tbuckley/cabot-search huggingface dataset:
Ovarian cancer treatment patterns and outcomes in the United States: A National Program of Cancer Registries (NPCR) study
Authors: S. L. Stewart, J. M. Wike, R. Cress, C. O’Malley, S. Neloms, A. R. Kahn, M. J. Schymura
Journal: Journal of Clinical Oncology (2006)

15031 Background: Ovarian cancer (ovca) is the fifth leading cause of cancer death among women in the United States. In 2001, the NPCR program (administered by the Centers for Disease Control and Prevention) initiated a multi-year study to determine the first course of treatment for ovca patients in order to assess whether the ovca standard of care (as defined by the NIH Physician Data Query) was met. Methods: Population-based cancer registries in Maryland, New York, and Northern California were funded to collect patient, tumor, provider, and treatment data on patients diagnosed in these areas between 1997 and 2000. Information was collected through a retrospective medical record abstraction; all ovca records in Northern California and Maryland were included in the study, a simple random sample of ovca medical records in New York was included. Data on over 3000 patients from Northern California and New York were obtained (about 1500 patients each); data on about 1000 patients from Maryland was obtained. Patient vital status was followed through 2002. Results: Most patients were non-Hispanic white and between the ages of 50 and 79. About 30% of the tumors were papillary serous cystadenocarcinomas and almost 40% were poorly differentiated; about 66% of tumors were distant stage at diagnosis. The percentage of distant stage diagnoses increased with increasing age through age 79. Over half of patients were treated by gynecologic oncologists; obstetrician/gynecologists treated a little over 10% of patients. Overall, over 80% of patients underwent cancer directed surgery; about 50% were treated with carboplatin and about 55% were treated with paclitaxel. Patients ages 70 and older received cancer-directed surgery less often than younger patients. Overall, about 50% of patients were alive at the end of the follow-up period, with the percentage alive within age categories decreasing with increasing age. Conclusions: Age remains a negative factor in ovca presentation, treatment, and survival. Continued assessment of ovca patterns of care will enhance ovca knowledge and may aid clinicians in determining appropriate treatments for their ovca patients. No significant financial relationships to disclose.
Influence of<i>TYK2</i>in systemic sclerosis susceptibility: a new<i>locus</i>in the IL-12 pathway
Authors: Elena López-Isac, Diana Campillo-Davo, Lara Bossini-Castillo, Sandra G Guerra, Shervin Assassi, Carmen Pilar Simeón, Patricia Carreira, Norberto Ortego-Centeno, Paloma García de la Peña, Lorenzo Beretta, Alessandro Santaniello, Chiara Bellocchi, Claudio Lunardi, Gianluca Moroncini, Armando Gabrielli, Gabriela Riemekasten, Torsten Witte, Nicolas Hunzelmann, Alexander Kreuter, Jörg HW Distler, Alexandre E Voskuyl, Jeska de Vries-Bouwstra, Ariane Herrick, Jane Worthington, Christopher P Denton, Carmen Fonseca, Timothy RDJ Radstake, Maureen D Mayes, Javier Martín
Journal: Annals of the Rheumatic Diseases (2015)

TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc.This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method.Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10(-13), OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10(-3), OR=0.80; p=1.27×10(-3), OR=0.59; p=2.63×10(-5), OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants.We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology.
Abstract 12465: Short-term Rapid Atrial Pacing Promotes Gene Expression of Prothrombotic Molecules in the Liver - Cardio-hepatic Interaction in Atrial Fibrillation
Authors: Takanori Yaegashi, Takeshi Kato, Soichiro Usui, Hiroshi Furusho, Masaki Okajima, Shinichiro Takashima, Masayuki Takamura, Shuichi Kaneko
Journal: Circulation (2013)
Evaluation of smoking cessation among patients with respiratory or cardiac disease after 6 months of hospitalization
Authors: Stephania S. Margotto, Thaís Garcia, Talita J. Cesare, Caroline A. Torres, André L. Bertani, Angelica T. Biral, Liana S. Coelho, Simone do Vale, Ilda de Godoy, Irma de Godoy, Suzana E. Tanni
Journal: European Respiratory Journal (2014)

The approach of smoking cessation during hospitalization is recommended by international guidelines; however, there are few Brazilian data about the success of interventions during hospitalization.  Objective:  Evaluate the rate of smoking cessation among patients with respiratory (RD) or cardiac disease (CD) after 6 months of hospitalization.  Methods:  63 patients with RD and 53 CD active smokers were evaluated during hospitalization according to gender, age, smoking history, Fagerstrom test for nicotine dependence (FTND) and motivational stage. We assessed the smoking cessation after 6 months. During the hospitalization, all patients received individual motivational counseling and specific medications to control the symptoms of abstinence. After discharge, all patients were referred to continue the treatment at the intensive behavior counseling group once a week during for 1 month.  Results:  From the total, 62(53%) patients returned after 6 months. Characteristics are presented in the table.   Conclusion:  The RD group presented higher cessation rate than CD, however, the smoking cessation treatment during hospitalization showed effectiveness.
Teenage pregnancy rate falls to record low
Authors: Anne Gulland
Journal: BMJ (2016)

The conception rate among under 18s in England and Wales has fallen to its lowest level in over 40 years, to 22.9 conceptions in every 1000 young women aged 15-17.1

Figures from the Office for National Statistics show that the conception rate in under 18s peaked in 1971, at 54.9 in 1000 women. It then dropped throughout the 1970s and rose again through the 1980s, until it peaked at 47.1 per 1000 in 1998. From that time the rate began to fall, dropping sharply since 2007, when the rate was 41.6 per 1000.

The estimated number of conceptions in women under 18 fell from 24 306 in 2013 to 22 653 in 2014, …
KIT D816V–mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression
Authors: Andres C. Garcia-Montero, Maria Jara-Acevedo, Ivan Alvarez-Twose, Cristina Teodosio, Laura Sanchez-Muñoz, Carmen Muñiz, Javier I. Muñoz-Gonzalez, Andrea Mayado, Almudena Matito, Carolina Caldas, Jose M. Morgado, Luis Escribano, Alberto Orfao
Journal: Blood (2015)
Neoadjuvant use of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by docetaxel (T) with concurrent COX-2 inhibitor in women with stage II/III breast cancer: A subanalysis of cardiac function.
Authors: L. W. Chow, A. Y. Yip, R. H. Chan, M. Toi
Journal: Journal of Clinical Oncology (2010)

e11073 Background: Anthracycline and taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Although addition of COX-2 inhibitors might enhance the anticancer effect of chemotherapy, many studies were halted with the concern of possible cardiotoxicity. This substudy is to evaluate the change in cardiac function of patients during treatment with preoperative FEC-T with concurrent celecoxib until and after surgery. Methods: A group of 47 patients, age ranged from 33 to 58 years (mean age 46 ± 6 years), who received four cycles of 3-weekly FEC followed by four cycles of 3-weekly T with concurrent oral celecoxib before surgery (F: 500 mg/m2; E: 100 mg/m2; C: 500 mg/m2; T: 100 mg/m2; celecoxib: 200 mg bid), were studied. Echocardiography was performed at baseline, after 4 cycles of FEC and after 4 cycles of T before surgery, and 6 months, 12 months and 18 months after surgery to evaluate changes in left ventricular ejection fraction (LVEF) across time-points. Paired sample statistics was conducted. Results: Patients tolerated well with this regimen. Neither life-threatening toxicity nor clinical symptom of cardiac toxicity was observed. Of 47 evaluable cases, LVEF was assessed in 47 patients preoperatively and in 32 patients post-operatively. During concurrent celecoxib treatment, the mean LVEF increased from 68.5% ± 6.6% at baseline to 72.3% ± 3.6% after FEC and to 73.0% ± 4.1% after T. When compared to baseline, the changes were statistically significant after FEC (p = 0.002) and after T (p < 0.0001) in 47 patients. LVEF however did not change at 6 months (72.8% ± 3.8%), 12 months (72.7% ± 3.1%) and 18 months (72.4% ± 3.3%) after surgery in 32 patients. The remaining 15 patients are still under follow up for cardiotoxicity until 1 year after surgery. Conclusions: Neoadjuvant FEC-T with concurrent celecoxib is well tolerated. The short-term treatment increased LVEF during the course of neoadjuvant chemotherapy and remains good LVEF after surgery. This is an interesting finding which warrants further investigation of the possible protective effect on cardiac function. No significant financial relationships to disclose.
Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE)
Authors: Marcus J. Drake, Christopher Chapple, Ahmet A. Esen, Stavros Athanasiou, Javier Cambronero, David Mitcheson, Sender Herschorn, Tahir Saleem, Moses Huang, Emad Siddiqui, Matthias Stölzel, Claire Herholdt, Scott MacDiarmid
Journal: European Urology (2016)

Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5 mg and mirabegron 50 mg) versus solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4 wk of solifenacin 5 mg. OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10 mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4. The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24 h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24 h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5 mg, noninferiority (and potential superiority) of combination versus solifenacin 10 mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy. A total of 2174 patients were randomised to combination (n = 727), solifenacin 5 mg (n = 728), or solifenacin 10 mg (n = 719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p = 0.001), daily micturitions (p < 0.001), and incontinence noted in a 3-d diary (p = 0.014). Combination was noninferior to solifenacin 10 mg for key secondary end points and superior to solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated. Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms versus solifenacin 5 or 10 mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg. In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5 mg treatment received additional treatment with mirabegron 50 mg. Combining mirabegron 50 mg with solifenacin 5 mg was superior to solifenacin 5 mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. ClinicalTrials.gov NCT01908829.
The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial
Authors: Martin Reck, Mark A. Socinski, Alexander Luft, Aleksandra Szczęsna, Mircea Dediu, Rodryg Ramlau, György Losonczy, Olivier Molinier, Christian Schumann, Richard J. Gralla, Philip Bonomi, Jacqueline Brown, Victoria Soldatenkova, Nadia Chouaki, Coleman Obasaju, Patrick Peterson, Nick Thatcher
Journal: Journal of Thoracic Oncology (2016)

IntroductionNecitumumab, a second-generation, recombinant human immunoglobulin G1 epidermal growth factor receptor antibody in the phase 3 SQUIRE trial (NCT00981058), increased survival benefit for patients randomized to receive necitumumab plus gemcitabine-cisplatin compared with those who received gemcitabine-cisplatin. Here we characterize health-related quality of life (HRQoL) and tolerability results.MethodsA total of 1093 patients with stage IV squamous non–small cell lung cancer were randomized 1:1 to receive necitumumab (800 mg absolute dose intravenously [IV]) plus gemcitabine-cisplatin (gemcitabine = 1250 mg/m2 IV on days 1 and 8; cisplatin = 75 mg/m2 IV on day 1) or gemcitabine-cisplatin alone (every 21 days) for up to six cycles. Patients receiving necitumumab plus gemcitabine-cisplatin without disease progression continued necitumumab until progression. HRQoL was measured by Eastern Cooperative Oncology Group performance status, the Lung Cancer Symptom Scale (LCSS), and the European Quality of Life Five-Dimensions questionnaire. Efficacy and LCSS outcomes were analyzed using the baseline maximum severity score of the LCSS. Tolerability was measured in terms of exposure to the study treatment and adverse events. Hospitalization rates were collected.ResultsMost patients in both study arms similarly maintained Eastern Cooperative Oncology Group performance status and comparable LCSS and European Quality of Life Five-Dimensions questionnaire assessments. Patients with a higher baseline LCSS had a greater survival benefit on the necitumumab arm. Chemotherapy exposure was similar in both treatment arms; 51% of patients on the necitumumab plus gemcitabine-cisplatin arm continued on single-agent necitumumab. The most frequent grade 4 adverse events were neutropenia (6.1% versus 7.9%) and thrombocytopenia (3.2% versus 4.3%) in the necitumumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin arms, respectively. Hospitalizations were slightly higher with necitumumab plus gemcitabine-cisplatin (36.4%) than with gemcitabine-cisplatin (34.0%).ConclusionsThe addition of necitumumab to gemcitabine-cisplatin was well tolerated, did not negatively affect HRQoL or toxicity, and particularly benefited patients with more severe baseline symptoms or lower HRQoL.
Second- and third-generation ALK inhibitors for non-small cell lung cancer
Authors: Jingjing Wu, John Savooji, Delong Liu
Journal: Journal of Hematology & Oncology (2016)

Crizotinib as the first-generation ALK inhibitor has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC). Second- and third-generation ALK inhibitors are entering clinical applications for ALK+ NSCLC. In addition, a third-generation ALK inhibitor, lorlatinib (PF-06463922), was reported to resensitize NSCLC to crizotinib. This review provided a summary of clinical development of alectinib, ceritinib, brigatinib (AP26113), and lorlatinib.
제10차 춘계 학술대회 초록집 : 구연 14 ; 인간 간암세포에서 저산소증에 의한 Hexokinase 2 발현 유도의 세포성장에 미치는 영향 및 Hexokinase 2 억제제의 세포사 유도 기전
Authors: Geum Youn Gwak, Jung Hwan Yoon, Hyo Suk Lee, Chung Yong Kim
Journal: Clinical and Molecular Hepatology (2004)
Targeting vasculogenesis to prevent progression in multiple myeloma
Authors: M Moschetta, Y Mishima, Y Kawano, S Manier, B Paiva, L Palomera, Y Aljawai, A Calcinotto, C Unitt, I Sahin, A Sacco, S Glavey, J Shi, M R Reagan, F Prosper, M Bellone, M Chesi, L P Bergsagel, A Vacca, A M Roccaro, I M Ghobrial
Journal: Leukemia (2016)
The classification of depression: traditional versus mathematical approaches
Authors: N C Andreasen, W M Grove
Journal: American Journal of Psychiatry (1982)

The authors examine the classification of depressive disorders with an empirically and mathematically based method, cluster analysis. In a sample of 228 patients from the NIMH Collaborative Study of the Psychobiology of Depression, clusters were generated by using crossectional symptoms; course of illness, family history, and treatment variables were used as independent variables to evaluate the validity of the clusters. The four clusters identified correspond roughly to severe depressions with endogenous features, less severe depressions, bipolar depression with cycling within the episode, and psychotic depressions. This study supports the Research Diagnostic Criteria and DSM-III approaches to the classification of depressive disorders.
Time-to-Event Analysis
Authors: Juliana Tolles, Roger J. Lewis
Journal: JAMA (2016)

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A pilot study of sentinel lymph nodes identification in patients with endometrial cancer
Authors: B. Li, L. Wu, X. Li, W. Zhang, S. Li, J. Gao
Journal: Journal of Clinical Oncology (2007)

16022 Background: The sentinel lymph node (SLN) biopsy has showed the feasibility to limit the extent of lymphadenectomy in vulvar and cervical cancer, but few studies have examined this procedure in endometrial cancer. The aim of this study is to examine the feasibility of SLN identification for the patients with endometrial cancer. Methods: Twenty patients with endometrial cancer undergoing hysterectomy and lymphadenectomy were included in the study. At laparotomy, methylene blue dye was injected into the subserosal myometrium of corpus uteri at multiple sites. Dye uptake into lymphatic channels was observed and blue nodes were identified as SLNs. The SLNs were biopsied before lymphadenectomy performed. The samples of SLNs and non-SLNs were recorded separately and correlated with the final pathological results. Results: Dye uptake into lymphatic channels was seen in all 20 cases. Among them, SLN was identified in 15 (75%) cases. A total of 71 SLNs with a mean number of 4.7 (range, 1–10) were identified from all pelvic sites. The most frequent locations of SLNs included obturator in 29 (41%), interiliac in 16 (26%). No dye-containing paraaortic node was found. Two patients (10%) had nodal metastases, and they all had at least one SLN found to be positive, the false-negative-rate was 0. No adverse reactions or injures were attributed to the study. Conclusions: This study shows the feasibility and safety of SLN identification with blue dye in patients with endometrial cancer undergoing staging surgery. The SLNs accuratly predicted the nodal metastases in the study.This approach might provide an alternative to limit the extent of nodal sampling. No significant financial relationships to disclose.
A new patient-derived orthotopic malignant meningioma model treated with oncolytic herpes simplex virus
Authors: Fares Nigim, Shin-ichi Esaki, Michael Hood, Nina Lelic, Marianne F. James, Vijaya Ramesh, Anat Stemmer-Rachamimov, Daniel P. Cahill, Priscilla K. Brastianos, Samuel D. Rabkin, Robert L. Martuza, Hiroaki Wakimoto
Journal: Neuro-Oncology (2016)

Higher-grade meningiomas (HGMs; World Health Organization grades II and III) pose a clinical problem due to high recurrence rates and the absence of effective therapy. Preclinical development of novel therapeutics requires a disease model that recapitulates the genotype and phenotype of patient HGM. Oncolytic herpes simplex virus (oHSV) has shown efficacy and safety in cancers in preclinical and clinical studies, but its utility for HGM has not been well characterized. Tumorsphere cultures and serial orthotopic xenografting in immunodeficient mice were used to establish a patient-derived HGM model. The model was pathologically and molecularly characterized by immunohistochemistry, western blot, and genomic DNA sequencing and compared with the patient tumor. Anti-HGM effects of oHSV G47Δ were assessed using cell viability and virus replication assays in vitro and animal survival analysis following intralesional injections of G47Δ. We established a serially transplantable orthotopic malignant meningioma model, MN3, which was lethal within 3 months after tumorsphere implantation. MN3 xenografts exhibited the pathological hallmarks of malignant meningioma such as high Ki67 and vimentin expression. Both the patient tumor and xenografts were negative for neurofibromin 2 (merlin) and had the identical NF2 mutation. Oncolytic HSV G47Δ efficiently spread and killed MN3 cells, as well as other patient-derived HGM lines in vitro. Treatment with G47Δ significantly extended the survival of mice bearing subdural MN3 tumors. We established a new patient-derived meningioma model that will enable the study of targeted therapeutic approaches for HGM. Based on these studies, it is reasonable to consider a clinical trial of G47Δ for HGM.