tbuckley/cabot-search huggingface dataset:
The effect of induction therapy with novel agents on stem cell mobilization in multiple myeloma
Authors: A. Mazumder, S. Jagannath, D. Vesole
Journal: Journal of Clinical Oncology (2007)

8102 Background: Thalidomide or bortezomib combined with dexamethasone (TD or BD respectively) are now being increasingly used as induction regimens for newly diagnosed multiple myeloma. There are conflicting reports on the effects of T on stem cell mobilization. Since we have used both these regimens at our center, we performed a retrospective analysis of stem cell mobilization after induction therapy with either TD (n = 22) or BD (n = 18). Methods: The patients were balanced with respect to initial Durie-Salmon stage, median number of cycles of induction therapy prior to collection, response to induction therapy, bone marrow cellularity and involvement, and time from end of therapy to collection. All patients were mobilized with G-CSF 10mcg/kg and collected in a large volume pheresis, with a goal of at least 6x10(6) CD34+ cells/kg (for tandem transplant). Results: To achieve our stem cell goal, the number of patients who required 3 or more phereses in the TD group was 17/22 whereas it was only 4/18 in the BD group. (p&lt;0.005). 3/3 patients who had received lenalidomide also required 3 or more phereses. Also, the number of CD34+ cells/kg obtained in the TD group was less–mean of 2.8x10(6) per pheresis, as compared to a mean of 5.2x10(6) per pheresis in the BD group (p&lt;0.01). Time to neutrophil engraftment was similar in both groups. However in the TD group there was a 1 day delay in platelets &gt; 20,000/ul (p&lt;0.05). Conclusions: Thus, thalidomide induction led to a lower yield of stem cells when compared to bortezomib. Differences in stem cell markers are being investigated. This may become especially important when limiting numbers of stem cells are available from elderly patients, those with prior radiation or bulk disease and when used for in vitro manipulation. It is possible that agents such as bortezomib may alter the bone marrow microenviroment differently from imids such as thalidomide. No significant financial relationships to disclose.
Phase II study of induction chemotherapy (ICT) with gemcitabine (G) and vinorelbine (V) followed by concurrent chemoradiation therapy (CCRT) with oral etoposide (E) and cisplatin (P) for inoperable stage IIIA/B non-small cell lung cancer (NSCLC)
Authors: D. H. Lee, J. Y. Han, K. H. Cho, J. H. Chun, H. G. Lee, J. J. Lee, H. R. Pyo, S. J. Yoon, J. I. Zo, J. S. Lee
Journal: Journal of Clinical Oncology (2004)

7255
Comparison between gemcitabine-based combination (G) and single-agent chemotherapy (S) for elderly patients (EP) with advanced non-small cell lung cancer (NSCLC): A literature-based meta-analysis
Authors: I. Carreca, F. Bellomo, G. Bronte, M. Burgio, A. Carreca, D. Piazza, S. Rizzo, S. Russo, L. Balducci
Journal: Journal of Clinical Oncology (2007)

19586 Background: It was estimated that a quarter of all patients who have a diagnosis of NSCLC worldwide are more than 70 years old. This meta-analysis tries to shed light on the controversial results of phase III trials evaluating in NSCLC EP doublets against third generation S. Methods: We performed a literature search using MEDLINE and Cochrane Library. We selected only clinical trials responding to the question of our meta-analysis. Outcomes recorded were 1-year survival rate (1-y SR), overall response rate (ORR) and haematological toxicity (HT). Fixed-effects and random-effects models were used to calculate pooled odds ratios (OR). An OR greater than 1 indicates that doublet is more effective for 1-y SR and ORR and more toxic for HT. Results: Three published randomized controlled phase III trials (SICOG 9909; MILES; AISCAP-SICOG) were selected yielding a total of 1082 patients (G: 426; S: 655) clustered in seven comparisons. Drugs delivered to randomized patients included gemcitabine, vinorelbine and paclitaxel. EP treated with doublets showed respect to control patients a pooled estimate for 1-y SR advantage of 36%, not statistically significant (OR=1.356; 95% CI=0.925–1.990; p&gt;0.05). The pooled estimate for ORR advantage was 57% and statistically significant (OR=1.559; 95% CI=1.220–2.015; p&lt;0.05). However G showed not significant difference for HT (OR=1.168; 95% CI=0.685–1.992; p&gt;0.05). Conclusions: These data confirm in EP superior efficacy and equal tolerability of G in comparison with S previously demonstrated for adult patients. Anyway G seems to not change prognosis of NSCLC EP. It is worthy to note that all the trials analysed showed some biases: early closure of the study, second-line therapy or crossover, lower dosage of drugs in combination regimen, inclusion of unfit or strongly comorbid patients. This meta-analysis doesn’t solve troubles in decision-making of treatment for EP, but suggest to design a better phase III trial including more patients and improving accrual criteria for reducing biases. An indication of a potentially active combination regimen (gemcitabine + paclitaxel) is suggested in SICOG 9909 trial. No significant financial relationships to disclose.
A Novel Splicing Mutation in NEMO Gene in a Patient with X-Linked Ectodermal Dysplasia with Immunodeficiency.
Authors: Syuhei Karakawa, Satoshi Okada, Miyuki Tsumura, Yoko Mizoguchi, Tomoki Kawai, Ryota Nishikomori, Shin'ichiro Yasunaga, Yoshihiro Takihara, Masao Kobayashi
Journal: Blood (2009)
Sphingosine 1-Phosphate (S1P) Induces Migration and ERK/MAP-Kinase-Dependent Proliferation in Chronic Lymphocytic Leukemia (B-CLL) Due to Expression of the G Protein-Coupled Receptors S1P1/4.
Authors: Gabriele Seitz, Sedat Yildirim, Andreas M. Boehmler, Lothar Kanz, Robert Möhle
Journal: Blood (2005)
Manual Chronic Partial Exchange In Children and Adolescents with Sickle Cell Disease: Impact on Clinical Outcome and Iron Overload
Authors: Michel Aloni, Alina Ferster, Phu-Quoc Le, Catherine Heijmans, Sophie Huybrechts, Christine Devalck, Malou Ngalula Mujinga, Nadira Azzi, Hanane El Kenz
Journal: Blood (2010)
An Integrative Genomics Approach Uncovers the Basis of Resistance to AZA Therapy in MDS and CMML
Authors: Ashwin Unnikrishnan, Elli Papaemmanuil, Dominik Beck, Arjun Verma, Ashu Kumari, Laura A. Richards, Kathy Knezevic, Vashe Chandrakanthan, Julie A.I. Thoms, Melinda L. Tursky, Yizhou Huang, Sally Galbraith, Austin G. Kulasekararaj, Magnus Tobiasson, Petter S. Woll, Andrea Pellagatti, Susan R. Wilson, Robert Lindeman, Jacqueline Boultwood, Kevin Lynch, Sten Eirik Jacobsen, Ghulam J Mufti, Eva Hellstrom-Lindberg, Karen Lee Mackenzie, Jason W.H. Wong, Peter J Campbell, John E. Pimanda
Journal: Blood (2015)
GW26-e0685 Identification of accessory pathways connecting the right atrial appendage and right ventricle
Authors: Fangzhou Liu, Xianzhang Zhan, Yumei Xue, Hongtao Liao, Xianhong Fang, Weidong Lin, Wei Wei, Hai Deng, Xin Li, Shulin Wu, ShuLin Wu
Journal: Journal of the American College of Cardiology (2015)
What role do cancer patients want to play in treatment decision making: A pooled-analysis
Authors: J. A. Sloan, M. Huschka, P. Atherton, L. F. Degner, T. Hack, T. Smith, T. Rummans, M. Clark
Journal: Journal of Clinical Oncology (2006)

8521 Background: The extent of patient involvement in the decision making process for cancer treatment can impact satisfaction with care. A pooled-analysis of clinical studies from the US and Canada incorporating the Control Preferences Scale (CPS) was conducted to produce normalized data regarding patient preferences and examine differences in role preference related to country, tumor type, gender and other demographics. Methods: Patient data culled from six trials indicated the treatment decision making role preferred and the role actually experienced clinically. Fisher’s Exact Tests were performed to compare role distribution concordance and association with clinical and demographic variables. Results: Data available for 3,491 patients indicated that 25% preferred an active role, 46% a collaborative role, and 29% a passive role in their medical treatment decision making. In terms of actual experience, 30% of patients reported taking on an active role, 34% collaborative, and 36% passive. Overall, 61% of patients reported playing the role they prefer. Differences between genders in the preferred role were slight, but males achieved their preferred role more often than females (66% vs. 60%, p=0.011). More women actually took a passive role than men (40% vs. 24%, p&lt;0.0001) as did more patients in the US than Canada (84% vs. 54%, p&lt;0.001). Canadian patients preferred more passive than active roles (33% vs 22.4%) and US patients preferred more active to passive roles (31.9% vs 14.2%) (p&lt;0.001). Older patients preferred a more passive role and took on that role. Differences in role preference across tumor types were negligible. Conclusions: Roughly one half of the cancer patients studied indicated that they preferred to have a collaborative relationship with physicians, the remaining patients split equally between an active and passive role. The US cohort seemed to want to be more assertive than their Canadian counterparts and women ended up playing a more passive role than they preferred. Given these gender and cross-county differences these findings highlight the need for individualized patient communication styles to be incorporated into treatment plans No significant financial relationships to disclose.
Tositumomab and Iodine I 131 Tositumomab (the BEXXAR® Therapeutic Regimen) Shows Efficacy in Elderly Patients (pts) with Relapsed/Refractory Low-Grade (LG), Follicular, and Transformed Non-Hodgkin’s Lymphoma (NHL).
Authors: Stephanie A. Gregory, Andrew Zelenetz, Susan J. Knox, Julie Vose, John P. Leonard, Mark Kaminski
Journal: Blood (2004)
Graft-Versus-Lymphoma Effect After Non-Myeloablative Allogeneic Transplant Induces Molecular Remission Assessed by High-Throughput Sequencing of T Cell Receptor in Patients with Advanced Stage Mycosis Fungoides and Sezary Syndrome
Authors: Wen-Kai Weng, Randy Armstrong, Sally Arai, Katherine Sutherland, Richard T. Hoppe, Youn H. Kim
Journal: Blood (2011)
Anthracycline regimens versus CMF in the adjuvant treatment of early breast cancer (EBC): A matter of difference
Authors: A. Gennari, M. Sormani, M. Costantini, P. Pronzato, R. Rosso, P. Bruzzi
Journal: Journal of Clinical Oncology (2006)

569 Background: Anthracycline-based adjuvant chemotherapy (CT) in EBC was found, in the latest EBCTCG overview, to be associated with a 15% reduction in mortality, when compared to CMF. However, differences among trials, and specifically the use of suboptimal experimental arms (underdosed anthracyclines) and non conventional CMF (i.v.), require a careful interpretation of this finding. Methods: To evaluate the reduction in mortality, associated to different anthracycline and CMF regimens, we performed a systematic overview of abstracted data from published randomised trials comparing CMF with anthracyclines. Those studies including other drugs were excluded. Fifteen retrieved trials, comprising 15.831 women, were divided into 6 groups according to the type of CMF (oral or i.v.), and to the type of anthracycline regimen: 3 drugs (FAC/FEC), 2/1 drugs (AC/EC, A/E) and sequential schedules (Anthra→CMF). From each study, the estimates of the Hazard Ratio (HR; anthra vs CMF) and of its variance were abstracted or estimated from the presented results. HRs from studies of the same group were combined according to standard meta-analytic techniques. Summary estimates of HR for oral or i.v. CMF and for different anthracycline schedules were similarly obtained. Results: The overall comparison confirms a superiority of anthracyclines over CMF (HR 0.83 - 95%CI 0.77–0.90, p&lt;0.001). HRs in the 6 groups of studies are reported in the table . When i.v. CMF is compared to any anthracycline regimen, the HR is 0.76 (95%CI 0.67–0.86, p&lt;0.001; heterogeneity p 0.01), while with oral CMF, the HR is 0.88 (95%CI 0.80–0.97, p 0.01; heterogeneity p 0.06). Conclusions: The magnitude of the survival benefit of anthracyclines over CMF seems to be strongly affected by the type of anthracycline regimen and by the type of CMF, the largest effect being observed in trials using sequential schedules and i.v. CMF. Final results will be presented at the meeting, including evaluation of regimen type and its effects on toxicity and quality of life. [Table: see text] No significant financial relationships to disclose.
Moderate exercise cuts type 2 diabetes risk but more is better, review finds
Authors: Susan Mayor
Journal: BMJ (2016)

People who are moderately physically active for 150 minutes a week have a 26% lower risk of developing type 2 diabetes than those who are inactive, a meta-analysis has shown,1 and a higher level of physical activity is associated with an even greater risk reduction.

The link between type 2 diabetes and physical inactivity is well known, but it is not clear how much activity is needed to reduce the risk of developing diabetes or whether higher levels of activity reduce this risk …
High-Level IGF1R Expression Is Required for Leukemia Stem Cell Activity In T-ALL and Is Supported by Notch Signaling.
Authors: Hind Medyouf, Samuel Gusscott, Carol Wai, Oksana Nemirovsky, Vincenzo Giambra, Joan M Carboni, Marco Gottardis, Francoise Pflumio, Michael Pollak, Martin Holzenberger, Andrew P Weng
Journal: Blood (2010)
Wireless Video-Capsule Endoscopy Is a More Sensitive Investigative Method Than Gastro-Intestinal Endoscopy and Biopsies for the Diagnosis of Acute GI-Gvhd.
Authors: Jean-Baptiste Micol, Valerie Coiteux, Laurent Pascal, Louis Terriou, Christophe Willekens, Jean-Pierre Jouet, Vincent Maunoury, Ibrahim Yakoub-Agha
Journal: Blood (2008)
Bloodstream Progenitor-Cell Traffic In Primary Myelofibrosis Reveals Cell Subsets Showing Some Features Of Very-Small Embryonnic-Like Stem Cells (VSELs), Along With Endothelial (PEC), Mesenchymal (MPC) and Hematopoietic (HPC) Progenitor Cells
Authors: Mario Ojeda-Uribe, Hanna Sovalat, Laura Jung, Christophe Desterke, Sylvie Thiebault, Pierre Bories, Laurent Mauvieux, Philippe Tropel, Jean-Claude Eisenmann, Bruno Lioure, Anne-Claire Voegeli, Eric Jeandidier, Stephane Viville, Valerie Rimelen, Marie-Caroline Le Bousse-Kerdiles
Journal: Blood (2013)
Dasatinib Induces a Higher Molecular Response in Japanese Patients with Chronic Myeloid Leukemia After Imatinib Failure Than in Western Populations: Kanto CML Study
Authors: Yoshihiro Hatta, Koiti Inokuchi, Takashi Kumagai, Kazuteru Ohashi, Atsushi Shinagawa, Jin Takeuchi, Shinichiro Okamoto, Hisashi Wakita, Yasuji Kouzai, Yukari Shirasugi, Chikashi Yoshida, Koji Oba, Junichi Sakamoto, Hisashi Sakamaki
Journal: Blood (2011)
Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes
Authors: Jonne Doorduin, Joeke L. Nollet, Lisanne H. Roesthuis, Hieronymus W. H. van Hees, Laurent J. Brochard, Christer A. Sinderby, Johannes G. van der Hoeven, Leo M. A. Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes.To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support.In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured.Rocuronium titration resulted in significant declines of Vt (mean ± SEM, 9.3 ± 0.6 to 5.6 ± 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 ± 2.5 to 10.7 ± 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 ± 2.3 to 4.5 ± 0.7 μV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 ± 0.02 to 7.35 ± 0.02; P < 0.0001), and mean arterial blood pressure increased (84 ± 6 to 99 ± 6 mm Hg; P = 0.0004), as did heart rate (83 ± 7 to 93 ± 8 beats/min; P = 0.0004).Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.
Respiratory symptoms in people living with HIV and the effect of antiretroviral therapy: a systematic review and meta-analysis
Authors: James Brown, Anjana Roy, Ross Harris, Sarah Filson, Margaret Johnson, Ibrahim Abubakar, Marc Lipman
Journal: Thorax (2016)

<h3>Background</h3> Antiretroviral therapy (ART) has significantly altered the pattern of acute and chronic HIV-related disease. However, it is not clear what this means in terms of respiratory symptoms. We sought to investigate the association between HIV status and respiratory symptoms and how these have changed with the availability of ART. <h3>Methods</h3> We searched Cochrane, Medline and Embase databases for studies published between 1946 and August 2015 comparing the prevalence of respiratory symptoms in populations with and without HIV infection. We undertook random effects meta-analysis of the main symptoms reported. We studied heterogeneity and completed sensitivity analyses and funnel plots. <h3>Results</h3> From 5788 unique references identified, 24 papers provided relevant data: 18 documented the prevalence of cough and 11 examined the prevalence of breathlessness among other symptoms reported. Compared with the HIV negative, people living with HIV (PLWH) were more likely to have respiratory symptoms with pooled ORs for the prevalence of cough of 3.05 (95% CI 2.24 to 4.16) in resource-limited populations without access to ART; 2.18 (1.56 to 3.18) in resource-rich populations without access to ART and 1.11 (0.99 to 1.24) in resource-rich populations with access to ART. In resource-rich settings, although the availability of ART was associated with a reduction in the difference between HIV-positive and HIV-negative individuals, PLWH were more likely to report breathlessness, OR 1.39 (95% CI 1.11 to 1.73). <h3>Conclusions</h3> Respiratory symptoms are more common in PLWH than controls. This association persists although at a reduced level in populations with access to ART.
Programmed Death–Ligand 1 (PD-L1) immumohistochemistry in NSCLC: Comparison and correlation between two antibodies.
Authors: Gareth Rivalland, Malaka Ameratunga, Khashayar Asadi, Marzena Walkiewicz, Simon Knight, Thomas John, Paul Mitchell
Journal: Journal of Clinical Oncology (2016)

e20036 Background: Many antibodies targeting PD-L1 are used in immunohistochemistry (IHC) analyses of NSCLC without direct comparison between them and correlation with clinical outcomes. To date, most research labs have used the Cell Signaling Technology (CST): clone E1L3N as it has been the only antibody commercially available. However the companion diagnostic antibody for nivolumab used the Dako clone 28-8, a reagent we were given access to by the manufacturer. We compared PD-L1 IHC analyses with both antibodies to determine concordance, association with clinciopathologic features and survival in a large resected patient cohort. Methods: PD-L1 IHC was assessed in 527 resected Stage I-III NSCLC tumors using two PD-L1 antibodies on tissue microarrays with triplicate cores. The proportion of tumour cells with membranous staining of any intensity were analysed at 5% and 50% positivity cut-offs by an experienced pathologist and histologist. Associations with stage, histology, age of sample, mutation and smoking status, as well as survival were calculated using Fishers exact test and the Kaplan-Meier method. Results: At the 5% and 50% levels respectively PD-L1 was positive in 38.3% and 19.4% (E1L3N) compared to 25.2% and 11.6% (Dako 28-8). E1L3N stained a significantly higher proportion of tumors at both cut-offs (p < 0.001), and in almost all clinicopathologic subgroups. Squamous cell carcinoma stained significantly more frequently than adenocarcinoma with Dako 28-8 (35.7% vs 17.4%, p < 0.001) but not with E1L3N (44% vs 35.1%, p 0.08). The concordance was 75.0% and 86.2% at 5% and 50% cut-offs respectively. A significant correlation was observed in staining between antibodies (R2= 0.40, p < 0.0001). PD-L1 positivity with clone 28-8 was not prognostic in either the whole cohort or any subgroup. PD-L1 positivity at 50% with E1L3N was correlated with improved survival in those with N2 disease (p < 0.05). There was no effect of histologic subtype on PD-L1-related prognosis. Conclusions: Overall PD-L1 positivity was correlated between these two antibodies, however the CST antibody stained significantly more samples. PD-L1 expression was not prognostic for the whole cohort with either antibody.
National Clinical Data Base for Sickle Cell Disease In Belgium
Authors: Phu-Quoc Lê, Alina Ferster, Françoise Vertongen, Christiane Vermylen, Anna Vanderfaeillie, Catherine Heijmans, André Efira, Ba-Cuong Nguyen, Malou Ngalula Mujinga, Beatrice Gulbis
Journal: Blood (2010)
Can tumor biomarkers predict response to neoadjuvant anthracycline/taxane chemotherapy in LABC?
Authors: J. F. Hilton, J. I. Weberpals, I. Lorimer, M. Nabavi, F. Kanji, S. Hopkins, S. Robertson, M. Daneshmand, S. Verma
Journal: Journal of Clinical Oncology (2010)

633 Background: Treatment of LABC requires the use of appropriate neoadjuvant chemotherapy (NCT) to improve BC specific outcomes. It has been demonstrated that an improved relapse free survival occurs in those who experience a pathologic complete response (pCR). Currently, the combination of doxorubin and cyclophosphamide followed by docetaxel (AC-D) has become Ontario's accepted standard. However, prediction of response remains challenging. As response is likely dependent on the underlying genetic profile of the tumour, we hypothesize that BRCA1 protein levels, where low levels are associated with reduced chemotherapy efficacy, and activating PI3K mutations, which confer chemotherapy resistance, are predictive of response to NCT. Methods: For this pilot study, The Breast Cancer Database at The Ottawa Hospital has identified 123 eligible patients between 2006 and 2008. Following informed consent, demographic and response data were collected. All patients underwent pretreatment biopsy and following AC-D, the majority underwent mastectomy. HER2 positive patients had trastuzumab initiated with docetaxel and continued for 1 year. Tumor specimen pre and post therapy were assessed for ER, PR, HER2, Grade, Ki67, BRCA1 protein and PI3KA. BRCA1 protein levels were assessed through immuno-staining of preserved tissue. PI3KCA mutation status was assessed by isolating DNA from pathology sample sections followed by nested PCR amplification and DNA sequencing. Results: 65.6% of treated patients were ER positive and 27.6% were HER2 positive. The median age at presentation was 51 years, 94.5% of patients had ductal pathology and 68.3% were node positive. 11.4% of our treated patients showed no response or progression, 17.8% showed < 50% response, 43.9% showed between 50%-99% response and 26.8% obtained a pCR. Tissue studies have been performed on 10 patients at this point. A total of 60 patients will be assessed. Conclusions: Our preliminary analysis suggests that there is sufficient sample size in each of the possible responder groups to proceed with a retrospective biomarker analysis for PI3KCA mutation status and BRCA1 protein levels. Preliminary results correlating outcomes will be presented in detail. No significant financial relationships to disclose.