tbuckley/cabot-search huggingface dataset:
Low-Dose Methotrexate as Salvage Therapy for Refractory Graft-Versus-Host Disease (GVHD) after Reduced-Intensity Conditioning (RIC) for Allogeneic Stem Cell Transplantation (allo-SCT).
Authors: Mohamad Mohty, Hugues de Lavallade, Catherine Faucher, Sabine Furst, Jean El-Cheikh, Didier Blaise
Journal: Blood (2005)
Perifollicular Variant of Peripheral T-Cell Lymphoma, UNS: A Distinct Lymphoma Type with Cytogenetic andcytogenetic and Clinical Findings Different from Those of Angio-Immunoblastic Lymphoma
Authors: Assia Bassarova, Francesca Micci, Gunhild Trøen, Harald Holte, Jan Delabie
Journal: Blood (2014)
Outcome of Patients with Relapsed/Refractory AIDS-Related Lymphoma In the AIDS Malignancy Consortium (AMC) 1997–2008
Authors: Ariela Noy, Ulas Darda Bayraktar, Neel Gupta, Adam M. Petrich, Page Moore, Shelly Lensing for the AIDS Malignancy Consortium
Journal: Blood (2010)
P94 The management of respiratory tract fungal disease in cystic fibrosis – a uk survey of current practice
Authors: M Boyle, JE Moore, DG Downey
Journal: Thorax (2016)

<i>Aspergillus fumigatus</i> is commonly found in the airways of patients with Cystic Fibrosis, (CF). Allergic Bronchopulmonary Aspergillosis, (ABPA), is the most recognised clinical condition associated with <i>Aspergillus.</i> The most widely used diagnostic criteria are from the Cystic Fibrosis Foundation Consensus Conference 2003. However, diagnosis remains challenging due to the overlap of classical symptoms and radiological features of ABPA and CF. There are a lack of clinical trials with clear outcomes to guide management of fungal disease, leading to variability between CF centres. The aim of this survey was to assess the variability in current practice across the UK in diagnosis and management of fungal lung disease in CF patients. A 21 question anonymous online survey was sent to 94 paediatric and adult CF consultants in the UK. The response rate was 60.6% with 55 full and 2 partially completed surveys. Thirty-two respondents were adult physicians and twenty-five paediatricians. For a first diagnosis of ABPA 20 (35.1%) treat with Prednisolone alone, 19 (33.3%) use Prednisolone with Itraconazole capsules, 19 (33.3%) use Prednisolone with Itraconazole liquid and 2 (3.5%) choose Voriconazole. Only 5 (8.8%) treat with Prednisolone alone for a 1<sup>st</sup> relapse, preferring Prednisolone with Itraconazole Liquid (33.3%) or with Itraconazole capsules (24.6%). To reduce treatment, 21 (36.8%) decrease steroids to zero over time and maintain azole therapy, 18 (31.6%) stop the azole and steroid after a fixed time and 5 (8.8%) stop azole after a fixed time and maintain a small steroid dose. Variations in specific therapies were reported, including the use of pulsed Methylprednisolone, Posaconazole, nebulised Amphotericin and Omalizumab. Thirty-eight (66.7%) respondents believe <i>Aspergillus</i> colonisation of the airway can cause clinical deterioration and 37 (66.1%) would treat this. <i>Scedosporium apiospermum</i> infection has been diagnosed and treated by 35 (61.4%) of respondents. Results of this survey highlight significant differences in treatment regimes for ABPA, with increasing variation seen in the management of subsequent relapses. Respondent comments showed a wide range of opinions. This survey highlights the lack of evidence currently available to guide the management of CF fungal disease.
S52 Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor β1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis
Authors: OJ Brand, A Pasini, A Habgood, AJ Knox, G Jenkins, L Pang
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease that is refractory to current treatment options. Transforming growth factor (TGF)-β1 is a key pro-fibrotic cytokine that plays a crucial role in IPF pathogenesis. Our group previously demonstrated distinct epigenetic modifications involved in repression of the antifibrotic gene cyclooxygenase-2 (COX-2) in fibroblasts from IPF (F-IPF) lungs compared with fibroblasts from non-fibrotic lungs (F-NL). Epigenetic drugs capable of inhibiting DNA and histone modifications may, therefore, represent a putative novel therapy. The aim of this study was to investigate the ability of 4 epigenetic inhibitors to regulate TGF-β-driven fibrosis in <i>ex vivo</i> mouse lung. <h3>Methods</h3> A precision-cut lung slice (PCLS) model of fibrosis was established using the previously described<sup>1</sup> CC10-tTS-rtTA-TGFβ<sub>1</sub> transgenic (tgTGF-β<sub>1</sub>) mouse. The model was first assessed by investigating PCLS overexpression of TGF-β<sub>1 </sub>in response to stimulation of the transgene by doxycycline treatment. Gene expression of COX-2 and fibrotic markers including collagen were assessed after 4 days of treatment. The anti-fibrotic potential of 4 epigenetic inhibitors; BIX01294 (BIX, inhibitor of G9a histone methyltransferase), 3-deazaneplanocin A (DZNep, inhibitor of EZH2 histone methyltransferase), SAHA (inhibitor of histone deacetylases, HDACs) and Decitabine (DAC, DNA demethylating agent) was investigated. Viability of PCLS was assessed by MTT and Prestoblue® assay. <h3>Results</h3> Treatment of PCLS from tgTGF-β<sub>1 </sub>mice with doxycycline induced a concentration-dependent increase in global TGF-β<sub>1</sub>, pro-fibrotic markers including collagen and pro-inflammatory COX-2, which was comparable to recombinant TGF-β<sub>1</sub> treatment. Treatment with three of the epigenetic inhibitors BIX01294, DZNep and DAC did not reduce the pro-fibrotic response following doxycycline treatment. However SAHA demonstrated a significant suppressive effect on COX-2 and collagen expression, while not directly affecting TGF-β<sub>1 </sub>transgene expression. <h3>Conclusions</h3> The data suggests that SAHA has the potential to reduce fibrosis in a TGF-β<sub>1</sub> driven model of pulmonary fibrosis. Further work is currently underway to assess the anti-fibrotic potential of this drug in tgTGF-β<sub>1 </sub>animals. <h3>Reference</h3> Lee CG, Cho SJ, Kang MJ, <i>et al</i>. Early growth response Gene 1-mediated apoptosis is essential for transforming growth Factor β<sub>1</sub>-induced pulmonary fibrosis. <i>J Exp Med</i> 2004; <b>200</b>(3):377–389.
P3.07-009 Use of Adjuvant Chemotherapy for Non-Small Cell Lung Cancer: The Real-World Clinical Practice in Taiwan
Authors: Bin-Chi Liao, Yu-Yun Shao, James Chih-Hsin Yang, Ho-Min Chen, Ann-Lii Cheng, Mei-Shu Lai
Journal: Journal of Thoracic Oncology (2017)
Survival Impact of Time Repeated bcl2/IgH Rearrangement Measurements in Follicular Lymphoma Patients Treated with Front-Line Autotransplantation in the GELF-94 Trial by the GELA.
Authors: Broussais Florence, Mounier Nicolas, Delfau Marie-Hélène, Cayuela Jean-Marie, MacIntyre Elisabeth, Davi Frederic, Sebban Catherine, Belanger Coralie, Brousse Nicole, Brice Pauline, Haioun Corinne, Tilly Andre, Feugier Pierre, Bosly Andre, Coiffier Bertrand, Salles Gilles
Journal: Blood (2005)
Clofarabine Plus Low-Dose Cytarabine Induction Followed by Consolidation with Clofarabine Plus Low-Dose Cytarabine Alternating with Decitabine as Frontline Therapy for Patients (pts) with Acute Myeloid Leukemia (AML) ≥ 60 Years (yrs).
Authors: Sameer A Parikh, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Tapan Kadia, Farhad Ravandi, Alessandra Ferrajoli, Zeev Estrov, Jenny Feliu, Stefan Faderl
Journal: Blood (2009)
A Panel of Artificial Antigen-Presenting Cells (AAPC) Expressing Prevalent HLA Alleles Permits Generation of Cytotoxic T Cells Specific for Both Subdominant and Dominant Viral Epitopes for Adoptive Therapy.
Authors: Aisha Hasan, Wouter J. Kollen, A. Selvakumar, D. Trivedi, M. Sadelain, Richard J. O’Reilly
Journal: Blood (2007)
Angiogenic factors and soluble receptors in NCIC CTG BR.24.
Authors: C. L. Addison, K. Ding, H. Zhao, A. Le Maitre, S. A. Laurie, G. D. Goss, F. A. Shepherd, P. A. Bradbury, L. Seymour
Journal: Journal of Clinical Oncology (2011)

3047 Background: BR.24 randomized 296 NSCLC (IIIB/IV) patients (pts) to cediranib (CED; 30 or 45 mg/kg) vs placebo + ≤ 6 cycles paclitaxel (200mg/m2) and carboplatin (AUC 6) q3 weeks followed by CED/placebo. CED improved response and progression free survival (PFS). We examined potential predictive or prognostic biomarkers. Methods: Pretreatment VEGF, sVEGFR2, sVEGFR3 and SDF1a were analyzed by blinded duplicate ELISA (sensitivity ~3-70 pg/ml). Cut-points (VEGF:< or ≥1ng/ml, sVEGFR2: < or ≥ 11ng/ml, sVEGFR3: < or ≥ 35.5ng/ml and SDF-1a: ≤ or > 3.5ng/ml) were determined using graphical methods based on Martingale residuals derived from the prognostic model for placebo pts, and the estimated baseline cumulative hazard and coefficients. Cox regression models were used to correlate biomarker data with pt characteristics and PFS or overall survival (OS). Results: Characteristics for 149 pts with baseline biomarker values were similar to those without (147). PFS was longer in the marker vs no-marker cohort (p=0.03), but hazard ratio (HR) for PFS benefit from CED was similar in both (HR 0.81, 95% C.I. 0.54-1.24 with and HR 0.81, 95% C.I. 0.56-1.17 without marker data, interaction p=0.84). No biomarker was prognostic or predictive for OS. High sVEGFR2 was prognostic for better PFS for placebo (aHR 0.40, 95% C.I. 0.20-0.70, p=0.0008). Low baseline sVEGFR2 and sVEGFR3 were predictive of benefit from CED, but only low sVEGFR3 remained predictive in multivariate analysis (interaction p=0.05). Conclusions: While high sVEGFR2 was prognostic for better PFS, only low baseline sVEGFR3 was significantly predictive for PFS benefit from CED. Prospective studies validating these findings are planned. Biomarker level Placebo (n) Cediranib (n) HR (95% CI) p value Interaction Progression-free survival VEGF-low 5.6m (59) 6.9m (52) 0.86 (0.53-1.42), p=0.56 p=0.46 VEGF-high 5.5m (19) 5.7m (19) 0.69 (0.30-1.60), p=0.38 sVEGFR2-low 4.3m (33) 6.6m (33) 0.52 (0.28-0.97), p=0.04 p=0.06 sVEGFR2-high 6.6m (45) 6.8m (38) 1.07 (0.60-1.92), p=0.82 sVEGFR3-low 5.6m (60) 6.9m (53) 0.60 (0.36-0.99), p=0.04 p=0.05 sVEGFR3-high 6.2m (18) 4.4m (18) 1.79 (0.80-4.01), p=0.15 SDF-1a-low 5.5m (72) 6.6m (61) 0.71 (0.45-1.12), p=0.13 p=0.22 SDF1a-high 6.4m (6) 3.3m (10) 1.69 (0.54-5.21), p=0.36
Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen
Authors: Gilda G. Hillman, Lyndsey A. Reich, Shoshana E. Rothstein, Lisa M. Abernathy, Matthew D. Fountain, Kali Hankerd, Christopher K. Yunker, Joseph T. Rakowski, Eric Quemeneur, Philippe Slos
Journal: Journal for ImmunoTherapy of Cancer (2017)

We previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal adenocarcinoma (Renca) cells transfected with MUC1.Established subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation. Growth delays were monitored by tumor measurements and histological responses were evaluated by immunohistochemistry. Specific immunity was assessed by challenge with Renca-MUC1 cells. Generation of tumor-specific T cells was detected by IFN-γ production from splenocytes stimulated in vitro with tumor lysates using ELISPOT assays.Tumor growth delays observed by tumor irradiation combined with MVA-MUC1-IL-2 vaccine were significantly more prolonged than those observed by vaccine, radiation, or radiation with MVA empty vector. The sequence of cancer vaccine followed by radiation two days later resulted in 55-58% complete responders and 60% mouse long-term survival. This sequence was more effective than that of radiation followed by vaccine leading to 24-30% complete responders and 30% mouse survival. Responding mice were immune to challenge with Renca-MUC1 cells, indicating the induction of specific tumor immunity. Histology studies of regressing tumors at 1 week after therapy, revealed extensive tumor destruction and a heavy infiltration of CD45+ leukocytes including F4/80+ macrophages, CD8+ cytotoxic T cells and CD4+ helper T cells. The generation of tumor-specific T cells by combined therapy was confirmed by IFN-γ secretion in tumor-stimulated splenocytes. An abscopal effect was measured by rejection of an untreated tumor on the contralateral flank to the tumor treated with radiation and vaccine.These findings suggest that cancer vaccine given prior to local tumor irradiation augments an immune response targeted at tumor antigens that results in specific anti-tumor immunity. These findings support further exploration of the combination of radiotherapy with cancer vaccines for the treatment of cancer.
Routine assessment of the gut microbiome to promote preclinical research reproducibility and transparency
Authors: Hannah R Wardill, Joanne M Bowen, Ysabella ZA Van Sebille, Rachel J Gibson
Journal: Gut (2017)

The irreproducibility of preclinical, biomedical research is becoming increasingly problematic, as recently highlighted by Omary et al ,1 in the June issue of Gut . As discussed, variations in study design, mouse strain, sex and age are important factors that should be adequately described to promote study reproducibility.1 In line with recent speculation,2 authors also emphasised the gut microbiome as a potential confounder underlying inconsistencies in preclinical research data.

Recently, there has been a large influx of studies reporting dysbiotic changes in many preclinical models of human disease, both GI and non-GI.3 ,4 Although informative, much of this research continues to be associative. To dissect causative disease mechanisms, the impact of benign environmental factors relating to study design and rodent husbandry must be acknowledged.

Based on twin studies,5 it is understood that a core subset of bacteria are hereditary.6 However, environmental factors are thought to contribute more heavily to the composition of the gut microbiome. For example, in …
PUB071 Fragile-Site Associated Tumor Suppressor (FATS) Gene Expression Effect on the Sensitivity of Cisplatin and Gemcitabine in Advanced NSCLC
Authors: Ahmed Rabea, Ahmed Atef, Eman Desouky, Ola Khorshid, Ayman Gaber, Rabab Gaafar
Journal: Journal of Thoracic Oncology (2017)
P2.03a-043 A Retrospective Analysis of the Chemotherapy for ‘Very Old' Patients Aged 80 Years and Order with Advanced Lung Cancer
Authors: Yosuke Tamura, Yasuhito Fujisaka, Keiji Miyoshi, Ninso Matsunaga, Kenjiro Tsuruoka, Takahiko Nakamura, Shuhei Yoshida, Tetsufumi Kawaguchi, Masafumi Imanishi, Soichiro Ikeda, Isao Goto
Journal: Journal of Thoracic Oncology (2017)
OA14.05 A Framework to Support the Lung Cancer Nurse Specialist in the Development and Evaluation of Nurse-Led Clinics
Authors: Sarah Morgan, Sharon Savory, Jeanette Draffan, Vanessa Beattie, Josie Roberts, Diana Borthwick, June Morley, Simon Bolton, Jackie Fenemore, Sarah Field, Christine Thomas, Patricia Rees, Kelly Davies, Suzanne Vizor
Journal: Journal of Thoracic Oncology (2017)
P0060 : Antiviral therapy with sofosbuvir plus ribavirin in HCV-infected cirrhotic patients awaiting liver transplantation: Preliminary data from a single-centre experience
Authors: S. Strona, S. Martini, D. Arese, M. Sacco, R. Romagnoli, F. Tandoi, A. Ottobrelli, M.R. Torrani Cerenzia, F. Balzola, M. Salizzoni, M. Rizzetto
Journal: Journal of Hepatology (2015)
HbA Is More Effective Than HbF for Improving the Clinical Course in Sickle Cell Disease.
Authors: Marcos A.C. Bezerra, Andre Fattori, Magnum N. Santos, Dulcineia M. Albuquerque, Maria F. Sonati, Sara T.O. Saad, Aderson S. Araujo, Fernando F. Costa
Journal: Blood (2006)
Pancreatic cancer cell lines as patient-derived avatars: genetic characterisation and functional utility
Authors: Erik S Knudsen, Uthra Balaji, Brian Mannakee, Paris Vail, Cody Eslinger, Christopher Moxom, John Mansour, Agnieszka K Witkiewicz
Journal: Gut (2017)

Objective Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. Design 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines. Exome sequencing was performed on the originating tumour and developed models. RNA sequencing, histological and functional analyses were employed to determine the relationship of the patient-derived models to clinical presentation of PDAC. Results The cohort employed captured the genetic diversity of PDAC. From most cases, both cell lines and xenograft models were developed. Exome sequencing confirmed preservation of the primary tumour mutations in developed cell lines, which remained stable with extended passaging. The level of genetic conservation in the cell lines was comparable to that observed with patient-derived xenograft (PDX) models. Unlike historically established PDAC cancer cell lines, patient-derived models recapitulated the histological architecture of the primary tumour and exhibited metastatic spread similar to that observed clinically. Detailed genetic analyses of tumours and derived models revealed features of ex vivo evolution and the clonal architecture of PDAC. Functional analysis was used to elucidate therapeutic vulnerabilities of relevance to treatment of PDAC. Conclusions These data illustrate that with the appropriate methods it is possible to develop cell lines that maintain genetic features of PDAC. Such models serve as important substrates for analysing the significance of genetic variants and create a unique biorepository of annotated cell lines and xenografts that were established simultaneously from same primary tumour. These models can be used to infer genetic and empirically determined therapeutic sensitivities that would be germane to the patient.
FDG-PET for Assessment of Residual Tissue after Completion of Chemotherapy in Hodgkin Lymphoma - Report on the 2nd Interim Analysis of the PET Investigation in the Trial HD15 of the GHSG.
Authors: Volker Diehl, Carsten Kobe, Heinz Haverkamp, Markus Dietlein, Andreas Engert
Journal: Blood (2007)
Large-Scale CLL Genome Analysis Reveals Novel Cancer Genes, Including SF3B1
Authors: Youzhong Wan, Michael S Lawrence, Lili Wang, Petar Stojanov, Carrie Sougnez, Kristen Stevenson, Lillian Werner, Wandi Zhang, Eric G Folco, Bethany Tesar, Quinlan L Sievers, Stacey Gabriel, Nir Hacohen, Robin Reed, Matthew Meyerson, Todd R. Golub, Eric S Lander, Donna Neuberg, Jennifer R. Brown, Gad Getz, Catherine J Wu
Journal: Blood (2011)
6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells
Authors: Xiaowei Zhang, Daniela Castanotto, Sangkil Nam, David Horne, Cy Stein
Journal: Molecular Therapy (2017)

Approximately 15%–25% of men diagnosed with prostate cancer do not survive their disease. The American Cancer Society estimated that for the year 2016 the number of prostate cancer deaths will be 26,120. Thus, there is a critical need for novel approaches to treat this deadly disease. Using high-throughput small-molecule screening, we found that the small molecule 6-bromo-indirubin-3′-oxime (6BIO) significantly improves the targeting of antisense oligonucleotides (ASOs) delivered by gymnosis (i.e., in the absence of any transfection reagents) in both the cell cytoplasm and the nucleus. Furthermore, as a single agent, 6BIO had the unexpected ability to simultaneously downregulate androgen receptor (AR) expression and AR signaling in prostate cancer cells. This includes downregulating levels of the AR-V7, a drug-resistance-related AR splice variant that is important in the progression of prostate cancer. Combining 6BIO and an anti-AR oligonucleotide (AR-ASO) can augment the downregulation of AR expression. We also demonstrated that 6BIO enhances ASO function and represses AR expression through the inhibition of the two main glycogen synthase kinase 3 (GSK-3) isoforms: GSK-3α and GSK-3β activity. Our findings provide a rationale for the use of 6BIO as a single agent or as part of a combinatorial ASO-based therapy in the treatment of human prostate cancer. Approximately 15%–25% of men diagnosed with prostate cancer do not survive their disease. The American Cancer Society estimated that for the year 2016 the number of prostate cancer deaths will be 26,120. Thus, there is a critical need for novel approaches to treat this deadly disease. Using high-throughput small-molecule screening, we found that the small molecule 6-bromo-indirubin-3′-oxime (6BIO) significantly improves the targeting of antisense oligonucleotides (ASOs) delivered by gymnosis (i.e., in the absence of any transfection reagents) in both the cell cytoplasm and the nucleus. Furthermore, as a single agent, 6BIO had the unexpected ability to simultaneously downregulate androgen receptor (AR) expression and AR signaling in prostate cancer cells. This includes downregulating levels of the AR-V7, a drug-resistance-related AR splice variant that is important in the progression of prostate cancer. Combining 6BIO and an anti-AR oligonucleotide (AR-ASO) can augment the downregulation of AR expression. We also demonstrated that 6BIO enhances ASO function and represses AR expression through the inhibition of the two main glycogen synthase kinase 3 (GSK-3) isoforms: GSK-3α and GSK-3β activity. Our findings provide a rationale for the use of 6BIO as a single agent or as part of a combinatorial ASO-based therapy in the treatment of human prostate cancer.
Total Number of CD34 + Cells Per Ten High Power Fields in Bone Marrow Trephines of Patients with Chronic Myeloid Leukaemia Correlates with Probability of Complete Cytogenetic Response during the First Year of Treatment with Imatinib.
Authors: Victoria J. Elliot, D. Marin, D. Horncastle, K. Elderfield, J. Howard, J. F. Apperly, I. A. Lampert, K. N. Naresh
Journal: Blood (2004)
Treatment and Outcome Analysis of 2,904 Pateints from the EUTOS Population Based Registry
Authors: Verena Sophia Hoffmann, Michele Baccarani, Joerg Hasford, Doris Lindoerfer, Sonja Burgstaller, Dubravka Sertic, Paul Costeas, Jiri Mayer, Karel Indrak, Hele Everaus, Perttu Koskenvesa, Joelle Guilhot, Gabriele Schubert-Fritschle, Fausto Castagnetti, Francesco Di Raimondo, Sandra Lejniece, Laimonas Griskevicius, Noortje Thielen, Thomas Sacha, Andrzej Hellmann, Anna Turkina, Andrey Zaritskey, Andrija Bogdanovic, Zuzana Sninska, Irena Zupan, Felipe Casado, Bengt Simonsson, Richard E. Clark, Susanne Saussele, Andreas Hochhaus, Ruediger Hehlmann
Journal: Blood (2015)
P1.03-063 Quantitative Imaging Features Predict Incidence Lung Cancer in Low-Dose Computed Tomography (LDCT) Screening
Authors: Dmitry Cherezov, Samuel Hawkins, Dmitry Goldgof, Lawrence Hall, Yoganand Balagurunathan, Robert Gillies, Matthew Schabath
Journal: Journal of Thoracic Oncology (2017)