tbuckley/cabot-search huggingface dataset:
Treatment of chemotherapy-induced peripheral neuropathy (CIPN) with topical menthol: A phase I study.
Authors: D. J. Storey, L. A. Colvin, A. C. Scott, D. Boyle, L. Green, A. P. Jones, M. T. Fallon
Journal: Journal of Clinical Oncology (2010)

9129 Background: CIPN is a common dose-limiting toxicity. Mostly symptoms resolve several months post-treatment, but a significant proportion of patients are left with long-term pain and disability which is difficult to treat. The available systemic agents have limited efficacy, cause significant side effects and take several weeks/months to work. Based on preclinical work showing marked analgesic effects of topical transient receptor potential melastatin (TRPM8) receptor activators in neuropathic pain (Proudfoot, Curr Biol 2006;16;1591-1605) we conducted a phase I study of topical menthol. Methods: 22 patients with long-term CIPN a median of 17 months (range 2 to 35) post-treatment with bortezomib (n=2), carboplatin (n=1), docetaxel (n=2), cisplatin (n=3), and oxaliplatin (n=14) applied 1% topical menthol, twice daily to affected areas and skin overlying the corresponding dorsal root ganglia. At baseline, 2 and 6 weeks, patients completed: Brief Pain Inventory (BPI–measures pain severity and interference with function), Hospital Anxiety and Depression Scale (HADS) and Pain Catastrophizing Scale (PCS). Responders and partial responders were defined as 30% and 10-20% reduction in mean BPI respectively. Results: At 2 weeks, 36%(8/22) were responders, 14%(3/22) were partial responders and 50%(11/22) were non-responders. This further improved by 6 weeks: 47%(9/19) were responders 21%(4/19) were partial responders and 32%(6/19) were non-responders. 3 patients discontinued treatment after 2 weeks: 1 had progressive disease; 2 had difficulty applying the cream. Between baseline and 6 weeks, distress decreased in responders [mean HADS 10.9 (SD 6.2) to 7.7 (6.1)] but not in partial responders [6.5 (2.9) to 7.0 (4.5)] or non-responders [17.2 (4.9) to 17.2 (7.1)]. Catastrophizing decreased in all groups but most markedly in responders [mean 16.3 (SD6.2) to 7.7 (8.2)]; partial responders from 7.3 (3.1) to 5.0 (3.9); non-responders from 22.0 (15.2) to 18.4 (12.5). Conclusions: Two thirds of patients with long-term CIPN experienced an improvement in pain and function with topical menthol. This novel treatment appears to be well tolerated, have minimal side effects, works relatively quickly and warrants further study. No significant financial relationships to disclose.
SCNP identifies CLL donor subgroups by profiling functional immune signaling in the context of immune modulatory receptor expression
Authors: Erwan Le Scolan, Christie Fanton, Andy Conroy, Albert Tai, Nguyen Tan, Brent Louie, Erik Evensen, Rachael Hawtin
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Antibody therapeutics targeting the Immune Modulatory Receptor (IMR) PD-1 have efficacy in multiple indications, and molecules targeting other IMRs are in development. Increased understanding of IMR biology is required to design rational combination therapies and identify
Problems at Addenbrooke’s caused by failure to implement electronic patient record system effectively
Authors: Stephen Black
Journal: BMJ (2015)

Most commentators agree that NHS hospitals face mounting pressures. But these don’t explain the sudden emergence of problems at Addenbrooke’s Hospital. And Keith McNeil’s interpretation of management grip as Stalinist control suggests that he doesn’t understand it either.1

McNeil’s philosophy of empowering clinical teams, with the support …
HLA-Mismatch Is Associated With Worse Outcomes After Unrelated Donor Reduced Intensity Conditioning Hematopoietic Cell Transplantation: A Cibmtr Analysis
Authors: John Koreth, Kwang Woo Ahn, Joseph Pidala, James L. Gajewski, Hailin Wang, Marcelo A. Fernandez Viña, Stephen Spellman, Stephanie J. Lee
Journal: Blood (2013)
Karyotype complexity and prognosis in acute myeloid leukemia
Authors: F Stölzel, B Mohr, M Kramer, U Oelschlägel, T Bochtler, W E Berdel, M Kaufmann, C D Baldus, K Schäfer-Eckart, R Stuhlmann, H Einsele, S W Krause, H Serve, M Hänel, R Herbst, A Neubauer, K Sohlbach, J Mayer, J M Middeke, U Platzbecker, M Schaich, A Krämer, C Röllig, J Schetelig, M Bornhäuser, G Ehninger
Journal: Blood Cancer Journal (2016)

A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.
Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma
Authors: Zhong-hua Ning, Zhi-gang Wang, Jun Chen, Xiao-dong Li, Lu-jun Chen, Bin Xu, Wen-dong Gu, Ying-jie Shao, Yun Xu, Jin Huang, Hong-lei Pei, Jing-ting Jiang
Journal: Journal of Thoracic Oncology (2015)
Prevalence analysis of OX40-positive cell populations in solid tumors
Authors: James Ziai, Gretchen Frantz, Liping Zhang, Cleopatra Kozlowski, Houston Gilbert, Jacquelyn Smith, Marcin Kowanetz, Jeong M Kim, Mahrukh Huseni
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Increased numbers of OX40+ T cells within the primary tumor of colorectal cancer (CRC) patients has been associated with improved survival. Similarly, OX40 expression in sentinel lymph nodes is inversely associated with tumor grade and clinical stage in melanoma patients. However
Neuropilin-2 and epithelial to mesenchymal transition in colorectal cancer cells.
Authors: C. Grandclement, R. Bedel, B. Kantelip, A. Bouard, V. Mougey, M. Klagsbrun, C. Ferrand, P. Tiberghien, X. B. Pivot, C. Borg
Journal: Journal of Clinical Oncology (2010)

10628 Background: Neuropilin (NRP) gene family consists of two genes, neuropilin-1 (NRP1) and neuropilin-2 (NRP2). NRPs are multifunctional glycoprotein originally described in the nervous system, capable of mediating axon retraction and guidance by binding class III semaphorins. Interestingly, NRP2 was shown to support an angiogenic activity by binding several growth factors including vascular endothelial growth factor (VEGF) and by interacting with the family of VEGF tyrosine kinase receptors. The multiple functions of NRPs were recently highlighted by the identification of NRP role in oncogenesis. Methods: We used human colon cancer cell lines transfected with NRP2 transgene or siRNA to investigate NRP2 involvement in epithelial to mesenchymal transition (EMT). First, the influence of NRP2 expression on proliferation and tumor formation was studied in vitro by MTT and soft agar assays and in vivo using xenografts experiments. Ability of NRP2 to orchestrate EMT was then investigated by flow cytometry, immunohistochemical (IHC) staining and quantitative real-time PCR. Results: Using NRP2 gene transfer we showed that NRP2 endows colon cancer cell lines for colony and xenograft formation. IHC studies reveals that expression of NRP2 was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed that NRP2 can positively regulate TGF-ß1 pathway, by enhancing phosphorylation of Smad2/3. Conclusions: Our findings have reinforced the essential role of NRP2 in cancer progression and demonstrated that NRP2 expression confers to tumor cell lines the hallmarks of EMT. Moreover, in the current work, we present evidence for the therapeutic value of NRP2 targeting. These results suggest that NRP2 fulfill all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors. No significant financial relationships to disclose.
Imaging endothelial cell invasion and network formation in response to human breast cancer cells
Authors: Barjor Gimi, Noriko Mori, Ellen Ackerstaff, Emma E. Frost, Jeff W. M. Bulte, Zaver M. Bhujwalla
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1145 

We have developed a non-invasive assay to study endothelial cell invasion, migration and network formation, in a microenvironment that mimics solid tumors. Such an assay is useful to develop effective strategies for anti-angiogenic treatment. Our assay was housed in a 24-well Millipore insert with 4 μm membrane pore size. MDA-MB-231 breast cancer cells were seeded between two layers of ECM gel within this insert. Human Umbilical Vein Endothelial Cells (HUVECs) were seeded on top of this sandwich-like structure, resulting in a layer of ECM gel separating cancer cells from the HUVECs. For MRI tracking, HUVECs were magnetofected with a superparamagnetic iron-oxide contrast agent (Feridex®, 2 μg per ml of EGM-2 medium) that shortens the T2 relaxation time of bulk water, producing hypointensity in MR images. HUVECs migrated toward the MDA-MB-231 breast cancer cells in response to paracrine factors secreted by the cancer cells. In the presence of cancer cells, HUVECs formed and retained a lumen-like network structure, and increasingly invaded the ECM gel toward the cancer cells. T2-weighted MR images of the chambers were obtained in 1 scan with TE = 60 ms, TR = 517 ms, field-of-view = 1.6 cm, slice thickness = 0.5 cm, acquisition matrix = 256 x 256. The MR images were binarized and adaptive thresholding was applied to identify areas of hypointensity indicating HUVEC presence. The effect of invasion and migration was quantified by calculating the fractional area of HUVECs in the cancer cell seed layer (day 2: 1.9 ± 1.2 and day 6: 5.0 ± 1.5; MEAN ± SD; n = 3). HUVEC presence in the cancer cell seed layer was cross-validated with endothelial cell specific monoclonal antibody CD31 fluorescence staining, and Prussian blue staining of iron-content. In controls (chambers without cancer cells), fewer HUVECs invaded and/or migrated into the ECM gel (day 2: 0.82 ± 0.58 and day 6: 0.11± 0.19; MEAN ± SD; n = 3); while HUVECs initially formed a network on the surface of the ECM gel, this structure lost integrity during the 6-day experiments. Here, for the first time, we have non-invasively and longitudinally characterized HUVEC motility, invasive potential, and network-formation in the presence and absence of cancer cells. Our assay can be used to study endothelial cell and network response to various growth and inhibition factors involved in the angiogenic process. We are currently studying endothelial response to hypoxia and VEGF overexpression. The assay can also be used to study endothelial response to synergistic effects of various competing pro- and anti-angiogenic factors. This novel assay might prove very useful in longitudinal high throughput studies to determine the efficacy of anticancer drugs. Additionally, our assay may add insights into the 3-dimensional remodeling of basement membranes in response to various factors and conditions.
Integrating Cadaver Exome Sequencing Into a First-Year Medical Student Curriculum
Authors: Glenn S. Gerhard, Barbara Paynton, Steven N. Popoff
Journal: JAMA (2016)

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Response to the 2009 influenza A(H1N1) pandemic in Italy
Authors: C Rizzo, M C Rota, A Bella, S Giannitelli, S De Santis, G Nacca, M G Pompa, L Vellucci, S Salmaso, S Declich
Journal: Eurosurveillance (2010)

In Italy, the arrival of the 2009 pandemic influenza A(H1N1) virus triggered an integrated response that was mainly based on the 2006 National Pandemic Preparedness and Response Plan. In this article we analyse the main activities implemented for epidemiological surveillance, containment and mitigation of the pandemic influenza and the lesson learned from this experience. Overall, from week 31 (27 July – 2 August) of 2009 to week 17 (26 April – 2 May) of 2010, we estimate that there were approximately 5,600,000 cases of influenza-like illness (ILI) who received medical attention (with almost 2,000 laboratory-confirmed cases of pandemic influenza from May to October 2009). A total of 1,106 confirmed cases were admitted to hospital for serious conditions, of whom 532 were admitted to intensive care units. There were 260 reported deaths due to pandemic influenza. Approximately 870,000 first doses of the pandemic vaccine were administered, representing a vaccine coverage of 4% of the target population. One of the possible reasons for the low uptake of the pandemic vaccine in the target population could be the communication strategy adopted, for both the general population and healthcare workers, which turned out to be a major challenge. Active involvement of all health professionals (at local, regional and national level) in influenza pandemic preparedness and response should be encouraged in the future.
Abstract 19332: Results of Transfemoral Transcatheter Aortic Valve Implantation in Partner-Like Patients - A Comparison with Real-World Patients - The Bonn-Essen Experience
Authors: Alexander Sedaghat, Fadi Al-Rashid, Jan-Malte Sinning, Thomas Konorza, Alexander Ghanem, Georg Nickenig, Daniel Wendt, Nikos Werner, Eberhard Grube, Matthias Thielmann, Heinz Jakob, Raimund Erbel, Philipp Kahlert
Journal: Circulation (2012)

Background: Transcatheter aortic valve implantation (TAVI) has rapidly evolved to the standard-of-care for inoperable patients with severe, symptomatic aortic valve stenosis and to an accepted treatment option for high-risk, but operable patients. However the randomized PARTNER trial excluded patients with conditions frequently encountered in our clinical practice (e.g. ejection fraction &lt;20%, severe mitral regurgitation, recent coronary stenting, cerebrovascular accident within 6-months, bicuspid valve, severe aortic regurgitation, prior valve surgery, creatinine &gt;3.0 mg/dl and/or hemodialysis). Methods: From 2006 to 2011, 485 high-risk patients (Age: 80 ± 7 years; AVA: 0.6 ± 0.2 cm²; log. EuroSCORE 22 ± 16%) underwent transfemoral TAVI (Edwards Sapien n=176, Medtronic CoreValve n=309). The patients were divided into a “PARTNER-like” group (n=272) and a “PARTNER-exclusion” group (n=213), on base of the published inclusion criteria of the PARTNER B cohort. Differences in perioperative, 30-day and 2-year survival were assessed by Kaplan-Meier survival analysis. Results: There was no statistical difference in patient-survival concerning site of treatment or the type of valve system. Patients in the “PARTNER-exclusion”- group had a worse two-year survival (Figure 1) than patients of the “PARTNER-like” group (83.8% vs. 77.5%, p=0.089). Also a non-significant trend towards a higher 30-day mortality (10.3% vs. 6.2%, p=0.102) was found in the exclusion group. The most frequent exclusion criteria were prior valve surgery (16%), followed by chronic renal failure (14%), severe mitral regurgitation (11%) and reduced ejection fraction (9%). Conclusion: In our two-center real world experience, TAVI patients who meet exclusion criteria for the PARTNER trial represent a cohort with higher long-term mortality. These findings emphasize the importance of optimal patient selection and might have implications on selection-strategies
Hematopoietic Stem Cells and Circulating Myelomonocytic Precursors With BRAF-V600E Are Identified In High-Risk Patients and Define LCH As a Myeloid Neoplasia
Authors: Karen Phaik-Har Lim, Tricia L Peters, Marie-Luise Berres, Jeremy Price, Hitoshi Takizawa, Philip Lupo, M. John Hicks, Albert Shih, Stephen James Simko, Kenneth Matthew Heym, Venetia Bigley, Matthew P. Collin, Markus G. Manz, Kenneth McClain, Miriam Merad, Carl E. Allen
Journal: Blood (2013)
Docetaxel for Patients With Paclitaxel-Resistant Müllerian Carcinoma
Authors: Claire F. Verschraegen, Tul Sittisomwong, Andrzej P. Kudelka, Ernesto de Paula Guedes, Melissa Steger, Tarra Nelson-Taylor, Monique Vincent, Roger Rogers, E. Neely Atkinson, John J. Kavanagh
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the efficacy and toxicity of docetaxel in patients with müllerian carcinoma resistant to paclitaxel. PATIENTS AND METHODS: Thirty-two patients with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who failed paclitaxel-based chemotherapy received either 100 or 75 mg/m 2 of docetaxel every 3 weeks. Resistance to paclitaxel was defined as either progression of disease during treatment, failure to achieve regression of disease after at least four courses, or rapid recurrence (within 6 months) after completion of therapy. RESULTS: Eighteen patients were treated on a formal protocol and fourteen with the commercially available docetaxel. Thirty were assessable for response. Toxicities were thoroughly evaluated in the 18 patients on protocol. Twenty-seven patients (85%) had epithelial ovarian cancer. The overall response rate was 23% (one complete and six partial responses), with a median survival time of 44 weeks (9.5 months). Nine patients had stable disease and 14 progressive disease. Among 19 patients who progressed during prior paclitaxel treatment, two (11%) responded to docetaxel, compared with five (45%) of 11 patients in other paclitaxel-resistance categories. The responders had a median taxane-free interval (ie, the time between the last paclitaxel and first docetaxel treatment) of 73 weeks, compared with 19 weeks for the nonresponder group. Toxic effects were as expected. CONCLUSION: Docetaxel is an active chemotherapeutic agent in patients with müllerian carcinoma previously treated with paclitaxel-based chemotherapy, especially in the patients who had a long taxane-free interval after a previous short response to paclitaxel.
The interaction of acetylcholine and histamine on human bronchial smooth muscle contraction
Authors: DA Knight, MJ Phillips, GA Stewart, PJ Thompson
Journal: European Respiratory Journal (1991)

The interaction of histamine (Hist) and acetylcholine (ACh) on human isolated bronchial smooth muscle (HIBSM) contraction, and the influence of the epithelium, was assessed using HIBSM obtained from 15 patients undergoing thoracotomy. Cumulative concentration effect curves for ACh and Hist, together with combinations of equipotent concentrations of both agonists, were generated using both epithelium-intact and epithelium-denuded HIBSM. In epithelium-denuded HIBSM both ACh (p less than 0.05) and Hist (p less than 0.005) produced a significantly enhanced maximal response and a 2.1 fold increase in the potency of ACh (p less than 0.02, n = 13). When ACh and Hist were added simultaneously, in equipotent concentrations, to epithelium-intact HIBSM, a significantly less (p less than 0.0005, n = 13) than additive response occurred with only 60% of the predicted maximum response being observed. However, following epithelium removal, an additive interaction between the two agonists (n = 8) occurred. Using HIBSM from five of the original 15 patients, similar experiments were performed to determine the influence of the muscarinic receptor antagonist atropine (0.1 microM) and the H1 receptor antagonist mepyramine (10 microM). Both resulted in a significantly less than additive interaction (40-50% of predicted tensions). Similar experiments were also performed in the presence of the cyclo-oxygenase inhibitor indomethacin (5 microM) and these failed to reverse the inhibition observed in HIBSM contraction (n = 5). The inhibitory interaction between ACh and Hist appears to be epithelium dependent and is not mediated via the release of prostanoids. Thus, there appears to be a complex interaction between contractile agonists and the epithelium, which is not just a simple summation of the activation of individual receptors on HIBSM.
Macrophage-Derived Chemokine Is Localized to Thymic Medullary Epithelial Cells and Is a Chemoattractant for CD3+, CD4+, CD8low Thymocytes
Authors: David Chantry, Paola Romagnani, Carol J. Raport, Christi L. Wood, Angela Epp, Sergio Romagnani, Patrick W. Gray
Journal: Blood (1999)