tbuckley/cabot-search huggingface dataset:
Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1.
Authors: Arjun Vasant Balar, Matt D. Galsky, Yohann Loriot, Nancy Ann Dawson, Andrea Necchi, Sandy Srinivas, Richard Wayne Joseph, Ulka N. Vaishampayan, Srikala S. Sridhar, David I. Quinn, Alexandra Drakaki, Ignacio Duran, Jonathan E. Rosenberg, Thomas Powles, Jean H. Hoffman-Censits, Na Cui, Sanjeev Mariathasan, Ann Christine Thastrom, Oyewale O. Abidoye, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2016)

LBA4500 Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR &gt; 30 but &lt; 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71% had CrCl &lt; 60 mL/min; 13% had hearing loss ≥ 25 dB; 6% had prior PN ≥ G2; 20% had ECOG PS2. ORR was 19% (95% CI 13-28; 5% CR), and responses occurred in all IC subgroups (Table; includes DCR/PFS/OS) and in pts with poor prognostic factors. 22/23 responses were ongoing with mDOR not reached. Median follow-up was 8.5 mo (range 0.2-14.3); median tx duration was 15 wk. Atezo was generally well tolerated. Tx-related all-G and G3-4 AEs were seen in 64% and 12% of pts, respectively. Related all-G AEs ≥ 10% included fatigue, pruritus, diarrhea. 1 G5 related AE occurred (sepsis). 3% had a G3-4 immune-mediated AE. Conclusions: Atezo has clinically meaningful activity in 1L cisplatin-ineligible mUC pts, and preliminary OS is encouraging. The durable nature of response and favorable AE profile makes this an attractive alternative to chemo. NCT02108652. Clinical trial information: NCT02108652. [Table: see text]
Abstract 2502: Bioengineered-induced cancer-like stem cells: characterization and applications
Authors: Sungpil Cho, Hongsuk Park, Elke A. Jarboe, C Matthew Peterson, You Han Bae, Margit Matthew Janat-Amsbury
Journal: Cancer Research (2016)

Abstract Cancer stem cells (CSCs) are a small subset of tumor cells capable of self-renewal, tumor initiation, and growth. Isolation, expansion, and differentiation of CSCs in the proper stem niches remain a topic of great debate. To address some of the challenges, we developed bioengineered-induced cancer like stem cells (iCLSCs) through in vitro oncogenic reprograming of C57BL/6 mouse embryonic stem cells (mESCs). We constructed retroviral plasmids through integration of well-defined oncogenic elements such as SV40LTg and HrasV12 into a mouse stem virus long terminal repeat (MSCV-LTR) plasmid fused with either a GFP or RFP gene. We successfully acquired these bioengineered-iCLSCs through retroviral introduction alongside with FACS sorting of positively infected mESCs. We then cultured the bioengineered-iCLSCs on mouse embryonic fibroblast (mEF) feeder cells. Bioengineered-iCLSCs expressed the introduced oncogenic genes and showed enhanced proliferation similar to cancer cells. In addition, we ascertained the unhampered stem properties of the bioengineered-iCLSCs by examining the maintenance of alkaline phosphatase activity as well as the expression of mouse stem cell marker SSEA-1. Furthermore, the orthotopic inoculation of these bioengineered-iCLSCs into either the mammalian fat pad or the ovarian bursa of female C57BL/6 mice lead to the formation of teratomas in supportive niches. Interestingly, the teratomas formed in the ovarian bursa exhibited malignant and immature features, whereas the iCLSCs introduced to the mammary fat pad were not able to generate teratomas with similar features. These observations call for additional research to identify the dependency on a supportive niche and their role in metastasis based on a tumor-favorable microenvironment. Our study helped to establish the use of in vitro oncogenic reprograming to generate bioengineered-iCLSCs and suggests the potential application for the initiation of organ-specific, malignant tumor formation in an orthotopic small animal cancer model. Citation Format: Sungpil Cho, Hongsuk Park, Elke A. Jarboe, C Matthew Peterson, You Han Bae, Margit Matthew Janat-Amsbury. Bioengineered-induced cancer-like stem cells: characterization and applications. [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 2502.
An ongoing measles outbreak linked to a suspected imported case, Ireland, April to June 2016
Authors: Peter Barrett, Katerina Chaintarli, Fiona Ryan, Suzanne Cotter, Anthony Cronin, Louise Carlton, Mary MacSweeney, Mairead McDonnell, Jeff Connell, Rose Fitzgerald, Douglas Hamilton, Mary Ward, Ronan Glynn, Chantal Migone
Journal: Eurosurveillance (2016)

We report an outbreak of measles which started in April 2016 and which, by 13 June, has resulted in 22 confirmed and five probable measles cases occurring in four regions of Ireland. Genotype B3 was identified. We describe the identification, ongoing investigation and control measures being implemented. This outbreak occurs during a period of very low measles transmission in Ireland, with only one confirmed case (imported) notified in 2016 before this event.
Abstract LB-359: Knowledge of prostate cancer and screening attitude of residents of a Nigerian community
Authors: Emeka E.J Iweala, Conrad A. Omonhinmin, Dominic E. Azuh, Isioma J. Okwudi
Journal: Cancer Research (2016)

Abstract This study assessed the level of awareness and knowledge of prostate cancer amongst the residents of a Nigerian University and its environs. A cross-sectional descriptive study using self-administered questionnaires was carried out among 443 people, aged 20 to 80 residing in Covenant University, Nigeria and its environs. Data analysis was done with SPSS version 15.0. The level of significance was set at p &amp;lt;0.05. The majority (45.1%) of respondents was aged between 31 - 40 years and only 41.3% were aware of the existence of Prostate cancer. Educational background, occupation and religion were observed to significantly increase (p &amp;lt;0.05) awareness of prostate cancer while gender and age did not. The awareness and previous participation in prostate cancer screening negatively (p &amp;lt;0.05) influenced respondents’ decision to participate in future screening. Electronic media via radio and television was the commonest source of awareness for prostate cancer. Only 13.4% became aware through health facility or personnel. Only 30.5% correctly identified the location of the prostate. Most of the respondents identified poor diet and environmental conditions as risk factors while 13.7%, 2.0% and 5.9% identified aging, race and genetics respectively as the causes of prostate cancer. Most of the respondents (31.2%) correctly identified difficult urination as a symptom of prostate cancer. About 30.8% have a relative, family or friend that had prostate cancer out of which 18.5% resulted in deaths. Only one respondent had been previously diagnosed with an enlarged prostate. Majority of the respondents were unaware of a possible cure or therapy. Only 9.9%, of the respondents strongly agreed that prostate cancer was peculiar to all men while a low percentage (4.1%) of respondents strongly agreed that it is a health disparity issue among black men. Over all a very low percentage of 37.9% of the respondents considered prostate cancer to be a serious ailment. The study showed a generally poor knowledge and wrong conceptions about prostate cancer, screening and treatment. This suggests the need for public health education and screening programs on prostate cancer for this population and others. Citation Format: Emeka E.J Iweala, Conrad A. Omonhinmin, Dominic E. Azuh, Isioma J. Okwudi. Knowledge of prostate cancer and screening attitude of residents of a Nigerian community. [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 LB-359.
Association of baseline CEA, VEGF, and soluble VEGF receptor-2 with treatment outcomes in two randomized phase III trials of cediranib in metastatic colorectal cancer (mCRC).
Authors: H. Schmoll, P. M. Hoff, J. D. Robertson, L. Pike, S. Morgan, D. Wilson, J. M. Jürgensmeier
Journal: Journal of Clinical Oncology (2011)

3590^ Background: Cediranib is an oral VEGFR tyrosine kinase inhibitor. In the HORIZON (HZ) II and III studies in mCRC, cediranib plus standard chemotherapy (CT) showed improvements in PFS vs CT alone (HR 0.84, P=0.012; HZII), but not vs bevacizumab plus CT (HR 1.1, P=0.119; HZIII). To explore potential prognostic/predictive factors, we conducted a retrospective analysis of baseline (BL) levels of CEA, VEGF and sVEGFR2. Methods: In HZII, 860 pts received FOLFOX or XELOX with cediranib 20 mg (n=502) or placebo (n=358). In HZIII, 1,422 pts received mFOLFOX6 with cediranib 20 mg (n=709) or bevacizumab (n=713). Plasma VEGF and sVEGFR2 were measured centrally by ELISA; serum CEA was measured locally. Cut-off values were 98 pg/mL for VEGF, 11,586.6 pg/mL for sVEGFR2 and 50 ng/mL for CEA, based on the median BL values across HZII and III. HRs were derived from a Cox PH model with covariates for performance status, CT received, BL liver function and study phase. The results presented relate to the primary endpoints (HZII: PFS, OS; HZIII: PFS). Results: For each factor, BL data were available for >85% patients in each study. Prognostic factors: High BL VEGF was associated with a worse overall outcome for PFS in HZII (HR 1.41 [1.21, 1.65]) and HZIII (HR 1.20 [1.04, 1.38]), and OS in HZII (HR 1.35 [1.12, 1.63]). BL sVEGFR2 was not prognostic for PFS in HZII (HR 0.99 [0.85, 1.15]) or HZIII (HR 0.98 [0.86, 1.13]), or OS in HZII (HR 0.92 [0.77, 1.10]). High BL CEA was associated with a worse overall outcome for PFS in HZII (HR 1.34 [1.14, 1.57]) and HZIII (HR 1.20 [1.04, 1.37]), and OS in HZII (HR 1.63 [1.36, 1.96]). Predictive factors: There was no strong evidence that BL VEGF, sVEGFR2 or CEA predicted for PFS or OS outcome to cediranib treatment in HZII or HZIII; however, the groups with low BL sVEGFR2 levels were associated with a trend to an improved cediranib PFS effect in HZII and HZIII (HZII low HR 0.81, high HR 0.96; HZIII low HR 1.04, high HR 1.21). Conclusions: In this retrospective subset analysis of two large randomized Phase III trials, BL VEGF and CEA emerged as prognostic biomarkers for both PFS and OS. The prognostic value of CEA and VEGF should be considered when designing studies in mCRC.
Strategies for Improving Surgical Care
Authors: Karan R. Chhabra, Justin B. Dimick
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Dose Intensity and Risk of Relapse for NHL after Allogeneic Transplant.
Authors: Roberto Rodriguez, Auayporn Nademanee, Nora Carter, Eileen Smith, Amrita Krishnan, Leslie Popplewell, Jasmine Zain, Mark Kirschbaum, Allison Sano, Kathy Patane, Mudra Nathwani, Ricardo Spielberger, Clarence Sarkodee-Adoo, Stephen J. Forman
Journal: Blood (2004)
Living alone after myocardial infarction. Impact on prognosis
Authors: R. B. Case
Journal: JAMA (1992)

<h3>Objective.</h3> —To determine if the presence of a disrupted marriage or living alone would be an independent prognostic risk factor for a subsequent major cardiac event following an initial myocardial infarction. <h3>Design.</h3> —Prospective evaluation in the placebo wing of a randomized, double-blind drug trial in patients with an enzyme-documented acute myocardial infarction who were admitted to a coronary care facility. Data for living alone and/or a marital disruption were entered into a Cox proportional hazards model constructed from important physiologic and nonphysiologic factors in the same database. <h3>Setting.</h3> —Multicenter trial in a mixture of community and academic hospitals in the United States and Canada. <h3>Patients.</h3> —All consenting patients who were 25 to 75 years of age and without other serious diseases were enrolled (placebo, N = 1234) within 3 to 15 days of the index infarction and followed for a period of 1 to 4 years (mean, 2.1 years). Nine hundred sixty-seven patients were followed for 1.1 years and 530 for 2.2 years. <h3>Primary Outcome Measure.</h3> —Recurrent major cardiac event (either recurrent nonfatal infarction or cardiac death). <h3>Results.</h3> —Living alone was an independent risk factor, with a hazard ratio of 1.54 (95% confidence interval, 1.04 to 2.29;<i>P</i>&lt;.03). Using the Kaplan-Meier statistical method for calculation, the recurrent cardiac event rate at 6 months was 15.8% in the group living alone vs 8.8% in the group not living alone. Risk remained significant throughout the follow-up period (<i>P</i>=.001). A disrupted marriage was not an independent risk factor. <h3>Conclusion.</h3> —Living alone but not a disrupted marriage is an independent risk factor for prognosis after myocardial infarction when compared with all other known risk factors. (<i>JAMA</i>. 1992;267:515-519)
Abstract 3704: TRISENOX disrupts MDM2-DAXX-HAUSP interaction and increased promyelocytes formation in murine model of APL
Authors: Sanjay Kumar, Paul Tchounwou
Journal: Cancer Research (2016)

Abstract Trisenox (ATO) is widely used in the treatment of all age group of acute promyelocytic leukemia (APL) patients in both induction and consolidation therapy. In vitro studies are shown that it works through oxidative stress, cell cycle regulation and apoptosis to kill APL cells having PML-RAR α oncogene. Some ATO resistant case of APL patients are reported with different oncogenes combination. However, in vivo anti-leukemic mechanism of action of ATO in APL patients poorly known. We have used transgenic murine model to elucidate the anti-cancer properties of ATO through new target. We hypothesized that ATO disrupts MDM2-DAXX-HAUSP interaction and also increased more number of promyelocytes formation inside bone marrow cells of APL mice. To test the hypothesis, we used different groups of younger (4-5weeks old) transgenic APL mice and standardized different dose of ATO (1.25, 2.5, 5.0 and 7.5 mg/kg body wt) after 21days continuous treatment in PBS. We utilized western blotting, immunocytochemistry, confocal imaging and other molecular techniques to identify molecular mechanisms of ATO action in APL mice hepatocytes as well as bone marrow cells. We found that it increases number of promyelocyte formation in bone marrow cells and also degradation of PML-RARα dose dependent fashion. ATO nicely activated p53 expression in both liver tissue as well as bone marrow cells of APL mice through degradation of MDM2. It was also disrupted both expression and association of MDM2-DAXX-HAUSP complex molecules dose dependent manner in mice liver tissues. On the basis of these findings, we conclude that ATO disrupts MDM2-DAXX-HAUSP interaction, increased promyelocytes formation, MDM2 degradation by accumulating P53 in APL mice liver tissues. It is novel target for treatment of APL patients through designing of new anti-leukemic drugs. Keywords: Trisenox, P53, MDM2-DAXX-HAUSP complex molecules APL Mice hepatocytes and bone marrow cells. Acknowledgements: This research was financially supported by National Institutes of Health NCRR Grant No. 5G12RR013459 and MIMHD Grant No. 8G12MD007581, through the RCMI-Center for Environmental Health at Jackson State University. Citation Format: Sanjay Kumar, Paul Tchounwou. TRISENOX disrupts MDM2-DAXX-HAUSP interaction and increased promyelocytes formation in murine model of APL. [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 3704.
Abstract 4163: Molecular and physiological effects of splicing factor mutant U2AF1 in human lung cell lines and in mice
Authors: Dennis Fei, Hayley Motowski, Sameer Prasad, Jovian Yu, Robert Bradley, Harold Varmus
Journal: Cancer Research (2016)

Abstract The splicing factor gene, U2AF1, is commonly mutated in myeloid neoplasms and occasionally in solid tumors such as lung adenocarcinomas (LUADs), yet the molecular and physiological consequences of U2AF1 mutations are not well understood. Through genome editing of the endogenous locus, we created a common U2AF1 mutant allele (U2AF1-S34F) in an immortalized human bronchial epithelial cell line, and we inactivated the U2AF1-S34F allele in two LUAD cell lines that naturally harbor this mutation. Cells expressing U2AF1-S34F deployed altered splicing of many transcripts, and they displayed a S34F-characteristic sequence pattern at the proximal 3’ splice site, as previously reported. Remarkably, S34F-associated alternative splicing patterns remained unaffected by changes in the amount of mutant U2AF1 protein, as long as the ratio of mutant and wild-type U2AF1 remained constant, as evidenced by RNA interference-mediated knockdown of the expression of both mutant and wild-type alleles. On the other hand, perturbing the ratio of mutant and wild-type U2AF1, either through overexpression or allelic-specific inactivation of wild-type U2AF1, greatly affected S34F-associated splicing. These results suggest that the ratio of mutant and wild-type U2AF1, rather than the absolute amount of either protein, is critical in controlling splicing outcome. Expression of U2AF1-S34F does not cause cell transformation and LUAD cells with endogenous U2AF1-S34F expression are not dependent on the U2AF1-S34F allele. Instead, wild-type U2AF1 is absolutely required for cell survival in the presence of the mutant allele. To study the effect of U2AF1-S34F in vivo, we created transgenic mice carrying a conditional mutant allele, MG-S34F, at the endogenous U2af1 locus. By crossing the MG-S34F mice with mice carrying a Mx1-Cre transgene and treating the progeny with poly IC, we activated MG-S34F by Cre-mediated recombination to express U2af1-S34F in bone marrow cells. This resulted in cytopenia in multiple blood cell lineages. Similar results were observed in recipient mice following non-competitive transplant. Bone marrow cells expressing U2af1-S34F were competitively disadvantaged in repopulating the hematopoietic system in irradiated mice, suggesting defective hematopoietic stem cell function, and we are currently assessing the long-term impact of U2af1-S34F expression on the incidence of myeloid neoplasms. Citation Format: Dennis Fei, Hayley Motowski, Sameer Prasad, Jovian Yu, Robert Bradley, Harold Varmus. Molecular and physiological effects of splicing factor mutant U2AF1 in human lung cell lines and in mice. [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 4163.
A live cell microfluidics device utilizing phenotypic biomarkers for prostate cancer.
Authors: David Albala, Vladimir Mouraviev, Kimberly M. Rieger-Christ, Travis B. Sullivan, Naveen Kella, Kevin B. Knopf, Hani H. Rashid, Michael S. Manak, Brad J. Hogan, Gauri Dixit, Delaney Berger, Wendell R. Su, Matthew J. Whitfield, Jonathan S. Varsanik, Mani Foroohar, Stephen M Zappala, Ashok C. Chander, Grannum R. Sant
Journal: Journal of Clinical Oncology (2016)

338 Background: A novel tissue based biomarker panel is introduced to objectively assess disease aggressiveness and invasive potential of Prostate Cancer (CaP). The biomarker diagnostic platform incorporates both molecular and phenotypic data that may allow an improved understanding of local growth and metastatic potential. The tissue based diagnostic incorporates matrix biology, phenotypic biomarkers, microfluidics, and machine vision. This technology presents the opportunity to culture samples, and both determine and automate biomarker measurements from machine vision algorithm analysis. Data are presented towards clinical validation, the ability to risk stratify, and prediction of local aggressiveness and metastasis. Methods: Conditions were optimized for reliably culturing primary cancer cells in vitro by simulating in vivo conditions on an extracellular matrix formulation. A mcirofluidics device was used to culture live tumor samples ex vivo enabling automated imaging of the label free and label-based biomarkers. Results: The validation study was IRB approved and performed in 200 consecutive CaP radical prostatectomy derived specimens collected between 03/2014 and 09/2015. Data was analyzed with receiver operating characteristics (ROC) generated Area-under-the-Curve (AUC) and specifically included capsular penetration, seminal vesicle invasion, as well as margin-positive disease. AUC Graphs are presented. The study further demonstrated that a normal set of phenotypic biomarkers can produce secondary metrics termed oncogenic potential (OP) and metastatic potential (MP). Concordance analysis supports that OP and MP are integral for distinguishing between benign histology and malignancy, predicting both stage and adverse pathology such as extra-prostatic extension (EPE) and lympho-vascular invasion (LVI). The study results demonstrate AUCs greater than 0.90 in predicting EPE and LVI. Conclusions: Results support the clinical validation of a novel live- cell phenotypic in vitro tumor diagnostic test. This test has the potential to predict adverse pathologies for CaP and may have extended clinical applications to optimize staging and risk stratification.
Common Genetic Variants Associated With Higher Lp(a) Concentrations and Increased Risk of Coronary Heart Disease
Authors: R Clarke, J Peden, J Hopewell, T Kyriakou, A Goel, S Heath, S Parish, S Barlera, M Grazia, M Negri, S Rust, D Bennett, A Silveira, A Malarstig, F Green, M Lathrop, B Gigante, K Leander, U de Faire, U Seedorf, A Hamsten, R Collins, H Watkins
Journal: Circulation (2009)