tbuckley/cabot-search huggingface dataset:
Late non-malignant complications in aggressive non-Hodgkin's lymphoma across four randomized EORTC-trials
Authors: E. C. Moser, H. C. Kluin-Nelemans
Journal: Journal of Clinical Oncology (2004)

6528 Background: Late toxicity has become an important factor influencing the management in survivors of childhood cancer and Hodgkin lymphoma. Although, significant proportions of patients with aggressive non-Hodgkin's lymphoma (NHL) become long-term survivors, a systematic analysis on late non-malignant toxicity in these patients is lacking. An EORTC database of these patients, consistently treated with CHOP-like regimens since 1980, offered the possibility to explore late complications in detail. Methods: Using detailed questionnaires, late complications (>2 years after start therapy) of 757 patients (90%) with a median follow-up of 9.4 (2.1–20.4) years were scored. The cumulative incidences of complications were computed in a competing risk model by Gray (death being the competing event) to avoid bias caused by the high percentage of NHL-related deaths. Risk factors were estimated in a Cox proportional-hazards model, but also evaluated with the Gray-test. Results: Late non-neoplastic complications were found in 46% of the patients, see Table. Conclusions: Half of the patients with aggressive NHL experience late non-neoplastic, mainly cardiovascular or gonadal, complications. Regulation of hypertension and quitting smoking after treatment may preserve a better quality of life. No significant financial relationships to disclose.
Association Between Unconventional Natural Gas Development in the Marcellus Shale and Asthma Exacerbations
Authors: Sara G. Rasmussen, Elizabeth L. Ogburn, Meredith McCormack, Joan A. Casey, Karen Bandeen-Roche, Dione G. Mercer, Brian S. Schwartz
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Asthma is common and can be exacerbated by air pollution and stress. Unconventional natural gas development (UNGD) has community and environmental impacts. In Pennsylvania, UNGD began in 2005, and by 2012, 6253 wells had been drilled. There are no prior studies of UNGD and objective respiratory outcomes. <h3>Objective</h3> To evaluate associations between UNGD and asthma exacerbations. <h3>Design</h3> A nested case-control study comparing patients with asthma with and without exacerbations from 2005 through 2012 treated at the Geisinger Clinic, which provides primary care services to over 400 000 patients in Pennsylvania. Patients with asthma aged 5 to 90 years (n = 35 508) were identified in electronic health records; those with exacerbations were frequency matched on age, sex, and year of event to those without. <h3>Exposures</h3> On the day before each patient’s index date (cases, date of event or medication order; controls, contact date), we estimated activity metrics for 4 UNGD phases (pad preparation, drilling, stimulation [hydraulic fracturing, or “fracking”], and production) using distance from the patient’s home to the well, well characteristics, and the dates and durations of phases. <h3>Main Outcomes and Measures</h3> We identified and defined asthma exacerbations as mild (new oral corticosteroid medication order), moderate (emergency department encounter), or severe (hospitalization). <h3>Results</h3> We identified 20 749 mild, 1870 moderate, and 4782 severe asthma exacerbations, and frequency matched these to 18 693, 9350, and 14 104 control index dates, respectively. In 3-level adjusted models, there was an association between the highest group of the activity metric for each UNGD phase compared with the lowest group for 11 of 12 UNGD-outcome pairs: odds ratios (ORs) ranged from 1.5 (95% CI, 1.2-1.7) for the association of the pad metric with severe exacerbations to 4.4 (95% CI, 3.8-5.2) for the association of the production metric with mild exacerbations. Six of the 12 UNGD-outcome associations had increasing ORs across quartiles. Our findings were robust to increasing levels of covariate control and in sensitivity analyses that included evaluation of some possible sources of unmeasured confounding. <h3>Conclusions and Relevance</h3> Residential UNGD activity metrics were statistically associated with increased risk of mild, moderate, and severe asthma exacerbations. Whether these associations are causal awaits further investigation, including more detailed exposure assessment.
Abstract 476: Differential prognostic value of MYC immunohistochemistry in papillary RCC subtypes
Authors: Julia Bellut, Simone Bertz, Elke Nolte, Christine Stoehr, Iris Polifka, Edwin Herrmann, Rudolf Jung, Arndt Hartmann, Bernd Wullich, Helge Taubert, Sven Wach
Journal: Cancer Research (2016)

Abstract Introduction The histomorphological classification of type 1 and type 2 papillary renal cell carcinomas (pRCCs) has substantially improved the prognostication of patients’ long-term outcome. We previously established microRNA (miRNA) expression profiles of type1 and type 2 pRCCs and, based upon the results, hypothesize a differential expression of the MYC proto-oncogene in pRCCs. Material and methods An multi-institutional tissue microarray with more than 200 histomorphological classified pRCCs was acquired from the PANZAR consortium. Immunohistochemistry for MYC, the MYC-induced nuclear antigen MINA53 and Ki67 was performed. The prognostic value for patients’ long-term survival was examined using uni- and multivariate survival models. Results As expected, a pRCC type 2 morphology was associated with reduced overall and cancer-specific survival. Interestingly, pRCCs with a mixed type 1/2 morphology showed an even worse clinical outcome. When combining the pRCC morphology and immunohistochemical staining, only the combination of morphology and MYC staining patterns was able to further sub-stratify the group of pRCC type 1 tumors in a good and worse prognosis group. None of the patients with pRCC1 tumors and the favorable MYC staining pattern (&amp;gt;44% of all pRCC type 1 tumors) suffered a tumor-related death. Patients with pRCC type 1 tumors and the adverse MYC staining pattern had an 4.5-fold elevated risk of death (multivariate corrected for pathological tumor stage). Conclusions Although a pRCC type 1 histomorphology is regarded as a favorable prognostic factor, associated with good clinical outcome, still patients die of tumor-related causes. We conclude, that in particular for patients with pRCC type 1 tumors, MYC immunohistochemistry is able to provide additional prognostic information for a sub-stratification of this patient population. This knowledge could be used for the establishment of risk-stratified follow-up schemes for patients after surgical treatment. Citation Format: Julia Bellut, Simone Bertz, Elke Nolte, Christine Stoehr, Iris Polifka, Edwin Herrmann, Rudolf Jung, Arndt Hartmann, Bernd Wullich, Helge Taubert, Sven Wach. Differential prognostic value of MYC immunohistochemistry in papillary RCC subtypes. [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 476.
DIRECT ESTIMATES OF CANCER MORTALITY DUE TO LOW-DOSES OF IONIZING-RADIATION - AN INTERNATIONAL STUDY
Authors: E Cardis, E S Gilbert, L Carpenter, G Howe, I Kato, E C Lave, B K Armstrong, V Beral, G Cowper, A Douglas, J Fix, S Fry, J Kaldor, C Lave, L Salmon, P G Smith, G Voelz, L Wiggs
Journal: The Lancet (1994)
Abstract 2520: IRS-1/LC3 nuclear structures and glioblastoma drug resistance
Authors: Adam Lassak, Dorota Wyczechowska, Anna Wilk, Adriana Zapata, Mathew Dean, Luis DelValle, Jann N. Sarkaria, Augusto Ochoas, Francesca Peruzzi, Krzysztof Reiss
Journal: Cancer Research (2016)

Abstract Drug resistance and frequent tumor relapses are the major obstacles in glioblastoma therapy, and recurrent tumors are practically incurable. We previously reported that insulin receptor substrate 1 (IRS-1), which is a typical signaling molecule for insulin and insulin-like growth factor 1 receptors, can translocate to nucleus, and that nuclear IRS-1 (nIRS-1) was found in different tumor cells, including glioblastomas. To unravel its function, we employed glioblastoma cell culture, animal models, and clinical samples. Using confocal imaging, molecular cloning, subcellular fractionation, mass spectrometry, gene expression analysis, and different approaches to verify protein-protein interactions, we demonstrate for the first time that nIRS-1 can form complex nuclear structures in a restricted number of cancer cells in glioblastoma biopsies and in intracranial glioblastoma xenografts. We also demonstrated the formation of highly organized ring-like structures in several cell lines, following ectopic expression of IRS-1 cloned in frame with nuclear localization signal (NLS-IRS-1). In these nuclear structures IRS-1 localizes at the periphery, and the core of the structure harbors a key autophagy protein, LC3; however, other autophagy proteins or biological membranes were not detected. In living cells expressing NLS-IRS-1-GFP fusion protein, IRS-1/LC3 structures are highly dynamic. They rapidly exchange IRS-1 molecules with nucleoplasm and interact with other nuclear complexes including BMI1-positive Polycomb bodies, PML bodies and Cajal bodies. Importantly, clones and mixed populations of cells expressing the NLS-IRS-1 and capable of forming the IRS-1/LC3 ring-like structures undergo extensive remodeling of gene expression, which suggests a transition to stem-like phenotype and associated resistance to several different anticancer drugs, including temozolomide. This is the first demonstration of IRS-1/LC3 nuclear complexes, which are highly dynamic and may play a role in epigenetic remodeling of glioblastoma cells towards stemness. Further studies are required to determine detailed molecular composition and to explain how these new nuclear structures function. Citation Format: Adam Lassak, Dorota Wyczechowska, Anna Wilk, Adriana Zapata, Mathew Dean, Luis DelValle, Jann N. Sarkaria, Augusto Ochoas, Francesca Peruzzi, Krzysztof Reiss. IRS-1/LC3 nuclear structures and glioblastoma drug resistance. [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 2520.
Lapatinib (L) plus capecitabine (C) in HER2+ advanced breast cancer (ABC): Genomic and updated efficacy data
Authors: C. E. Geyer, A. Martin, B. Newstat, M. A. Casey, M. S. Berger, C. R. Oliva, S. D. Rubin, S. Stein, D. Cameron
Journal: Journal of Clinical Oncology (2007)

1035 Background: EGF100151 demonstrated L+C improved TTP relative to C alone in women with HER2 positive, trastuzumab- exposed ABC (Geyer, NEJM;355(26):2006). We report updated efficacy data and results of correlative studies to determine if gene expression levels in the 5-FU and HER pathways are associated with clinical benefit in L+C. Methods: Tumor blocks are available on 217/399 patients, and so far sufficient mRNA has been extracted from 64/217 blocks using qRT-PCR. Tumors were evaluated for expression of HER1–4, TS, TP, PTEN, c-MYC. In addition to univariate and multivariate analyses, a SpotFire™ DecisionTree analysis was performed to determine the genes most significantly associated with RR; these genes were further analyzed for association with TTP. Results: Updated efficacy results through April 3, 2006 demonstrate: TTP L+C (27 wks)vs C (19 wks) HR 0.57 [0.43,0.77] p=0.00013; ORR L+C (24%)vs C (14%), Odds Ratio 1.9[1, 1.34] p=0.017; OS L+C vs C HR 0.78 [0.55,1.12] p=0.177; progression in CNS L+C (2%)vs C (11%) p=0.0445. Preliminary analysis of the first 64 samples indicates that elevated baseline mRNA expression of HER2 is associated with a higher RR and longer TTP (p&lt;0.0001) with L+C. The opposite was seen in the C arm, where elevated HER2 mRNA expression seemed to predict for a poorer outcome. Analyses of ErbB3,4, PTEN and MYC as well as TS did not correlate with RR. Conclusion: The updated efficacy results confirm the prior demonstrated benefit of L+Cvs C and provide the first evidence for a systemic anti-HER2 therapy to have an effect on the development of CNS metastases. This preliminary analysis suggests a correlation between elevated HER2 mRNA levels and RR/TTP. Further investigation, including full genome microarray analysis of samples is ongoing. [Table: see text]
Novel educational interventions in residency increase knowledge of chronic liver disease and career interest in hepatology
Authors: Adam E. Mikolajczyk, Jeanne M. Farnan, John F. McConville, Donald M. Jensen, K. Gautham Reddy, Helen S. Te, Nancy Reau, Andrew I. Aronsohn
Journal: Hepatology (2016)

There is an increasing burden of chronic liver disease (CLD) in the United States but a significant shortage of hepatologists. Thus, it is necessary to develop new recruitment strategies to the field of hepatology as well as ensure that non‐gastroenterology‐trained physicians are able to capably assist in the care of CLD. We established a novel, nonelective, inpatient hepatology rotation that uses required modules in the American Association for the Study of Liver Diseases Curriculum and Training‐First Hepatitis B and C curriculums as well as in Liver Learning . A paper‐based anonymous assessment was distributed to the inaugural 25 postgraduate years 2 and 3 internal medicine residents before and after the 2‐week rotation over the course of 1 year. Both the prerotation and postrotation assessments included validated multiple‐choice questions and Likert‐type questions, which evaluated self‐perceived knowledge and comfort with managing CLD. The mean comfort level (1 = not at all comfortable/strongly disagree, 5 = very comfortable/strongly agree) of managing several common liver diseases increased significantly after completion of the rotation (i.e., cirrhosis 2.8 versus 3.8, P &lt; 0.001; hepatitis B 2.4 versus 3.4, P = 0.001; hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus 4.0, P &lt; 0.001; liver transplant care 2.1 versus 3.4, P &lt; 0.001). There was also a significantly increased interest in hepatology as a career (2.6 versus 3.0, P = 0.03). Finally, the mean percentage of multiple‐choice questions answered correctly on the pretest was 62% and posttest was 77% ( P = 0.02). Conclusion : Our novel curriculum and nonelective hepatology rotation has effectively demonstrated improvement in internal medicine residents' comfort with and knowledge of CLD, and increased career interest in hepatology was also observed after completion of the curriculum, which suggests that more exposure to CLD could positively impact recruitment to the workforce; larger, multicenter studies are needed to validate these results. (H epatology 2016;64:2210‐2218).
Response to Comment on Schwartz et al. The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema. Diabetes Care 2016;39:179–186
Authors: Stanley S. Schwartz, Solomon Epstein, Barbara E. Corkey, Struan F.A. Grant, James R. Gavin, Richard B. Aguilar
Journal: Diabetes Care (2016)

We thank Drs. Kalra and and Baruah for their comments (1) on our article (2) in an effort improve the utility of our proposed β-cell–centric classification.

We agree that “treatment” is more important than “classification.” We find it frustrating that governments and insurers often think otherwise, limiting therapies of choice on the basis of labels of diabetes mellitus (DM) that are not optimally useful. Thus a “precision medicine” classification system that identifies specific causes of hyperglycemia and their corresponding therapies augurs for payment coverage parity across the range of glucose-lowering medications for patients with any form of DM.

Although the insulin-to-glucagon ratio (IGR) construct is interesting and could serve as a “marker” to help choose between various therapies in our approach, our …
Reducing Health Inequities in the U.S.
Authors: Uchechukwu K.A. Sampson, Robert M. Kaplan, Richard S. Cooper, Ana V. Diez Roux, James S. Marks, Michael M. Engelgau, Emmanuel Peprah, Helena Mishoe, L. Ebony Boulware, Kaytura L. Felix, Robert M. Califf, John M. Flack, Lisa A. Cooper, J. Nadine Gracia, Jeffrey A. Henderson, Karina W. Davidson, Jerry A. Krishnan, Tené T. Lewis, Eduardo Sanchez, Naomi L. Luban, Viola Vaccarino, Winston F. Wong, Jackson T. Wright, David Meyers, Olugbenga G. Ogedegbe, Letitia Presley-Cantrell, David A. Chambers, Deshirée Belis, Glen C. Bennett, Josephine E. Boyington, Tony L. Creazzo, Janet M. de Jesus, Chitra Krishnamurti, Mia R. Lowden, Antonello Punturieri, Susan T. Shero, Neal S. Young, Shimian Zou, George A. Mensah
Journal: Journal of the American College of Cardiology (2016)
Abstract 3675: Loss of Pkhd1 promotes intestinal tumorigenesis in Apc mice
Authors: Bo Hu, Wei Li, Qingchao Qiu, Zhengxi He, Xiusheng He, Guanqing Wu
Journal: Cancer Research (2016)

Abstract Objectives: PKHD1 (Polycystic Kidney and Hepatic Disease 1), a causal gene for ARPKD (Autosomal Recessive Polycystic Kidney Disease), has been proposed to play a role in the colorectal carcinogenesis. This study is to explore the role of PKHD1 in colorectal carcinogenesis. Methods: Mouse model with Pkhd1 mutation (Pkhd1-/-) was used to mate with ApcMin/+ mouse in the same genetic background. The resulting ApcMin/+ mice with and without Pkhd1-/- alleles were randomly sorted into two experimental groups (i.e. Pkhd1-/-;ApcMin/+ n = 36; ApcMin/+ n = 23). Tumorigenic susceptibility of Pkhd1-/-;ApcMin/+ and ApcMin/+ mice was compared. The number, size, pathology of intestinal tumors in the mice were analyzed at the age of 1-, 3-, and 6-month. The survival rates were investigated in the two groups of mice. Results: There was no statistical difference in tumor number and size between 1-month-old ApcMin/+ and Pkhd1-/-;ApcMin/+ mice. However, the number and size of the intestinal tumors in 3- and 6-month-old Pkhd1-/-;ApcMin/+ mice were significantly increased compared with those of ApcMin/+ mice alone (P = 0.017,P = 0.022). In addition, the pathology of tumors was also analyzed between the two groups. There was no pathological difference between 1-month-old ApcMin/+ and Pkhd1-/-;ApcMin/+ mice. However, at 3-month-old, Pkhd1-/-;ApcMin/+ mice exhibited severer atypical hyperplasia in the intestinal tumor than those of ApcMin/+ mice; while at 6-month-old, focal necrosis were often seen in intestinal tumors of Pkhd1-/-;ApcMin/+ mice, but none from ApcMin/+ mice. Strikingly, tumor infiltration into the muscular mucosa was also seen in a 6-month-old Pkhd1-/-;ApcMin/+ mice. There was no statistically survival difference between ApcMin/+ and Pkhd1-/-;ApcMin/+ mice. Conclution: Loss of Pkhd1 promotes the intestinal tumorigenesis and induces tumor malignant transformation in ApcMin/+ mice. Citation Format: Bo Hu, Wei Li, Qingchao Qiu, Zhengxi He, Xiusheng He, Guanqing Wu. Loss of Pkhd1 promotes intestinal tumorigenesis in Apc 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 3675.
Abstract 3131: Expression of FGF19/FGFR4 related biomarkers in hepatocellular carcinoma
Authors: Zhong-Zhe Lin, Yung-Ming Jeng, Chiun Hsu, I-Lun Tsai, Kuan-Yu Chen, Fu-Chang Hu, Chih-Hung Hsu, Hey-Chi Hsu, Ann-Lii Cheng
Journal: Cancer Research (2016)

Abstract Background: Fibroblast growth factor 19 (FGF19) and fibroblast growth factor receptor 4 (FGFR4) signaling play critical roles in hepatocarcinogenesis. This study explored the expression and clinical significance of FGF19/FGFR4 related signaling molecules in hepatocellular carcinoma (HCC). Method: We examined the mRNA expression of FGF19, FGFR4, klotho-beta (KLB), cyclin D1 (CCND1), and FGF4 in 151 surgically resected, primary unifocal HCC using quantitative real-time PCR analysis. The correlation of gene amplification and mRNA overexpression for FGF19 and FGF4 was investigated using a real-time PCR based copy number assay. FGF19 amplification was verified using fluorescence in situ hybridization. Univariate and multivariate analyses were performed to evaluate the prognostic value of these biomarkers for tumor recurrence and survival of patients. Results: Overexpression of FGF19, FGFR4, KLB, CCND1, and FGF4 mRNA was detected in 40%, 32%, 26%, 15%, and 35% of 151 tumors, respectively. In multivariate analyses, large tumor size (&amp;gt; 12.7 cm) and advanced tumor stage (stage ≥ II) independently predict worse patient survival. Using generalized additive models, we found mRNA expression of FGFR4 and KLB was significantly associated large tumor size (&amp;gt; 12.7 cm); mRNA expression of FGF19 and KLB was significantly associated advanced tumor stage (stage ≥ II). Furthermore, gene amplification of FGF19 and FGF4 significantly correlated to their mRNA overexpression (P = 0.006 for FGF19; P = 0.039 for FGF4). Conclusions: Overexpression of FGF19/FGFR4 related biomarkers is frequently found in HCC. Overexpression of FGF19 and FGF4 mRNA significantly correlates to their gene amplification. Expression status of FGFR4, KLB, and FGF19 may determine patient survival through their impact on tumor size (FGFR4 and KLB) and tumor stage (FGF19 and KLB). Citation Format: Zhong-Zhe Lin, Yung-Ming Jeng, Chiun Hsu, I-Lun Tsai, Kuan-Yu Chen, Fu-Chang Hu, Chih-Hung Hsu, Hey-Chi Hsu, Ann-Lii Cheng. Expression of FGF19/FGFR4 related biomarkers in hepatocellular carcinoma. [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 3131.