tbuckley/cabot-search huggingface dataset:
Cancer Precision Medicine in China
Authors: Hui Li
Journal: Genomics Proteomics & Bioinformatics (2016)

BackgroundCancer, as a global health issue, has been attracting increasing attention from scientists, medical professionals, as well as the general population.During the past several decades, many therapeutic approaches, including surgery, chemotherapy, radiotherapy and immunotherapy, have come into play for cancer treatment.Nonetheless, many of these treatments are not personalized according to the specific situation or genetic context of a particular patient.Nowadays, precision medicine, defined by President Obama as ''delivering the right treatments at the right time-every time-to the right person", opens a new era of cancer research with the hope to provide personalized treatment for different patients.To foster the knowledge share and promote potential collaboration on cancer precision medicine domestically and internationally, the first Interna-
Endogenous Protease Inhibitors in Airway Epithelial Cells Contribute to Eosinophilic Chronic Rhinosinusitis
Authors: Hideaki Kouzaki, Koji Matsumoto, Hirotaka Kikuoka, Tomohisa Kato, Ichiro Tojima, Shino Shimizu, Hirohito Kita, Takeshi Shimizu
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Cystatin A and SPINK5 are endogenous protease inhibitors (EPIs) that may play key roles in epithelial barrier function.Objectives: To investigate the roles of EPIs in the pathogenesis of chronic rhinosinusitis (CRS).Methods: We examined the expression of cystatin A and SPINK5 in the nasal epithelial cells of patients with CRS. Additionally, the in vitro effects of recombinant EPIs on the secretion of the epithelial-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin in airway epithelial cells, and the in vivo effects of recombinant EPIs in the nasal epithelium of mice exposed to multiple airborne allergens (MAA) were examined.Measurements and Main Results: Compared with control subjects and patients with noneosinophilic CRS, patients with eosinophilic CRS showed significantly lower protein and mRNA expression of cystatin A and SPINK5 in the nasal epithelium. Allergen-induced production of IL-25, IL-33, and thymic stromal lymphopoietin in normal human bronchial epithelial cells was inhibited by treatment with recombinant cystatin A or SPINK5. Conversely, the production of these cytokines was increased when cystatin A or SPINK5 were knocked down with small interfering RNA. Chronic MAA exposure induced goblet cell metaplasia and epithelial disruption in mouse nasal epithelium and decreased the tissue expression and nasal lavage levels of cystatin A and SPINK5. Intranasal instillations of recombinant EPIs attenuated this MAA-induced pathology.Conclusions: Cystatin A and SPINK5 play an important role in protecting the airway epithelium from exogenous proteases. The preservation of EPIs may have a therapeutic benefit in intractable airway inflammation, such as eosinophilic CRS.
Comparison of aPTT (Platelin LS®) and Dilute Russell’s Viper Venom (Viperquik LA Test®) for the Screening of Lupus Anticoagulant in Patients with Venous Thromboembolism.
Authors: Celso A. Roprigues, Aline A. Martinez, Vania M. Morelli, Raniely C. Silveira, Maria Aparecida E. Noguti, Dayse M. Lourenco
Journal: Blood (2005)
Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts
Authors: Alexander J. Hose, Martin Depner, Sabina Illi, Susanne Lau, Thomas Keil, Ulrich Wahn, Oliver Fuchs, Petra Ina Pfefferle, Elisabeth Schmaußer-Hechfellner, Jon Genuneit, Roger Lauener, Anne M. Karvonen, Caroline Roduit, Jean-Charles Dalphin, Josef Riedler, Juha Pekkanen, Erika von Mutius, Markus J. Ege, Carl Peter Bauer, Johannes Forster, Fred Zepp, Volker Wahn, Antje Schuster, Renate L. Bergmann, Karl E. Bergmann, Andreas Reich, Linus Grabenhenrich, Bianca Schaub, Georg J. Loss, Harald Renz, Michael Kabesch, Marjut Roponen, Anne Hyvärinen, Pekka Tiittanen, Sami Remes, Charlotte Braun-Fahrländer, Remo Frei, Vincent Kaulek, Marie-Laure Dalphin, Gert Doekes, Nicole Blümer, Urs Frey
Journal: Journal of Allergy and Clinical Immunology (2016)
RAEB-1 with Erythroid Hyperplasia and Erythroleukemia Share Clinico-Biological Features and Outcome: A Same Disease with Different Labels?
Authors: Xavier Calvo, Leonor Arenillas, Mar Tormo, David Valcárcel, Elisa Luño, Esther Alonso, María Díez-Campelo, Fernando Ramos, Carmen Pedro, Beatriz Arrizabalaga, Alicia Bailén, José María Raya, María Teresa Ardanaz, Guillermo Sanz, Lourdes Florensa
Journal: Blood (2015)
Molecular analysis of hormone refractory prostate cancer biopsies supports the rationale of using mTOR inhibitors
Authors: O. Stoss, D. Zielinski, K. Czeloth, P. Middel, T. Henkel, P. Albers
Journal: Journal of Clinical Oncology (2007)

21126 Background: The aim of our group is to identify molecular signatures in samples of hormone refractory prostate cancer (HRPC) patients (pts) that lead to novel rationales for medical treatment. We have previously shown that transurethral resections (TUR) of the prostate in HRPC pts are useful specimens for gene expression profiling using microarrays (ASCO 2006). Aim of this study was to prove the feasibility of gene expression profiling on prostate biopsies and to develop a standardised tissue handling protocol in order to facilitate multicenter research. Methods: Biopsy material and corresponding TUR chips or classical specimens from 8 pts with HRPC, 13 pts with localized PCA, 6 pts with benign prostatic hyperplasia (BPH) and 11 pts without cancer or BPH were investigated and compared. The tumor type and content was evaluated by a pathologist. Tissues were preserved in liquid nitrogen or RNAlater. Different tissue lysis and RNA purification methods were compared by the quantity (NanoDrop measurement) and quality (Bioanalyser, Agilent) of isolated RNA. Gene expression profiling occurred on Affymetrix HG-FOCUS arrays. Results: Most reliable gene expression results were obtained by biopsy lysis in Trizol using the QIAshredder. A total of more than 1 μg RNA was isolated from one biopsy. RNA quality fulfilled pre-defined criteria such as a 28S/18S rRNA ratio of &gt; 0.8, an area under the curve of &gt; 10% and a RNA integrity number &gt; 6.5. A comparison of HRPC and PCA samples clearly confirmed previous results of a deregulation of protein biosynthesis (translation initiation and elongation factors, ribosome biogenesis) and PI3K signalling pathway components. Conclusions: Gene expression profiling supports the induction of the PI3K-AKT-mTOR pathway in HRPC. A standardised protocol for gene expression profiling from prostate biopsy samples applicable for translational research programs within multicenter clinical trials is now available. As a part of a clinical phase II trial that aims to investigate survival benefits on HRPC pts treated with docetaxel ± RAD001, a translational research program is now set up in parallel to identify biomarkers for response prediction using microarray gene expression analysis from prostate biopsies. No significant financial relationships to disclose.
First-line treatment with single agent rituximab, followed by maintenance rituximab plus anti-idiotype Id-KLH active immunotherapy vaccine (FavId) in patients (pts) with low-grade non-Hodgkin lymphoma (NHL): Preliminary results of a phase II trial
Authors: E. Raefsky, F. A. Greco, D. R. Spigel, S. Litchy, V. Gian, J. Bender, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2007)

8080 Background: Single agent rituximab produces a high response rate when used as first-line treatment, and maintenance rituximab prolongs remission duration. Active immunotherapy is a promising treatment approach, when administered following remission induction by initial therapy. In this phase II trial, we evaluate the feasibility, toxicity, and efficacy of administering concurrent maintenance rituximab plus Id-KLH vaccine in pts with low-grade NHL. Methods: Pts with previously untreated low-grade NHL (grade 1/2 follicular or SLL) who were judged to be candidates for single agent rituximab therapy were eligible. All pts had initial biopsy for production of the Id-KLH vaccine. All pts received rituximab 375mg/m 2 IV, weekly × 4. Pts with CR/CR u , PR, or stable disease at 8 weeks proceeded with maintenance rituximab (standard 4 week courses at 6 month intervals for 3 courses) and Id-KLH vaccination (Id-KLH 1cc day 1; GMCSF 250μg SQ days 1–4) monthly × 8, beginning month 3, then every 2 months during the second year. Pts were monitored for response rate, progression- free survival, and toxicity. Results: To date, 36 of a planned 56 pts have been enrolled. Idiotype vaccine was successfully manufactured in 27 of 32 pts (84%), with 4 in production. Of the 27 pts for whom Id-KLH was successfully manufactured, 2 progressed during rituximab. 19 of 25 pts (14FL;5SLL) have had response determined after rituximab: 8 PR (42%), 11 stable (58%; 4 of 5 SLL). Pts have now received rituximab maintenance therapy plus Id-KLH for durations of 6 - 34 months. 6 of 19 pts (3 SLL) progressed at months 5, 6, 9, 9, 10, and 12, respectively. Treatment has been well tolerated, with no unusual toxicities observed. Rituximab-related hypotension and atrial fibrillation occurred in 1 pt. The most common Id-KLH related adverse event has been injection site reaction. Conclusions: Concurrent maintenance therapy with rituximab plus Id-KLH is safe and well tolerated. At present, 6 of 25 pts (24%) have progressed (including 3 of the 5 SLL pts) with a median followup of 19 months. This trial is continuing. No significant financial relationships to disclose.
Smoking and quality of life among elderly survivors of non-smoking related cancers in a prospective cohort study
Authors: S. Jang, A. Prizment, D. Lazovich
Journal: Journal of Clinical Oncology (2009)

9600 Background: Although the effect of smoking on quality of life (QOL) has been examined among survivors of lung or head and neck cancers, little is known about how smoking affects QOL among elderly survivors of non-smoking related cancers. Methods: The Iowa Women's Health Study (IWHS), a prospective cohort study initiated in 1986, collected self-reported QOL using the SF-36 in 2004. Cancer diagnosis and treatment among cohort participants were obtained from Iowa's cancer registry. Behavioral and health characteristics, including smoking status, were collected from periodic follow-up questionnaires between 1986 and 2004. We included 1,920 women, aged 55 to 69 years at baseline, who developed breast, colorectal, or endometrial cancers and responded to the 2004 questionnaire. We compared age-adjusted and multivariate-adjusted mean scores for eight SF-36 scales between nonsmokers (no reported smoking in 1986 or 2004), quitters (reported smoking in 1986 but not 2004), and persistent smokers (reported smoking in 1986 and 2004). Results: Among 1,920 cancer survivors, 1,720 (89.6%) were nonsmokers, 141 (7.3%) were quitters, and 59 (3.1%) were persistent smokers. After age adjustment, quitters had lower scores for vitality, physical functioning, mental health, social functioning, and general health scales compared to nonsmokers. Persistent smokers scored worse on the physical functioning, mental health, role emotional, and social functioning scales compared to nonsmokers. Except for mental health, these differences in QOL scores were attenuated after further adjustment for physical activity. Accounting for other factors, including baseline general health perception and education, cancer type, surgery, radiation therapy, chemotherapy, and length of survival, or occurrence of hypertension, diabetes, heart disease, stroke or fracture by 2004 did not change the differences observed between survivors who had ever reported smoking versus nonsmokers. Conclusions: Quitters and persistent smokers tended to fare worse than nonsmokers on many QOL scales. In most instances, these differences were explained by lower levels of physical activity which may have been a consequence of smoking. No significant financial relationships to disclose.
Phase II Trial of Weekly Bortezomib in Combination with CCI-779 (temsirolimus) in Relapsed or Relapsed/Refractory Multiple Myeloma.
Authors: Irene M. Ghobrial, Ravi Vij, Nikhil C. Munshi, Robert L Schlossman, Jacob Laubach, Erica L. Campagnaro, Renee Leduc, Meghan Rourke, Stacey Chuma, Janet Kunsman, Akari M. Dollard, Diane Warren, Brianna Harris, Amy Sam, Kenneth C. Anderson, Paul Richardson
Journal: Blood (2009)
Multicolor Flow Cytometry Detects Monoclonal Plasma Cells In the Vast Majority of Marrows From Patients with Plasma Cell Disorders Shown to Have Genetic Abnormalities by Fluorescence In Situ Hybridization (FISH)
Authors: Raul C. Braylan, Karina Baggiani, Tiana Golding, Eric Kroman, Michael L. Miller, Wendy L Flejter
Journal: Blood (2010)
Phase II trial of sorafenib plus interferon-alpha 2b (IFN-α2b) as first- or second-line therapy in patients (pts) with metastatic renal cell cancer (RCC)
Authors: J. Gollob, T. Richmond, J. Jones, W. K. Rathmell, G. Grigson, C. Watkins, B. Peterson, J. Wright
Journal: Journal of Clinical Oncology (2006)

4538 Background: Sorafenib is a VEGFR/PDGFR-β/Raf inhibitor that improves PFS in metastatic RCC with a RR of 2%. IFN-α improves OS in RCC with a RR of ≈10%. Methods: Based on the activity of sorafenib and IFN-α in RCC, a phase II combination trial was undertaken. Pts with RCC of any histology were eligible if they had received ≤1 prior treatment (excluding IFN-α). Treatment consisted of 8-wk cycles of sorafenib 400 mg po bid + IFN-α2b 10 MU sc tiw. Cycles were repeated until disease progression with 2-wk breaks between cycles permitted. This single-stage trial has a planned n = 40; primary objectives are RR and tolerability. Results: From November 2004-December 2005, 31 pts were enrolled. Pt characteristics included: median age 47, M/F: 23/8, PS 0/1: 25/6, clear cell/papillary: 24/3, no prior Rx/prior high-dose IL-2: 17/12, prior Nx: 26. Toxicities (n = 27) were mostly grade 1/2: fatigue (78%), anorexia (74%), rash (70%; 11% grade 3), diarrhea (67%), weight loss (63%), hypophosphatemia (59%; 33% grade 3), nausea (56%), neutropenia (48%; 19% grade 3), alopecia (44%), and oral mucositis (26%). Dose reductions of both agents for toxicity occurred in 58% of pts. The most common reasons for dose reduction were grade 3 rash or neutropenia and grade 2 fatigue or anorexia. Among 24 pts evaluable for response, the RR by RECIST criteria was 42% (38% PR, 4% CR). An additional 46% had stable disease for at least 1 cycle, including 8% with ≥20% regression. Responses were seen in lungs, pleura, kidney, liver, pancreas, and nodes. Three of the 10 responses occurred in patients who had failed prior high-dose IL-2. Conclusions: Sorafenib + IFN-α2b is a well-tolerated outpatient regimen with substantial antitumor activity in both untreated and IL-2-resistant metastatic RCC. Further investigation of this regimen in RCC is warranted. [Table: see text]
Factors affecting time to active therapy (AT) among patients (pts) with myelodysplastic syndromes (MDS) in a US electronic medical records (EMR) database.
Authors: Bart L. Scott, Pavel Kiselev, Albert Fliss, Minqiang Huang, David P. Steensma, Xiaomei Ma, Arlene S. Swern, Mary M. Sugrue
Journal: Journal of Clinical Oncology (2016)

e18548 Background: Initiation of therapy after diagnosis of MDS is influenced by numerous factors. Using a previously identified cohort of 5,162 MDS pts (Ma X, et al. Blood. 2015;126:abstr 3319), we investigated how specific pt factors are associated with initiation of AT (azacitidine, decitabine, or lenalidomide) using the GE Centricity EMR database (GE Healthcare IT, Princeton, NJ). Methods: Time from baseline (date of first ICD-9-CM MDS code entry) to AT onset was evaluated using a Cox model. Pts who never started AT were censored as of last visit. Included in this analysis were: gender, race, baseline age, geographic area, baseline hemoglobin (Hb), use of supportive care (including hematopoietic growth factors, iron chelation therapy, or transfusions), insurance type, presence of comorbidities (diabetes, renal, vascular), and year of diagnosis (to assess changes in treatment patterns over time). All covariates with P < 0.1 in a univariate model were considered in a multivariable model; all significant covariates (P < 0.05) were retained. Results: Among the 5,162 pts, 9% (n = 464) received AT. Factors predictive of time to AT in multivariate analyses are shown in the Table. Conclusions: Younger pts and pts with no comorbidities, lower baseline Hb, and diagnosis after 2008 started AT sooner than comparators. These findings from a large, real-world cohort may help raise awareness of potential biases in the treatment of elderly MDS pts and healthcare providers’ knowledge gaps regarding when to initiate therapy, which may impact treatment of pts with MDS. Baseline characteristic Association with time to AT (n = 464) Co-morbidities (absent* vs present) HR 1.81 (95% CI 1.48–2.22) Date of diagnosis (vs before Feb 2008) Feb 2008–Feb 2011* HR 2.56 (95% CI 1.80–3.64) Feb 2011–Feb 2014* HR 5.18 (95% CI 3.52–7.64) Hb level (per unit increase**) HR 0.78 (95% CI 0.73–0.82) Age < 70* vs ≥ 80 years HR 1.66 (95% CI 1.28–2.15) 70–79* vs ≥ 80 years HR 1.49 (95% CI 1.16–1.90) Sex (male* vs female) HR 1.50 (95% CI 1.23–1.84) *Factor associated with shorter time to AT. **Pts with lower Hb had shorter time to AT. All HR values were significantly different (P < 0.002). CI, confidence interval; HR, hazard ratio.
Effect of obesity on overall survival following permanent prostate brachytherapy
Authors: R. Galbreath, G. S. Merrick, W. Butler, K. Wallner, Z. Allen, E. Adamovich
Journal: Journal of Clinical Oncology (2007)

15576 Background: To evaluate the impact of obesity on cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) following prostate brachytherapy. Methods: From April 1995 through March 2003, 1,093 consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJCC) prostate cancer. The median follow up was 5.6 years. All patients were implanted at least 3 years prior to analysis. Evaluated body mass index (BMI) subgroups were &lt; 25 (n=258), 25.0 to 29.9 (n=547), 30.0 to 34.9 (n=214) and = 35 (n=74) kg/m2, respectively. Four-hundred and thirty (39.9%) and 589 (53.9%) of the patients received androgen deprivation therapy or supplemental external beam radiation therapy, respectively. Multiple clinical, treatment and dosimetric parameters were evaluated as predictors of CSS, bPFS and OS. Results: The 11 year CSS, bPFS and OS for the entire cohort were 97.5%, 95.6% and 77.6% respectively. BMI did not impact CSS or bPFS for any of the BMI cohorts. However, OS was statistically lower in patients with a BMI &lt; 25 kg/m2 (p = 0.014). A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent-positive biopsies, risk group,V100 and hypertension predicted for bPFS. Patient age and tobacco use were the strongest predictors of OS. One-hundred and twenty-eight patients have died with 108 (84.4%) of the deaths the result of cardiovascular/pulmonary disease (73) and second malignancies (35). To date, 12 patients have died of metastatic prostate cancer. Conclusions: Following brachytherapy, obesity did not impact CSS, bPFS or OS. Cardiovascular or pulmonary disease and second malignancies substantially outweighed prostate cancer as competing causes of death. No significant financial relationships to disclose.
포스터전시 : 만성 B형간염 환자에서 클레부딘 치료의 항바이러스 효과 및 안전성 연구 -바이러스 돌파 발생과 근육관련 증상 발현을 중심으로-
Authors: 김병국, 권소영, 최원혁, 고순영, 이창홍, 오지영
Journal: Clinical and Molecular Hepatology (2009)
Significance of BAALC, MN1, ERG, CEBPa Gene Expression as New Prognostic Factors, in the Context of Other Molecular Markers in Intermediate Risk AML Group According to Cytogenetics, Including Patients Younger Than 60 Years
Authors: Marta Antonina Libura, Beata Piatkowska-Jakubas, Olga Haus, Izabela Florek, Bozena Jazwiec, Krystyna Soszynska, Zoriana Salamanchuk, Malgorzata Jakobczyk, Szymon Fornagiel, Tomasz Sacha, Marek Kielbinski, Kazimierz Kuliczkowski, Ewa Duszenko, Anna Jaskowiec, Barbara Mucha, Katarzyna Skonieczna, Aleksander Skotnicki
Journal: Blood (2008)
Simultaneous measurement of cancer specific quality of life and general health status in gynecologic malignancies
Authors: K. M. Gil, V. E. Von Gruenigen, H. E. Frasure, M. Grandon, M. P. Hopkins, E. L. Jenison
Journal: Journal of Clinical Oncology (2004)

8253 Background: Cancer specific questionnaires such as the Functional Assessment of Cancer Therapy (FACT) are sensitive to quality of life (qol) effects due to illness and treatment, but interpretation may be hampered by response shifts if women's perception of qol changes over the course of their illness. The SF-36 Health Survey is designed to measure health in a variety of disease states and may be more likely to measure a decline with severity of illness. Using the SF-36 would allow for interpretation of qol relative to defined populations as well as previously measured health status. Methods: Ninety women undergoing surgery for endometrial cancer, ovarian cancer or a benign adnexal mass completed the FACT-G and the SF-36 pre-operatively and 6 months following surgery. Spearman correlation coefficient was used to compare scores from similar scales obtained by the two questionnaires at baseline. Significance was set at .01 due to multiple tests performed. Results: Significant changes over 6 months were seen in the FACT emotional and functional scales and the bodily pain and mental health subscales of the SF-36. SF-36 data at baseline and 6 months were similar to age and gender specific national norms. The physical and functional scales of the FACT were significantly correlated with the physical scales of the SF-36 (p's<.01). The emotional scale of the FACT was significantly correlated with the mental health scales of the SF-36 (p's<.01), but the social scale of the FACT was only correlated with the SF-36 vitality subscale (p<.01). Conclusions: The FACT and SF-36 physical scales were highly correlated suggesting that women are responding similarly within the physical domain at the beginning of their illness. The FACT questionnaire appears more sensitive to changes resulting from cancer and treatment, but may benefit from being used with the SF-36 for malignancy that progresses. Under these conditions, SF-36 scores are likely to decrease but women may “compensate” by changing their definition of qol as measured with the FACT. Reported qol using the FACT can then be evaluated within the context of their general health status measured with the SF-36. No significant financial relationships to disclose.
Role of PET/CT As a Measure of Minimal Residual Disease (MRD) Negativity Among Patients with Myeloma Post Autologous Stem Cell Transplant (ASCT)
Authors: Ajay K. Nooka, Jonathan L. Kaufman, A. Tuba Karagulle Kendi, Yan Li, Chikaodili O Obidike, Charise Gleason, Lawrence H Boise, Sagar Lonial
Journal: Blood (2015)