tbuckley/cabot-search huggingface dataset:
Abstract 16854: An Ungated, Rapid Rest/Stress Myocardial Perfusion Protocol is Useful for Detection of Coronary Artery Disease in Patients With Atrial Fibrillation
Authors: Imran Haider, Edward V DiBella, Akram Shaaban, Ganesh Adluru, Lowell Chang, Promporn Suksaranjit, Christopher J McGann, Devavrat Likhite, Nassir F Marrouche, Daniel Sommers, Leif Jensen, Brent D Wilson
Journal: Circulation (2015)

Introduction: In patients with atrial fibrillation, the diagnostic accuracy of standard, gated stress/rest perfusion cardiovascular magnetic resonance (CMR) for detection of coronary artery (CAD) disease remains uncertain. Here we investigated using instead an ungated approach with no ECG gating with a rapid rest/stress perfusion protocol to determine its accuracy for detection of CAD in this patient population. To overcome the potential issue of peri-infarct ischemia with a rest-first sequence, we gave very little time between rest and stress perfusion scans. Methods: 23 patients with atrial fibrillation (68 ± 13 years, 13 males and 10 females) underwent a very rapid rest/regadenoson stress perfusion imaging protocol and X-Ray angiography in this study. An ungated radial myocardial perfusion sequence was used (TR/TE = 2.2/1.2 msec, 3T, 20 rays/slice, 5 slices after each saturation pulse, ~2х2х8 mm). Rest/stress protocol was performed in the following order: rest image acquisition (0.05 mmol/kg gadoteridol), administration of regadenoson 0.4 mg intravenously (0.4 mg/5 mL) to induce hyperemia, 70 second wait, then stress image acquisition (0.075 mmol/kg gadoteridol). CMR perfusion images were interpreted by a blinded reader as normal or abnormal, without viewing cine or late gadolinium enhanced images, and also evaluated for quality (1 to 5, lowest to highest). Diagnostic accuracy was evaluated by comparison to X-Ray angiography: significant lesions were defined as stenosis &gt;70 % stenosis or functional flow reserve &lt;0.8. Results: 18 of the scans were negative and 5 were positive by angiography criteria. Sensitivity, specificity and accuracy for detection of CAD were 100%, 89% and 91%, respectively. Average scan time for imaging acquisition was 6.5 ± 4.0 minutes. Average image quality for both rest and stress perfusion images was 3.2 ± 0.9. Conclusions: An ungated myocardial perfusion sequence with rapid rest/regadenoson stress perfusion protocol addresses the concern of lingering hyperemia with regadenoson and problematic gating. This study suggests that assessment of myocardial perfusion with an ungated technique is an approach with high accuracy for detection of significant CAD in patients with atrial fibrillation.
P01.019 Blood derived exosomal hTERT mRNA in glioblastoma: A potential circulating biomarker
Authors: O Uziel, E Beery, M Lahav, R Abu Shkara, S Yust-Katz, A Amiel, A A Kanner, Y Laviv, I Ben Zvi, T Siegal
Journal: Neuro-Oncology (2018)

Primary glioblastoma multiforme (GBM) have a high proportion (~80%) of TERT-expressing tumors, indicating that this is the primary mechanism of telomerase (hTERT) activation. Exosomes are nano-sized secreted vesicles containing nucleic acids and proteins, which reflect the content of the mother cells. We have previously shown that hTERT transcripts in serum exosomes may serve as a “pan-cancer” diagnostic method, reflecting the load of hTERT in systemic cancer cells. The goal of the current study was to evaluate whether exosomal hTERT may serve as a circulating biomarker for GBM. hTERT mRNA levels were determined in serum derived exosomes obtained from 20 GBM patients and 45 healthy controls. The level of exosomal hTERT mRNA was measured prior to surgery in all GBM patients. In 10 patients additional longitudinal evaluation was performed in blood samples obtained prior to and after concurrent radio/chemotherapy and again during adjuvant temozolomide treatment. Circulating hTERT transcripts were absent in controls and were variably detected in 40% of GBM patients with significantly elevated mean level at diagnosis (p=0.049). These transcripts were gradually downregulated on longitudinal evaluations and during treatment period with significant reduction observed after 3 months of adjuvant treatment when compared to initial sampling (p=0.026). In 10 patients an analysis of hTERT promoter mutation was performed and in 8/10 one of the two common mutations (C228T and C250T) was detected on tumor samples. hTERT mRNA levels may reflect the tumor burden and the clinical status of patients with GBM. In systemic tumors exosomal hTERT mRNA expression is detected in about 60% of cases while in GBM the percentage is probably lower. In patients with detectable levels, this assay may serve as a serum biomarker. These results warrant further confirmation and an update on an extended cohort of patients will be presented at the meeting.
Factors contributing to the black/white colorectal cancer survival disparity in nonelderly patients.
Authors: Helmneh M. Sineshaw, Kimmie Ng, W. Dana Flanders, Otis W. Brawley, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2017)

3587 Background: Previous studies reported that black/white survival disparities among elderly colorectal cancer (CRC) patients largely reflect differences in tumor presentation rather than differences in treatment. We sought to determine the contribution of differences in tumor presentation and receipt of treatment to the black/white survival disparity among nonelderly CRC patients. Methods: We selected non-Hispanic black (black) and Non-Hispanic white (white) patients aged 18-64 years, and diagnosed between 2004-2012 with single or first primary invasive stage I-IV CRC in the National Cancer Data Base. Blacks were sequentially matched with three white comparison cohorts, using propensity score and greedy matching algorithm, by demographics (age, sex, diagnosis year, region), tumor presentation (stage, grade, margin, tumor location, node status, comorbidity score), and treatment (surgery, chemotherapy, radiotherapy, metastatectomy) characteristics. We used Kaplan-Meier method to estimate 5-year survival for blacks compared with whites in the entire cohort and in the three sequentially matched cohorts. Results: In the entire cohort, 5-year survival was 9.2% lower in nonelderly blacks than whites (57.3% vs 66.5%). The survival difference remained unchanged after demographic matching, but it decreased to 3.3% (5.9% absolute and 64% relative reductions) after tumor presentation matching, and to 2.6% (0.7% absolute and 7.6% relative reductions) after treatment matching. By anatomic subsite, treatment matching reduced the black/white 5-year survival difference by 26% (3%/11.5%) for rectal cancer, only by 5.6% (0.5%/9%) for left colon cancer, and no change for right colon cancer. Conclusions: Differences in tumor presentation characteristics explained about two-thirds of the black/white survival disparity in nonelderly CRC patients, while treatment explained less than ten percent of the disparity. Future research should explore the biological mechanisms underlying these observed differences in tumor presentation and implications for treatment.
Effect of cancer cell cluster with hollow spheroid formation on chemosensitivity of colorectal cancer cells: Three-dimension culture for evaluation of chemosensitivity.
Authors: Shozo Yokoyama, Naoyuki Yamamoto, Junji Ieda, Yasuyuki Mitani, Akihiro Takeuchi, Hiromitsu Iwamoto, Katsunari Takifuji, Tsukasa Hotta, Kenji Matsuda, Takashi Watanabe, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2016)

e15075 Background: Chemosensitivity is modulated by cancer cell cluster. We have shown that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promoted hollow spheroid (HS) formation of cancer cell cluster. HS induced by CEACAM1 and inner cells apoptosis is observed in three-dimensional (3D) in vitro culture. The aim of the present study is to clarify whether HS and CEACAM1 cytoplasmic domain isoform balance are associated with resistance to 5-fluorourasil (5FU), and to address usefulness of 3D culture for evaluation of chemosensitivity. Methods: 2-D or 3-D culture systems were employed to evaluate the effects of CEACAM1 cytoplasmic isoform balance and HS formation on the chemosensitivity of colorectal cancer cells to 5FU. It is also presented that the risk factors for postoperative recurrence were calculated based on the presence of HS and various clinicopathological characteristics in 82 patients with Stage III colorectal cancer who had undergone curative surgery followed by 5FU-based chemotherapy. Results: CEACAM1-4L-transfected HT29 and CEACAM1-4L and 4S expressing parental LS174T cells had significantly higher resistance to 5FU in comparison with CEACAM1-4S- or vector control-transfected cells. In 3-D culture, HS formation induced by CEACAM1-4L induced chemoresistance to 5FU, whereas the solid spheres formed in response to CEACAM1-4S were destroyed by 5FU treatment. The sensitiveness to 5FU was observed by morphological change as sphere burst. HS was identified as an independent factor for recurrence of Stage III colorectal cancer after curative resection followed by 5FU-based chemotherapy. Kaplan-Meier survival curves demonstrated that patients with HS had lower recurrence-free survival rate. Conclusions: Morphological change in 3-D culture system is useful for evaluation of chemosensitivity to 5FU. HS formation and CEACAM1 long cytoplasmic domain isoform dominance are phenotypes associated with chemoresistance to 5FU.
Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells
Authors: Andreas Kyburz, Angela Fallegger, Xiaozhou Zhang, Aleksandra Altobelli, Mariela Artola-Boran, Timothy Borbet, Sabine Urban, Petra Paul, Christian Münz, Stefan Floess, Jochen Huehn, Timothy L. Cover, Martin J. Blaser, Christian Taube, Anne Müller
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract P283: Healthy Food Marketing Can Potentially Increase Consumption of Fruit and Vegetables in New York City Neighborhoods
Authors: Yan Li, David S Siscovick, Donglan Zhang, José A Pagán
Journal: Circulation (2016)

Introduction: Consumption of fruit and vegetables is associated with a lower risk of obesity, diabetes, hypertension, and cardiovascular disease . While five or more servings of fruits and vegetables are recommended, only 50% of residents of New York City (NYC) consume two or more servings a day. While food marketing can change individual dietary behaviors, there is limited evidence on the extent to which healthy food marketing strategies—such as community-based and mass-media campaigns—influence fruit and vegetable consumption at the neighborhood level. Agent-based modeling (ABM) has the potential to provide new insights on how healthy food marketing may impact dietary behaviors by simulating interventions, consumption decisions, and interactions among people in different contexts. Hypothesis: Healthy food marketing significantly increases consumption of fruit and vegetables in NYC neighborhoods. The impact of healthy food marketing varies across different neighborhoods depending on population characteristics and the local food environment. Methods: We developed an ABM that takes into account individual and neighborhood-level factors (e.g., age, gender, education, food environment) and influences of social networks (peers, friends, and family) to predict dietary behaviors of individuals at the neighborhood level. Model parameters were estimated from the Food Attitudes and Behaviors Survey, United States Census data, and previous studies. Healthy food marketing can strengthen positive social norms with regard to dietary behaviors. We simulated two hypothetical healthy food marketing interventions that could improve the influence of positive social norms by 5% and 10%, respectively. We predicted the impact of these interventions on the proportion of the population who consume two or more servings of fruits and vegetables across 34 NYC neighborhoods (defined by the United Hospital Fund) in three years. We validated our model using data from the NYC Community Health Survey. Results: The simulation results suggested that the healthy food marketing interventions have the potential to increase the proportion of the population who consume two or more servings of fruits and vegetables over three years: for a 5% improvement on positive social norms, the increase in the proportion was 0.58% - 8.97% by neighborhood; and for a 10% improvement on positive social norms, 2.68% - 13.94% by neighborhood. Exploratory analyses suggested that among population characteristics, a high proportion of population without a high school diploma was associated with lower effectiveness of healthy food marketing in increasing consumption of fruits and vegetables. Conclusions: Healthy food marketing may increase consumption of fruits and vegetables in NYC, but more attention to the mechanisms that account for the lower increase in neighborhoods with low educational attainment is needed.
TCT-238 Comparing 3 year outcomes between medical therapy and percutaneous revascularisation for the surgically ineligible cohort.
Authors: Avedis Ekmejian, Astin Lee, Pratap Chandra Shetty, Tuan Nguyen-Dang, Aaron Yeung, James Sapontis, Sami Firoozi, Ravinay Bhindi, Peter Hansen, Jonathan Hill, Rafal Dworakowski, Philip Maccarthy, None ajay shah, Jonathan Byrne
Journal: Journal of the American College of Cardiology (2018)
The therapeutic effect of a new method on reducing local recurrence rate of desmoid tumors involving adjacent nerves and blood vessels based on blocking-capsule theory.
Authors: Junqiang Yin, Yiwei Fu, Jingnan Shen
Journal: Journal of Clinical Oncology (2018)

e23546 Background: Capsule and pseudocapsule are correlated with higher complete tumor excision rate and lower incidence of recurrence by restricting tumor’s growth and block its invasion. Based on the blocking-capsule theory, we applied artificial capsule to desmoid tumors, which are locally infiltrative neoplasms with a high local recurrence rate especially when involving nerves and blood vessels, and tested whether local recurrence rate can be reduced. Methods: We performed a retrospective review of seven cases of desmoid tumor adjacent to nerves and blood vessels. Neurovascular structures were partly involved by tumor in five of them, and surrounded in the rest two. To preserve the nerves and vessels, residual tumor may exist after marginal excision. We used polyester patch to envelope or separate the involved nerves and blood vessels after the excision of desmoid tumors of the seven patients. They were followed up for 10.6-28.5 months. Results: Among the seven patients, five of them had recurrent desmoid tumors before the excision and blocking-patch surgery. After the surgery, no local recurrence was observed in six of them. As for the rest one with local recurrence one year after the excision, MR images demonstrated that tumor located only in the region where neurovascular structures were not enveloped by polyester patch. No particular side-effect was noticed in all patients. Conclusions: Patch enveloping is a new method to protect neurovascular structures from the invasion of desmoid tumors, and reduces the local recurrence rate after excision, potentially supporting the blocking-capsule theory. Prospective study will be conducted to further examine the theory and method in the future. Case Sex Year Status of nerves and vessels Presentation Tumor site Follow up (months) Recurrence after surgery 1 M 9 Partly involved Recurrent Left upper arm 28.5 No 2 F 23 Surrounded Recurrent Left lower limb 11.5 Yes 3 F 10 Surrounded Recurrent Right thigh 23.8 No 4 M 17 Partly involved Recurrent Left buttock 19.3 No 5 M 27 Partly involved Recurrent Right forearm 10.6 No 6 M 51 Partly involved Primary Right shoulder 12.4 No 7 F 22 Partly involved Primary Right shoulder 14.4 No
SPANOM: A cost-effective method of detecting MSI in ctDNA.
Authors: Zhenghang Wang, Hao Qin, Mei Wang, Jifang Gong, Xicheng Wang, Jian Li, Jing Gao, Zhongwu Li, Dalei Wang, Shangli Cai, Yuezong Bai, Fu-Gen Li, Lin Shen
Journal: Journal of Clinical Oncology (2018)

e24263 Background: Not only has been proved to be an effective biomarker for prognosis and chemotherapies, but also becomes the first pan-cancer biomarker for immunotherapies, MSI/MMR detection has increasing values in clinical applications. The conventional methods, such as PCR and IHC, could merely be applied to tumor tissues. However, tissue biopsy or surgery might not be applicable for some late-stage cancer patients, such as stage IV patients, where most of the immunotherapies are applied. Hence the MSI detection based on ctDNA is crucial. Here we developed SPANOM, a flexible and normal-control-free NGS-based method of comparable cost to the conventional methods, to accurately detect MSI status in tissues of low quality and ctDNA. Methods: A small panel (about 24000 base pairs) was designed directly targeting 100 selected microsatellite loci. The detection model was built on the in silico samples randomly generated from 3 MSI-H and 3 MSS tumor tissues and their corresponding white-blood-cell controls. The model was validated by the clinical samples. The tissues were sequenced at 1000x and the ctDNA was sequenced at 10000x for the validation set. Results: Considering conventional methods (IHC or PCR) on tissues as golden standard, the overall concordance was 92.3% in 27 dMMR/MSI-H and 25 pMMR/MSS tumor tissues whose tumor contents were larger than 50%, and the overall concordance was 86.5% in 17 dMMR/MSI-H and 20 pMMR/MSS ctDNA samples from stage IV treatment-naive patients of colorectal or stomach adenocarcinoma. Conclusions: SPANOM is an accurate method of detecting MSI status in tumor tissues and ctDNA from late-stage patients of colorectal or stomach adenocarcinoma. The sequencing cost of SPANOM could be as low as 3 USD for tumor tissues and 25 USD for ctDNA, which is comparable to the conventional method. The small panel of MSI could be utilized independently or merged with a larger panel, which could benefit more patients in clinical applications.
Roadmap for supportive care according to patients' perspectives.
Authors: François Eisinger, Helene Simon, Gerard Ganem, Chantal Touboul, Christine Lhomel, Jean F. Morere, Herve L. Naman, Jerome Viguier
Journal: Journal of Clinical Oncology (2018)

e18821 Background: In addition to increasing treatment efficacy and reducing adverse effects, appropriate supportive care can improve patient quality of life. The Calista2 survey sought to identify, understand and rank the expectations of cancer patients with regard to supportive care and activities. Methods: The 82 physicians who took part in the survey recruited 666 patients; all were already on specific therapy for breast cancer (BC), colorectal cancer (CRC) or lung cancer (LC). Patient questionnaires (collected September 2016-October 2017) were self-reported. Questions covered various types of patient care. Our analysis focused on virtual maximum use (VMU) of a given type of supportive care, defined as the sum of its actual rate of use and the percentage of patients interested (currently non-users). VMU helps determine the demand for such support and provides useful data on how best to supply appropriate services. Results: After exclusion of non-valid questionnaires, 467 were analyzed. All cancer localizations combined, drug management of adverse effects (78%), pain (64%), diet/nutrition (51%) and fatigue (49%) were seen to be in greatest demand. Complementary medicine, physical activity and relaxation techniques were in lower demand (VMU: 46%, 42%, 36%, respectively). Few patients requested spiritual support (14%), support from the workplace (14%), or group discussion for children (14%). VMU is influenced by cancer localization, i.e., sleep disorder management was more important for LC and BC patients (46% LC and 43% BC vs 29% CRC, P < 0.05), as was improving self-image for BC patients (62% vs 32% CRC and 31% LC, P < 0.05). We also observed differences according to gender (relaxation techniques were more in demand for women than men, 44% vs. 22%, P < 0.05), and age (adverse effect management was more often requested by patients ≤60 yrs than > 60 yrs, 83% vs 73%, P < 0.05). Conclusions: Although medical supportive care is the most sought-after, patients also seek the support of non-medical interventions. Certain care procedures that are typically in very low demand may however prove crucial in specific situations. Our findings may help healthcare providers build a comprehensive offer of patient care to meet the expectations and needs of their patients.
Initial report of a phase I study of LY2510924 with idarubicin and cytarabine (IA) in relapsed/refractory (R/R) AML.
Authors: Prajwal Boddu, Gautam Borthakur, Kiran Naqvi, William G. Wierda, Prithviraj Bose, Elias Jabbour, Zeev Estrov, Jan Andreas Burger, Yesid Alvarado, APRIL Deshmukh, Ami Patel, Antonio Cavazos, Lina Han, Hagop M. Kantarjian, Michael Andreeff, Marina Konopleva
Journal: Journal of Clinical Oncology (2018)

7026 Background: LY2510924 is a peptide antagonist of CXCR4, a key component of the CXCR4/SDF-1 signaling axis that is critical for homing of stem cells in the bone marrow and activation of downstream pathways involved in cell proliferation and survival. In a preclinical AML model, LY2510924 showed significant activity as a single agent and in combination with chemotherapy (Cho et al. Blood 2015). Methods: A phase I study was designed to determine the safety and toxicity profile of combination therapy of LY2510924 with IA in patients (pts) with R/R AML. Pts aged 18 to 70 years who failed prior therapy (≤ salvage 3) were eligible. LY2510924 is administered from days 1-7 followed by IA starting day 8. In responders, 4-6 consolidation cycles were administered. Two dose escalation levels (10 and 20 mg) were planned, according to a 3+3 design; up to 12 pts to be enrolled in phase I portion. Results: Eleven pts have been enrolled with a median age of 55 (range, 19-70) years. Of 10 pts tested, 2 (20%) had complex cytogenetics. Median prior therapies were 1 (1-3). Six pts were treated at dose level ‘0’ (10 mg) and 5 at dose level ‘1’ (20 mg); 3 of 5 treated at dose level ‘1’ were evaluable for response. Most non-hematologic toxicities were grade 1-2 in severity. At dose level ‘0’, 1 pt experienced dose limiting toxicity (DLT) (2 grade 3 DLTs: rash and hypo-cellular marrow). No major toxicities occurred at dose level ‘1’. At ‘0’ dose level, 1 pt had a CR and 2 had CRi; at dose level ‘1’, 1 achieved CR; the overall response rate was 44%. By flow cytometry, 4 of 9 had ≥ 50% decrease in CXCR4 mean fluorescence intensity. Conclusions: Combination of LY2510924 with IA is safe in R/R AML pts. Dose-escalation to 40 mg of LY2510924 is planned to achieve > 90% blockade of CXCR4 receptor occupancy, followed at the expansion phase of the study at recommended phase 2 dose level. Clinical trial information: NCT02652871.