tbuckley/cabot-search huggingface dataset:
A novel multimodality treatment for resectable pancreatic cancer (PC)
Authors: H. Takamori, K. Kanemitsu, A. Chikamoto, T. Ishiko, T. Beppu, M. Hirota, H. Baba
Journal: Journal of Clinical Oncology (2007)

4630 Background: Patients with PC often suffer from tumor recurrence despite curative resection, thus indicating that systemic therapy added to local control might be required to further improve the survival. The aim of this phase II trial was to assess the feasibility and tolerance as well as overall survival of a novel multimodality therapy composed of pancreatic resection and intraoperative radiation therapy (IORT) combined with neoadjuvant (NAC) and adjuvant (AC) combination chemotherapy for patients with PC. Methods: Eligibility criteria included: no distant metastases / no tumor extension to the CA or the SMA by imaging, tumor size ≥ 1 cm, ECOG PS ≤ 2, age &lt; 80, and normal organ function. For NAC, 5-FU was administered at a dose of 125 mg/m2 on days 1–5 every week as a continuous pancreatic and hepatic arterial infusion, and gemcitabine was infused intravenously at a dose of 800 mg/m2 for 30 min once weekly for 2 weeks. Pancreatic resection combined with IORT (30 Gy, 12 Mev of electron beam) was performed after a one-week rest following the completion of NAC. AC was performed in the same regimen as NAC after the recovery from surgery. We performed intension to treat analyses. Results: Between 2001 and 2006, 32 pts were enrolled: 32 received NAC, 28 received AC, and 28 received IORT. Of 32 pts given NAC, 13 had grade 3–4 hematological toxicity. All pts underwent surgery, including R0 resection in 26 pts, without delay by NAC- related toxicity. Of 28 pts given AC, 18 had grade 3–4 hematological, and 6 had non-hematological toxicity, although no chemotherapy-related death was observed. The median follow-up period was 20 months (rang 3.9 to 67.4). Overall survivals at 1, 3, and 5 years were 77.0 %, 60.2 %, and 48.1 %, respectively. Median survival was 38.5 months. Conclusions: This new multimodality treatment is feasible and tolerable, and may contribute to the survival benefit of patients with PC. No significant financial relationships to disclose.
춘계학술대회 : 포스터발표 ; 간세포암종에 대한 수술적 치료 200예의 예후인자 분석
Authors: 박상재, 서영일, 김성훈, 김영일, 박홍석, 이순애, 신정아, 안민, 이우진, 홍은경, 박중원, 김창민
Journal: Clinical and Molecular Hepatology (2005)

배경 및 목적: 간절제술은 간세포암의 치료에 있어 가장 근치성이 높은 방법이지만 최근 고주파열치료 등 국소 치료의 결과가 특히 조기 간암에서 절제술에 근접하다고 보고되고 있다. 그러므로 간세포암에서 간절제술이 1차 치료법으로 적용되기 위해서는 어떤 환자군에서 치료 효과가 탁월하면서도 안전하게 적용될 수 있는지에 대한 연구가 필요하다고 판단된다. 이에 본 연구에서는 간세포암 환자에서 연속적으로 시행된 200예 간절제술에 대한 예후인자 분석을 통하여 간절제
Tumor markers of efficacy and resistance to cetuximab (C) treatment in metastatic colorectal cancer (mCRC): Results from CALGB 80203 (Alliance).
Authors: Herbert Hurwitz, Stephanie Cushman, Chen Jiang, Ivo Shterev, Michelle R. Mahoney, Donna Niedzwiecki, Robert J. Mayer, Alan Paul Venook, Kouros Owzar, Andrew B. Nixon
Journal: Journal of Clinical Oncology (2013)

11011 Background: Beyond KRAS status, there are no validated markers for anti-EGFR therapy in mCRC. While expression of genes within the EGF signaling axis has been reported to correlate with benefit, most reports used data from non-randomized trials which cannot distinguish between general prognostic markers and markers that predict for benefit from C. CALGB 80203 was a 238-patient (pt), 4-arm, randomized phase II study of FOLFOX or FOLFIRI +/- C in mCRC pts. Formalin-fixed, paraffin-embedded (FFPE) tumor samples from CALGB 80203 were analyzed for gene expression of HER family ligands, receptors and regulators. Methods: FFPE tumor samples from consenting pts were analyzed for AREG, BTC, CD73, DUSP4, EGF, EGFR, EPGN, EREG, HB-EGF, HER2, HER3, HER4, PHLDA1 and TGFa by RT-qPCR. Interaction between baseline gene expression levels and treatment (C) with respect to progression-free survival (PFS) and overall survival (OS) was modeled using a multiplicative Cox proportional hazards model. Results: Baseline tumor tissue was available from 103 pts; 55% of tumors were KRAS wild type (WT). Two prognostic markers were identified; higher tumor mRNA levels of HER2 (HR=0.64, p=0.002) and EREG (HR=0.89, p=0.016) were associated with longer PFS across all pts. Potential predictive markers of benefit for C were identified. In KRAS WT tumors, lower HER3 expression was associated with longer OS from C treatment while higher HER3 expression was associated with shorter OS from C treatment (chemo + C: HR=1.15; chemo only: HR=0.48, interaction p=0.029). No association was observed for HER3 and outcome in KRAS mutant (MT) tumors. Interestingly, higher CD73 expression was associated with longer PFS in C-treated pts in both KRASWT (chemo + C: HR=0.91; chemo only: HR=1.57, interaction p=0.026) and MT tumors (chemo + C: HR=0.80; chemo only: HR=1.29, p=0.025). Conclusions: In one of the first reports using data from a randomized study, gene expression of HER3 and CD73 were identified as potential predictive markers for C. These data implicate not only HER axis signaling but also immune modulation as potential mechanisms of C action and sensitivity, and warrant confirmation in other large randomized trials.
Abstract 40: Induced Basal Autophagy in Atg7 Mice Ameliorates Cardiac Proteinopathy
Authors: M. Shenuarin Bhuiyan, J Scott Pattison, Jeanne James, James Gulick, Hanna Osinska, Jeffrey Robbins
Journal: Circulation Research (2012)

Backgrounds: Basal autophagy is a cellular homeostatic mechanism that can eliminate damaged and potentially toxic proteins and organelles. We hypothesized that cardiac proteinopathies, such as desmin-related cardiomyopathy (DRC) that lead to accumulations of misfolded proteins, can trigger alterations in cardiomyocyte autophagy as an adaptive process. However, a mouse model of cardiac specific-induced basal autophagy is lacking and the effects of acute or chronic increased basal autophagy remains unclear. Hypothesis: To determine whether induction of basal autophagy in the induced Atg7 mice can ameliorate cardiac proteinopathy in a model of DRC. Methods and Results: The protein Atg7 is thought to be essential for autophagy and, in an attempt to induce high levels of basal autophagy we generated an inducible-transgenic (Tg) mouse. This mouse is able to undergo cardiac specific overexpression of the Atg7 gene, where the transgene can be switched on or off by doxycycline. The Atg7-Tg mouse showed 10 fold overexpression of Atg7 protein with normal heart morphology and function being maintained even after 10 months. Overexpression of Atg7 had no detectable effect on other proteins involved in the autophagy-lysosomal pathways. However, the hearts show increased basal autophagy, as measured by increased autophagic flux activity and cardiomyocyte ultrastructural examination. We showed earlier that autophagy can be down-regulated in cardiac proteinopathy as observed in a mutant αB-crystallin (CryAB R120G ) mouse model of DRC. Therefore, we crossed the CryAB R120G mice to transgenic mice with cardiac specific overexpression of Atg7. Sustained Atg7-induced autophagy in CryAB R120G hearts prolonged CryAB R120G survival by 40% and is associated with the maintenance of cardiac function and decreased cardiac hypertrophy. Conclusions: Cardiac-specific Atg7 inducible-Tg mice with increased basal autophagy may serve as a novel model to study the regulatory role of autophagy in the heart. Induced basal autophagy in Atg7-Tg mice can extend the life-span in a model of cardiac proteinopathy. Modulating the overall autophagic state may be useful therapeutically in heart disease.
Study on micrometastases in sentinel lymph node, peripheral blood and bone marrow from breast cancer patients
Authors: S. Wang, P. Fan, X. Liu
Journal: Journal of Clinical Oncology (2004)

690 Background: Lymph node, peripheral blood, and bone marrow are frequently transferred by breast cancer cells. Micrometastases in lymph node, peripheral blood, and bone marrow are difficult to be found by conventional histological examination. We first detected micrometastases in bone marrow by the method of immunohistochemistry(IHC) in 1989. It had significant correlation with patients' prognosis. In this study, several methods were used to study on the micrometastases in sentinel lymph node(SLN), peripheral blood, and bone marrow from the same breast cancer patients. Methods: Continuous slices, IHC and RT-PCR assays were used to detect micrometastases in SLN, peripheral blood and bone marrow from breast cancer patients. These samples were collected from 38 patients, with no palpable lymph node preoperatively, performed sentinel lymph node biopsy (SLNB) by 1% isosulfan blue and pathologically diagnosed negative under HE staining. Results: Of the 38 paired bone marrow and peripheral blood samples, 11 bone marrow samples were positive for keratin-19 by RT-PCR, whereas only 3 peripheral blood samples were positive for keratin-19, with a higher expression rate of keratin-19 mRNA in bone marrow than that of in peripheral blood (P=0.018). In detection bone marrow micrometastases, 6 were IHC-positive and 11 were RT-PCR positive for keratin 19. RT-PCR seemed to be more sensitive than IHC did, whereas there was no significant difference (P=0.169). In SLN samples, 10 were RT-PCR-positive, whereas 4 were IHC-positive for keratin 19. RT-PCR seemed to detect a higher positive rate than that of IHC, but there was no statistic difference (P=0.076). Of ten SLNs positive on mRNA level, 4 were both RT-PCR positive and IHC-positive, six were mRNA level positive only. Two of 38 paired bone marrow and SLN samples were detected both positive by RT-PCR, which indicated that bone marrow micrometastases did not always simultaneously occur with SLN. Conclusions: Micrometastases in bone marrow is higher than that of in peripheral blood.Bone marrow micrometastases did not always simultaneously occur with SLN . No significant financial relationships to disclose.
Phenotyping chronic pulmonary aspergillosis by cluster analysis
Authors: Cendrine Godet, François Laurent, Guillaume Béraud, Cécile Toper, Boubou Camara, Bruno Philippe, Patrick Germaud, Vincent Cottin, Catherine Beigelman-Aubry, Antoine Khalil, Pascal Blouin, Mathilde Pouriel, France Roblot, Anne Bergeron, Jacques Cadranel
Journal: European Respiratory Journal (2015)

Chronic pulmonary aspergillosis (CPA) is a complex disorder involving various underlying conditions and risk factors, clinical and radiological features, and natural histories or responses to treatment [1]. Untreated, patients with CPA have ≥50% 5-year mortality [2, 3]. Recently, it was proposed that CPA includes simple aspergilloma, chronic cavitary pulmonary aspergillosis (CCPA) and chronic necrotising pulmonary aspergillosis (CNPA) [1]. Cluster analysis based on clinical and radiological settings does not distinguish any specific phenotype of CPA http://ow.ly/QZq7V Philippe Gegou (INTRASENSE technical and computer support team, Montpellier, France) who enabled us to work on Myrian, the software suite used for the visualisation and post-processing of our medical images. The authors also wish to thank Jeffrey Arsham (an American medical translator working at CHU Poitiers, Poitiers, France) for reviewing and editing the original English language manuscript. Marie France Carette (Service de Radiologie, AP-HP, Hôpital Tenon, Paris, France) and Gilbert Ferriti (Service de Radiologie, CHU Grenoble, Grenoble, France) both radiologists who assisted us with data collection. Jean-Pierre Frat (Service de Réanimation médicale, CHU Poitiers, Poitiers, France) for editing the original manuscript. The following investigators participated in the ACHROSCAN study group: François Laurent, CHU Bordeaux, Bordeaux, France; Boubou Camara and Christophe Pison, CHU Grenoble, Grenoble, France; Catherine Beigelman-Aubry, CHUV Lausanne, Lausanne, Switzerland; Vincent Cottin CHU Lyon, Lyon, France; Patrick Germaud, CHU Nantes, Nantes, France; Anne Bergeron, APHP Paris, Paris, France; Jacques Cadranel, Antoine Khalil and Cécile Toper, APHP, Paris, France; Guillaume Béraud, Pascal Blouin and Cendrine Godet CHU Poitiers, Poitiers, France; Bruno Philippe, CH Pontoise, Pontoise, France. Cendrine Godet, Jacques Cadranel and Anne Bergeron are members of the GREPI (French Group for Research and Education in Respiratory Infectious Diseases).
Clinical and molecular phase II study of gefitinib in patients (pts) with recurrent squamous cell cancer of the head and neck (H&amp;N Ca)
Authors: R. H. Wheeler, D. Jones, P. Sharma, R. K. Davis, H. Spilker, K. Boucher, S. Leachman, D. Grossman, K. Salzman, W. Akerley
Journal: Journal of Clinical Oncology (2005)

5531 Background: : Gefitinib an inhibitor of the epidermal growth factor receptor tyrosine kinase is commercially available for the treatment of refractory non-small cell lung cancer, and has shown clinical activity in squamous cell cancer of the head and neck. We report a phase II study undertaken to confirm clinical efficacy in head and neck cancer, and investigate the tumor molecular events associated with therapy. Methods: Group 1 pts could not have received systemic therapy for recurrent disease, and had to have relapsed at least 6 months after chemotherapy used during primary management. Group 2 pts could have received one treatment regimen for recurrent disease or have recurred within 6 months of primary management that included chemotherapy. Other eligibility criteria were ECOG PS ≤ 2, and adequate hematologic and serum chemistry values. Clinical Benefit was defined as a CR, PR or stable disease for ≥ 4 months by RECIST criteria. Gefitinib was administered at 500 mg orally daily with dose reduction to 250 mg for grade 3 toxicity. Results: 32 pts have been treated. Of 20 pts in Group 1 3 achieved PR and 6 SD (45% Clinical Benefit). 3 of 12 pts achieved SD in Group 2 (25% Clinical Benefit). Median duration of response was 6 months, and median time to progression 3 months and median survival 6 months. Eight pts required dose reduction for grade 3 toxicity (4 skin, 2 GI, 2 both). There was no association between rash incidence or grade, or overall toxicity grade, and Clinical Benefit. 16 pts consented to tumor biopsies prior to and 10–14 days after starting gefitinib. 10 paired tumor samples have been assayed by RT-PCR for c-myc and cyclin D1 gene expression, with no association noted between changes in gene expression and Clinical Benefit. Comparative microarray results will be presented. Conclusions: gefitinib has useful clinical efficacy in both untreated and treated pts with recurrent H&N ca. The molecular mechanisms associated with treatment failure or response remains to be defined. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Statistical Methods for Cardiovascular Researchers
Authors: Lem Moyé
Journal: Circulation Research (2016)

Biostatistics continues to play an essential role in contemporary cardiovascular investigations, but successful implementation of biostatistical methods can be complex.To present the rationale behind statistical applications and to review useful tools for cardiology research.Prospective declaration of the research question, clear methodology, and study execution that adheres to the protocol together and serve as the critical foundation of a research endeavor. Both parametric and distribution-free measures of central tendency and dispersion are presented. T testing, ANOVA, and regression analyses are reviewed. Survival analysis, logistic regression, and interim monitoring are also discussed. Finally, common weaknesses in statistical analyses are considered.Biostatistics can be productively applied to cardiovascular research if investigators (1) develop and rely on a well-written protocol and analysis plan, (2) consult with a biostatistician when necessary, and (3) write results clearly, differentiating confirmatory from exploratory findings.
A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma
Authors: G. Rosati, G. Ambrosini, S. Barni, B. Andreoni, G. Corradini, G. Luchena, B. Daniele, F. Gaion, G. Oliverio, M. Duro, G. Martignoni, N. Pinna, P. Sozzi, G. Pancera, G. Solina, G. Pavia, S. Pignata, F. Johnson, R. Labianca, G. Apolone, A. Zaniboni, M. Monteforte, E. Negri, V. Torri, P. Mosconi, R. Fossati
Journal: Annals of Oncology (2015)
Mailing free nicotine patches to smokers reduces smoking rates, study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Mailing free nicotine patches to smokers without offering any behavioural support can reduce smoking rates, researchers have reported in JAMA Internal Medicine .1

The study recruited 1000 adults who smoked more than 10 cigarettes a day from across Canada by random digit dialling of home and mobile numbers. The participants were then randomly assigned to receive a free five week course of nicotine patches with no behavioural support or …
Final results of a phase II trial of bexarotene capsules as 3rd or subsequent line therapy in patients with advanced non-small cell lung cancer (NSCLC)
Authors: R. Govindan, J. Crowley, L. Schwartzberg, P. Kennedy, C. Williams, B. Ekstrand, A. Sandler, D. Jaunakais, R. Ghalie
Journal: Journal of Clinical Oncology (2006)

7099 Background: Bexarotene, a rexinoid that binds to RXR nuclear receptors, has antiproliferative, differentiating, and apoptotic effects. Phase II studies of bexarotene plus chemotherapy in previously untreated NSCLC suggested improved patient survival. This study evaluated bexarotene for relapsed advanced NSCLC. Methods: Patients were eligible if they had NSCLC Stage IIIB wet/IV, had failed ≥ 2 prior systemic therapies, had previously received a taxane and platinum, had ECOG performance status (PS) 0–2, and had adequate organ function. Bexarotene 400 mg/m 2 daily plus prophylactic levothyroxine and a lipid-lowering agent were given until disease progression or unacceptable toxicities occurred. The primary efficacy endpoint was survival. To detect a 50% increase in median survival from 4 months, as shown with 3rd line chemotherapy, to 6 months, 125 evaluable patients were required for a 90% power at a 1-sided 5% significance. Results: A total of 146 patients were enrolled at 32 sites. Median age = 66 (range, 34–87), male = 51%, PS 2 = 23%, adenocarcinoma = 54%, and median prior therapies = 3 (range 1–7) with 55% having failed gefitinib. Bexarotene was usually well tolerated and there were no therapy-related deaths. For the 124 patients who were treated for at least 14 days and were considered evaluable for efficacy, median and 1-year survival were 6 months and 25%, respectively. Baseline albumin &lt; 3 g/dL and PS = 2 were significantly associated with shorter survival. For 26 patients who developed hypertriglyceridemia plus skin rash by Day 21, median and 1-year survival were 12 months and 44%, respectively, vs. 2 months and 12% in 36 patients with neither (p = 0.0003). Partial response was reported in 1 patient. When assessed by FACT-G, quality of life was improved or stabilized in 65% of patients. Conclusions: Survival of patients with heavily pretreated NSCLC may be extended with oral bexarotene therapy. Confirmation of these results with a randomized trial is warranted. Ongoing investigations attempt to explain the notable outcome reported in this and other bexarotene trials in the subset of patients who developed hypertriglyceridemia with or without skin rash. [Table: see text]
Abstract P119: Erythrocyte n-3 and n-6 Polyunsaturated and Trans Fatty Acids and Survival of Sudden Cardiac Arrest
Authors: Rozenn N Lemaitre, Irena B King, Catherine O Johnson, Nona Sotoodehnia, Barbara McKnight, Kenneth Rice, David S Siscovick, Thomas D Rea
Journal: Circulation (2012)

Lower levels of erythrocyte n-3 polyunsaturated fatty acid (PUFA) and higher levels of trans-fatty acid are associated with incident cardiac arrest (SCA) risk. However, it is not known whether these fatty acids also influence post-arrest survival. In addition, n-3 and n-6 PUFA play key roles in brain function and may be involved in brain resuscitation. We investigated the association of n-3, n-6 and trans-fatty acid levels with resuscitation outcomes in a population-based study of SCA. Subjects (mean age 68, 82% male) were out-of-hospital SCA patients found in ventricular fibrillation and attended by paramedics in King County, Washington, with available fatty acid measurements (n=492). Using logistic regression, we examined association between fatty acid levels and surviving to hospital admission (a proxy for heart resuscitation), and also to surviving to hospital discharge (a proxy for brain resuscitation). Both analyses adjusted for age; sex; race; year of cardiac arrest; time to arrival of emergency medical services; whether the event was witnessed, occurred in public, and whether bystander CPR was administered. Levels of arachidonic acid and trans-18:2 fatty acids were associated with SCA survival ( Table ). An increase of one SD in levels of arachidonic acid was associated with decreased likelihood of survival to both hospital admission and hospital discharge (OR (95% CI), uncorrected p-value: 0.75 (0.62-0.92), p =0.006 and 0.69 (0.55, 0.87), p =0.002, respectively). A one SD difference in trans-18:2 fatty acid levels was associated with decreased likelihood of survival to hospital discharge (0.74 (0.57-0.96), p =0.02)). Levels of n-3 PUFAs and trans-18:1 fatty acids were not associated with SCA survival. Our findings suggest arachidonic acid and trans-18:2 may influence SCA survival. Further work is needed to explore the role of fatty acid metabolism in heart and brain resuscitation. Association of Erythrocyte Fatty Acids with Resuscitation Outcomes Survival to hospital admission Survival to hospital discharge OR * (95% CI) p-value OR * (95% CI) p-value n-3 fatty acids α-Linolenic acid 1.01 (0.83-1.22) 0.95 0.85 (0.67-1.07) 0.60 EPA+DHA 1.05 (0.87-1.28) 0.60 1.10 (0.87-1.38) 0.44 n-6 fatty acids Linoleic acid 0.97 (0.80-1.18) 0.77 1.05 (0.83-1.33) 0.66 Arachidonic acid 0.75 (0.62-0.92) 0.006 0.69 (0.55-0.87) 0.002 Trans-fatty acids Trans-18:1 1.06 (0.87-1.29) 0.56 1.06 (0.84-1.34) 0.47 Trans-18:2 0.99 (0.80-1.22) 0.93 0.74 (0.57-0.96) 0.02 * OR corresponding to one SD higher levels
The consistency of several phylogeny-inference methods under varying evolutionary rates.
Authors: R W DeBry
Journal: Molecular Biology and Evolution (1992)

A phylogenetic method is a consistent estimator of phylogeny if and only if it is guaranteed to give the correct tree, given that sufficient (possibly infinite) independent data are examined. The following methods are examined for consistency: UPGMA (unweighted pair-group method, averages), NJ (neighbor joining), MF (modified Farris), and P (parsimony). A two-parameter model of nucleotide sequence substitution is used, and the expected distribution of character states is calculated. Without perfect correction for superimposed substitutions, all four methods may be inconsistent if there is but one branch evolving at a faster rate than the other branches. Partial correction of observed distances improves the robustness of the NJ method to rate variation, and perfect correction makes the NJ method a consistent estimator for all combinations of rates that were examined. The sensitivity of all the methods to unequal rates varies over a wide range, so relative-rate tests are unlikely to be a reliable guide for accepting or rejecting phylogenies based on parsimony analysis.