tbuckley/cabot-search huggingface dataset:
Bronchial asthma triggered by house dust mites in patients with local allergic rhinitis
Authors: Paloma Campo, Ibon Eguiluz‐Gracia, María Carmen Plaza‐Serón, María Salas, María José Rodríguez, Natalia Pérez‐Sánchez, Miguel González, Ana Molina, Cristobalina Mayorga, María José Torres, Carmen Rondón
Journal: Allergy (2019)

Abstract Background Over 30% of local allergic rhinitis (LAR) patients self‐report bronchial symptoms suggestive of asthma, but the relationship between the allergen exposure and the bronchial symptoms has not been studied. Objective To investigate whether a bronchial counterpart of LAR exists. Methods Patients were classified by clinical history, skin prick test/serum specific IgE (sIgE), and nasal allergen provocation test (NAPT) into the LAR, allergic rhinitis (AR), and nonallergic rhinitis (NAR) phenotypes. Twenty‐eight LAR, 18 AR, and 19 NAR patients self‐reporting bronchial symptoms suggestive of asthma and 8 healthy controls (HC) were subjected to a methacholine test (MT) before (Visit 1) and 24 hours after (Visit 3) a bronchial provocation test with Dermatophagoides pteronyssinus (BPT‐DP) (Visit 2). Induced sputum and peripheral blood obtained after each MT were analyzed for immune cell populations, tryptase, ECP, and sIgE. Results A positive MT was found in 50% of LAR, 83.3% of AR, 57.89% of NAR, and 0% of HC individuals ( P = 0.022 AR vs LAR) at V1. BPT‐DP was positive in 8 LAR and 15 AR patients (28% vs 83.3%, P &lt; 0.001), with no positive responses in NAR and HC. All BPT‐DP+ patients experienced a significant decrease of PC 20 at V3 vs V1 ( P = 0.016 LAR, P ≤ 0.001 AR). BPT‐DP+ patients also showed a significant increase of eosinophils, monocytes, and ECP in induced sputum at V3 compared with V1. Conclusion The results suggest the existence of a new asthma phenotype (local allergic asthma) defined by absence of systemic atopy and positivity to BPT with allergen.
BPI19-017: Clinical Pathway Toward Quality and Efficient Care of Breast Cancer in Women Under 50
Authors: Elizabeth Reed, Robin M. Lally, Roksana Zak
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Nationally, gaps exist in the timely and appropriate care of young women with breast cancer. Few women receive genetic and fertility counseling, while contralateral prophylactic mastectomy rates rise. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer direct breast cancer treatment and symptom management, but care of young newly diagnosed women requires providers to combine elements of several guidelines and consider an appropriate order of assessments and treatments utilizing multidisciplinary consultation. In Nebraska, fewer than 300 women under age 50 are diagnosed with breast cancer annually. One-third of these women live rurally, miles from the NCCN Member Institution. Thus, rural physicians encounter these patients infrequently and may lack local specialists with whom to consult and refer, thus challenging the provision of the highest quality care. Purpose: To improve the efficacy and efficiency with which rural oncology care providers recognize and address physical, psychosocial, and decision-making needs of young women with breast cancer through development and delivery of education, multidisciplinary consultation, and clinical pathways. Methods: Baseline, 2-year electronic medical record data on surgical, medical, and supportive oncology practice patterns for women with breast cancer under age 50 were collected from the University of Nebraska Medical Center and collaborating rural cancer centers. Records were hand searched for fertility and genetic data. The PROMIS Global Health Survey and Sexual Function Profile, the Brief Subjective Decision Quality Measure, and a project-specific care satisfaction survey were mailed to these patients. Data were entered into SPSS and descriptive statistics used to identify the project’s starting point. Results: To date, clinics (rural and urban) identified a 2-year total of 199 women with breast cancer, ages 21 to 49 years. Cancers were stage 0 (n=21), 1 (n=50), 2 (n=40), 3 (n=19), 4 (n=3), and unavailable (n=66). Eight clinical pathways based on ER, PR, and HER2 status were developed to guide treatment, considerations, evidence-based neoadjuvant and adjuvant therapy, and survivorship care. Pathways, with associated educational webinars and links to NCCN Guidelines, are accessible to providers and patients on the project-derived Pathway to Cure website. Website use and webinar views following program implementation will be reported as will comparison of baseline practice patterns with data at the first 3-month analysis.
Systemic approach to study the crosstalk between EGF, IGF, and Insulin Pathways - computational and experimental analysis
Authors: Rafal Zielinski, Pawel Przytycki, Teresa Przytycka, Jacek Capala
Journal: Cancer Research (2008)

3509   Signal transduction is the primary mechanism used by cells to respond to external stimuli. Defects of signaling pathways cause perturbation in signal flow leading to pathological states including cancer. New targeted therapies are being developed to correct such defects by either selective blocking of pro-survival or activation of pro-apoptotic pathways. However, individual signaling pathways do not act in isolation. They interact with each other, forming complex signaling networks that respond to diverse, often contradictory, stimuli. Therefore, a systems level understanding of signaling network is needed to improve the outcome of targeted therapies.  Our efforts focus on the signaling network formed by the interaction of three signaling pathways: Epidermal Growth Factor (EGF), Insulin-like Growth Factor (IGF), and Insulin (Ins). All three pathways are pro-survival and have been experimentally linked to cancer. Here we report, to our best knowledge, the first computational and experimental analysis of the crosstalk occurring between these three pathways.  First, using STKE data base, we created network encompassing EGF, IGF and Ins receptor pathways. The network was represented as a weighted directed graph with two types of edges: activation and inhibition edges. To determine the role of each signaling molecule in signal transduction, we introduced two measurements: pathway crosstalk and network crosstalk. Based on the static analysis of the network, we selected 13 molecules with grater than zero network and pathway crosstalk value: MAPK, Grb2, c-Src, Raf-1, Akt1, Shc, PI3/4//5/P3, PKC, JNK, CREB, p70S6K, PI3K Ia, Rho. All these molecules were dynamically tested using a simple computational model. The effects of changes in activation of three receptors: EGF receptor, IGF1 receptor, and Ins receptor on signal transduction through the selected molecules was simulated. The results showed that each tested molecule has its unique activation pattern.  Partial  in vitro  validation of the obtained results was performed using ovarian cancer cell line SKOV3 expressing all three receptors. Serum starved cells were differentially stimulated with EGF, IGF and Insulin, reflecting simulation conditions. Resulting changes in the activation of pro-survival and pro-proliferation pathways were monitored by measurement of phosphorylation of Akt1 and Erk1/2, respectively, using MSD biomarker detection assay. Obtained results indicated that even in its simplest version, the model was able to predict some (although not all) experimentally observed trends and thus it is a good starting point for our iterative model building procedure.
Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinases Is Associated with Multiple Myeloma Progression, Prognosis and Extramedullary Plasmacytoma
Authors: Rei Ishihara, Yuki Murakami, Kazuki Homma, Saki Watanabe, Tsukasa Oda, Masanobu Sunaga, Eiko Yamane, Nobuhiko Kobayashi, Yohei Osaki, Takuma Ishizaki, Hiroaki Shimizu, Hirono Iriuchishima, Hiromi Koiso, Norifumi Tsukamoto, Akihiko Yokohama, Gotoh Nanami, Rumi Ino, Takayuki Saitoh, Hirokazu Murakami, Hiroshi Handa
Journal: Blood (2018)
Chromatin remodelling controls pancreatic tissue fate
Authors: Elisabeth Hessmann, Volker Ellenrieder
Journal: Gut (2019)

Despite of severe clinical and scientific efforts, treatment of pancreatic ductal adenocarcinoma (PDAC) remains a major challenge. Significant improvement of PDAC prognosis is hampered by restricted therapy response of PDAC patients which is—on the molecular level—primarily caused by an extreme intertumoral heterogeneity.1 Besides the core genetic alterations (oncogenic mutation of KRAS , inactivation of the core tumour suppressors TP53, CDKN2A and DPC4 ) PDAC is characterised by a plethora of additional molecular events that, although occurring less frequently, are of prognostic and predictive significance.2 3 For instance, approximately one-third of PDAC tumours carry mutations in genes coding for chromatin regulatory proteins.2 Epigenetic alterations installed by changes of the chromatin landscape critically impact on tissue homeoestasis and can foster malignant transformation and tumour progression.1 This is particularly true for the SWI/SNF (SWItch/sucrose non-fermentable) complex of chromatin remodelling proteins, which physiologically disrupts the tight contact between DNA and histones and mobilises nucleosomes to reveal previously …
Abstract 11151: Vascular Pulsatility During Mechanical Actuation of the Fibrillating Heart is Equivalent to the Native Beating Heart
Authors: Benjamin A Schmitt, Nathan V Wright, Yirong Zhou, David B Reynolds, Mark P Anstadt
Journal: Circulation (2016)

Introduction: Direct Mechanical Ventricular Actuation (DMVA) is a non-blood-contacting direct cardiac compression device shown to resuscitate both humans and animals without myocardial injury. The purpose of this study was to determine if DMVA support during ventricular fibrillation (VF) generates pulsatility similar to the native heart. Methods: Large canine (n=10) and swine (n=10) were anesthetized, underwent sternotomy, and instrumented for hemodynamic monitoring and intracardiac echocardiography. VF was induced for 5 mins of circulatory arrest and DMVA applied for 15 mins. Hearts were then defibrillated and allowed to recover. Repeated periods of arrest were used to increase cardiac dysfunction post-resuscitation. Paired t-tests were used to compare the post-sternotomy baseline, supported VF, and unsupported post-resuscitation states. Mean pressures and flows were statistically equalized between supported arrest and unsupported post-resuscitation. Previously described metrics of pulsatility were calculated using 10 sec flow and pressure intervals. Results: Conclusions: DMVA was able to generate physiologic levels of pulsatility even during support of the fibrillating heart across a range of heart sizes. Differences in overall energy (EEP) between the possibly hyperdynamic baseline and support can be explained by discrepancies in mean (continuous) pressures and flows given observed similarities in the pulsatile component (PP, PI, SHE). Mechanical actuation of the fibrillating heart was shown to provide superior pulsatility compared to post-resuscitation hearts with comparable hemodynamic means and power curves.
Unforeseen N2 Disease after Negative Endosonography Findings with or without Confirmatory Mediastinoscopy in Resectable Non–Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Jelle E. Bousema, Martijn van Dorp, Valentin J.J.M. Noyez, Marcel G.W. Dijkgraaf, Jouke T. Annema, Frank J.C. van den Broek
Journal: Journal of Thoracic Oncology (2019)
Three Different Jak2/Stat3-Related Pathways Favor the Survival of Chronic Lymphocytic Leukemia Neoplastic Clone
Authors: Filippo Severin, Federica Frezzato, Veronica Martini, Flavia Raggi, Valentina Trimarco, Andrea Visentin, Monica Facco, Gianpietro Semenzato, Livio Trentin
Journal: Blood (2018)
QIM19-136: Developing an Ideal CAR-T Cell Therapy Patient Experience Through Human-Centered Design and Innovation
Authors: Allison Matthews, Surbhi Sidana, Lauren Seymour, Nancy Pick, James Pringnitz, David Argue, Gina Lange, Eva Brandes, Allison McClanahan, Adrienne Nedved, Suzanne Hayman, Saad Kenderian, Shaji Kumar, David Dingli, Taxiarchis Kourelis, Rahma Warsame, Prashant Kapoor, Mithun Shah, Hassan Alkhateeb, Patrick Johnston, Stephen Ansell, Nabila Bennani, Mustaqeem Siddiqui, Yi Lin
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The patient/caregiver experience during CAR-T therapy is stressful, overwhelming, terrifying, and often a patient’s last treatment option. The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Innovation and Design team has worked with the CAR-T therapy clinical team to develop a patient experience that provides patients with a sense of caring, supportive environment, timely knowledge, and realistic expectations. Using a human-centered design approach, the Innovation and Design team worked with patients and caregivers to understand latent and unspoken needs in order to develop an ideal CAR-T therapy patient journey. Methods: With qualitative interviewing techniques, patient observation, and low fidelity experimentation, 21 patients/caregiver pairs were interviewed throughout their CAR-T therapy experience in 2018. Patients were interviewed at several touch points as well as encouraged to reach out to the Innovation and Design team at any point with reflections on their experiences. Patients were recruited as they began their evaluation phase for CAR-T therapy. The interviews were unscripted to allow for a breadth of discovery by not constraining the conversations to previously developed themes. As themes emerged from patient/caregiver interviews, artifacts and interventions were designed to alleviate pain points and improve the patient/caregiver experience. These artifacts and interventions were integrated into the clinical processes in real time and patient/caregivers were interviewed to understand the impact of these activities. Results: Several themes emerged from qualitative interviews with patients and caregivers. From the themes, interventions were developed. We were able to demonstrate a qualitative improvement in patient/caregiver experience through these interventions (Figure 1). Conclusions: Patients/caregivers undergoing CAR-T therapy have unique issues surrounding the logistics of care, emotional burden, and physical effects of treatment. We implemented processes to address these issues and observed a qualitative improvement via patient interviews/feedback. Ongoing work includes optimizing remote monitoring, digital platforms for patient education, and a quantitative study looking at patient reported outcomes (PROs) in such patients. To our knowledge, this is the first report for care delivery optimization in real-world practice for this new therapy.
CLO19-032: Skin Cancer of the Nose: Outcome in 405 Cases Treated With Accelerated High Dose Rate Radiation Therapy
Authors: Nicholas E. Flores, T. A. Mian, D. Liu
Journal: Journal of the National Comprehensive Cancer Network (2019)

Overview: Between 2013 and 2016, we treated 1,500 cases of nonmelanoma skin cancer using high-dose radiation therapy. In this series, 405 cases involved the nose. Patient selection was limited to age &gt; 35 years, tumor size &lt; 40 mm in diameter and &lt;5 mm thick. Demographics included 86.7% basal, 12.8% squamous, 1 lymphoma, 1 melanoma. Size by treatment field: 66.9% 10mm, 28.1% 20mm, 4.7% 35mm, and &lt;1% 50mm. Age: 76.8 years median (37.3–99.7 years) Methods: Radiation therapy was administered following guidelines suggested by ASTRO and AAPM using either a 6MeV LINAC electron beam or 50kV x-ray source. The majority of patients received 4,000 cGy in 500 cGy fractions given twice weekly. Prescribed treatment depth was zero (0) mm for non-bulky disease. Bolus was used for all electron treatments. Wax-coated nasal shields were used for lateralized or large midline lesions. Devitalized tumor was debrided and/or treatment depth modified during treatment as needed. Treatment interruptions were rare, usually due to infection, and limited to less than 2 weeks. Results: 99% of patients maintained a complete response at 2 years (0.2–3.7 years) median follow-up, with 1 edge-of-field progression and 1 in-field recurrence. Side effects seen included transient nasal mucositis (10%) limited to lateralized or large midline lesions, superficial infection (&lt;1%) limited to patients with a history of moderate to severe acne and/or patients applying cosmetic concealers during treatment. No chronic nasal dryness, cartilage necrosis, ophthalmic injury, nasolacrimal disruption, or dental complications occurred. Patient satisfaction/cosmesis: patient-scored functional and cosmetic outcomes ranged from very good to excellent in 100% of patients. Conclusion: Accelerated high dose rate radiation therapy using either LINAC electron beam or electronic brachytherapy is an effective and well-tolerated treatment option for carefully selected patients with basal and squamous cell skin cancer of the nose. Response rates for electron beam or low-energy x-rays with this dose schedule were similar. When compared to surgery, radiation therapy results in high patient satisfaction and excellent cosmesis without the need for lengthy postoperative care or reconstruction. When compared to conventional radiation therapy, the high response rates, smaller field sizes, shorter treatment times, and reduced radiation dose to adjacent critical tissues makes electronic brachytherapy a useful addition to standard techniques.
HSR19-088: Severe Obesity Does Not Worsen Transplantation Outcome in Multiple Myeloma
Authors: Zhubin J. Gahvari, Michael Lasarev, Jens C. Eickhoff, Aric C. Hall, Peiman Hematti, Mark B. Juckett, Vaishalee P. Kenkre, Natalie S. Callander
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Obesity, and in particular severe obesity, is increasingly prevalent in the United States. Epidemiological studies have shown an association in multiple myeloma (MM) between obesity and mortality (Teras et al, Br J Haematol 2014). Autologous peripheral blood stem cell transplantation (autoPBSCT) remains a crucial aspect of treating MM, and the NCCN Guidelines recommend all eligible patients be evaluated for transplant. There is limited data analyzing the relationship between severe obesity and transplant outcomes in MM patients in the era of modern therapy, routine post-transplant maintenance, and genetic-based risk stratification. Methods: We retrospectively reviewed consecutive patients undergoing autoPBSCT for MM at our institution from 2010–2017. Patients were categorized by body mass index (BMI) and Revised International Staging System (R-ISS) score. Patients were followed from time of first transplant until death. Surviving patients and those lost to follow-up were censored at last point of contact. Cox proportional hazard regression models and associated log-rank tests were used to assess whether age, BMI, lag time between diagnosis and transplant, and R-ISS score were associated with risk of death. Post-transplant hospital length of stay (LOS) was evaluated using generalized linear models with response following a gamma distribution. Results: 314 patients (59.2% male) were included. BMI was categorized as nonobese ([16, 30) kg/m 2 ; n =178, 56.7%), obese ([30, 35) kg/m 2 ; n =72, 22.9%) or severely obese ([35, 55) kg/m 2 ; n =64, 20.4%) and was not found to be associated with risk of death following transplant, either independently ( P =.17) or when adjusting for age, sex, lag, and R-ISS ( P =.26). As expected, R-ISS score was associated ( P =.006) with risk of death after transplant. No association was found between mean LOS and BMI ( P =.875). Kaplan-Meier mortality estimates are shown in Figure 1. Conclusions: Obesity and severe obesity were not associated with an increased risk of mortality for MM patients receiving autoPBSCT. Although severe obesity is a health hazard, this should not be used to exclude patients from transplant.
PDRG, a novel tumor marker for colorectal cancer.
Authors: Lingyan Jiang, Xiuquan Luo, Jingxue Shi, Hong Sun, Ying Huang, M. Saeed Sheikh
Journal: Cancer Research (2008)

1804  Colorectal cancer is a major cause of cancer-related deaths and an example of diseases for which peak incidence and death rates are highest in the ageing population. Cells are constantly exposed to a variety of stresses including genotoxic stress (DNA damage) and cellular ability to effectively manage stresses starts to decline with age. Cellular responses to genotoxic stress are complex and therefore, more studies are needed to better understand the mechanisms that control such responses. In this regard, we have previously cloned and characterized a novel p53 and DNA damage-regulated gene (PDRG) that is differentially regulated by genotoxic stress and p53. We have recently found that PDRG resides at chromosomal region 20q11.2 that is frequently amplified in human colorectal cancers. Based on this information, we sought to investigate the expression status of PDRG in primary colorectal tumors. First, we examined PDRG mRNA expression in cancer profiling arrays of primary colorectal tumors and matching normal tissues representing 39 patients. Our results indicated that PDRG expression was upregulated in ~82% of the primary colorectal tumors when compared with matching normal tissues. Next, we performed Western blot analysis to investigate PDRG expression at the protein level using 7 matched pairs of normal and tumor tissues; our results indicated PDRG levels to be significantly higher in all 7 cancer samples when compared to normal tissues. We also performed immunohistochemical analysis of PDRG in paired colorectal normal and tumor samples and the result showed its expression to be weaker in normal tissues but stronger in malignant tissues. Taken together, our results indicate that PDRG expression, at both the mRNA and protein levels, is significantly increased in primary human colorectal tumors suggesting PDRG to be a high-value novel tumor marker for colorectal malignancies.