tbuckley/cabot-search huggingface dataset:
EGFR family and c-Met expression profiles and prognostic significance in esophagogastric adenocarcinoma.
Authors: Ellie Chan, Ahmad Alkhasawneh, Lizette Vila Duckworth, Tania Zuluaga-Toro, Xiaomin Lu, Steven J. Hughes, Thomas J. George
Journal: Journal of Clinical Oncology (2013)

e15108 Background: Targeted therapy of HER2 overexpression in patients with esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Targeting of EGFR alone in EGA was not active. cMet overexpression is suggested to be a possible resistance pathway for EGFR and HER-2 inhibition. We characterized the expression profile of the EGFR family of receptors and cMet as well as their prognostic significance in EGA. Methods: This retrospective analysis included all patients (pts) with EGA who underwent primary resection at the University of Florida from 2001 to 2011 without neoadjuvant therapy. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on paraffin embedded tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low (0, 1+) or high expression (2+, 3+). Descriptive statistics, Fisher exact test, Cox regression and Kaplan-Meier methods were used for statistical analyses. Results: 52 pts (42 M/10 F) were analyzed with median age 66 years (37-83). Most tumors (58%) were stage I (T1N0). Receptors expression profiles and their associations are presented in the Table. High HER3-HER4 co-expression was found in 35% of cases (p = 0.002). Univariate analysis did not show significant correlation of age, tumor differentiation, BMI, tobacco use and receptor expression with survival. Stage was the only variable that correlated significantly with survival (p=0.02). Conclusions: This is the first study to our knowledge examining the EGFR family expression relationships and cMet in treatment naïve resected EGA tumors. Associations between receptor expression patterns are of clinical interest for rational development of multi-targeted inhibition. Although our data do not significantly show receptor status as a prognostic factor, some receptor expression associations suggest trends towards worse survival. Larger studies are warranted for further investigation. [Table: see text]
Electronic Dura Mater Meddling in the Central Nervous System
Authors: Jocelyne Bloch, Stéphanie P. Lacour, Grégoire Courtine
Journal: JAMA Neurology (2017)

A growing number of neurologic treatments rely on neural implants capable of delivering electrical and chemical stimulation to targeted regions of the central nervous system for extended periods.To assess the potential of a novel class of multimodal neural implants, termed electronic dura mater or e-dura, to fulfill this need.Results from preclinical applications of e-dura implants and clinical evidence.The silicone-based implant e-dura embeds interconnects, electrodes, and chemotrodes that are entirely stretchable. These unique mechanical properties allow e-dura to conform to the circumvolutions of the brain and spinal cord without damaging neural tissues or triggering foreign body reactions.Although challenges lie ahead to reach clinical fruition, the unique mechanical properties and integrated modalities of e-dura provide future opportunities to treat or alleviate neurologic deficits.
Identification of Differentially Expressed Genes in the Rituximab- Resistant Clone (Ramos RR1) Compared to Wildtype Sensitive Ramos: Therapeutic Implications in Rituximab-Resistance
Authors: Stavroula Baritaki, Jose Rodriguez, Gustavo Helguera, Melisa Martinez-Paniagua, Mario Vega, Sara Huerta-Yepez, Ali Jazirehi, Demetrios Spandidos, Manuel L Penichet, Benjamin Bonavida
Journal: Blood (2008)
Development of 99mTcHYNIC-Tocilizumab as Imaging Agent In Multiple Myeloma
Authors: Eloísa Riva, Victoria Calzada, Eugenia Gutiérrez, Marcelo Fernández, Natalia Oddone, María Moreno, Juan Benech, José A. Chabalgoity, Atanasio Pandiella, Pablo Cabral
Journal: Blood (2010)
Immunophenotypic Analysis and Rapid Diagnosis of Acute Promyelocytic Leukemia by Flow Cytometry.
Authors: Yongmin Tang, Hongqiang Shen, Lixia Li, Hua Song, Shuwen Shi, Shilong Yang, Jian Wei, Weiqun Xu, Baiqin Qian, Chunfang Luo
Journal: Blood (2006)
Biology and Therapeutic Targeting of Sp1 Transactivation In Myeloma
Authors: Mariateresa Fulciniti, Samir B. Amin, Puru Nanjappa, Scott J Rodig, Teru Hideshima, Jagannath Pal, Varuna Mohan, Keeyun Lee, Masood Shammas, Stephane Minvielle, Rao Prabhala, Hervé Avet-Loiseau, Li Cheng, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2010)
In Reply
Authors: Wendy R. Cornett, Linda M. McCall, Rebecca P. Petersen, James E. Herndon, Douglas S. Tyler
Journal: Journal of Clinical Oncology (2007)

As Dr Steensma aptly notes, it is impossible to know the number of "zombies" in the system, that is, those study proposals that have been approved for development but have never been activated.Zombies are notorious in other industries for demanding excessive amounts of time, energy, and money.Finally, one of the purposes of our article was to highlight the "Oliphaunt in the room" and "to light a fire" under those with the authority and the responsibility to reduce it to a reasonable size.We certainly agree that reform requires collaboration and commitment among all parties to improve the system.If not, we fear that oncology clinical trials in the United States as we know them today may be following the same path as that of the United States automotive industry (ie, swamped by international competition, historical complacency, and dissatisfied customers).As
Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA
Authors: B.J. Metcalf, S. Chochua, R.E. Gertz, P.A. Hawkins, J. Ricaldi, Z. Li, H. Walker, T. Tran, J. Rivers, S. Mathis, D. Jackson, A. Glennen, R. Lynfield, L. McGee, B. Beall, A. Reingold, S. Brooks, H. Randel, L. Miller, B. White, D. Aragon, M. Barnes, J. Sadlowski, S. Petit, M. Cartter, C. Marquez, M. Wilson, M. Farley, S. Thomas, A. Tunali, W. Baughman, L. Harrison, J. Benton, T. Carter, R. Hollick, K. Holmes, A. Riner, C. Holtzman, R. Danila, K. MacInnes, K. Scherzinger, K. Angeles, J. Bareta, L. Butler, S. Khanlian, R. Mansmann, M. Nichols, N. Bennett, S. Zansky, S. Currenti, S. McGuire, A. Thomas, M. Schmidt, J. Thompson, T. Poissant, W. Schaffner, B. Barnes, K. Leib, K. Dyer, L. McKnight, O. Almendares, J. Hudson, L. McGlone, C. Whitney, S. Schrag, G. Langley
Journal: Clinical Microbiology and Infection (2017)

ObjectivesOur objective was to evaluate and exploit a whole genome sequence (WGS) bioinformatics pipeline for predicting antimicrobial resistance and capsular serotypes from invasive group B streptococci (iGBS).MethodsFor 1975 iGBS recovered during 2015 from CDC's Active Bacterial Core surveillance, we compared pipeline predictions with broth dilution testing. Fifty-six isolates from earlier surveillance were included for testing β-lactams. Conventional serotyping was compared to WGS-based assignments for 302 isolates.ResultsAll 28 isolates with reduced susceptibility to β-lactam antibiotics harboured one of 19 rare PBP2x types. Resistances to erythromycin/clindamycin (808/1975 isolates, 41.0%), erythromycin (235/1975, 11.9%) and lincosamide/streptogramin A/pleuromutilins (56/1975, 2.8%) were predicted by the presence of erm-methylase, mef and lsa determinants, respectively (41 of 56 lsa gene-positive isolates also contained lnu, erm and/or mef genes). Presence of both erm and lsa determinants (25 isolates) predicted non-susceptibility to quinupristin/dalfopristin. Most isolates (1680/1975, 85.1%) were tet gene-positive, although 41/1565 (2.6%) tetM-positive isolates were tetracycline-susceptible. All 53 fluoroquinolone-resistant isolates contained ParC and/or GyrA substitutions. Resistances to rifampin (eight isolates), trimethoprim, chloramphenicol and vancomycin (two isolates each) were predicted by the pipeline. Resistance to macrolides/lincosamides without pipeline prediction was rare and correlated to divergent resistance genes or rRNA A2062G substitution. A selection of 267 isolates assigned WGS-based serotypes were also conventionally serotyped. Of these, 246 (92.1%) were in agreement, with the remaining 21 (7.8%) conventionally non-serotypeable. For 32 of 1975 isolates (1.6%), WGS-based serotypes could not be assigned.ConclusionThe WGS-based assignment of iGBS resistance features and serotypes is an accurate substitute for phenotypic testing.
Erratum: Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all–iPS cell mice from terminally differentiated B cells
Authors: Matthias Stadtfeld, Effie Apostolou, Francesco Ferrari, Jiho Choi, Ryan M Walsh, Taiping Chen, Steen S K Ooi, Sang Yong Kim, Timothy H Bestor, Toshi Shioda, Peter J Park, Konrad Hochedlinger
Journal: Nature Genetics (2012)
Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States
Authors: Yihung Huang, Anca Tilea, Brenda Gillespie, Vahakn Shahinian, Tanushree Banerjee, Vanessa Grubbs, Neil Powe, Nilka Rios-Burrows, Meda Pavkov, Rajiv Saran
Journal: Journal of the American Society of Nephrology (2017)

Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.
Pharmacogenetics of Cyclophosphamide in Patients with Beta Thalassemia Major Undergoing Bone Marrow Transplantation.
Authors: Balasubramanian Poonkuzhali, Desire Salamun, Ramachandran V. Shaji, Biju George, Vikram Mathews, Mammen Chandy, Rajagopal Krishnamoorthy, Alok Srivastava
Journal: Blood (2004)
Global Skin Disease Morbidity and Mortality
Authors: Chante Karimkhani, Robert P. Dellavalle, Luc E. Coffeng, Carsten Flohr, Roderick J. Hay, Sinéad M. Langan, Elaine O. Nsoesie, Alize J. Ferrari, Holly E. Erskine, Jonathan I. Silverberg, Theo Vos, Mohsen Naghavi
Journal: JAMA Dermatology (2017)

Disability secondary to skin conditions is substantial worldwide. The Global Burden of Disease Study 2013 includes estimates of global morbidity and mortality due to skin diseases.To measure the burden of skin diseases worldwide.For nonfatal estimates, data were found by literature search using PubMed and Google Scholar in English and Spanish for years 1980 through 2013 and by accessing administrative data on hospital inpatient and outpatient episodes. Data for fatal estimates were based on vital registration and verbal autopsy data.Skin disease data were extracted from more than 4000 sources including systematic reviews, surveys, population-based disease registries, hospital inpatient data, outpatient data, cohort studies, and autopsy data. Data metrics included incidence, prevalence, remission, duration, severity, deaths, and mortality risk.Data were extracted by age, time period, case definitions, and other study characteristics. Data points were modeled with Bayesian meta-regression to generate estimates of morbidity and mortality metrics for skin diseases. All estimates were made with 95% uncertainty intervals.Disability-adjusted life years (DALYs), years lived with disability, and years of life lost from 15 skin conditions in 188 countries.Skin conditions contributed 1.79% to the global burden of disease measured in DALYs from 306 diseases and injuries in 2013. Individual skin diseases varied in size from 0.38% of total burden for dermatitis (atopic, contact, and seborrheic dermatitis), 0.29% for acne vulgaris, 0.19% for psoriasis, 0.19% for urticaria, 0.16% for viral skin diseases, 0.15% for fungal skin diseases, 0.07% for scabies, 0.06% for malignant skin melanoma, 0.05% for pyoderma, 0.04% for cellulitis, 0.03% for keratinocyte carcinoma, 0.03% for decubitus ulcer, and 0.01% for alopecia areata. All other skin and subcutaneous diseases composed 0.12% of total DALYs.Skin and subcutaneous diseases were the 18th leading cause of global DALYs in Global Burden of Disease 2013. Excluding mortality, skin diseases were the fourth leading cause of disability worldwide.
Abstract P1-02-10: Reduced serum B-cell maturation antigen levels predict poor outcome in metastatic breast cancer patients in a phase 3 randomized 2nd-line hormone therapy trial
Authors: SM Ali, K Leitzel, M Li, K Udd, J Wang, E Sanchez, H Chen, J Berenson, A Lipton
Journal: Cancer Research (2017)

Abstract Background: B-cell maturation antigen (BCMA) is a member of the tumor necrosis factor receptor family and has two ligands, B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL). These ligands activate cell proliferation and inhibit apoptosis of normal and malignant B-cells including in multiple myeloma (MM) cell lines. Berenson et al have recently reported that circulating BCMA levels are elevated in B-cell malignancies and can be used to monitor disease and predict PFS and OS for patients with MM, Waldenstroms's macroglobulinemia and chronic lymphocytic leukemia (CLL). On the other hand, recent studies have shown that serum BCMA levels are very low among patients with MM in complete remission with low antibody levels and those with primary immune deficiencies specifically those with combined variable immune deficiency and X-linked agammaglobulinemia. Studies of the potential role of serum BCMA for patients with solid tumors has not been evaluated to date. Methods: The pretreatment serum from 139 patients with hormone receptor-positive metastatic breast cancer who were enrolled in a phase 3 randomized clinical trial of second-line hormone therapy was evaluated using an ELISA for BCMA. The BCMA ELISA was from R&amp;D Systems (Minneapolis, MN). Serum BCMA was correlated with TTP using categorical serum BCMA cutpoints. Results: Pretreatment serum BCMA levels had a median of 55.61 ng/ml, an interquartile range of 34.20 and 78.79 ng/ml, and full range from 3.99 to 1193.26 ng/ml. In univariate analysis for TTP, reduced serum BCMA correlated with shorter TTP at the following dichotomous cutpoints: 15 ng/ml [HR=2.60, p=0.064, n=6 (4.3%) of patients below cutpoint]; 20 ng/ml [HR=2.88, p=0.005, n=10 (7.2%) of patients below cutpoint]; 25 ng/ml [HR=2.16, p=0.023, n=13 (9.4%) of patients below cutpoint]; and 30 ng/ml [HR=1.77, p=0.016, n=27 (19.4%) of patients below the cutpoint]. Conclusions: In a phase 3 randomized clinical trial of second-line hormone therapy among patients with hormone receptor-positive metastatic breast cancer, reduced pretreatment serum BCMA was associated with shorter TTP. This may be due to the association of reduced serum BCMA with immune deficiency; and, thus, lead to shorter TTP among patients with metastatic breast cancer. Evaluation of serum BCMA as a new biomarker to predict outcomes for breast cancer and other solid tumor patients deserves further study. Citation Format: Ali SM, Leitzel K, Li M, Udd K, Wang J, Sanchez E, Chen H, Berenson J, Lipton A. Reduced serum B-cell maturation antigen levels predict poor outcome in metastatic breast cancer patients in a phase 3 randomized 2nd-line hormone therapy trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-10.
Applying Trauma Transfusion Practices to Nontrauma Care
Authors: Tanya N. Rinderknecht, Sherry M. Wren
Journal: JAMA Surgery (2017)

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Adjuvant Treatment for High-Risk Clear Cell Renal Cancer
Authors: Naomi B. Haas, Judith Manola, Janice P. Dutcher, Keith T. Flaherty, Robert G. Uzzo, Michael B. Atkins, Robert S. DiPaola, Toni K. Choueiri
Journal: JAMA Oncology (2017)

Given recently published results of a 750-patient adjuvant sunitinib trial showing improved disease-free survival (DFS), the appropriate strategy for treating high-risk patients is unclear. We sought to determine whether there is improved disease-free survival benefit to taking the active drug in patients with high-risk (pT3, pT4, node-positive) clear cell renal cancer (ccRCC) in the ASSURE trial (adjuvant sunitinib or sorafenib vs placebo in resected unfavorable renal cell carcinoma [RCC]), the largest adjuvant trial published to date.To evaluate DFS and overall survival (OS) in ccRCC high-risk patients randomized to sunitinib or sorafenib vs placebo among patients with stages comparable to other high-risk adjuvant trials.The DFS and OS at 10 years postactivation were calculated for 1069 patients in US and Canadian cooperative groups with high-risk patients who had ccRCC histology and pT3, pT4, or node-positive disease accrued between 2006 and 2010 to the double-blind randomized placebo-controlled phase 3 trial. Outcome analyses by dose quartiles of these patients receiving sunitinib or sorafenib were also performed.Patients received 1 year of adjuvant sunitinib (50 mg), sorafenib (800 mg) daily, or equivalent placebo. The study was amended for patient intolerance to sunitinib (37.5 mg), sorafenib (400 mg) daily, or equivalent placebo with mandatory dose escalation if no serious adverse effects were experienced.Disease-free survival, defined as time from randomization to recurrence, second primary cancer, or death.Of 1069 patients, 358 (243 [67.9%] men, 115 [32.1%] women) received sunitinib, 355 (248 [69.9%] men, 107 [30.1%] women) received sorafenib, and 356 (254 [71.3%] men, 102 [28.7%] women) received placebo as adjuvant therapy. The mean (SD) age for each group was 58.3 (10.6) years, 56.8 (10.3) years, and 57.5 (10.4) years, respectively. Five-year DFS rates were 47.7%, 49.9%, and 50.0%, respectively for sunitinib, sorafenib, and placebo (HR, 0.94 for sunitinib vs placebo; and HR, 0.90; 97.5% CI, 0.71-1.14 for sorafenib vs placebo), with 5-year OS of 75.2%, 80.2%, and 76.5% (HR, 1.06; 97.5% CI, 0.78-1.45; P = .66, sunitinib vs placebo; and HR, 0.80; 97.5% CI, 0.58-1.11; P = .12 for sorafenib vs placebo). There was no difference by dose quartile.Neither prognostic category of the tumor nor dose intensity of therapy altered the lack of difference in DFS or OS in this population of patients with high-risk ccRCC.clinicaltrials.gov Identifier: NCT00326898.
CD26 Inhibition Preferentially Enhances In Vitro Migration of G-CSF + Plerixafor (AMD3100) Mobilized PB as Compared to G-CSF Mobilized PB In Multiple Myeloma Autografts.
Authors: Eun-Sun Yoo, Sucheta Jagan, Sridevi Palaparthy, Mary A Enriquez, Karen Samuels, Sarah Walters, Elizabeth Mieras, Laura A Paganessi, Chu-Myong Seong, Elizabeth Shima Rich, Henry C. Fung, Kent W. Christopherson
Journal: Blood (2010)
Progesterone Receptor Isoform Ratio: A Breast Cancer Prognostic and Predictive Factor for Antiprogestin Responsiveness
Authors: Paola A. Rojas, María May, Gonzalo R. Sequeira, Andrés Elia, Michelle Alvarez, Paula Martínez, Pedro Gonzalez, Stephen Hewitt, Xiaping He, Charles M. Perou, Alfredo Molinolo, Luz Gibbons, Martin C. Abba, Hugo Gass, Claudia Lanari
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Compelling evidence shows that progestins regulate breast cancer growth. Using preclinical models, we demonstrated that antiprogestins are inhibitory when the level of progesterone receptor isoform A (PR-A) is higher than that of isoform B (PR-B) and that they might stimulate growth when PR-B is predominant. The aims of this study were to investigate ex vivo responses to mifepristone (MFP) in breast carcinomas with different PR isoform ratios and to examine their clinical and molecular characteristics. Methods: We performed human breast cancer tissue culture assays (n = 36) to evaluate the effect of MFP on cell proliferation. PR isoform expression was determined by immunoblotting (n = 282). Tumors were categorized as PRA-H (PR-A/PR-B ≥ 1.2) or PRB-H (PR-A/PR-B ≤ 0.83). RNA was extracted for Ribo-Zero-Seq sequencing to evaluate differentially expressed genes. Subtypes and risk scores were predicted using the PAM50 gene set, the data analyzed using The Cancer Genome Atlas RNA-seq gene analysis and other publicly available gene expression data. Tissue microarrays were performed using paraffin-embedded tissues (PRA-H n = 53, PRB-H n = 24), and protein expression analyzed by immunohistochemistry. All statistical tests were two-sided. Results: One hundred sixteen out of 222 (52.3%) PR+ tumors were PRA-H, and 64 (28.8%) PRB-H. Cell proliferation was inhibited by MFP in 19 of 19 tissue cultures from PRA-H tumors. A total of 139 transcripts related to proliferative pathways were differentially expressed in nine PRA-H and seven PRB-H tumors. PRB-H and PRA-H tumors were either luminal B or A phenotypes, respectively (P = .03). PRB-H cases were associated with shorter relapse-free survival (hazard ratio [HR] = 2.70, 95% confidence interval [CI] = 1.71 to 6.20, P = .02) and distant metastasis–free survival (HR = 4.17, 95% CI = 2.18 to 7.97, P < .001). PRB-H tumors showed increased tumor size (P < .001), Ki-67 levels (P < .001), human epidermal growth factor receptor 2 expression (P = .04), high grades (P = .03), and decreased total PR (P = .004) compared with PRA-H tumors. MUC-2 (P < .001) and KRT6A (P = .02) were also overexpressed in PRB-H tumors. Conclusion: The PRA/PRB ratio is a prognostic and predictive factor for antiprogestin responsiveness in breast cancer.