. <h3>Exposures</h3> Continuity of care score measured on patient visits across physicians over 12 months. A higher continuity score is assigned to visit patterns in which a larger share of the patient's total visits are with fewer clinicians. Score range from 0 to 1 was examined in low-, medium-, and high-continuity tertiles. <h3>Main Outcomes and Measures</h3> Outcomes include all-cause hospitalization, ambulatory care sensitive condition hospitalization, emergency department visit, imaging, and laboratory testing (computed tomographic [CT] scan of the head, chest radiography, urinalysis, and urine culture), and health care spending (overall, hospital and skilled nursing facility, and physician). <h3>Results</h3> Beneficiaries with dementia who had lower levels of continuity of care were younger, had a higher income, and had more comorbid medical conditions. Almost 50% of patients had at least 1 hospitalization and emergency department visit during the year. Utilization was lower with increasing level of continuity. Specifically comparing the highest- vs lowest-continuity groups, annual rates per beneficiary of hospitalization (0.83 vs 0.88), emergency department visits (0.84 vs 0.99), CT scan of the head (0.71 vs 0.83), urinalysis (0.72 vs 1.09), and health care spending (total spending, $22 004 vs $24 371) were higher with lower continuity even after accounting for sociodemographic factors and comorbidity burden (<i>P</i> &lt; .001 for all comparisons). The rate of ambulatory care sensitive condition hospitalization was similar across continuity groups. <h3>Conclusions and Relevance</h3> Among older fee-for-service Medicare beneficiaries with a dementia diagnosis, lower continuity of care is associated with higher rates of hospitalization, emergency department visits, testing, and health care spending. Further research into these relationships, including potentially relevant clinical, clinician, and systems factors, can inform whether improving continuity of care in this population may benefit patients and the wider health system.