tbuckley/cabot-search huggingface dataset:
Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma
Authors: Shinichi Yachida, Laura D. Wood, Masami Suzuki, Erina Takai, Yasushi Totoki, Mamoru Kato, Claudio Luchini, Yasuhito Arai, Hiromi Nakamura, Natsuko Hama, Asmaa Elzawahry, Fumie Hosoda, Tomoki Shirota, Nobuhiko Morimoto, Kunio Hori, Jun Funazaki, Hikaru Tanaka, Chigusa Morizane, Takuji Okusaka, Satoshi Nara, Kazuaki Shimada, Nobuyoshi Hiraoka, Hirokazu Taniguchi, Ryota Higuchi, Minoru Oshima, Keiichi Okano, Seiko Hirono, Masamichi Mizuma, Koji Arihiro, Masakazu Yamamoto, Michiaki Unno, Hiroki Yamaue, Matthew J. Weiss, Christopher L. Wolfgang, Toru Furukawa, Hitoshi Nakagama, Bert Vogelstein, Tohru Kiyono, Ralph H. Hruban, Tatsuhiro Shibata
Journal: Cancer Cell (2016)
Myc Induces miRNA-Mediated Apoptosis in Response to HDAC Inhibition in Hematologic Malignancies
Authors: Clare M. Adams, Scott W. Hiebert, Christine M. Eischen
Journal: Cancer Research (2015)

Alterations in the expression or function of histone deacetylases (HDAC) contribute to the development and progression of hematologic malignancies. Consequently, the development and implementation of HDAC inhibitors has proven to be therapeutically beneficial, particularly for hematologic malignancies. However, the molecular mechanisms by which HDAC inhibition (HDACi) induces tumor cell death remain unresolved. Here, we investigated the effects of HDACi in Myc-driven B-cell lymphoma and five other hematopoietic malignancies. We determined that Myc-mediated transcriptional repression of the miR-15 and let-7 families in malignant cells was relieved upon HDACi, and Myc was required for their upregulation. The miR-15 and let-7 families then targeted and downregulated the antiapoptotic genes Bcl-2 and Bcl-xL, respectively, to induce HDACi-mediated apoptosis. Notably, Myc also transcriptionally upregulated these miRNA in untransformed cells, indicating that this Myc-induced miRNA-mediated apoptotic pathway is suppressed in malignant cells, but becomes reactivated upon HDACi. Taken together, our results reveal a previously unknown mechanism by which Myc induces apoptosis independent of the p53 pathway and as a response to HDACi in malignant hematopoietic cells.
Self-directed learning module for radiation therapy treatment planning
Authors: M. Campeau, S. Lasalle, C. Lambert, É. Filion
Journal: Journal of Clinical Oncology (2007)

17051 Background: Radiation Oncology is a rich and rewarding specialty that requires in-depth understanding of anatomy, physics, dosimetry and oncology. The area of dosimetry is an important and basic fundamental concept to be acquired during residency, and pertinent educational tools are few and far between. The purpose of this project was to develop a self-assessment tool to facilitate radiation therapy treatment planning for non-small cell lung cancer (NSCLC). Methods: We focused our learning module on basic dosimetric and NSCLC treatment planning objectives that radiation oncology residents will encounter during residency. Interactive questions incorporating objective-related concepts were then devised. Treatment planning program templates were developed using the Eclipse software application. Results: A web-based self-directed learning module was developed as the tool's delivery mechanism. The module's questions were divided into the following sections: Chest Anatomy, ICRU Concepts, Beam Modificators, Integrated NSCLC Treatment Plans, Systematic Treatment Planning Approach and Inhomogeneity Corrections. By answering questions via the module, learners receive immediate feedback, corrections and concept-related explanations. A variety of different question techniques were employed, such as multiple choice questions, open-ended questions and associations. Learners are prompted by the system to draw isodoses and volumes on the screen. Other tasks in the module involve identifying structures, setting treatment fields and analyzing dose volume histograms. The website is publicly available in both English and French at: http://www.radiol.umontreal.ca/radio-onco/ . Conclusions: This self-directed learning module is a complementary tool that will help residents gain a solid grasp of NSCLC treatment planning objectives. Other modules covering radiation therapy treatment planning for a variety of anatomical sites, as well as diseases at different stages will eventually be created and added to the website. This educational project aims to facilitate learning and understanding the concepts of treatment planning, according to the different types of cancer. No significant financial relationships to disclose.
Abstract 13607: Gender Differences in Myocardial Ischemia-Related Symptoms During Transient Balloon Occlusion of the Coronary Artery
Authors: Akira Tamura, Kumie Torigoe, Shigeru Naono, Satoshi Maeda, Mitsutaka Hino, Kazuhiro Shinozaki, Hirofumi Zaizen, Junichi Kadota
Journal: Circulation (2012)

Background: Previous investigations have shown gender differences in symptoms of angina pectoris and acute coronary syndrome. However, these investigations have certain limitations, including retrospective in nature, interview-related bias, and various duration of myocardial ischemia, all of which would affect the results. Accordingly, we prospectively examined whether there are any gender differences in myocardial ischemia-related symptoms during percutaneous coronary intervention (PCI), which provides a unique model of transient myocardial ischemia. Methods: We prospectively evaluated myocardial ischemia-related symptoms during 60-second balloon inflation in the setting of elective PCI in 110 males and 80 females with coronary artery disease. Results: Myocardial ischemia-related symptoms, including chest pain and/or other symptoms (occipital pain, neck pain, back pain, shoulder pain, upper arm pain, and nausea), were observed during balloon inflation in 72 males and 52 females. In patients with any symp...
Patterns of recurrence in patients with high-grade soft-tissue sarcomas.
Authors: D A Potter, J Glenn, T Kinsella, E Glatstein, E E Lack, C Restrepo, D E White, C A Seipp, R Wesley, S A Rosenberg
Journal: Journal of Clinical Oncology (1985)

From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)
Congenital Heart Defects and Indices of Fetal Cerebral Growth in a Nationwide Cohort of 924 422 Liveborn Infants
Authors: Niels B. Matthiesen, Tine B. Henriksen, J. William Gaynor, Peter Agergaard, Cathrine C. Bach, Vibeke E. Hjortdal, John R. Østergaard
Journal: Circulation (2016)

Background— Neurodevelopmental disorders are the most common and distressful comorbidities associated with congenital heart defects (CHD). Head circumference at birth (HC), a proxy for prenatal cerebral growth, is an established risk factor for neurodevelopmental disorders. Methods and Results— In a nationwide cohort, we included all 924 422 liveborn Danish singletons, 1997 to 2011. CHD was present in 5519. The association between CHD and growth indices was analyzed by multivariable linear regression, adjusted for potential confounders. We report mean differences in gestational age–specific z scores in comparison with the general population. CHD was associated with lower HC z scores, –0.10 (95% confidence interval [CI], –0.13 to –0.08). Several CHD subtypes were associated with smaller HC, eg, hypoplastic left heart syndrome, –0.39 (95% CI, –0.58 to –0.21); common arterial trunk, –0.41 (95% CI, –0.74 to –0.09); and major ventricular septal defects, –0.25 (95% CI, –0.35 to –0.15). Other single-ventricle defects, transposition of the great arteries, tetralogy of Fallot, and anomalous pulmonary venous return, were also associated with smaller HC. Transposition of the great arteries was associated with smaller HC relative to birth weight, –0.26 (95% CI, –0.39 to –0.13). Major ventricular septal defects were associated with larger HC relative to birth weight. The results were consistent under various conditions, eg, when siblings of infants with CHD (n=5311) or infants with other major malformations (n=24 974) were used as the reference. Conclusions— Several subtypes of CHD were associated with smaller HC. The associations with major ventricular septal defects, common arterial trunk, and anomalous pulmonary venous return have not previously been described. Only infants with transposition of the great arteries had smaller HC relative to birth weight.
A phase I/II trial of pemetrexed and sirolimus in advanced NSCLC.
Authors: G. M. Blumenthal, M. S. Ballas, W. Bernstein, B. K. Shamloo, H. Root, C. Helsabeck, G. Chun, W. D. Figg, G. Giaccone, P. A. Dennis
Journal: Journal of Clinical Oncology (2010)

7600 Background: Pemetrexed (P) is a multitargeted antifolate approved for second-line and maintenance therapy in NSCLC. Sirolimus (S) is an oral inhibitor of mTOR. Our group has shown that combining P and S synergistically inhibits NSCLC tumor growth in preclinical models. We designed a phase I/II trial of P and S in advanced NSCLC. Methods: Eligibility: Platinum-refractory or resistant NSCLC, ECOG PS 0-2, and adequate organ function. Phase I objective: determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of combined P + S using classic 3+3 dose escalation design, with 5 dose levels. Dose Level 1: S 1 mg daily + P 375 mg/m2; Dose Level 2: S 2 mg daily + P 375 mg/m2; Dose Level 3: S 2 mg daily + P 500 mg/m2; Dose Level 4: S 3 mg daily + P 500 mg/m2; Dose Level 5: S 5 mg daily + P 500 mg/m2. P given on day 1 every 21 day cycle. PET CT performed at baseline and cycle 2. Tumor measurements performed every 2 cycles. S trough levels drawn every cycle. Results: Fourteen pts have enrolled. Of 13 pts evaluable for toxicity: 10 adenocarcinoma, 3 squamous. Median age 69 (range 33-79). Median number of prior therapies: 2.5 (range 1-5). To date, three pts each are evaluable on Dose Levels 1-4, and one pt on DL5. No DLTs observed to date. The most common treatment-related non-hematologic toxicities (all grades): hypoalbuminemia (64%), hyperglycemia (45%), AST (45%), hypercholesterolemia (36%), and hypertriglyceridemia (36%). One reversible grade 3 hyperglycemia observed at Dose Level 4. One grade 1 interstitial pneumonitis at Dose Level 3. No opportunistic infections observed. Most common treatment-related hematologic toxicities (all grades): lymphopenia (72%), anemia (72%), ANC (45%), and thrombocytopenia (45%). No grade 4 hematologic events. At Dose Level 1, pt with stable disease (SD) for 15+ cycles. At Dose Level 2, pt with minor response (MR), 21% decrease in lesions and SD for 12+ cycles. At Dose Level 3, 2 partial responses (PR) and 1 MR (26% reduction). At Dose Level 4, one pt with PR. Mean S trough concentrations (ng/mL): 3.5 (DL1), 6.8 (DL2), 9.4 (DL3), 11 (DL4), 14.5 (DL5). Conclusions: The combination of P and S is well tolerated to date with no DLT and promising anti-tumor activity in subjects with heavily pre-treated NSCLC. If MTD not reached in Phase I, Phase II will proceed at DL5. No significant financial relationships to disclose.
Prognostic significance of the follicular lymphoma international prognostic index (FLIPI) in the E1496 trial of chemotherapy with or without maintenance rituximab
Authors: N. Colocci, E. Weller, H. S. Hochster, R. Gascoyne, B. Kumm, T. Ryan, T. M. Habermann, S. R. Frankel, S. J. Horning
Journal: Journal of Clinical Oncology (2005)

6526 Background: In the E1496 trial, maintenance rituximab significantly prolonged progression free survival (PFS) after CVP (cyclophosphamide, vincristine, prednisone) chemotherapy in patients (pts) with advanced indolent non-Hodgkin’s lymphoma (Proc ASCO 2004:6502). A new follicular lymphoma international prognostic index (FLIPI) for overall survival (OS) has been recently reported (Blood 2004, 105:1258) in pts treated with conventional therapy but its significance for other endpoints and in the setting of chemo-immunotherapy has not been reported. Methods: The FLIPI score (low=0,1; intermediate=2; poor=3–5) was determined for 297 pts (227 follicular) who received CVP and 239 stable or responding pts (185 follicular) subsequently randomized to observation or rituximab. Correlations with response rate (RR), PFS and OS are reported. Results: The distribution of FLIPI score was 21% low, 32% intermediate (int) and 47% poor risk. FLIPI score correlated with RR to CVP for all pts (RR: 81% low, 74% int, 63% poor risk, p=0.02) and follicular pts (RR: 80% low, 76% int, 64% poor risk, p=0.09). For follicular lymphoma pts, two-year PFS (62% v 47%, p=0.04) and OS (97% v 84%, p=0.05) were shorter in FLIPI high compared to low risk pts after CVP induction. For all pts, FLIPI high compared to low risk resulted in shorter PFS (p=0.09) and OS (p=0.03). The distribution of FLIPI score among maintenance pts was 24% low, 35% int and 41% poor. To date, no difference in PFS and OS were observed according to FLIPI risk group for all pts or for follicular pts in the randomized groups, rituximab or observation. Conclusions: FLIPI score ≥3 was predictive for response to CVP and also for PFS and OS after CVP in the E1496 trial. To date, the FLIPI score in stable and responding pts was not significantly associated with PFS or OS in the observation and maintenance rituximab groups. These data suggest that much of the predicitive power of the FLIPI score is associated with response to induction therapy and indicate the importance of study pt characteristics in the interpretation of clinical results in indolent lymphoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Promoting evidence-based management of anemia in cancer patients: Background and scientific validation of RESPOND, a web-based clinical decision support system
Authors: J. Van Erps, M. Aapro, K. MacDonald, P. Soubeyran, M. Muenzberg, R. Dunlop, C. Eeckhout, H. Warrinnier, M. van Well, I. Abraham
Journal: Journal of Clinical Oncology (2007)

19676 Background: The 2006 European Organisation for Research and Treatment of Cancer (EORTC) guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. To promote clinicians’ adoption of evidence- based (EB) practice guidelines (EBPGs), it is critical to bring guidelines to the point of care. RESPOND is an EB clinical decision support system (CDSS) based on the EORTC guidelines. CDSSs are seldom validated. We describe the methodologies of two studies being conducted to validate RESPOND. Methods. Study 1: descriptive design - accuracy and content validity. Five experts are asked to rate the accuracy of algorithms derived from the guidelines; the objective being an intraclass correlation coefficient =0.90 for each of 27 algorithmic sets. Study 2: hybrid matched pre-post design - concurrent and discriminant validity. Two patient cohorts (n=33 each) matched by type of cancer and similarity of chemotherapy regimen ie, sample 1 (4 months prospective data after RESPOND [post]) and sample 2 (4 months retrospective data prior to RESPOND [pre]) were used to test concurrent validity (congruence scores [CS] of sample 1) and discriminant validity (difference between sample 2 and sample 1 CS). A score is calculated for each patient to quantify the extent to which treatment and outcomes are congruent with the EORTC EBPG. Table 1 . Calculation of the congruence score ESA, erythropoiesis-stimulating agent; Hb, hemoglobin, Q1W, once weekly, Q3W, once every three weeks Conclusions. These studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool. [Table: see text] [Table: see text]
Interleukine 10 -592 c/a and interleukine 8 -251 t/a polymorphisms in ovary cancer: New prognostic biomarkers?
Authors: Ramon Andrade De Mello, Dania Sofia Marques, Joana Savva-Bordalo, Monica Gomes, Joana Assis, Ana Coelho, Rosario Couto, Susana Sousa, Noemia Afonso, Rui Medeiros, Deolinda Pereira
Journal: Journal of Clinical Oncology (2012)

e15532 Background: Interleukine (IL) 10 –592C/A and IL8 –251T/A polymorphisms previous showed an important role in cell proliferation, cell migration and angiogenesis. Therefore, we conduct a study in order to assess the role of those genetic polymorphisms as prognostic biomarkers in epithelial ovary cancer (EOC). Methods: Design: Retrospective study from 1996 to 2010. Setting: Histological confirmed EOC patients treated at our institution. Laboratory: Genotyping of IL10–592 C/A and IL8 -251T/A were performed by PCR-RFLP. DNA samples were obtained from patients’ peripheral blood. Statistical analysis: Logistic regression were used to calculate odds ratio (OR) and 95% confidential interval (95% CI). Overall survival (OS) and progression-free-survival (PFS) were performed using Kaplan-Meier analysis. Statistical significance was considered for p &lt; 0.05. Results: It was recruited 156 participants. Median age was 53 (16 – 80) years-old. Genotype frequency distribution for IL8-251 were T/T (50%), T/A (50%) and for IL10–592, C/C (53.8%), C/A (39.7%), A/A (6.4%). These follow genotypes were associated with lymph node, pelvic and peritoneal relapse: IL10–592C/A (OR 0.229, 95% CI: 0.055 – 0.943, p = 0.041) and IL8–251T/A (OR 6.667, 95% CI: 1.359 – 32.701, p = 0.019). In overall, IL8–251T/A genotype had higher OS than IL8-251T/T genotype: 115 versus 95 months, p = 0.010. In clear cell tumors (CCT), IL8–251T/A genotype had less OS than IL8-251T/T genotype: 92 versus 107 months, p = 0.004. To IL10–592 genotypes, OS were 104 (A/A), 107 (C/A), 103 (C/C) months, p = 0.637, and PFS were 9 (A/A), 14 (C/A), 20 (C/C) months, p = 0.057. However, in CCT, PFS for IL10–592 genotypes were 4 (A/A), 56.73 (C/A), 20 (C/C) months, p = 0.023. Conclusions: Our results suggest that IL8–251T/A polymorphism could represent a prognostic biomarker in overall EOC. IL10–592C/A polymorphisms are associated with relapse and PFS mainly in CCT. Nevertheless, furthers prospective studies are warranted in order to assess its role in pharmacogenomics framework.
Signatures of early frailty in the gut microbiota
Authors: Matthew A. Jackson, Ian B. Jeffery, Michelle Beaumont, Jordana T. Bell, Andrew G. Clark, Ruth E. Ley, Paul W. O’Toole, Tim D. Spector, Claire J. Steves
Journal: Genome Medicine (2016)

Frailty is arguably the biggest problem associated with population ageing, and associates with gut microbiome composition in elderly and care-dependent individuals. Here we characterize frailty associations with the gut microbiota in a younger community dwelling population, to identify targets for intervention to encourage healthy ageing. We analysed 16S rRNA gene sequence data derived from faecal samples obtained from 728 female twins. Frailty was quantified using a frailty index (FI). Mixed effects models were used to identify associations with diversity, operational taxonomic units (OTUs) and taxa. OTU associations were replicated in the Eldermet cohort. Phenotypes were correlated with modules of OTUs collapsed by co-occurrence. Frailty negatively associated with alpha diversity of the gut microbiota. Models considering a number of covariates identified 637 OTUs associated with FI. Twenty-two OTU associations were significant independent of alpha diversity. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. A Faecalibacterium prausnitzii OTU was less abundant in frailer individuals, and retained significance in discordant twin analysis. Sixty OTU associations were replicated in the Eldermet cohort. OTU co-occurrence modules had mutually exclusive associations between frailty and alpha diversity. There was a striking negative association between frailty and gut microbiota diversity, underpinned by specific taxonomic associations. Whether these relationships are causal or consequential is unknown. Nevertheless, they represent targets for diagnostic surveillance, or for intervention studies to improve vitality in ageing.
Studies on the Exchange of Fluids Between Host and Tumor. III. Regulation of Blood Flow in Hepatomas and Other Rat Tumors
Authors: Pietro M. Gullino, Flora H. Grantham
Journal: JNCI Journal of the National Cancer Institute (1962)

The response of the vascular net of hepatomas and other rat tumors to epinephrine, acetyl-ß-methylcholine, cold, and ganglionectomy has been studied in ovarian and renal “tissue-isolated” transplants. With this technique the vascular response of the tumor can be separated from the response of the vascular net of the host. Under the action of the stimuli tested, the vessels of a tumor behaved like the vessels of the host organs, even when the tumor was 200-fold larger, and no residue of the host-tissue was demonstrable in the histologic sections. Acetyl-β-methyl-choline produced an increase of blood flow in tumors, the other stimuli produced a drop in the blood supply. The transformation of the vascular tree of the host into the vascular tree of the tumor was followed by the preparation of vinylite casts of the blood vessels. By this technique it was possible to demonstrate that the main vascular branches which supply the host organ became the main vascular branches which supply the tumor. These vessels do not increase in number but greatly increase in length and diameter. The vessels of a regenerating liver behaved in the same manner.