tbuckley/cabot-search huggingface dataset:
Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight
Authors: Ronald P. Gaykema, Brandon A. Newmyer, Matteo Ottolini, Vidisha Raje, Daniel M. Warthen, Philip S. Lambeth, Maria Niccum, Ting Yao, Yiru Huang, Ira G. Schulman, Thurl E. Harris, Manoj K. Patel, Kevin W. Williams, Michael M. Scott
Journal: Journal of Clinical Investigation (2017)

Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.
The predictive value of immunohistochemical expression of Bcl-2, Bcl-6, MUM1, CD10 and CD30 in patients with diffuse large cell lymphoma
Authors: I. Kryachok, A.V. Martynchyk, K. Filonenko, A.N. Grabovoy, S.A. Antoniuk, I. Tytorenko, O. Novosad, T. Kadnikova, O. Aleksik, I. Stepanishyna
Journal: Annals of Oncology (2016)
Peripheral Blood Analysis By Flow Cytometry for the Diagnosis of Type I Chronic Myelomonocytic Leukemia
Authors: Hae Tha Mya, Maria Diez Campelo, Sandra Valle Herrero, Agustin Díaz-Alvarez, Domingo Bustos, Luis M Vaquero, José J Pérez, Verónica González, Jose M Bastida, Alfonso Garcia-Coca, Erik de Cabo, Tomas Gonzalez, Noemi Puig, Alejandro Martin-Sancho, Patricia FernÃ°ndez, Julio Davila, Ana Africa Martín López, Marcos González, Consuelo Del Cañizo, Maria Belen Vidriales
Journal: Blood (2015)
Bernard-Soulier in Iceland. Bleeding Symptoms and Platelet Parameters in Patients, Carriers and Controls.
Authors: Pall Torfi Onundarson, Elisabet R. Birgisdottir, Gudrun Bragadottir, Bylgja Hilmarsdottir, Brynja Gudmundsdottir, Brynjar Vidarsson, Magnus K. Magnusson
Journal: Blood (2006)
Phase Ib study of intratumoral oncolytic coxsackievirus A21 (CVA21) and pembrolizumab in subjects with advanced melanoma
Authors: H.L. Kaufman, K. Spencer, J. Mehnert, A. Silk, J. Wang, A. Zloza, M. Kane, D. Moore, M. Grose, D. Shafren
Journal: Annals of Oncology (2016)
Characterization of Human Cancer Cell Lines by Reverse-phase Protein Arrays
Authors: Jun Li, Wei Zhao, Rehan Akbani, Wenbin Liu, Zhenlin Ju, Shiyun Ling, Christopher P. Vellano, Paul Roebuck, Qinghua Yu, A. Karina Eterovic, Lauren A. Byers, Michael A. Davies, Wanleng Deng, Y.N. Vashisht Gopal, Guo Chen, Erika M. von Euw, Dennis Slamon, Dylan Conklin, John V. Heymach, Adi F. Gazdar, John D. Minna, Jeffrey N. Myers, Yiling Lu, Gordon B. Mills, Han Liang
Journal: Cancer Cell (2017)
TNF-α and Its Receptors in Patients with Acute Myeloid Leukemia Undergoing alloHSCT.
Authors: Slawomira Kyrcz-Krzemien, Monika Zielinska, Agnieszka Wieclawek, Tomasz Czerw, Aleksandra Holowiecka, Patrycja Zielinska, Urszula Mazurek
Journal: Blood (2009)
Vorinostat in Combination with Pegylated Liposomal Doxorubicin (PLD) and Bortezomib (B) in Patients with Relapsed/Refractory Multiple Myeloma (R/R MM): Final Results of a Phase I Study,
Authors: Peter M. Voorhees, Cristina Gasparetto, Keren Osman, Kristy L. Richards, Madlyn Ferraro, Reynaldo Garcia, Jennifer MacLean, Diane Winans, Dominic Moore, John Strader, Robert Z. Orlowski, David Duane Hurd
Journal: Blood (2011)
Minor Histocompatibility Antigen Mismatch and Incidence of Graft Versus Host Disease, Event-Free, and Overall Survival in Patients Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation
Authors: Brian C Shaffer, Christine Tremblay, Daniel Peaceman, Jennifer Hsu, Seth M. Steinberg, Marcela Uribe, Sharon Adams, Willy A. Flegel, Steven Z. Pavletic
Journal: Blood (2012)
Multiple Doses of Intravenous Pegylated Asparaginase with a “Pediatric-like” Protocol in Adults with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL): Toxicity, Clinical Outcome and Low Rate of Anti Asparaginase Antibody Formation.
Authors: Dan Douer, Kristy Watkins, Lisa Mark, Janice Vrona, Ann Mohrbacher, Allen S. Yang, Vassilos I Avramis
Journal: Blood (2009)
Tumor-Associated Neutrophils and Macrophages Promote Gender Disparity in Hepatocellular Carcinoma in Zebrafish
Authors: Chuan Yan, Qiqi Yang, Zhiyuan Gong
Journal: Cancer Research (2017)

Hepatocellular carcinoma (HCC) occurs more frequently and aggressively in men than women, but the mechanistic basis of this gender disparity is obscure. Chronic inflammation is a major etiologic factor in HCC, so we investigated the role of cortisol in gender discrepancy in a zebrafish model of HCC. Inducible expression of oncogenic KrasV12 in hepatocytes of transgenic zebrafish resulted in accelerated liver tumor progression in males. These tumors were more heavily infiltrated with tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) versus females, and they both showed protumor gene expression and promoted tumor progression. Interestingly, the adrenal hormone cortisol was predominantly produced in males to induce Tgfb1 expression, which functioned as an attractant for TAN and TAM. Inhibition of cortisol signaling in males, or increase of cortisol level in females, decreased or increased the numbers of TAN and TAM, respectively, accompanied by corresponding changes in protumor molecular expression. Higher levels of cortisol, TGFB1, and TAN/TAM infiltration in males were also confirmed in human pre-HCC and HCC samples, features that positively correlated in human patients. These results identify increased cortisol production and TAN/TAM infiltration as primary factors in the gender disparity of HCC development in both fish and human. Cancer Res; 77(6); 1395-407. ©2017 AACR.
Parents’ Commitment to Participation in Mesenchymal Stem Cell Donation and Research Demonstrates Extensive Altruism to Other Patients.
Authors: Anne-Marie Walraven, Maria-Ester Bernardo, Anneke Brand, Helene Roelofs, Franco Locatelli, R. Maarten Egeler, Willem E. Fibbe, Lynne M. Ball
Journal: Blood (2007)
Interim Results from a Dose Escalating Study of AMT-060 (AAV5-hFIX) Gene Transfer in Adult Patients with Severe Hemophilia B
Authors: Frank W.G. Leebeek, Marco Tangelder, Karina Meijer, Giancarlo Castaman, Federica Cattaneo, Michiel Coppens, Peter Kampmann, Robert Klamroth, Roger E.G. Schutgens, Erhard Seifried, Joachim Schwaeble, Halvard Boenig, Maaike Hendriks, Deya Corzo, Wolfgang A. Miesbach
Journal: Blood (2016)
The impact of genetic variability on severe toxicity of (neo-) adjuvant chemotherapy in breast cancer patients receiving 5-fluorouracil, epirubicin, and cyclofosfamide (FEC).
Authors: Christof Vulsteke, Diether Lambrechts, Anne-Sophie Dieudonné, Sigrid Hatse, Barbara Brouwers, Thomas Van Brussel, Patrick Neven, Ann Belmans, Patrick Schoffski, Robert Paridaens, Hans Wildiers
Journal: Journal of Clinical Oncology (2012)

1020 Background: We assessed the impact of single nucleotide polymorphisms (SNP) of potential genes of interest in germline DNA on severe adverse events in breast cancer (bc) patients receiving (neo-) adjuvant FEC chemotherapy. Methods: Cases were retrospectively evaluated through electronic chart review for febrile neutropenia (primary endpoint), febrile neutropenia first cycle, prolonged grade 4 or deep (&lt;100/µl) neutropenia, anemia grade 3-4, thrombocytopenia grade 3-4 and non-hematological grade 3-4 events. The panel of genes, genotyped using iPLEX technology on a MALDI-TOF based MassARRAY Compact Analyser (Sequenom Inc., CA, USA), included ABCBI, ABCC1, ABCC2, ABCG2, ALDH3A1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5, DPYD, FGFR4, GPX4, GSTA1, GSTP1, MTHFR, NQ01, TYMS, XPD/ERCC2, XRCC1, UGT1A1, UGT1A6 and UGT2B7. These genes are involved in the metabolization of the studied chemotherapeutics. Because of multiple testing the false discovery rate (FDR) was calculated. Results: We identified 1089 patients treated between 2000-2010 with 3-6 cycles of FEC, for whom germline DNA was available.Homozygous (TT, 0.5%) and heterozygous (GT,11%) genotypes for rs4148350 in the Multi Drug Resistance Protein I (ABCC1/MRP1), compared to wild-type (GG, 88.5%), were associated with febrile neutropenia, febrile neutropenia in first cycle, prolonged grade 4 or deep neutropenia and thrombocytopenia (80 vs 25 vs 15.7%, 40 vs 17.6 vs 9.5%, 100 vs 41.7 vs 33.8% and 20 vs 2.8 vs 0.34% respectively; p 0.0006, 0.01, 0.002 and 0.008 FDR 0.03, 0.65, 0.06 and 0.2). Variant genotypes for rs45511401 (GT/TT, 12%) in ABCC1, compared to wild-type (GG, 88%), were associated with febrile neutropenia, febrile neutropenia in first cycle and thrombocytopenia (26.5 vs 15,8%, 17.1 vs 9.7% and 3.4 vs 0.3%, respectively; p 0.007, 0.03 and 0.005, FDR 0.2, 0.75 and 0.2). Conclusions: Genetic variation in the ABCC1 gene was strongly associated with severe hematological toxicity of FEC. Other previously described SNP were not validated. This is the largest bc study in which the impact of genetic variability on the adverse events of FEC chemotherapy was investigated.
Patient-reported fatigue and overall survival in locally advanced esophageal cancer: A Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry Consortium study.
Authors: M. C. Stauder, Y. Romero, B. Kabat, P. J. Atherton, M. B. Fredericksen, C. Deschamps, A. Jatoi, J. A. Sloan, M. Botros, R. C. Miller
Journal: Journal of Clinical Oncology (2011)

9 Background: We examined patient-reported fatigue scores and overall survival (OS) in patients with esophageal cancer (EC) enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry (EABE). Methods: 1,481 patients enrolled in the EABE between September 2001 and January 2009 returned a baseline quality of life questionnaire including a Linear Analog Self Assessment (LASA) fatigue score which was scored on a 0-10 scale, with 0 as the most extreme fatigue. Patients were categorized as having clinically deficient fatigue (DF) if they reported a score of ≤ 5 and clinically non-deficient fatigue (nDF) if they reported a score of &gt; 5. Kaplan-Meier methodology and Cox models explored OS in relation to fatigue scores in patients with EC. Results: A total of 667 patients with EC were included in the EABE, of which 659 returned a registry questionnaire with a valid LASA fatigue score recorded. Median age at the time of registry entry was 65 years (range 23-92). A total of 392 (59%) and 267 patients (41%) reported DF and nDF, respectively. On univariate analysis, patients with nDF had improved 5-year survival compared to patients with DF. In patients having esophagectomy prior to LASA, those reporting nDF had improved survival compared to patients with DF. Similarly, in patients having no esophagectomy prior to LASA, those with nDF had improved survival compared to those with DF. Among the 368 patients with locally advanced EC (LAEC), those reporting nDF had improved 5-year overall survival compared to patients with DF (28% vs 17%, HR = 0.67, p = 0.003). This remained significant on multivariate analysis (HR = 0.71, p = 0.015). Conclusions: Patient-reported fatigue is associated with overall survival in patients with LAEC. As a result, fatigue scores should be considered as a stratification factor in future clinical trial design. [Table: see text] No significant financial relationships to disclose.
Symptom burden and palliative care for patients with multiple myeloma: Cancer Experience Registry findings.
Authors: Joanne S. Buzaglo, Melissa F Miller, Clare Karten, Margaret Longacre, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2015)

81 Background: Multiple myeloma (MM) patients are living longer with treatment advances yet remain challenged by complications and adverse treatment effects. Concurrent oncology/palliative care can improve symptom burden and quality of life for cancer patients, but the benefits of concurrent care for the MM symptom burden is not well described. Methods: From July 2013-2014, the Cancer Support Community (CSC) registered 495 MM patients to the Cancer Experience Registry: MM, an online initiative to study and raise awareness about MM’s psychosocial impact. Registrants were recruited through an outreach program including the CSC and The Leukemia &amp; Lymphoma Society networks of communities and resources. 331 US-based registrants completed surveys about their MM history, treatment, and symptoms. Results: Median respondent age was 64 years; 54% were female, 87% Caucasian. Median time since diagnosis was 4.5 years, and 40% reported experiencing a relapse. Several symptoms interfered (quite a bit or very much) with respondents’ daily life: fatigue (40%), bone pain (22%), peripheral neuropathy (22%) sleep disturbance (21%), GI toxicity (16%), and mood swings (10%). The daily effects of fatigue, pain, sleep disturbance and mood swings were associated (p &lt; 0.05) with distress. 36% did not report all symptoms and side effects (SEs) to their health care team (HCT). The most common reason was “I don’t think anything can be done about these problems.” More than half (58%) reported sleep disturbances related to steroids, and 46% experienced weight gain, 41% mood swings, and 39% edema. One-third (34%) reported their HCT never told them steroids could cause this. 85% felt their HCT prepared them (somewhat, quite a bit, or very much) to manage SEs of MM treatment, yet half (50%) felt little or no control over the physical SEs of MM and its treatment. Conclusions: Patients with MM experience significant symptom burden that interferes with daily living but underreport symptoms to the HCT. Many symptoms are amenable to interventions by palliative care specialists, which may improve MM patients’ quality of life. These findings suggest the need for more integration of palliative care services with oncology and other care for MM patients.
Evaluation of O<sup>6</sup>-Benzylguanine−Potentiated Topical Carmustine for Mycosis Fungoides
Authors: Joselin D. Tacastacas, Derek V. Chan, Sean Carlson, Stanton L. Gerson, Afshin Dowlati, Pingfu Fu, Kurt Lu, Sarah Groft, Julie Rosenjack, Kord Honda, Thomas S. McCormick, Kevin D. Cooper
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> In a phase 1 trial, single-dose O<sup>6</sup>-benzylguanine with topical carmustine for patients with early stage (stage IA through stage IIA) cutaneous T-cell lymphoma, mycosis fungoides (MF) type, resulted in clinical responses proportional to inhibition of O<sup>6</sup>-alkylguanine–DNA alkyltransferase activity, but a maximum tolerated dose (MTD) was not reached. <h3>Objective</h3> To determine whether dose escalation of carmustine in combination with dual-dose O<sup>6</sup>-benzylguanine to prolong alkyltransferase inhibition could reach an MTD. <h3>Design, Setting, and Participants</h3> A single-arm, phase 1-2 clinical trial conducted at a university teaching hospital enrolled 17 adults with stage IA through stage IIA cutaneous T-cell lymphoma, MF type, to evaluate treatment using topical carmustine plus 2 subsequent daily doses of intravenous O<sup>6</sup>-benzylguanine, administered every 2 weeks for up to 24 weeks (12 cycles). All patients who received treatment were included in an intent-to-treat analysis of the response rate. The study was conducted from February 17, 2010, to April 8, 2014. Data analysis was performed from May 1, 2014, to December 1, 2015. <h3>Interventions</h3> Topical carmustine and intravenous O<sup>6</sup>-benzylguanine. <h3>Main Outcomes and Measures</h3> Clinical disease response was assessed by the Severity-Weighted Assessment Tool (score range, 0-400; higher score indicates worse disease). Safety data were acquired by review of adverse events at study visits. <h3>Results</h3> Of the 17 patients enrolled, 12 (71%) were men; mean (SD) age was 45.2 (14.6) years. There were 7 complete responses and 8 partial responses to combination carmustine and O<sup>6</sup>-benzylguanine treatment. The overall clinical response rate was 88%, with a mean (SD) duration of complete response of 14.43 (6.6) months. The MTD was 20 mg of carmustine applied once in combination with 2 daily doses of 120 mg/m<sup>2</sup>of O<sup>6</sup>-benzylguanine. Most adverse events (112 [67%]) were grade I. Of 15 patients with dermatitis, 5 individuals (33%) demonstrated grade II dermatitis that was unresponsive to topical corticosteroid therapy. The dermatitis was characterized by high levels of macrophage activation, and clearance was associated with vitamin D<sub>3</sub>administration. <h3>Conclusions and Relevance</h3> Compared with single-dose O<sup>6</sup>-benzylguanine and carmustine, dual-dose O<sup>6</sup>-benzylguanine resulted in higher overall response rates and reduced total carmustine doses but was associated with more cutaneous adverse events. The MTD for dual-dose O<sup>6</sup>-benzylguanine plus carmustine was also ascertained. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00961220
Correlation of HER2 overexpression evaluated by fluorescence in situ hybridization with response to docetaxel-based first-line chemotherapy in advanced breast cancer patients
Authors: A. Cavazzana, A. Camerini, R. Prosperi Porta, F. De Luca, N. Decarli, M. Rondini, C. Puccetti, O. Siclari, G. Tartarelli, D. Amoroso
Journal: Journal of Clinical Oncology (2008)

1124 Background: HER2 overexpression predicts response to trastuzumab in early and advanced breast cancer. Preliminar evidences indicate that HER2 signaling pathway may also influence chemotherapy sensitivity/resistance. Methods: We analysed the expression of HER2 in 36 (median age 55yrs; range 37–87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy regimens. All pts but one experience disease progression with a median time to progression of 8.5 (range 2 - 54) months. We correlate the expression of HER2 with pathologic parameters, treatment response and survival. HER2 was determined both by IHC and by fluorescence in situ hybridization (FISH). The standard cut-off value of 2 was used to determine HER2 overexpression. Treatment response was assessed according to RECIST criteria. Results: HER2 was overexpressed in 9 (25%) pts. HER2 was more frequently overexpressed in less differentiated (p= 0.05) and higher stage (p= 0.003) disease. Mean HER2 values were significantly higher in responder than in non-responder pts (2.50 ± 4.12 vs 8.53 ± 10.21, p = 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p = 0.046). We also observed at cross-tabulation analysis a clear correlation between HER2 testing with IHC and FISH (p= 0.001). No significant relation with survival was observed for HER2 status in our study population. Conclusions: Our data seem to indicate that FISH determined HER2 overexpression is associated with docetaxel sensitivity in metastatic breast cancer. No significant financial relationships to disclose.
Systematic <i>In Vivo</i> Inactivation of Chromatin-Regulating Enzymes Identifies Setd2 as a Potent Tumor Suppressor in Lung Adenocarcinoma
Authors: David M. Walter, Olivia S. Venancio, Elizabeth L. Buza, John W. Tobias, Charuhas Deshpande, A. Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J. Yates, David M. Feldser
Journal: Cancer Research (2017)

Abstract Chromatin-modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two KrasG12D-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome–remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression. Loss of either Brg1 or Arid1a were selected against in early-stage tumors, but Brg1 loss continued to limit disease progression over time, whereas loss of Arid1a eventually promoted development of higher grade lesions. In contrast to these stage-specific effects, loss of the histone methyltransferase Setd2 had robust tumor-promoting consequences. Despite disparate impacts of Setd2 and Arid1a loss on tumor development, each resulted in a gene expression profile with significant overlap. Setd2 inactivation and subsequent loss of H3K36me3 led to the swift expansion and accelerated progression of both early- and late-stage tumors. However, Setd2 loss per se was insufficient to overcome a p53-regulated barrier to malignant progression, nor establish the prometastatic cellular states that stochastically evolve during lung adenocarcinoma progression. Our study uncovers differential and context-dependent effects of SWI/SNF complex member loss, identifies Setd2 as a potent tumor suppressor in lung adenocarcinoma, and establishes model systems to facilitate further study of chromatin deregulation in lung cancer. Cancer Res; 77(7); 1719–29. ©2017 AACR.
RARE-19. A CASE REPORT OF ADENOID CYSTIC CARCINOMA IN THE BRAIN MIMICKING MALIGNANT GLIOMA ON NEUROIMAGING
Authors: Maryana Liedke, Agnes Kowalska
Journal: Neuro-Oncology (2016)

To describe a rare case of adenoid cystic carcinoma mimicking GBM. Adenoid cystic carcinoma (ACC) is a rare form of adenocarcinoma which originates in the glandular tissues. It is found most commonly in the head and neck primarily in the major and minor salivary glands. It is found uncommonly in the brain. 46 year old right handed male with past medical history of hypothyroidism initially evaluated at a community hospital due to headache, right eye pain, blurry vision and left leg weakness, several weeks prior to admission. His MRI of the brain revealed a mass at the right frontotemporal cerebellopontine angle with associated vasogenic edema. His CT of the chest/abdomen/pelvis did not reveal any masses. He subsequently underwent craniotomy for what was thought to be a malignant brain tumor. Tissue was sent for pathological examination and revealed adenoid cystic tumor. Whole body PET scan demonstrated uptake in the right maxillary and cavernous sinus. At his last neurology follow up he demonstrated symptoms of decreased sensation in right V1-V3 distribution and cranial nerve IV palsy. He was referred to radiation oncology for further treatment. Adenoid cystic carcinoma is found primarily in the salivary glands and rarely discovered in the brain tissue. The gold standard of treatment of ACC tumors is surgical resection followed by radiation treatment. The patient described above is a rare case of ACC in the brain who presented with symptoms of headache, eye pain and leg weakness now with symptoms of cranial nerve six palsy and trigeminal neuralgia. These tumors can frequently mimic malignant gliomas on MRI studies, therefore pathological examination of tissue is necessary to make the correct diagnosis.