tbuckley/cabot-search huggingface dataset:
Therapeutic Potential of Bacteria against Solid Tumors
Authors: Haralampos Hatzikirou, Juan Carlos López Alfonso, Sara Leschner, Siegfried Weiss, Michael Meyer-Hermann
Journal: Cancer Research (2017)

Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects. Cancer Res; 77(7); 1553-63. ©2017 AACR.
Induction of TRAIL and XAF-1 and inhibition of p-Akt and c-Kit expression by interferons (IFNs) is associated with apoptosis in GIST cells
Authors: E. C. Borden, B. Jacobs, G. Demetri, J. Fletcher
Journal: Journal of Clinical Oncology (2004)

9027 Background: Since few complete responses occur and a subset of patients do not respond at all, additional biologically targeted interventions are needed for patients with metastatic GIST. Among pleiotropic actions of IFNs are inhibition of cell proliferation and induction of apoptosis-effects we postulated might occur in cell lines derived from GIST. Methods: KIT-dependent GIST882 cells were treated with IFN-α2 or IFN-β at concentrations of 10–500 units and antiproliferative effects (cell counts) and apoptosis (flow cytometry) assessed at 3 and 7 days. Gene induction and signal pathway components were assessed by quantitative RT-PCR and western blot. Results: At 10 units of IFN-β cell counts decreased 70% and at 50 units 90%; IFN-α2 decreased cell counts 10% (10 units) and 75% (50 units). Imatinib mesylate (1μM) resulted in 75% inhibition. Apoptosis was assessed at 3 and 7 d with increasing doses of IFNs. A dose and time-related increase in apoptosis occurred with 100 units of IFN-β resulting in >50% TUNEL positive cells at 7 d (imatinib 1μM=23% TUNEL positive cells at 7 d). By 48 hrs, caspase 3 was activated by both IFN-α2 and IFN-β, though more potently by IFN-β. Potentially underlying apoptosis induction were interferon-stimulated genes that occurred as early as 6 hrs after IFN-α1, IFN-α2, and IFN-β and with up to 8x increases in ISG15, phospholipid scramblase, XAF-1 and TRAIL. To further explore signal transduction pathways underlying effects on apoptosis, stat3, p-stat3, Akt, p-Akt, and c-kit were assessed after 24, 48, and 72 hours of treatment with IFNs; IFN-β, and to a lesser extent IFN-α2, suppressed p-Akt and activated c-kit expression at 48 and 72 hrs. Conclusion: GIST 882 cells were quite sensitive to targeted gene modulation, antiproliferative effects and apoptosis by IFNs, particularly IFN-β. This effect, associated with increase in IFN-stimulated, apoptosis-mediating genes and decrease in activated c-kit and the anti-apoptotic p-Akt, suggests a possible role for IFN-β in patients with imatinib-refractory GIST. No significant financial relationships to disclose.
Prognostic role of circulating exosomal miRNAs in multiple myeloma
Authors: Salomon Manier, Chia-Jen Liu, Hervé Avet-Loiseau, Jihye Park, Jiantao Shi, Federico Campigotto, Karma Z. Salem, Daisy Huynh, Siobhan V. Glavey, Bradley Rivotto, Antonio Sacco, Aldo M. Roccaro, Juliette Bouyssou, Stéphane Minvielle, Philippe Moreau, Thierry Facon, Xavier Leleu, Edie Weller, Lorenzo Trippa, Irene M. Ghobrial
Journal: Blood (2017)
TMIC-11. HFE GENOTYPE ALTERS EXOSOME PROFILES IN CANCER
Authors: Oliver Mrowczynski, Achuthamangalam Madhankumar
Journal: Neuro-Oncology (2016)

Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. A major focus in cancer biology is the impact of exosomes on metastasis and the microenvironment. The major goal of this study was to determine if changes in HFE genotype, associated with aggressive cancer phenotype, have significant effects on exosome profile. HFE, the most common autosomal recessive polymorphism in the Caucasian population, originally associated with hemochromatosis, is also associated with increased tumor burden, therapeutic resistance boost, and negative impact on survival. We used immunoblots to analyze protein expression differences between exosomes. We also used functional assays, such as invasion and angiogenesis assays, to determine functional changes caused by HFE mutant cell derived exosomes. We demonstrate that HFE mutant derived exosomes have increased expression of proteins relating to the ferrome, invasion, angiogenesis, and cancer therapeutic resistance. These exosomes can induce altered functionality such as increased angiogenesis, migration, invasion and resistance to radiation in wild-type HFE cells. These novel findings are the first to demonstrate genotype influence on exosomes and that the exosomes from a cell line carrying a mutation can alter the phenotype in a wild-type cell line. Moreover, the exosomes from the mutant cell line transfer the more aggressive and treatment resistant phenotype to the wild-type cells. Our study has demonstrated that HFE mutant derived exosomes have increased expression of proteins related to oncogenesis, which has major implications on not only HFE variant patients with neuroblastoma, but can be expanded to all types of cancer because of the prevalence of the HFE gene variants. We also provide a novel model cell system for interrogation of functional impact of exosomes.
Education in oncology and career development in the web-era technology: a European survey conducted by the Hellenic Group of Young Oncologists (HeGYO)
Authors: N.G. Tsoukalas, K. Kamposioras, G. Papaxoinis, E. Aravantinou-Fatorou, A. Korogiannos, V. Papadopoulos, G. Lazaridis, M. Nikolaou, E. Voulgaris, E. Bournakis, K. Tsigaridas, M. Liontos, E. Papageorgiou, N. Chatzifoti, P. Zaxaropoulou, A. Athanasiadis, I. Varthalitis
Journal: Annals of Oncology (2016)
Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal cancer: final analyses
Authors: H.J. Schmoll, A. Stein, R.D. Hofheinz, T.J. Price, B. Nordlinger, J.-F. Daisne, J.-F. Daisne, J. Janssens, B. Brenner, P. Schmidt, H. Reinel, S. Hollerbach, K. Caca, F. Fauth, J. Zalcberg, S. Marreaud, M. Mauer, M. Lutz, E. Van Cutsem, K. Haustermans
Journal: Annals of Oncology (2016)
PDTB-23. CHEMI-GENOMIC ANALYSIS OF PATIENT-DERIVED XENOGRAFTS TO IDENTIFY PERSONALIZED THERAPIES FOR MEDULLOBLASTOMA
Authors: Jessica Rusert, Alexandra Garancher, Sebastian Brabetz, Yoko Udaka, James Jensen, Lourdes Esparza, Huriye Seker-Cin, Lin Qi, Mari Kogiso, Simone Schubert, Till Milde, Yoon-Jae Cho, Xiao-Nan Li, James Olson, Pablo Tamayo, John Crawford, Michael Levy, Marcel Kool, Jill Mesirov, Stefan M. Pfister, Robert Wechsler-Reya
Journal: Neuro-Oncology (2016)

Medulloblastoma (MB) is the most common malignant brain tumor in children. Even with an intensive regimen of surgery, radiation and chemotherapy, one-third of patients still die from their disease, and survivors suffer devastating side effects from the therapy. Thus, more effective and less toxic therapies are desperately needed. Genomic analyses have identified 4 major subgroups of MB – WNT, SHH, Group 3 and Group 4 – that differ in terms of mutations, gene expression and patient outcomes. Despite this heterogeneity, all MB patients currently receive the same therapy. To identify novel therapies for each subgroup of MB, we have assembled a panel of patient-derived xenograft (PDX) lines. These lines, established by orthotopic transplantation of tumor cells obtained from surgery, recapitulate the properties of patients’ tumors more accurately than cultured cell lines. We are using these lines to screen small molecule libraries for compounds that can inhibit tumor growth and survival. To date we have completed 19 lines, including 10 representing Group 3, the most aggressive and lethal form of the disease. Among ~7800 compounds tested, 22 were effective against all Group 3 lines. Ongoing studies are focused on validating the activity of these compounds and moving the most promising ones forward into in vivo efficacy studies. Similar approaches will be pursued for each of the other subgroups of MB. Drug response data will also be compared with genomic and epigenomic data (whole exome and low coverage whole genome DNA sequencing, DNA methylation analysis, and gene expression profiling) to identify biomarkers of drug responsiveness and key pathways that may be exploited for therapy. Based on these studies, we hope to move away from a one-size-fits-all approach, and begin to treat each patient with therapies that are likely to be effective against their tumor.
A comparison of IMRT and 3DCRT in the treatment planning of patients with distal esophageal cancer.
Authors: S. Patil
Journal: Journal of Clinical Oncology (2011)

143 Background: There is limited data comparing intensity modulated radiation therapy (IMRT) and 3D conformal radiation therapy (3DCRT) in node-negative patients with cancer of the distal esophagus. Methods: Eight patients with node-negative cancer of the distal esophagus measuring 1-5 cm tumors were selected for this study. Target volumes were generated for all patients based on standard current practice; 3DCRT and IMRT plans optimized to obtain minimum dose to the heart were then created using the using the Eclipse Treatment Planning. Conformality index (CI, the amount of target volume covered by the prescription dose) and conformation number (CN, the amount of normal tissue receiving prescription dose) were calculated. Dose volume histograms also were generated and clinically relevant parameters were extracted and compared for each planning modality using paired T-tests. Each patient served as his or her own control. Results: The difference in CI ranged from 0-0.01, indicating equivalent target coverage for each patient. IMRT produced superior CN (mean CN = 0.74) vs. the 3DCRT plans (mean CN = 0.45). Heart V40 and the maximum dose to spinal cord were lower for IMRT (mean difference in heart V40 = 34.5%, p=0.0006 and mean difference in the maximum dose to the spinal cord = 18.1 Gy, p=0.0005) but lung V5 and V20 were lower for 3DCRT (mean difference in lung V5 = -21.3%, p=0.0026 and mean difference in lung V20 = -5.2%, p=0.0014). Conclusions: When optimized to minimize dose to the heart, IMRT plans were substantially more conformal to the target structures with less dose to the heart as compared to 3DCRT plans; however this occurred at the expense of increased dose delivered to the lung. No significant financial relationships to disclose.
Eribulin vs. Eribulin + Bevacizumab in advanced-line treatment of Her-2 negative metastatic breast cancer
Authors: G. Rossi, I. Martellucci, S. Marsili, R. Petrioli, V. Nardone, M. Chirra, P. Torre, L. Messutti, A.G. Multari, G. Francini
Journal: Annals of Oncology (2016)
Pediatric, adolescent and young adult (PAYA) thyroid carcinoma harbors frequent and diverse targetable genomic alterations including kinase fusions
Authors: Pden Van Borre, A.B. Schrock, P. Anderson, A.M. Heilmann, O. Holmes, K. Wang, S. Khan, J.C. Morris, S.-H.I. Ou, S. Waguespack, P. Stephens, R.L. Erlich, V. Miller, J.S. Ross, S. Ali
Journal: Annals of Oncology (2016)
Multidisciplinary molecular tumour board : a tool to improve clinical practice and selection accrual for clinical trials in cancer patients
Authors: C. D. Rolfo, A. Machado Coelho, P. Van Dam, Amélie Dendooven, C. Weyn, M. Rasschaert, L. Van Houten, B. X. Trinh, J. Van Meerbeeck, P. Pauwels, M. Peeters
Journal: Annals of Oncology (2016)
RTHP-20. EVALUATION OF RADIATION THERAPY TECHNOLOGY AND DOSIMETRY IMPACT ON TREATMENT OUTCOME FOR GLIOBLASTOMA PATIENTS
Authors: Per Munck af Rosenschold, Ian Law, Svend Aage Engelholm, Aida Muhic, Michael Lundemann, Henrik Roed, Kirsten Grunnet, Hans Skovgaard Poulsen
Journal: Neuro-Oncology (2016)

We sought to assess the impact of the clinical introduction of new radiation therapy technologies on the outcome for glioblastoma patients. Newly diagnosed glioblastoma patients receiving 60 Gy with concomitant and adjuvant temozolomide in the period 2005-2014 were analyzed. Gross tumor volume (GTV) and a clinical target volume by addition of up to 2 cm margin were defined based on MRI (N=522). A subset of patients (N=188) had a biological target volume (BTV) defined based on amino-acid 18F-Flouro-ethyl-tyrosine positron emission tomography (FET-PET) scanning. The patients’ target volumes were treated using conformal radiation therapy (CRT, N=159) or volumetric modulated arc therapy (VMAT) with hippocampal sparing and daily image-guided radiation therapy (IGRT, N=322). Progression-free survival (PFS) was assessed using the McDonald criteria. Associations between dosimetry data, treatment technology, PFS and overall survival (OS) were explored. Average brain dose was lower for patients treated with VMAT compared to CRT (p<0.001, Mann-Whitney). The Kaplan-Meier estimate of PFS and OS was not influenced by use of CRT, VMAT and FET-PET technology (log-rank), and was 7 and 15 months, respectively, for the whole cohort. Univariate Cox models revealed correlation of higher average brain dose, average brainstem dose, GTV and BTV (p<0.002), and left hippocampus (p=0.017) with lower OS. Average brain dose was statistically significant in multivariate Cox models for the whole cohort and VMAT treated patients (HR=1.04, p<0.001). For patients with FET-PET-guided RT, average dose to brainstem (HR=1.025, p=0.001) and BTV (HR=1.006, p=0.007) was significant. Average brain and brainstem dose as well as BTV were strongly associated with OS, and might aid prognostication. VMAT and IGRT technology allowed for reduction of doses to healthy brain, including the hippocampi, which may reduce toxicity and preserve cognition. The benefit of VMAT and IGRT technology was not offset by a reduction of PFS or OS.
Patients' perspective on palliative chemotherapy of colorectal and non-colorectal tumors.
Authors: M. Rehm, A. Rentsch, K. Trautmann, B. Hornemann, U. Schuler, G. Ehninger, G. Folprecht
Journal: Journal of Clinical Oncology (2011)

581 Background: In contrast to trials investigating treatment efficacy, patients perspective on given chemotherapy is less studied. Known surveys indicate that patients accept therapy for very limited benefit. Methods: Patients who had received 3 or more months of systemic, palliative therapy for colorectal (CRC) or non-colorectal (upper GI, NSCLC, SCCHN) cancer were eligible. They completed a questionnaire including their retrospective report on symptomatic toxicity (according to NCI-CTC) and using numeric ranking scales their burden from the toxicity and the comparison to the informed consent. Depression and anxiety was measured by HADS. Finally, the patients were asked for the minimal gain in life expectancy they would feel it worth to repeat the therapy for. Results: Between August 2008 and December 2009, 134 patients were enrolled. Median age was 63 (32-86); 71% of patients were male. Colorectal cancer patients would repeat their therapy for a minimal gain of life expectancy of 36.0 mo (14.0-57.0 mo), non-CRC patients for 15.9 [12.3-19.5] months (p = 0.01). Considering additional time with best supportive care, the minimal expectation from treatment trended to be longer than the actual survival of the same patients (39.3 [33.6-45.0] and 19.9 [16.3- 23.5] months for CRC and non-CRC patients, respectively), p = 0.08. Depression, diarrhea and tumor entity (CRC vs. non-CRC) were an independent factors for the minimal expected life expectancy in a multivariate analysis. Most frequent self reported toxicity (grade 3/4) was fatigue (9.0%), nausea (8.1%), diarrhea (8.5%) and stomatitis (8.3%), severe burden was felt from fatigue (14.3%) followed by neuropathy (12.0%), diarrhea (11.1%), nausea (9.8%) and stomatitis (8.8%). Fatigue was felt ′a little bit more′ or ′much more′ than in the patient information in 29.9%, followed by neuropathy (20.5%), acne (18.4%) and diarrhea (17.6%). Conclusions: Patients' expectations of life-prolonging systemic therapy are higher than expected from previous studies or the median survival in phase III studies. Compared to their actual survival it may be regarded as realistic. Fatigue might deserve more attention when toxicity of treatment and symptoms of disease are explained. [Table: see text]
Left ventricular systolic function is associated with sympathetic nervous activity and markers of inflammation in cirrhosis
Authors: Raquel Yotti, Cristina Ripoll, Yolanda Benito, Maria Vega Catalina, Jaime Elízaga, Diego Rincón, Francisco Fernández‐Avilés, Javier Bermejo, Rafael Bañares
Journal: Hepatology (2017)

An accurate evaluation of cardiac function in patients with cirrhosis remains a challenge. We used robust echocardiographic indices to characterize left ventricular (LV) systolic function and its relationship to activation of the sympathetic nervous system and inflammation in 59 patients with cirrhosis and 59 age‐matched controls. Additionally, in 11 patients we withdrew beta‐blockers and diuretics and used phenylephrine and albumin infusion to evaluate the response to acute afterload and preload changes (interventional substudy). Measures of systolic LV function such as the ejection intraventricular pressure difference (EIVPD) and the systolic strain rate were higher in patients with cirrhosis than in controls (median [1st‐3rd quartile], 4.0 [3.1‐5.1] versus 2.9 [2.4‐3.6] mm Hg and –1.3 [–1.6 to –1.1] versus –1.2 [–1.6 to –1.1)] s –1 , respectively; P &lt; 0.05 for both). EIVPD was related to the severity of liver disease (Model for End‐Stage Liver Disease, rho = 0.45, P &lt; 0.001), the degree of sympathetic nervous system activation (noradrenaline, rho = 0.26, P = 0.05; heart rate variability, rho = –0.43, P = 0.003), and treatment with beta‐blockers ( P = 0.001). In the interventional substudy, EIVPD was higher in patients with ascites (6.5 [5.4‐8.5] versus 4.0 [3.9‐5.1] mm Hg, P = 0.045). The decrease in EIVPD induced by phenylephrine was inversely related to baseline systolic function ( P &lt; 0.05) and associated with markers of systemic vasodilatation (nitric oxide, rho = –0.66, P = 0.06; diastolic blood pressure, rho = 0.68, P = 0.04) and inflammation (interleukin‐1beta, rho = –0.80, P = 0.009). Conclusion : LV systolic function is enhanced in cirrhosis due to augmented adrenergic tone and modulated by treatment with beta‐blockers; acute afterload stress induces a deeper impairment of systolic function in patients with more advanced degrees of vasodilatation and inflammation; these changes in LV function related to cirrhosis can be assessed using robust echocardiographic methods. (H epatology 2017;65:2019‐2030).
Phase II Trials of Clofarabine in Relapsed or Refractory Pediatric Leukemia.
Authors: Sima Jeha, Bassem I. Razzouk, Michael E. Rytting, Paul S. Gaynon, Richard Kadota, Susan Rheingold, Lori Luchtman-Jones, Violet Shen, Robert J. Arceci, Manuel Fernandez, Steven Weitman, Peter G. Steinherz
Journal: Blood (2004)
Importance of tumour symptoms and extent of disease on efficacy of first-line FOLFOX4 ± panitumumab (pmab) in patients (pts) with RAS wild-type (WT)/BRAF WT metastatic colorectal cancer (mCRC) in the PRIME study
Authors: J. Taieb, M. Peeters, S. Siena, F. Rivera Herrero, R. Koukakis, G. Demonty, J.-Y. Douillard
Journal: Annals of Oncology (2016)
BRCA mutations and IGF-R1 expression in modulating sensitivity to Trastuzumab in patients with HER2-positive breast cancer
Authors: M. Pistelli, A. Santinelli, M. Santoni, F. Piva, F. Bianchi, T. Biscotti, L. Belvederesi, Z. Ballatore, G. Occhipinti, M. De Lisa, A. Pagliacci, N. Battelli, R. Bracci, E. Maccaroni, L. Bastinelli, L. Cantini, R. Berardi, S. Cascinu
Journal: Annals of Oncology (2016)
Efficacy of influenza vaccine (FluVax) in patients on chemotherapy (POCT): final data analysis from South Australia
Authors: A. Ayoola, S. Sukumaran, R. Kumar, D. Gordon, A. Roy, S. Vantandoust, B. Koczwara, G. Kichenadasse, C. Karapetis
Journal: Annals of Oncology (2016)
OS5.4 Not all 1p/19q non-codeleted oligodendroglial-like tumors are astrocytic
Authors: A. K. Chan, Y. X. Li, Z. F. Shi, A. Aibaidula, H. Chen, K. K. Li, D. T. Chan, W. S. Poon, Y. Mao, H. K. Ng
Journal: Neuro-Oncology (2016)
Oral Administration of Dacogen Mesylate Increases HbF and Decreases DNA Methylation of the ε- and γ-Globin Genes in Anemic Baboons (Papio anubis).
Authors: Donald Lavelle, Kestis Vaitkus, Janet Chin, Sanjeev Redkar, Pasit Phiasivongsa, Maria Hankewych, Joseph DeSimone
Journal: Blood (2005)
Neonatal Intensive Care — The Only Constant Is Change
Authors: Prakesh S Shah
Journal: New England Journal of Medicine (2017)

The rate of survival of infants born extremely early — previously considered to be periviable (≤24 weeks) — has increased with advances in perinatal–neonatal care. However, concerns regarding higher rates of neurodevelopmental impairment among survivors have been raised. A precise interpretation of outcomes in periviable neonates requires an understanding of competing outcomes bias, differences in outcome reporting, denominators used in the calculation of rates, and health care philosophies at the personal, institutional, regional, and national level that influence care provision.In this issue of the Journal, Younge et al.1 report data on 4227 neonates born at 22 to 24 weeks . . .
Radial glia cells are candidate stem cells of ependymoma
Authors: Michael D. Taylor, Helen Poppleton, Christine Fuller, Xiaoping Su, Yongxing Liu, Patricia Jensen, Susan Magdaleno, James Dalton, Christopher Calabrese, Julian Board, Tobey MacDonald, Jim Rutka, Abhijit Guha, Amar Gajjar, Tom Curran, Richard J. Gilbertson
Journal: Cancer Cell (2006)
Detectability of druggable gene fusions by amplicon-based next generation sequencing in nationwide lung cancer genomic screening project (LC-SCRUM-Japan)
Authors: S. Matsumoto, K. Yoh, M. Kodani, K. Ohashi, S. Saeki, N. Furuya, Y. Nishioka, Y. Ohe, T. Seto, R. Hayashi, Y. Kataoka, T. Fukui, T. Sakamoto, S. Ikemura, T. Kohno, K. Tsuta, K. Tsuchihara, K. Goto
Journal: Annals of Oncology (2016)
Radium-223 with concomitant bone-targeting agents in metastatic castration-resistant prostate cancer (CRPC) patients treated in an international early access program (EAP)
Authors: F. Saad, A. Heidenreich, D. Heinrich, D. Keizman, J.M. O'Sullivan, J. Carles, M. Wirth, K. Miller, J. Gratt, M. Seger-Van Tol, S. Nilsson, S. Gillessen
Journal: Annals of Oncology (2016)
Gastric Gyri — Pediatric Ménétrier’s Disease
Authors: Chisato Akita, Yutaka Saikawa
Journal: New England Journal of Medicine (2017)

A 5-year-old boy presented with nausea, vomiting, and intermittent abdominal pain. Images showed giant cerebriform enlargement of rugal folds in the fundus and the body, which were suggestive of Ménétrier’s disease.