tbuckley/cabot-search huggingface dataset:
Abstract 828: Methylation status of HPV16 E2-binding sites identifies subtypes of HPV-associated oropharyngeal squamous cell carcinomas
Authors: Ernst-Jan M. Speel, Miriam Reuschenbach, Christian U. Huebbers, Elena-Sophie Prigge, Justo L. Bermejo, Simon Kalteis, Simon Preuss, Jutta Kolligs, Nadine C. Olthof, Bernd Kremer, Steffen Wagner, Jens P. Klussmann, Svetlana Vinokurova, Magnus von Knebel Doeberitz
Journal: Cancer Research (2015)

Abstract Background: The viral E2 protein is a transcriptional repressor of the HPV oncogenes E6/E7 and loss of E2 function is considered a key step in carcinogenesis. Integration of HPV into the host genome may disrupt the E2 gene. Furthermore, methylation of CpG dinucleotides in E2 binding sites (E2BSs) in the HPV upstream regulatory region (URR) may interfere with transcriptional repression of E6 and E7 by the E2 protein. We hypothesized that CpG methylation of the E2BS is found in a proportion of HPV16-associated oropharyngeal squamous cell cancers (OPSCC) in association with E2 gene integrity and viral integration. Methods: Methylation of 10 CpGs within the URR, encompassing E2BSs 1, 2, 3 and 4, was quantitatively analyzed by bisulfite pyrosequencing in 57 HPV16-associated OPSCC. E2 status was analyzed by gene amplification and quantitative real-time RT-PCR. Viral integration was determined by integration-specific PCR methods. Results: Three subgroups with differential E2BSs3 and 4 methylation were identified: a) complete methylation (&amp;gt;80%) associated with presence of integrated HPV genomes with intact E2 gene, b) intermediate methylation levels (20-80%) with predominantly episomal HPV genomes with intact E2, and c) no methylation (&amp;lt;20%) with integrated HPV with disrupted E2. Patients with complete and without methylation had poor 5-year overall survival compared to patients with intermediate methylation (stage-adjusted hazard ratio 3.8 (95%CI 1.3-11.2) and 3.1 (95%CI 1.14-8.28); p = 0.03). Conclusions: E2BSs3 and 4 methylation in oropharyngeal cancers with episomal HPV and integrated HPV with intact E2 gene might explain deregulated viral oncogene expression in the presence of E2. The methylation level appears to be of prognostic significance for patients with HPV-associated OPSCC. Citation Format: Ernst-Jan M. Speel, Miriam Reuschenbach, Christian U. Huebbers, Elena-Sophie Prigge, Justo L. Bermejo, Simon Kalteis, Simon Preuss, Jutta Kolligs, Nadine C. Olthof, Bernd Kremer, Steffen Wagner, Jens P. Klussmann, Svetlana Vinokurova, Magnus von Knebel Doeberitz. Methylation status of HPV16 E2-binding sites identifies subtypes of HPV-associated oropharyngeal squamous cell carcinomas. [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 828. doi:10.1158/1538-7445.AM2015-828
Bone Marrow Transplantation in Acid Sphingomyelinase-Deficient Mice: Engraftment and Cell Migration Into the Brain as a Function of Radiation, Age, and Phenotype
Authors: Silvia R.P. Miranda, Shai Erlich, Jan W.M. Visser, Shimon Gatt, Arie Dagan, Victor L. Friedrich, Edward H. Schuchman
Journal: Blood (1997)
Hypoxic pulmonary vasoconstriction: clinical implications
Authors: J. Michael B. Hughes
Journal: European Respiratory Journal (2015)

Hypoxic pulmonary vasoconstriction (HPV) and its mechanism of action continue to be of great interest to clinicians and physiologists. Sommer et al. [1] have reviewed HPV in this issue of the European Respiratory Journal . The literature is so extensive that another recent comprehensive review contained 2229 references [2]. HPV is an adaptation for fetal development and affords some advantage in optimising gas exchange in adults http://ow.ly/Uh54o
Role of Circulating ICOS+ Follicular Helper T Cells in the Pathogenesis of Birch Pollen Allergy
Authors: Ryuta Kamekura, Koji Kawata, Sumito Jitsukawa, Tomonori Nagaya, Keiji Yamashita, Fumie Ito, Kenichi Takano, Katsunori Shigehara, Tetsuo Himi, Shingo Ichimiya
Journal: Journal of Allergy and Clinical Immunology (2016)
A Phase Ii Study on Combination of Axitinib and Transarterial Chemoembolization (Tace) for Treatment of Inoperable Hepatocellular Carcinoma (Hcc)
Authors: S.L. Chan, W. Yeo, F. Mo, L. Li, K. Lee, P. Hui, B. Ma, T.S.K. Mok, A.T.C. Chan, P.B.S. Lai, S.C.H. Yu
Journal: Annals of Oncology (2014)
Impact Of Prophylaxis With Defibrotide On The Occurrence Of Acute GvHD In Allogeneic HSCT
Authors: Selim Corbacioglu, Simone Cesaro, Maura Faraci, Bernd Gruhn, Jaap J Boelens, Ansgar Schulz, Ingo Mueller, Jerry Stein, Robert Wynn, Johann Greil, Karl-Walter Sykora, Jacek Toporski, Petr Sedlacek, Paul G. Schlegel, Karoline Ehlert, Christine Mauz-Koerholz, Peter Bader, Elena Tudone, Maria Ballabio, Carin Heringa, Christina Peters
Journal: Blood (2013)
In Vivo Purging with Hyper-CVAD Plus Rituximab Followed by Autologous Stem Cells Transplant and Rituximab Maintenance in Newly Diagnosed Mantle Cell Lymphoma: A Pilot Study for GISL (Italian Cooperative Study Group for Lymphoma).
Authors: Edoardo Benedetti, Francesco Caracciolo, Sara Galimberti, Federico Papineschi, Matteo Pelosini, Giulia Cervetti, Maido Gioacchino Castiglioni, Sandra Mechelli, Paola Scatena, Maura Brugiatelli, Mario Petrini
Journal: Blood (2005)
Secondary drug resistance during an intravenous intermittent chemotherapy in newly cases TB
Authors: Tatyana Petrenko, Vladimir Krasnov
Journal: European Respiratory Journal (2011)

The purpose: To study frequency secondary drug resistance M. tuberculosis (SDR) during an intravenous (IV) intermittent chemotherapy in newly cases TB.

Methods: 76 pulmonary TB patients without previous chemotherapy enrolled in study. IV intermittent chemotherapy (3 times a week) appointed to 38 patients (IIC-group): isoniazid (H) and rifampicin (R) – 10 mg/kg IV, streptomycin (S) – 16 mg/kg intramuscularly (IM), pyrazinamide (Z) – 25 mg/kg per os. 38 patients received daily same doses of H, R, Z per os and S IM (a group of comparison). Both groups were identical. We determined SDR initially and every 2 month of patient treatment during 5-14 months.

Results: Initially there were 16 patients IIC-group and 11 in a comparison group with fully sensitive TB. In IIC-group there were 6 patients with primary MDR and 16 with primary drug resistance (not the combination of H&R). In comparison group there were 4 patients with primary MDR, and 23 with primary drug resistance. During chemotherapy 36 patients IIC-group and 34 from comparison group became sputum negative after 3,17±0,4 and 2,7±0,5 months accordingly (p=0,17, Mann-Whitney U-test). During the IV intermittent chemotherapy SDR appeared at 5 patients, secondary MDR – at 1 from 5. In comparison group SDR appeared at 4 patients, secondary MDR at 3 from 4 (RR = 1,54, 95%CI: 1,34–1,75). The mean term of formation SDR appeared in 3±0,3 and 2±0 months accordingly (p = 0,03, Mann-Whitney U-test).

Conclusion: The occurrence risk of secondary MDR is lowered, SDR term is slower in IIC-group than in group of daily treatment, in about 3 months from the start of chemotherapy. This term coincides with sputum negative results at patients of both groups.
Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia
Authors: K E Wahlberg, L C Wynne, H Oja, P Keskitalo, L Pykäläinen, I Lahti, J Moring, M Naarala, A Sorri, M Seitamaa, K Läksy, J Kolassa, P Tienari
Journal: American Journal of Psychiatry (1997)

This study assessed the interaction of genetic risk and rearing-family risk as a subsyndromal test measure of schizophrenic thought disorder in adoptees.A group of 58 adoptees with schizophrenic biological mothers was compared with 96 comparison adoptees at ordinary genetic risk; putative adoptee vulnerability was assessed blindly and reliably by using the Rorschach Index of Primitive Thought. Environmental risk was measured by using frequency of communication deviance as a continuous variable, scored independently from Rorschach assessments of the adoptive parents.High genetic risk in itself was not associated with greater vulnerability to schizophrenic thought disorder in the adoptees, as indicated by the Index of Primitive Thought. Also, greater communication deviance in the adoptive parents was not associated with greater thought disorder in the comparison adoptees. However, there was a highly significant gene-environment interaction. Among the offspring of the adoptive parents with high levels of communication deviance, a higher proportion of high-risk than comparison adoptees showed evidence of thought disorder. In contrast, among the offspring of adoptive parents with low communication deviance, a lower proportion of high-risk than comparison adoptees showed evidence of thought disorder. The distribution of communication deviance scores did not differ significantly between the adoptive parents of high-risk offspring and the adoptive parents of comparison offspring.The findings are consistent with genetic control of sensitivity to the environment. There is no evidence that high genetic risk of schizophrenia among offspring is associated with high levels of communication problems in rearing parents.
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Agglutination of Leukemic and 2,4-Dinitrophenyl-Tagged Normal Human Lymphocytes by Wheat Germ Agglutinin&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: P R Madyastha, R F Barth, K R Madyastha
Journal: JNCI Journal of the National Cancer Institute (1975)

The present study was undertaken to determine if leukemic and 2,4-dinitrophenyl (DNP)-tagged normal human lymphocytes shared common receptors for Wheat Germ Agglutinin (WGA), a lectin capable of reacting with malignant cells. Normal peripheral blood lymphocytes were tagged with 2,4-dinitrofluorobenzene (DNFB) at a ratio of 1011 molecules/cell. Various concentrations of WGA were added to leukemic or tagged or untagged normal lymphocytes and incubated for 20 minutes at 37° C, after which agglutination was scored visually. A readily discernible quantitative difference in the agglutinability of leukemic and DNP-tagged versus untagged normal cells was seen at all concentrations of WGA in the range of 50–800 µg/ml. The reaction was maximal when a ratio of 1011 molecules of DNFB/cell was used for tagging and decreased progressively with 108, 106 , 104, or 102 molecules. The agglutination of leukemic and DNP-tagged normal lymphocytes by 200 µ,g/ml of WGA was completely blocked by 0.1 M N-acetylglucosamine (GlcNAc) while as Iowa concentration as 0.001 M GlcNAc inhibited the reactivity of untagged cells. Since the agglutination of leukemic and DNP-tagged normal lymphocytes was equally inhibited by GlcNAc, this suggests that the same or similar receptor sites were involved in the two reactions. On the basis of our observations we propose that the initial step in the agglutination of leukemic and DNP-tagged normal lymphocytes by WGA is the binding of the lectin to specific receptors rather than to DNP residues on the cell surface, since leukemic cells tagged with DNFB did not show increased agglutinability.
Rab11-FIP1C Is a Critical Negative Regulator in ErbB2-Mediated Mammary Tumor Progression
Authors: Pierre-Luc Boulay, Louise Mitchell, Jason Turpin, Julie-Émilie Huot-Marchand, Cynthia Lavoie, Virginie Sanguin-Gendreau, Laura Jones, Shreya Mitra, Julie M. Livingstone, Shirley Campbell, Michael Hallett, Gordon B. Mills, Morag Park, Lewis Chodosh, Douglas Strathdee, Jim C. Norman, William J. Muller
Journal: Cancer Research (2016)

Abstract Rab coupling protein (FIP1C), an effector of the Rab11 GTPases, including Rab25, is amplified and overexpressed in 10% to 25% of primary breast cancers and correlates with poor clinical outcome. Rab25 is also frequently silenced in triple-negative breast cancer, suggesting its ability to function as either an oncogene or a tumor suppressor, depending on the breast cancer subtype. However, the pathobiologic role of FIP family members, such as FIP1C, in a tumor-specific setting remains elusive. In this study, we used ErbB2 mouse models of human breast cancer to investigate FIP1C function in tumorigenesis. Doxycycline-induced expression of FIP1C in the MMTV-ErbB2 mouse model resulted in delayed mammary tumor progression. Conversely, targeted deletion of FIP1C in the mammary epithelium of an ErbB2 model coexpressing Cre recombinase led to accelerated tumor onset. Genetic and biochemical characterization of these FIP1C-proficient and -deficient tumor models revealed that FIP1C regulated E-cadherin (CDH1) trafficking and ZONAB (YBX3) function in Cdk4-mediated cell-cycle progression. Furthermore, we demonstrate that FIP1C promoted lysosomal degradation of ErbB2. Consistent with our findings in the mouse, the expression of FIP1C was inversely correlated with ErbB2 levels in breast cancer patients. Taken together, our findings indicate that FIP1C acts as a tumor suppressor in the context of ErbB2-positive breast cancer and may be therapeutically exploited as an alternative strategy for targeting aberrant ErbB2 expression. Cancer Res; 76(9); 2662–74. ©2016 AACR.
Afatinib Versus Methotrexate (Mtx) As Second-Line Treatment for Patients with Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (Hnscc) Who Progressed After Platinum-Based Therapy: Primary Efficacy Results of Lux-Head &amp; Neck 1, a Phase III Trial
Authors: J-P. Machiels, R.I. Haddad, J. Fayette, L.F. Licitra, M. Tahara, J.B. Vermorken, P.M. Clement, T. Gauler, D. Cupissol, J.J. Grau, J. Guigay, F. Caponigro, G. De Castro, L. De Souza Viana, U. Keilholz, J.M. Del Campo, X.J. Cong, L. Svensson, E. Ehrnrooth, E.E.W. Cohen
Journal: Annals of Oncology (2014)
High-intensity interval training: key data needed to bridge the gap from laboratory to public health policy
Authors: Stuart R Gray, Carrie Ferguson, Karen Birch, Laura J Forrest, Jason M R Gill
Journal: British Journal of Sports Medicine (2016)

The World Health Organization and a number of national bodies recommend adults undertake at least 150 min/week of moderate intensity physical activity, or 75 min/week of vigorous intensity physical activity. However, a large proportion of the population do not achieve these targets. Lack of time is often cited as a primary barrier,1 and many researchers have suggested that high-intensity interval training (HIIT), with interval durations from 10 s to 4 min and intensities ranging from 85% maximal heart rate (HRmax) to ‘all out’ efforts, may provide a time-efficient solution to improve public health.2 

A wealth of evidence has demonstrated that HIIT can elicit a range of health benefits such as improved cardiorespiratory fitness, insulin sensitivity and vascular function, with these benefits being of at least a similar magnitude to those seen with standard moderate intensity physical activity interventions.3 ,4 These data are clear and convincing. However, they largely emanate from …
Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL)
Authors: A.S. Cottereau, S. Becker, F. Broussais, O. Casasnovas, S. Kanoun, M. Roques, N. Charrier, S. Bertrand, R. Delarue, C. Bonnet, R. Hustinx, P. Gaulard, L. de Leval, P. Vera, E. Itti, N. Mounier, C. Haioun, H. Tilly, M. Meignan
Journal: Annals of Oncology (2016)
Canine Papilloma: The Structural Characterization of Oral Papilloma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A. M. Watrach, L. E. Hanson, R. C. Meyer
Journal: JNCI Journal of the National Cancer Institute (1969)

The structural characteristics of canine oral papilloma virus were studied by the negative-contrast technique and in resin-embedded, sectioned specimens. Virus particles tended to accumulate in large numbers in the nucleoplasm of the affected cells and had a distinct propensity to aggregate in crystalline formations. Individual particles ranged from 470–530 A, with an average diameter of 490 A. In negatively stained preparations, virus particles averaged 560 A. The outer shell of the particles consisted of a close-packed array of morphological units regularly disposed over the surface. Analysis of the configuration of morphological units revealed the following structural pattern: 1) The number of the units around the periphery of the particles was 15–16. 2) The total number of units resolved on one side of virus particles was estimated at 34–35. 3) The disposition of the neighboring 5-coordinated units was characteristic of a skew class of surface structure. These results indicate that the shell of canine oral papilloma virus consists of 72 morphological units and has a skew surface lattice in common with viruses of the papilloma-polyoma group.
A novel splenic B1 regulatory cell subset suppresses allergic disease through phosphatidylinositol 3-kinase–Akt pathway activation
Authors: Takashi Matsushita, Doanh Le Huu, Tadahiro Kobayashi, Yasuhito Hamaguchi, Minoru Hasegawa, Kazuhito Naka, Atsushi Hirao, Masamichi Muramatsu, Kazuhiko Takehara, Manabu Fujimoto
Journal: Journal of Allergy and Clinical Immunology (2016)
Conservative Management Vs. Allogeneic Hematopoietic Cell Transplantation For Polycythemia Vera: A Systematic Review and Decision-Analysis
Authors: Jasmin Lacevic, Tea Reljic, Najla El Jurdi, Mohamed A Kharfan-Dabaja, Taiga Nishihori, Rami S. Komrokji, Ambuj Kumar, Benjamin Djulbegovic
Journal: Blood (2013)
Sequential therapy for 10 days versus triple therapy for 14 days in the eradication of<i>Helicobacter pylori</i>in the community and hospital populations: a randomised trial
Authors: Jyh-Ming Liou, Chieh-Chang Chen, Chi-Yang Chang, Mei-Jyh Chen, Chien-Chuan Chen, Yu-Jen Fang, Ji-Yuh Lee, Tsung-Hua Yang, Jiing-Chyuan Luo, Jeng-Yih Wu, Tai-Cherng Liou, Wen-Hsiung Chang, Yao-Chun Hsu, Cheng-Hao Tseng, Chun-Chao Chang, Ming-Jong Bair, Tzeng-Ying Liu, Chun-Fu Hsieh, Feng-Yun Tsao, Chia-Tung Shun, Jaw-Town Lin, Yi-Chia Lee, Ming-Shiang Wu
Journal: Gut (2015)

<h3>Objective</h3> Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10 days (S10) versus triple therapy for 14 days (T14) in the first-line treatment of <i>Helicobacter pylori.</i> We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. <h3>Design</h3> We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with <i>H pylori</i> infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative <sup>13</sup>C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. <h3>Results</h3> The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. <h3>Conclusions</h3> S10 was not superior to T14 in areas with low clarithromycin resistance. <h3>Trial registration number</h3> NCT01607918.
A double blind placebo-controlled randomized phase III study of high dose continuous infusion cytosine arabinoside (araC) with or without VNP40101M in patients (pts) with first relapse of acute myeloid leukemia (AML)
Authors: D. DeAngelo, S. M. O'Brien, N. Vey, K. Seiter, W. Stock, A. Cahill, A. Pigneux, D. Claxton, R. Stuart, F. J. Giles
Journal: Journal of Clinical Oncology (2008)

7051 Background: VNP40101M (101M) is a novel alkylating agent that has demonstrated anti- leukemia activity both as a single agent and in combination with araC (Giles et al, 2004, 2005, 2007). Methods: Eligible pts were ≥ 18 years old, PS 0–2, and in relapse after first CR (CR1) of 3–24 months. Pts were randomized using a 2:1 schema to araC 1.5 g/m2 (d1–3) + 101M 600 mg/m2 (treatment group [T]), or araC 1.5 g/m2 (d1–3) + placebo (control group [C]). Pts with bone marrow improvement could receive a 2nd induction (ind). Pts with CR/CRp were consolidated according to original assignment (101M dose 400 mg/m2). Primary endpoint was CR/CRp (ORR). Secondary endpoints were response duration, progression-free and overall survival (OS). The design included 420 pts, with an interim analysis by data safety monitoring board (DSMB) for safety and efficacy of the first 210 patients. Results: Following DSMB review in May 2007 the study was placed on hold due to a disproportionate death rate between T & C. T (140 pts) and C (70 pts) were comparable in age (median 59 yrs), ECOG PS, duration of CR1 (median 290 days), and risk groups (age <60 or ≥ 60 yrs, CR1 3–12 or 12–24 mos). ORR for T vs C was 37% vs 19% (p=0.004); median OS for T vs C was 128 vs 182 days (p=0.039). Mortality analysis (deaths from all causes ≤ 30 days or from AEs ≤ 60 days from any study treatment) included 39% (55/140) T and 8.6% (6/70) C pts. 67% (37/55) of T deaths were due to infection, sepsis, or pneumonia. 18% (10/55) T deaths were due to pulmonary events (8/10 ARDS [4 with BMT prior to study], 7/10 with intercurrent infection) occurring between days 9–96 (7 post ind 1, 1 post ind 2, 2 post consolidation). C deaths were due to sepsis/pneumonia (2), AML (2) or multi-organ failure (2). Myelosuppression and infection AEs showed similar incidence of gr 3–4 events. Median neutrophil recovery for T=32 days; C=25 days. Conclusions: Higher ORR was achieved with 101M + araC; however this was offset by higher mortality compared to pts receiving araC alone. Myelosuppression and related complications remain a challenge in combining cytotoxic agents. Future considerations include dose reduction of 101M and stringent supportive care. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc.
Cox-2 Status Modulates the Activation of Hedgehog Pathway and Consequently the Expression of Stem Cell Markers in Patients with Pancreatic Ductal Adenocarcinoma
Authors: A. Conti, M. Santoni, A. Bittoni, K. Andrikou, A. Lanese, C. Pellei, C. Loretelli, A. Mandolesi, S. Alfonsi, M. Scarpelli, S. Cascinu
Journal: Annals of Oncology (2014)
Abstract 16182: Postoperative Outcome in Primary Mitral Regurgitation: Impact of Preoperative Exercise Pulmonary Hypertension
Authors: Julien Magne, Erwan Donal, Haifa Mahjoub, Beatrice Miltner, Christophe Thebault, Luc A Pierard, Philippe Pibarot, Patrizio Lancellotti
Journal: Circulation (2013)

Introduction: The management of asymptomatic patients with primary mitral regurgitation (MR) remains controversial. Exercise-induced pulmonary hypertension (ExPHT) was recently reported as a strong...