tbuckley/cabot-search huggingface dataset:
Abstract 3731: The course of fatigue and its correlates in colorectal cancer survivors: A prospective cohort study of the PROFILES registry
Authors: Olga Husson, Floortje Mols, Lonneke van de Poll-Franse, Melissa Thong
Journal: Cancer Research (2015)

Abstract Objective: Cancer survivors who remain fatigued during long-term follow-up are at risk for worse health outcomes. To achieve personalized management of cancer-related fatigue, insight into its correlates among long-term survivors is needed to identify survivors at risk of remaining fatigued and also the correlates for intervention. Methods: Colorectal cancer (CRC) survivors diagnosed between 2000-2009, as registered in the population-based Eindhoven Cancer Registry, completed three annual surveys that included the Fatigue Assessment Scale, the EORTC Quality of Life (EORTC-QLQ-C30) questionnaire, Hospital Anxiety and Depression Scale, and physical activity levels. Linear mixed-model were used to assess the course of fatigue and identify its correlates. Results: 1734 (66%) CRC survivors completed at least 2 surveys. Fatigue levels were relatively stable over time. Being female, young (≤65 years old), single, low education, chemotherapy treatment, or having ≥1 comorbid condition was associated with higher fatigue scores. Years since diagnosis, radiotherapy treatment and disease stage were not related to fatigue scores. Significant between- and within-subjects effects were found for well-being factors (social, emotional, and cognitive function, and global quality of life), symptoms (anxiety, depression, pain, and insomnia) and functional status (physical and role function, and physical activity levels) in relation to fatigue. Differences in fatigue could be largely attributed to behavior/well-being (59%) and functional status (37%), and to some extent to sociodemographic (4%) and clinical (8%) factors. Conclusion: This study showed that behavior/well-being and functional status explained more variance in fatigue levels among CRC survivors than sociodemographic and clinical factors. Citation Format: Olga Husson, Floortje Mols, Lonneke van de Poll-Franse, Melissa Thong. The course of fatigue and its correlates in colorectal cancer survivors: A prospective cohort study of the PROFILES registry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3731. doi:10.1158/1538-7445.AM2015-3731
167. Genome Editing to Generate the First Mouse Model of Alpha-One Antitrypsin Deficiency, the Leading Cause of Genetic COPD
Authors: Florie Borel, Brynn Cardozo, Andrew Cox, Weiying Li, Andrew Hoffman, Mai ElMallah, Christian Mueller
Journal: Molecular Therapy (2016)

Alpha-one antitrypsin (AAT) deficiency is a common autosomal co-dominant genetic disorder. This condition affects 1:2500 individuals of European ancestry, leading to the development of lung and liver disease. Within North American and Northern European populations, an estimated 4% of individuals are carriers of mutant alleles. AAT deficiency presents with an emphysema phenotype in the lungs of older subjects. AAT deficient subjects can also suffer from liver disease of varying severity; however, lung disease is the principle cause of death. AAT is a protease inhibitor predominantly synthesized in the liver that belongs to the serine protease inhibitor (serpin) family. Upon secretion into the blood stream, AAT enters the lungs where it inactivates excess neutrophil elastase, thereby preventing damage to the alveoli. Mutations of the Serpina1 gene can lead to reduced serum levels of AAT and decreased protein functionality, allowing for unrestricted elastin breakdown, pulmonary inflammation and eventual emphysema. Currently, an animal model simulating the lung condition does not exist, which severely limits the development of therapeutics. This is due to the higher genomic complexity of mice compared to humans. Indeed due to amplification events, C57BL/6 mice have five genes that are homologous to human SERPINA1. To address this we generated a quintuple gene knockout using CRISPR/Cas9 system via zygote microinjection. We generated three founding lines in which all 5 copies of the gene were disrupted. Mice from all three lines demonstrate absence of hepatic and circulatory AAT protein as well as a reduced capability to inactivate neutrophil elastase. We also characterized the lung phenotype in response to a lipopolysaccharide challenge, where the model recapitulated many characteristics of the human lung disease including decreased elastance and increased compliance, and lung morphometry was also affected. Genomic and transcriptomic characterization will be presented. Future work will include challenges with cigarette smoke, a well-known disease accelerator in patients. Further, the ongoing generation of a new transgenic model carrying both the quintuple disruption of the murine Serpina1 genes and a single copy of the Z variant of human SERPINA1 will bring to the field the ultimate disease model that will finally allow researchers to evaluate the effects of liver-directed gene augmentation in the presence of Z-AAT polymers.
A phase II study of neoadjuvant gemcitabine/5-fluorouracil followed by 5-fluorouracil/oxaliplatin concurrent with radiation in patients with locally advanced pancreatic cancer.
Authors: C. Lin, B. M. Kos, A. R. Sasson, J. L. Meza, J. L. Grem
Journal: Journal of Clinical Oncology (2011)

259 Background: We designed this phase II trial to determine the efficacy and safety of a neoadjuvant regimen involving gemcitabine, infusional 5-fluorouracil (5-FU), oxaliplatin and radiation therapy (RT) in patients with locally advanced pancreatic adenocarcinoma Methods: Induction chemotherapy (CT) consisted of two 3-week cycles of weekly gemcitabine with 24-hour continuous infusion of 5 FU for 2 of 3 weeks. Chemoradiation (CRT) consisted of RT of 50.4 Gy in 28 fractions or 50 Gy in 25 fractions and weekly oxaliplatin with 24-hour continuous infusion of 5 FU throughout RT. The first 7 patients also received celecoxib 200 mg BID throughout induction CT and CRT. Upon completion of CRT, surgical candidates underwent a pancreatoduodenectomy. Response rate was assessed according to RECIST criteria 4 weeks after the end of CRT. CTC AE v3 was used to grade the acute side effects. The failure-free survival (FFS), overall survival (OS) and median survival were analyzed by the Kaplan Meier method. Results: Twenty-nine patients who had borderline resectable pancreatic adenocarcinoma at the UNMC were enrolled and received induction CT. Twenty-four patients completed CRT. Nineteen patients had surgical exploration: 4 were unresectable, 6 had intra-abdominal metastases, and 9 had resection (seven had R0 resection, 2 had R1 resection, and 6 had negative nodes). The median follow up was 27 months. There were maximum 48% acute grade 3-4 toxicities during induction CT and CRT. The median FFS and OS were 7 and 10 months and the 2-year FFS and OS were 17% and 28%. Median OS and FFS for patients with and without resection was 26 vs. 9 months, p=0.06; and 19 vs. 5 months, p=0.01. Patients with CA19-9 above 90 U/L throughout treatment had significantly shorter FFS and OS than patients with CA19-9 less than 90 throughout treatment or had a decline from baseline to less than 90 after treatment. Conclusions: Induction gemcitabine/5-FU followed by 5-FU/oxaliplatin concurrent with RT led to down staging in 31% patients with subsequent resection. Further innovative strategies are needed to improve the outcome of patients with locally advanced pancreatic cancer. No significant financial relationships to disclose.
Prior Treatment with Alemtuzumab Interferes with T-Cell Engraftment After Allogeneic Stem Cell Transplantation in Patients with Chronic Lymphocytic Leukemia.
Authors: Johannes Schetelig, Christian Thiede, Alexander Kiani, Uwe Platzbecker, Uta Oelschlaegel, Matthias Haenel, Gaby Geissler, Rainer Schwerdtfeger, Karin Kolbe, Martin Kaufmann, Matthias Zeis, Kerstin Schaefer-Eckart, Wolfgang Siegert, Gerhard Ehninger
Journal: Blood (2009)
“Green oncology”: a new paradigm for medical oncology
Authors: G. Porcile, E. Aitini, S. Bretti, S. Crispino, C. Oliani, R. Romizi, D. Cova, F. Savia, M. Clerico, S. Palazzo, R. Labianca, F. Adami
Journal: Annals of Oncology (2015)
Impact of HFE mutations on cardiac status in survivors of childhood high-risk ALL: Dana-Farber Cancer Institute Childhood ALL 05-159.
Authors: S. E. Lipshultz, S. R. Lipsitz, J. Kutok, T. L. Miller, S. D. Colan, D. S. Neuberg, S. E. Dahlberg, L. B. Silverman, J. M. Henkel, V. I. Franco, S. E. Sallan
Journal: Journal of Clinical Oncology (2011)

9508 Background: Doxorubicin (DOX) chemotherapy has been associated with progressive cardiac dysfunction. Laboratory studies suggest DOX-induced cardiac damage may be due to the formation of DOX-iron complexes, leading to free radical formation. Individuals with hereditary hemochromatosis (HH), a genetic disorder that causes increased iron levels, may be at greater risk for developing DOX-associated cardiotoxicity. Methods: The Dana-Farber Cancer Institute Childhood Acute Lymphoblastic Leukemia (ALL) Consortium collected peripheral blood from 185 long-term survivors of high-risk ALL to assess the 2 most frequent allelic variants of the HFE gene associated with HH: C282Y and H63D. Genomic DNA was sequenced using a clinically validated kit from Biotage Inc (PyroMark HFE Cat#40-0053) run on a Pyrosequencer instrument (PSQ HS 96, Biotage Inc) and by taqman and sequenom SNP assay. Echocardiography assessed left ventricular (LV) structure and function. Serum cardiac troponin-T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) assayed during therapy reflect myocardial injury and cardiomyopathy, respectively. Z scores were derived by comparison to a normal healthy population. Results: 21% (39/185) of patients were heterozygous for H63D; 2 were homozygous. 9% (17/185) of patients were heterozygous for C282Y; 1 was homozygous. HFE mutations were not significantly associated with elevations in cTnT or NT-proBNP. At 2 years post randomization, mean LV fractional shortening, LV mass, and LV end diastolic posterior wall thickness z scores were significantly worse than normal for children who were heterozygous (-0.62, SD 1.35, p=0.03; -0.71, SD 0.85, p<0.001; -0.65, SD 1.53, p=0.04, respectively), but not for those who were wild type, except for LV mass (-0.50, SD 1.2, p=0.003). Homozygotes were not included in the analysis due to small numbers. Conclusions: The frequency of HFE mutations in these patients is similar to the general population. HFE heterozygotes showed significantly lower LV function, mass and wall thickness compared to a normal population. These results support the need for future research on the role of these mutations in DOX-induced cardiotoxicity.
Incomplete Platelet Dense Granule Formation in Normal Neonates.
Authors: Walter H. Kahr, Shoma Baidya, Animitra Das, Ayca Toprak, Hilary Christensen, Fanny Meulman, Margaret L. Rand, Fred G. Pluthero, David Chitayat, Prakeshkumar Shah, Victor S. Blanchette
Journal: Blood (2007)
18F-FDG PET/CT in the Staging and Management of Breast Cancer
Authors: JR Garcia, Cristina Pérez, Pere Bassa, Laia Capdevila, Francisco Ramos, Vicens Valenti
Journal: Clinical Nuclear Medicine (2016)

In hormone receptor-positive locally advanced breast cancer, endocrine therapy becomes an integral part of the therapeutic strategy. There are now significant numbers of available hormonal directed compounds, including selective aromatase and mTOR inhibitors, which allow an important therapeutic advance in these patients. Sequential F-FDG PET/CT studies provided essential information regarding response to different treatments, including targeted therapies, and adverse therapeutic effects that helped to better define the right moment to implement each therapeutic approach.
Abstract LB-303: Identification of a mammalian sterile-20 like kinase 4 (MST4) inhibitor to target pituitary tumorigenesis
Authors: Weipeng Xiong, Chris Matheson, Donald S. Backos, Mei Xu, Katja Kiseljak-Vassiliades, Smita Salian-Mehta, Philip Reigan, Margaret E. Wierman
Journal: Cancer Research (2015)

Abstract Pituitary tumors of the gonadotrope lineage are often large and invasive, resulting in hypopituitarism. There are no medical treatments currently available. Using a combined genetic and genomic screen of human pituitary tumor samples, we identified the Mammalian sterile-20 like kinase 4 (MST4) as a pro-tumorigenic effector, driving increased pituitary cell proliferation and survival in response to a hypoxic microenvironment. MST4 is a member of the germinal center kinase III subfamily of Ste-20 kinases with limited data available concerning its role in tumorigenesis. To identify selective inhibitors of the MST4 kinase, computational-based virtual library screening was employed to dock the commercially available SelleckChem kinase inhibitor library into the ATP binding site of the MST4 crystal structure. Several candidate MST4 kinase inhibitors were identified with the potential to bind with high affinity. Using a newly developed TRFRET in vitro kinase assay, one of the small molecule compounds exhibited a potent inhibition of the MST4 kinase (IC50 = 6.18 nM +/- 2.2 nM). To determine the ability of this inhibitor to antagonize MST4 actions, a hypoxic LβT2 gonadotrope pituitary cell model was used. Under chronic hypoxia (5% O2), cells stably overexpressing MST4 showed an increased rate of proliferation (at 7 days, 3.16-fold, p = 0.006) compared to vector control cells as assessed by BrdU staining. These effects were completely blocked by the inhibitor at 50nM (-2.61-fold, p = 0.01, NS from controls). Similarly, MST4 protection from hypoxia induced apoptosis under 1% O2 for 17h was also inhibited at the same dose as assessed by TUNEL staining (-2.72-fold, p&amp;lt;0.001, NS from controls). Analysis of transfectants expressing wildtype and Mst4-mutants (K53E-kinase dead, T178A-loss of autophosphorylation, and C-terminus deletion) confirmed the inhibitory effect was dependent on the kinase sequence. Together, these data identify a potent inhibitor of the MST4 kinase with the capacity to selectively block pituitary cell growth under a hypoxic microenvironment and support future studies of its ability to modulate pituitary tumor growth in rodent models. Citation Format: Weipeng Xiong, Chris Matheson, Donald S. Backos, Mei Xu, Katja Kiseljak-Vassiliades, Smita Salian-Mehta, Philip Reigan, Margaret E. Wierman. Identification of a mammalian sterile-20 like kinase 4 (MST4) inhibitor to target pituitary tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-303. doi:10.1158/1538-7445.AM2015-LB-303
High-Dose Melphalan Chemotherapy with Autologous Stem Cell Transplantation in Patients with AL Amyloidosis: No Increased Mortality Using Induction and Mobilization Chemotherapy.
Authors: Stefan O. Schonland, Ute Hegenbart, Jolanta B. Dengler, Axel Benner, Michael Hundemer, Tilmann Bochtler, Anthony D. Ho, Hartmut Goldschmidt
Journal: Blood (2005)
VEBEP Regimen and Highly Active Antiretroviral Therapy (HAART) in Patients (pts) with HD and HIV Infection (HD-HIV): Final Results of the Italian Cooperative Group on AIDS and Tumors (GICAT) Study.
Authors: Michele Spina, Andrea Antinori, Valentina Neri, Giuseppe Rossi, Alessandro Re, Bernardino Allione, Emanuela Chimienti, Renato Talamini, Umberto Tirelli
Journal: Blood (2008)
Abstract 5298: Serum angiogenic factors may predict prognosis in patients with epithelial ovarian cancer
Authors: HIROAKI KOMATSU, Tetsuro Oishi, Hiroaki Itamochi, Akiko Kudoh, Michiko Nonaka, Seiya Sato, Jun Chikumi, Shinya Sato, Muneaki Shimada, Junzo Kigawa, Tasuku Harada
Journal: Cancer Research (2015)

Abstract Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including epithelial ovarian cancer (EOC). The vascular endothelial growth factor (VEGF) family is one of the major pathways involved in tumor angiogenesis, and VEGF expression is activated by hypoxia-inducible factor (HIF)-1α. The aim of this study was to determine whether serum levels of these angiogenic factors could be used as prognostic biomarkers in patients with EOC. Methods: A total of 133 patients with EOC who were treated at Tottori University Hospital between 2006 and 2012 were enrolled in this study. The study was approved by the Institutional Review Board of the School of Medicine of Tottori University. All patients gave written informed consent before the collection of specimens according to institutional guidelines. Serum samples were collected before initial surgery and levels of VEGF-A, -C and HIF-1α were analyzed by enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the levels of VEGF-A, -C, and HIF-1α and clinicopathologic variables. We also determined the protein expression of VEGF-A, -C, and HIF-1α by immunohistochemical staining in paraffin-embedded tumors from EOC patients Results: The protein expressions of VEGF-A, -C, and HIF-1α were strongly observed in the cancer cells. Median levels of serum VEGF-A, -C and HIF-1α were 280, 4866 and 125 pg/ml, respectively. The levels of VEGF-A in patients at stage IV were significantly higher than those in patients at stage I. Both histologic subtypes and lymph node involvement were not related to levels of these angiogenic factors. We found a significant positive correlation between VEGF-A levels and the ascitic volume. The overall survival rate was significantly lower in FIGO stage III or IV patients with EOC. We set the cutoff value of these factors at the median levels of each angiogenic factors. The 5-year survival rate for patients with high VEGF-A levels was significantly lower than those with low levels (61.7% vs. 41.8%, P = 0.0147). Both HIF-1α and VEGF-C levels were not related to outcome of patients. Multivariate analysis revealed that serum VEGF-A level and FIGO stage were independent prognostic factors. Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for EOC. Citation Format: HIROAKI KOMATSU, Tetsuro Oishi, Hiroaki Itamochi, Akiko Kudoh, Michiko Nonaka, Seiya Sato, Jun Chikumi, Shinya Sato, Muneaki Shimada, Junzo Kigawa, Tasuku Harada. Serum angiogenic factors may predict prognosis in patients with epithelial ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5298. doi:10.1158/1538-7445.AM2015-5298
Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease
Authors: Luis Concha-Marambio, Sandra Pritzkow, Fabio Moda, Fabrizio Tagliavini, James W. Ironside, Paul E. Schulz, Claudio Soto
Journal: Science Translational Medicine (2016)

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrPSc) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrPSc could be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrPSc concentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology.
Total Therapy 2 (TT 2) for Newly Diagnosed Patients with Multiple Myeloma (MM): Examination of Dose Effect of Thalidomide (T) among Those Randomized to T.
Authors: Raymond Thertulien, Bart Barlogie, Maurizio Zangari, Athanasios Fassas, Julie Stover, Teresa Milner, Erik Rasmussen, Elias Anaissie, Choon-Kee Lee, Klaus Hollmig, Giampaolo Talamo, Guido Tricot
Journal: Blood (2004)
Neuroblastoma cells express all four PGE2 receptor subtypes and specific receptor antagonists may inhibit tumor growth
Authors: Agnes Rasmuson, John Inge Johnsen, Abiel Orrego, Per Kogner, Baldur Sveinbjornsson
Journal: Cancer Research (2006)

4343   Neuroblastoma (NB), the most common extracranial solid tumor in children, is characterized by a heterogeneous clinical behaviour. Some tumors may undergo spontaneous regression or differentiation while the majority of metastatic NB have poor prognosis despite intensive therapy. Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to prostaglandins. We have previously shown that COX-2 is highly expressed in NB and treatment of established NB xenografts with COX-2 inhibitors reduces tumour growth in vivo. The role of COX-2 in cancer is not fully understood but it appears that COX-2 derived prostaglandin E 2  (PGE 2 ) and its receptors play a predominant role. The effect of PGE 2  is mediated through four G-protein coupled receptors EP1, EP2, EP3 and EP4 that activates distinct intracellular signaling pathways. To evaluate the importance of PGE 2  and its receptors in NB, we analyzed the expression of EP1-EP4 in clinical primary NB tumors and cell lines and examined the effect of EP receptor antagonists on cell viability. All four EP receptor subtypes were detected at both the mRNA and protein level in human NB cell lines, as well as in NB primary tumors using immunohistochemistry. Treatment with a receptor antagonist against EP4 but not against EP1 induced a dose-dependent reduction in cell viability in vitro. These results indicate that agents targeting prostaglandin E 2  receptors may have a potential therapeutic significance in neuroblastoma treatment. Complementary studies are in progress, to fully elucidate the significance of PGE 2  and its receptors in neuroblastoma carcinogenesis.
Perioperative outcomes, health care costs and survival after robotic-assisted versus open radical cystectomy: A national comparative effectiveness study
Authors: J. Hu, B. Chughtai, P. O'Malley, J. Halpern, J. Mao, D. Scherr, D. Hershman, J. Wright, A. Sedrakyan
Journal: International Journal of Surgery (2016)