tbuckley/cabot-search huggingface dataset:
The preclinical phase of PsA: a challenge for the epidemiologist
Authors: Alexis Ogdie
Journal: Annals of the Rheumatic Diseases (2017)

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis and, like many chronic diseases, often has an insidious onset. The disease likely begins well before patients first present to a rheumatologist and even before they first have symptoms. Several studies have confirmed the presence of subclinical joint and entheseal inflammation in patients with psoriasis.1–5 However, relatively little is known about the preclinical phase of PsA. The ‘preclinical phase’ is emerging as an important issue in many rheumatic diseases and is an important area of ongoing research. A preclinical phase in rheumatoid arthritis (RA) has been fairly well described. Current research suggests that, among predetermined or genetically susceptible individuals, an inciting agent (eg, smoking) ignites asymptomatic inflammation. This is followed by asymptomatic synovitis, development of symptoms, a transition to clinically apparent RA and subsequent diagnosis, and then a chronic inflammatory phase.6–8 The preclinical phase of RA is supported by studies identifying the presence of autoantibodies ≥10 years prior to presentation of clinically apparent disease in RA.9 

In this issue of the Annals of Rheumatic Disease , Kristensen et al 10 provide a population-based description of the period leading up to the diagnosis of PsA, potentially the ‘preclinical phase’ of PsA in their paper ‘Societal costs and patients’ experience of health inequities before and after diagnosis of psoriatic arthritis’. In this paper, we see that healthcare costs begin to rise approximately 5 years prior to the diagnosis of PsA, peak around the time of diagnosis, improve slightly (likely from institution of therapy and appropriate care) but then remain high (figure 1). Additionally, the investigators demonstrate an elevated prevalence of comorbidities compared with the general population both in the three years before and three years after diagnosis of PsA.



Figure 1 
A preclinical phase of psoriatic arthritis (PsA) likely includes an asymptomatic inflammatory phase followed …
Upfront Allogeneic Stem Cell Transplantation for Remission Induction in High-Risk Acute Myeloid Leukemia Patients within the Randomized Multi- Center Trial AML2003.
Authors: Markus Schaich, Thomas Illmer, Walter E. Aulitzky, Martin Bornhaeuser, Martin Griesshammer, Matthias Haenel, Anthony D. Ho, Hartmut Link, Andreas Neubauer, Norbert Schmitz, Hubert Serve, Christian Thiede, Eckhard Thiel, Thomas Wagner, Hannes Wandt, Wolfgang Berdel
Journal: Blood (2008)
Early Recovery of Absolute Lymphocyte Count (ALC) Is a Predictor of Long-Term Outcome Following Related Allogeneic Peripheral Blood Stem Cell Transplantation in Adults with AML/MDS.
Authors: Gizelle Popradi, Dong Hwan (Dennis) Kim, John Kuruvilla, Vikas Gupta, Mark Minden, Jeffrey H. Lipton, Hans A. Messner
Journal: Blood (2007)
Abstract P3-06-09: Selection of presumed CD49f antagonists and their biological evaluation in breast cancer cells
Authors: M Velasco-Velázquez, I Velázquez-Quesada, C Aguirre-Alvarado, S Guerrero-Rodríguez, A Ruiz-Moreno, G Ramirez-Salinas, A Segura-Cabrera, M Pérez-Tapia
Journal: Cancer Research (2017)

Abstract Breast cancer is the second cause of cancer death in women and the large majority of those deaths are due to drug resistance and/or recurrence. The cancer stem cell (CSC) model suggests that tumor stem-like cells play key roles in resistance and recurrence in breast cancer patients. Thus, CSCs have been pointed as targets for new anti-cancer therapies. CD49f is an integrin subunit that participates in the CSC-niche interaction. Knock-down of CD49f in breast cancer cells impairs mammosphere formation in vitro and tumorigenesis in vivo, suggesting that this protein is needed for maintenance of stemness. Aiming to target breast CSC, we used consensus docking to select potential CD49f antagonists from a collection of 13,000+ drugs with previous clinical evaluations. Seven compounds with the lowest consensus Z score were selected for in vitro biological validation. Cell adhesion assays showed that four of the selected drugs (5193, 1382, 7631, and 12723) decrease the binding of CD49f+ MDA-MB-231 breast cancer cells to laminin, suggesting that those compounds antagonize the receptor. Mammosphere formation assays showed that compounds 5193, 1382, and 12723 limit the clonogenic capability of CD49f+ breast cancer cells in vitro. Compound 5193 was highly toxic in 2D cell viability assays. On the other hand, the clonogenic impairment produced by compounds 1382 and 12723 is independent of bulk cell line cytotoxicity, suggesting a direct impact on the CSC pool. The analyses of the effect of these drugs on the expression of breast CSC markers and CD49f-activated pathways are on their way. Thus, we have identified some drugs that might be repurposed to target breast CSC. Since the pharmacokinetics and toxicology of those drugs is known, they could easily be ready for clinical trials. We demonstrated that in silico screening is useful to identify antagonists of receptors with relevant roles in breast CSC biology. This work was supported by CONACYT 221105, PAPIIT-UNAM IN228616, and Red temática de células troncales y medicina regenerativa. Citation Format: Velasco-Velázquez M, Velázquez-Quesada I, Aguirre-Alvarado C, Guerrero-Rodríguez S, Ruiz-Moreno A, Ramirez-Salinas G, Segura-Cabrera A, Pérez-Tapia M. Selection of presumed CD49f antagonists and their biological evaluation in breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-06-09.
Platelet Aggregation Analysis of AMG 531 in a Randomized, Placebo-Controlled Study in Healthy Japanese Subjects.
Authors: Yuji Kumagai, Tomoe Fujita, Machiko Ozaki, Kunihiko Sahashi, Masayuki Ohkura, Tomoko Ohtsu, Yoshihiro Arai, Yusuke Sonehara, Janet Nichol
Journal: Blood (2006)
Phase II Study of the Frontline Hyper-CVAD in Combination with Ponatinib for Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Authors: Koji Sasaki, Elias J. Jabbour, Farhad Ravandi, Naval G. Daver, Naveen Pemmaraju, Deborah A Thomas, Rita B. Khouri, Musa Yilmaz, Tapan M. Kadia, Nicholas J. Short, Rebecca Garris, Guillermo Garcia-Manero, Courtney D DiNardo, Marina Konopleva, Zeev Estrov, Nitin Jain, William G. Wierda, Twilla Victoria Jeanis, Jorge E. Cortes, Susan M. O'Brien, Hagop M. Kantarjian
Journal: Blood (2016)
Carcinoma of the Breast
Authors: Frederick S. Hopkins, Nicholas Egnatz
Journal: New England Journal of Medicine (1947)

TWO hundred and fifty-eight patients with carcinoma of the breast were seen in the Cancer Section of the Westfield State Sanatorium in its first three years, 1938 through 1940. In 70 cases a radical operation was done in hope of cure. Simple mastectomies were performed in 7 cases, whereas 138 patients were referred after having been treated at other hospitals.Thanks to an extremely efficient social-service department, all these patients have been followed. All except 4 of the surviving patients who were operated on are still being regularly examined at the clinic, and the others have been visited by one . . .
Abstract ES4-2: Ex vivo and in vivo approaches to studying the immune tumor microenvironment
Authors: PP Lee
Journal: Cancer Research (2017)

Abstract Tumors consist not only of cancer cells, but also stromal and immune cells that constitute the tumor microenvironment (TME). Clinical outcome and response to therapy depend on the complex interplay between these cell populations within the TME. Cancer drug development has traditionally relied on screening against cancer cell lines on plastic dishes before in vivo testing. It is increasingly clear that cancer cell lines in 2D do not fully reflect the biology of primary cancer cells within the complex 3D TME. In the new era of cancer immunotherapy, models also need to incorporate immune cells. In this educational session, we will discuss new ex vivo and in vivo approaches to studying the immune tumor microenvironment and response to therapy. These include patient-derived tumor organoids (PDO), patient-derived xenografts (PDX), and humanized mouse models to evaluate cancer immunotherapies. Citation Format: Lee PP. Ex vivo and in vivo approaches to studying the immune tumor microenvironment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES4-2.
Quantitative ELISA Using N10 Antibody, Targeting on VWF-Y1605 Residue, Indicates That N-Linked Blood Group Type A Carbohydrate on VWF Molecule Functions Against ADAMTS13 Cleavage
Authors: Masaki Hayakawa, Seiji Kato, Taei Matsui, Kazuya Sakai, Yumi Yoshii, Hideo Yagi, Yoshihiro Fujimura, Masanori Matsumoto
Journal: Blood (2016)
Discontinuation of Second Generation (2G) Tyrosine Kinase Inhibitors (TKI) in Chronic Phase (CP)-Chronic Myeloid Leukemia (CML) Patients with Stable Undetectable BCR-ABL Transcripts
Authors: Delphine Rea, Philippe Rousselot, François Guilhot, Michel Tulliez, Franck E. Nicolini, Agnès Guerci-Bresler, Laurence Legros, Martine Gardembas, Stephane Giraudier, Gaelle Guillerm, Francois-Xavier Mahon
Journal: Blood (2012)
Pulse High-Dose Vorinostat Can Be Delivered with Rituximab, Ifosphamide, Carboplatin, and Etoposide In Patients with Relapsed Lymphoma: Final Results of a Phase I Trial.
Authors: Lihua E Budde, Andrei Shustov, John M. Pagel, Ted Gooley, George Oliviera, Tara Chen, Michelle Zhang, Thomas A. Warr, Thomas Boyd, Oliver W. Press, Ajay K Gopal
Journal: Blood (2010)
Abstract P4-02-06: Evaluation of contrast-enhanced ultrasonography for early prediction of response to neoadjuvant chemotherapy in triple negative breast cancer
Authors: N Masumoto, T Kadoya, C Murakami, N Gouda, S Sasada, A Emi, R Haruta, T Kataoka, M Okada
Journal: Cancer Research (2017)

Abstract Objectives We aimed to determine whether contrast-enhanced ultrasonography (CEUS) can predict the early effects of neoadjuvant chemotherapy on triple negative breast cancer. Methods The clinical responses of 20 consecutive patients with breast cancer (T1–2, N0–1, M0) to neoadjuvant chemotherapy between October 2012 and Feb 2016 were assessed using ultrasonography and contrast-enhanced ultrasonography before starting the therapy and after the treatment of 2 courses. Ascending slope (AS) of perfusion parameters for contrast-enhanced ultrasonography were created from time–intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings.We investigated whether rate of change of ascending slope (ΔAS) and tumor size (Δ US) could predict pCR. Results Eight (40.0%) of the 20 patients achieved pathological complete response. ΔAS were significantly higher (-25.5 ± 35.5 vs. 14.7 ± 33.2; P &amp;lt; 0.02) in patients who achieved pCR than in those who did not. On the other hand, ΔUS of pCR and non-pCR did not significantly differ among tumors (-40.8 ± 22.4 vs. -21.4 ± 20.6; P = 0.06). The AUC values for ΔAS and ΔUS were 0.792 (95% CI, 0.579 -1.000, P = 0.03) and 0.729 (95% CI, 0.501 - 0.957;p = 0.09), respectively. We set ΔAS and Δ US cut-offs for predicting pCR at-20.08 and - 33.75 based on the ROC curves. Clinical and pathological characteristics of the 20 patients are summarized in Univariate (odds ratio, 2.71; p= 0.02) and multivariate (odds ratio, 2.88; p= 0.03) analysis showed that ΔAS was the sole independent predictor of pCR. Clinical and pathological characteristics of patients with breast cancer.CharacteristicpCR (n)Non pCR (n)pClinical T status T1110.71T2711 Clinical N status Negative570.85Positive35 Nuclear Grade 1 or 2340.85358 ΔUS (%) &amp;lt; -33.75390.09≥ -33.7553 ΔAS (%) &amp;lt; -20.082100.009≥ -20.0862 Univariate and multivariate logistic analysis of significant predictive factors for pCR in triple negative subtype Univariate analysisMultivariate analysis OR, 95% CI, pOR, 95% CI, pΔUS &amp;gt; -33.751.61, 0.72-34.7, 0.101.85, 0.51-79.1, 0.15≤-33.75 ΔAS &amp;gt; -20.082.71, 1.65-136.1, 0.022.88, 1.44-218.7, 0.03≤ -20.08 Conclusion ΔAS assessed with CEUS can help the physician to early predict the probability of achieving pCR or not. Citation Format: Masumoto N, Kadoya T, Murakami C, Gouda N, Sasada S, Emi A, Haruta R, Kataoka T, Okada M. Evaluation of contrast-enhanced ultrasonography for early prediction of response to neoadjuvant chemotherapy in triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-02-06.
Expression of IDO (indoleamine 2,3-dioxygenase) In Blasts of Acute Myeloid Leukemia Patients Predicts Poor Clinical Outcome
Authors: Nobuhiko Nakamura, Soranobu Ninomiya, Takeshi Hara, Kenji Fukuno, Masato Hoshi, Nobuhiro Kanemura, Naoe Goto, Senji Kasahara, Kuniaki Saito, Hisashi Tsurumi, Hisataka Moriwaki
Journal: Blood (2010)
The BERNIE study: A phase II study evaluating addition of bevacizumab (Bv) to chemotherapy in children and adolescents with metastatic rhabdomyosarcoma (mRMS) and non-rhabdomyosarcoma soft tissue sarcoma (mNRSTS).
Authors: Julia C. Chisholm, Michela Casanova, Johannes H. Merks, Birgit Geoerger, Raphael F. Rousseau, Nicola Moore, Christophe Dhalluin, Odile Oberlin
Journal: Journal of Clinical Oncology (2012)

TPS9597^ Background: Despite therapeutic advances, patient outcomes in mRMS and mNRSTS remain poor. The phase I study (Glade-Bender et al., J Clin Oncol. 2008) indicated that Bv is well tolerated in children with refractory solid tumors and yielded pharmacokinetic (PK) data that support further studies of Bv in childhood cancer. Reports of Bv used in children with solid tumors showed safety profiles consistent with data from adults. Methods: In this phase II trial, 150 patients aged 6 months to 18 years who present with mRMS or mNRSTS are randomized to receive 18 months of standard combined modality therapy as per EpSSG guidelines, either alone or with Bv. Treatment consists of 2 phases: induction therapy [9 three-weekly cycles including 4 cycles of IVADo (ifosfamide, vincristine, actinomycin D, and doxorubicin), followed by 5 cycles of IVA (i.e., without doxorubicin)] and maintenance therapy (12 four-weekly cycles of vinorelbine and cyclophosphamide). Local therapy is considered after the 6th induction cycle. Primary endpoint is event-free survival (EFS). PK sampling is performed on all patients randomized to the experimental arm during the first 4 cycles of induction. After the primary efficacy and safety analysis, all patients who have not met the primary endpoint are followed for at least 47 months for survival and long-term effects of treatment. The study enrolled 75 patients between July 2008 and January 2012; 37 patients discontinued study treatment (including 17 patients who died, all due to disease progression) and 9 patients have completed study treatment.
Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform
Authors: Imke Rudnik-Jansen, Sascha Colen, Julien Berard, Saskia Plomp, Ivo Que, Mattie van Rijen, Nina Woike, Annelies Egas, Gerjo van Osch, Erik van Maarseveen, Ken Messier, Alan Chan, Jens Thies, Laura Creemers
Journal: Journal of Controlled Release (2017)

Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA loaded microspheres were shown to release TAA for over 60 days in PBS. Furthermore, the bioactivity lasted at least 28 days, demonstrated by a 80–95% inhibition of PGE2 production using TNFα-stimulated chondrocyte culture, indicating inhibition of inflammation. Microspheres loaded with the near infrared marker NIR780-iodide injected in healthy rat joints or joints with mild collagenase-induced OA showed retention of the microspheres up till 70 days after injection. After intra-articular injection of TAA-loaded microspheres, TAA was detectable in the serum until day seven. Synovial inflammation was significantly lower in OA joints injected with TAA-loaded microspheres based on histological Krenn scores. Injection of TAA-loaded nor empty microspheres had no effect on cartilage integrity as determined by Mankin scoring. In conclusion, the PEA platform shows safety and efficacy upon intra-articular injection, and its extended degradation and release profiles compared to the currently used PLGA platforms may render it a good alternative. Even though further in vivo studies may need to address dosing and readout parameters such as pain, no effect on cartilage pathology was found and inflammation was effectively lowered in OA joints.
Safety and Efficacy of Romiplostim in Immune Thrombocytopenia (ITP) in the “real-life” : Result of the French Experience in 72 Adults.
Authors: Mehdi Khellaf, Philippe Quittet, Jean-Francois Viallard, Magda Alexis, Stéphane Cheze, Jean-Marc Durand, Francois Lefrere, Lionel Galicier, Olivier Lambotte, Gerard Panelatti, Jean-Francois Rossi, Borhane Slama, Gandhi Damaj, Gerard Sebahoun, Emmanuel Gyan, Xavier Delbrel, Nathalie Dhedin, Bruno Royer, Nicolas Schleinitz, Françoise Roudot-Thoraval, Matthieu Mahévas, Laetitia Languille, Philippe Bierling, Marc Michel, Bertrand Godeau
Journal: Blood (2009)
Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake
Authors: Fang Li, Rongfeng Hu, Bin Wang, Yun Gui, Gang Cheng, Song Gao, Lei Ye, Jihui Tang
Journal: Acta Pharmaceutica Sinica B (2017)

Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01). The absorption rate constant (Ka) and the apparent permeability coefficient (Papp) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of Ka and Papp of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (Cmax) of the blocking model were significantly lower than those of the control model (P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.
PP79. DIAGNOSIS TO TREATMENT TIME FOR BRAIN TUMOURS: AUDIT
Authors: Dr Eno Umotong
Journal: Neuro-Oncology (2017)

BACKGROUND: Despite representing a relatively small proportion of human tumours, brain tumours carry a high mortality rate and remain the most common cause of neoplastic death amongst the paediatric population. Less than 1% of brain tumours are known to be preventable thus early diagnosis and prompt treatment have become particularly invaluable in improving outcomes. Current NICE guidance recommends that waiting times for brain tumours are similar to those for other non-CNS tumours: 2 months from first referral to definitive treatment and 1 month from diagnosis to definitive treatment. This audit sought to compare the practices at University Hospitals Coventry and Warwickshire (UHCW) with NICE guidelines regarding the time taken between the radiological diagnosis and the surgical treatment of brain tumours. METHODS: A total of 308 patients who were referred to brain MDT at UHCW between January 1st 2015 and December 31st 2015 were included in this audit. Electronic records were reviewed and data gathered according to a data collection tool based on NICE guidance CSG10: Improving outcomes for people with brain and other CNS tumours. RESULTS: 126 patients (41%) received surgical treatment which, on average, occurred 50.82 days following radiological diagnosis and 59.70 days following first referral for imaging. CONCLUSIONS: On average, the time between first referral and treatment was within the recommended standard of 60 days however, there was a delay from diagnosis to treatment of circa 21 days. Delays were most commonly attributed to radiological planning and patient suitability; which may require more attention in brain tumours than in non-CNS tumours. Here, the argument is made to update the guidance to account for such differences which may remove the haste to treat brain tumours.
High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.
Authors: Sadao Aoki, Jun Takizawa, Masutaka Higashimura, Akihito Momoi, Nobuhiro Tsukada, Koji Nikkuni, Nobuhiko Nomoto, Yoshifusa Aizawa
Journal: Blood (2004)
P-ERK1/2 Is a Predictive Factor of Response to ESA Treatment in Myelodysplastic Syndromes.
Authors: Emilie Frisan, Patrycja Pawlikowska, Cécile Pierre-Eugène, Valérie Bardet, Laure Gibault, Vivian Viallon, Olivier Kosmider, Frederique Verdier, Sophie Park, Frédérique Kuhnowsky, Martine Guesnu, Catherine Lacombe, Patrick Mayeux, Francois Dreyfus, Francoise Porteu, Michaela Fontenay
Journal: Blood (2009)
Safety and Efficacy of a Switch to Nilotinib in Patients with CML-CP Showing MMR to Imatinib: Results of a Multicenter Phase II Trial (NILSw Trial)
Authors: Hirohiko Shibayama, Tatsuya Kawaguchi, Junya Kuroda, Hirohisa Nakamae, Itaru Matsumura, Toshihiro Miyamoto, Jun Ishikawa, Tomohiko Kamimura, Kentaro Fukushima, Yutaka Imamura, Tetsuya Eto, Kazutaka Sunami, Mototsugu Shimokawa, Koichi Akashi, Yuzuru Kanakura
Journal: Blood (2016)
Essential Role for PU.1 in MEIS1 Activation and MLL Fusion Leukemia,
Authors: Jing Zhou, Bo Li, Jun Wu, Fuhong He, Qiang Li, Xiaomei Yan, Yue Zhang, Lixia Zhang, Xinghui Zhao, Jin Yan, Marcelo Nobrega, Daniel G. Tenen, Gang Huang, Qian-fei Wang
Journal: Blood (2011)
Increased risk of cancer death with type 2 diabetes, finds Asian study
Authors: Susan Mayor
Journal: BMJ (2017)

Type 2 diabetes is associated with a 26% higher risk of death from any cancer, a large study of people living in east and south Asia has found.

Growing evidence indicates a link between type 2 diabetes and increased risk of cancer, but previous studies have been carried out in Western populations. Asian people are more susceptible to insulin resistance and have a higher prevalence of diabetes than white people at any given body mass index, so the researchers wondered whether cancer risk …