tbuckley/cabot-search huggingface dataset:
Abstract 210: Progressive Mitochondrial Protein Acetylation and Microsteatosis is Associated with Diastolic Dysfunction in a Hypertrophic Cardiomyopathy Model
Authors: Amanda R Stram, Gregory R Wagner, P M Pride, R M Payne
Journal: Circulation Research (2014)

We tested the hypothesis that increased mitochondrial protein acetylation is associated with impaired fatty acid metabolism and diastolic dysfunction in Friedreich’s Ataxia (FRDA). FRDA results from deficiency of the mitochondrial protein, frataxin (FXN), and causes hypertrophic cardiomyopathy. FRDA hearts show decreased ATP production. We previously showed that FXN loss results in loss of activity of the NAD+-dependent mitochondrial deacetylase, sirtuin 3 (SIRT3), and cardiac mitochondrial protein hyperacetylation in a mouse model of FRDA. Long-chain and medium chain acyl CoA dehydrogenases (LCAD, MCAD) are targets of SIRT3, suggesting that abnormal acetylation may alter fatty acid metabolism. A cardiac specific mouse model with conditional deletion of FXN in heart and skeletal muscle (FXN MCK-Cre-/-) was compared to healthy controls (FXNfl/fl). Mice underwent echocardiogram and left heart catheterization in vivo at age 30 and 65 days. Heart lysate was examined for overall lysine acetylation at ages 30, 45 and 70 days, and acetylated LCAD and MCAD. Myocardial cells were stained with oil red to detect lipids. Hearts of FXN MCK-Cre-/- animals showed mitochondrial hyperacetylation, increased LCAD and MCAD acetylation, and microsteatosis compared to controls. Diastolic dysfunction was evident in FXN MCK-Cre-/- at day 65 by increased mitral valve E/A ratios and IVRT (p&lt;0.04 and p&lt;0.03, respectively, n=7), prolonged tau, and decreased -dP/dt (p&lt;0.02 and p &lt;0.03, respectively, n=6). Cardiac mechanics at day 65 showed systolic failure with reduced EF and FS (p&lt;0.002 and p&lt;0.003, respectively, n=7). Comparison of FXN deficient mice and controls at day 65 trended toward flattened ESPVR and left shifted EDPVR curves, but differences were not significant. Early diastolic dysfunction was evident at day 30 in FXN MCK-Cre-/- by high E/A ratio and EDP compared to day 65 controls (p &lt;0.03, n=7, and p&lt;0.03, n=6, respectively). We conclude that progressive mitochondrial protein acetylation and abnormal fatty acid metabolism is associated with early diastolic dysfunction and later systolic failure. This metabolic dysregulation and pathophysiology may share characteristics with other metabolic heart disorders, such as diabetes and metabolic syndrome.
Relationship between survival and PET measurements of tumour blood flow, in patients with metastatic colorectal cancer
Authors: N. G. Charnley, S. Azeem, N. Gupta, C. West, R. Swindell, J. Bruce, P. Price
Journal: Journal of Clinical Oncology (2006)

20021 Background: There are conflicting reports on the relationship between tumour blood flow and patient survival. Poor flow is associated with tumour hypoxia and has been associated with a poor outcome (Lehtio et al 2004;Int J Radiat Oncol Biol Phys:59, 971–982). However, good flow is associated with angiogenesis which drives tumorigenesis, and has also been linked with a poor prognosis (Hermans 200 Int J Radiat Oncol Biol Phys:57, 1351–6). In this study, we examined the relationship between PET measurements of blood flow in liver metastases, and survival, in patients with colorectal cancer. Methods: Thirty seven patients with metastatic colorectal cancer, with a range of previous treatments, were studied. Regional perfusion was measured in liver metastases using H 2 [ 15 O] or C[ 15 O] 2 PET. Blood flow was correlated with overall survival from the time of PET scan. Relationship between outcome and flow was analysed separately for patients with 1 or &gt;1 metastatic sites; a recent meta-analysis of patient with metastatic colorectal cancer showed number of metastatic sites to be an independent prognostic factor (Kohne et al 2002; Ann Oncol. 13, 308–317). Results: There was no significant relationship between survival and metastasis blood flow when the data were taken as a whole. However, when the data were corrected for number of metastatic sites, there was a trend for high flow to be associated with shorter survival (p = 0.063). Specifically, for patients with multiple metastatic sites, median survival times for patients with high flow (n = 9) was 171 days [95% CI 25–317] compared with 441 days [95% CI 12–870] for patients with low flow (n = 7) (p = 0.026). Conclusions: In patients with multiple sites of metastasis, high tumour blood flow is a poor prognostic factor. This may be due to angiogenesis, which promotes tumorigenesis. No significant financial relationships to disclose.
The Purification and Properties of Deoxyribonuclease and Ribonuclease from Normal and Neoplastic Tissues
Authors: Mary E. Maver, Antoinette E. Greco
Journal: JNCI Journal of the National Cancer Institute (1956)

The Purification and Properties of Deoxyribonuclease and Ribonuclease from Normal and Neoplastic Tissues Get access Mary E. Maver, Mary E. Maver Laboratory of Biochemistry, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Antoinette E. Greco Antoinette E. Greco Laboratory of Biochemistry, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 17, Issue 4, October 1956, Pages 503–516, https://doi.org/10.1093/jnci/17.4.503 Published: 01 October 1956 Article history Received: 18 June 1956 Published: 01 October 1956
Effect of Horse Serum, Fetal Calf Serum, Calf Serum, Bovine Serum, and Fetuin on Neoplastic Conversion and Chromosomes of Mouse Embryo Cells &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Ram Parshad, Katherine K. Sanford
Journal: JNCI Journal of the National Cancer Institute (1968)

Two cell lines of C3Hf mouse embryo cells were tested for the effect of various sera on neoplastic conversion and chromosomal alteration in number and morphology. The sera, added to chemically defined medium NCTC 135, included horse, fetal calf, calf, bovine, and a combination of horse and fetuin. In both lines, cells in horse and calf serum underwent neoplastic conversion earlier than in fetal calf serum. In one line cells in bovine serum also underwent the early conversion. The results suggested that fetuin might delay the neoplastic conversion, but further data are needed to establish this point. Calf and bovine sera, like fetal calf serum, reduced the rate of heteroploidization and appearance of abnormal chromosomes as compared with horse serum. Thus, the calf and bovine sera apparently contain some factor(s) common to fetal calf serum or lack the factor(s) in horse serum that influences chromosomal stability. However, the calf serum effects neoplastic conversion to the same extent as horse serum. From the distribution and morphology of the abnormal chromosomes, we conclude that the chromosome breaks during in vitro growth in all sera tested are at or near the centromere.
Genome-editing Technologies for Gene and Cell Therapy
Authors: Morgan L Maeder, Charles A Gersbach
Journal: Molecular Therapy (2016)

Gene therapy has historically been defined as the addition of new genes to human cells. However, the recent advent of genome-editing technologies has enabled a new paradigm in which the sequence of the human genome can be precisely manipulated to achieve a therapeutic effect. This includes the correction of mutations that cause disease, the addition of therapeutic genes to specific sites in the genome, and the removal of deleterious genes or genome sequences. This review presents the mechanisms of different genome-editing strategies and describes each of the common nuclease-based platforms, including zinc finger nucleases, transcription activator-like effector nucleases (TALENs), meganucleases, and the CRISPR/Cas9 system. We then summarize the progress made in applying genome editing to various areas of gene and cell therapy, including antiviral strategies, immunotherapies, and the treatment of monogenic hereditary disorders. The current challenges and future prospects for genome editing as a transformative technology for gene and cell therapy are also discussed.
Retrospective review of all patients with thymoma treated over the last 33 years at the Royal Marsden Hospital.
Authors: C. Benson, R. S. Kristeleit, S. Ashley, S. Dolly, C. Mikropoulos, M. O'Brien, S. Popat
Journal: Journal of Clinical Oncology (2010)

7095 Background: Thymomas are rare epithelial tumours of the thymus. A variety of strategies can be used for locally advanced/recurrent disease as well as differing systemic therapies for advanced stage. Few trials have been performed on these patients. Methods: We retrospectively reviewed case notes of all patients with thymoma at our institution (1976-2009). Demographic, pathological, and clinical details were recorded, including surgical intent and survival. Tumors were classified by WHO status and Masaoka stage. Survival was calculated from the date of presentation at the Marsden using the Kaplan-Meier method. Results: 104 patients were identified (59M, 45F; age 16-83, median 47 years). Most patients (n=63, 60%) had stage 3/4 disease (21 /42, respectively). 57 patients (55%) were classifiable to WHO subtype with 2/12/18/18/28/23% subtypes A/AB/B1/B2/B3/C, respectively. 45% were diagnosed prior to WHO classification. All stage 1 patients had surgery (n=3). In stage 2, 93% (n=14) had surgery, followed by radiotherapy in 53%. Stage 3 (n=21) management varied widely. Stage 4a (n=24) was treated with debulking surgery followed by chemo/radiotherapy. 4b were treated by chemotherapy. First-line chemotherapy regimes varied widely. Platinum based treatments accounted for 56 % of all regimes given, the commonest being CAP (19%). Platinum combinations also formed the mainstay of second-line chemotherapy (59%). Median overall survival was 5.4 years, and depended on stage: median for stage 1&2/3/4 was not reached/4.5/4.3 years, respectively (p=0.001). Whilst survival for males was marginally better (p=0.07), age at diagnosis was not prognostic: (p=0.2). Notably, survival was similar in patients diagnosed before and after 1995 (5.8 vs. 5.4 years, p=0. Conclusions: This heterogeneous dataset reflects the referral pattern to our center and tumor rarity. The lack of survival gain over the past 30 years strengthen the call for an international interest group and tumor registry to drive collaborative trials and translational research. No significant financial relationships to disclose.
Smoking habits among cancer survivors
Authors: L. Burke, A. Saad, L. Miller, J. Abraham
Journal: Journal of Clinical Oncology (2008)

20699 Background: Smoking is a known risk factor for cancer, such as lung, head and neck. Studies showed that smoking can adversely affects outcome of different treatment modalities of cancer including radiation and chemotherapy treatment. Our current study examines the smoking habits among cancer survivors in an attempt to create a successful smoking cessation intervention. Methods: An observational cohort study was done by sending a questionnaire to randomly selected 1,000 patients who were diagnosed with cancer between 2003 and 2007 in our cancer center. Data were analyzed by SPSS (v15) to determine the likelihood of quitting smoking when patients were diagnosed with cancer. The likelihood of having a house-hold smoker was assessed. Patients were also surveyed about the best option to help quit smoking. Results: We received 187 responses of 1,000 surveys (18.7%). Of these, 166 were eligible for analysis. The mean age of patients was 63.9 years ± 13.1. Males were more likely than females to be past smokers (55.2% of males and 31.6% of females, respectively, p=0.003). There were 87/166 respondents who reported positive smoking history. There were 34 patients who were diagnosed with cancer while smoking. Only 15/34 (44%) reported quitting smoking after diagnosis with cancer, while 19/34 (56%) continued to smoke. Only 21/34 (61.8%) reports that they were informed of the dangers of smoking during cancer treatment. Also 47% of current smokers reported having a house-hold smoker. Unfortunately 15% of non-smokers are exposed to second-hand smokers at home. Among 5 different options, patients preferred ‘lifestyle change program’ or ‘individual counseling program’ to help quit smoking. Conclusions: Our data shows that more than half of smoking cancer patients continued to smoke after cancer diagnosis. Only about 60% of smoking cancer patients were told to quit by their doctors. Peer influence was evident in those who continued to smoke. Ideal intervention program for those patients could be either ‘lifestyle change program‘ or ‘individual counseling program’. However, further non-randomized prospective trial would best answer this question. No significant financial relationships to disclose.
Abstract 13557: Chronic Treatment with Eicosapentaenoic Acid Suppresses Ischemia-induced Ventricular Fibrillation through Inhibiting Myocardial KATP Channel in Pigs in Vivo.
Authors: Ryuji Tsuburaya, Satoshi Yasuda, Yoshitaka Ito, Takashi Shiroto, Jun Yi Gao, Kenta Ito, Hiroaki Shimokawa
Journal: Circulation (2010)

Background: Although epidemiologic studies demonstrated the preventing effect of eicosapentaenoic acid (EPA) on sudden cardiac death, the mechanisms remain to be examined. Since activation of KATP ...
Potentially avoidable hospitalizations in older patients with acute myeloid leukemia (AML).
Authors: Areej El-Jawahri, Tanya Keenan, Gregory Alan Abel, David P. Steensma, Thomas William LeBlanc, Lara Traeger, Amir Tahmasb Fathi, Daniel J. DeAngelo, Martha Wadleigh, Gabriela Hobbs, Philip C. Amrein, Richard M. Stone, Karen K. Ballen, Yi-Bin Albert Chen, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

206 Background: Many older adults ( ≥ 60) with AML have a poor prognosis and spend a significant portion of their life from diagnosis until death in the hospital. We examined the reasons for hospitalizations and identified potentially avoidable hospitalizations. Methods: We conducted a retrospective analysis of 200 patients ( ≥ 60) diagnosed with AML between 1/1/2006 and 10/30/2011 at two hospitals in Boston to examine the reasons for hospitalizations during treatment. Practicing physicians used a consensus-driven medical record review process to identify primary reason for each hospitalization and categorize it as “potentially avoidable” or “not avoidable” based on a novel adaptation of the Graham’s criteria for potentially avoidable hospital admissions. We compared the rate of potentially avoidable hospitalization between older patients receiving intensive chemotherapy (n = 124) versus non-intensive chemotherapy (n = 76) using Fisher’s Exact test. Results: We evaluated 627 hospitalizations after the diagnosis of AML in 200 unique patients. The median age was 69 years [range 60-90] and the median number of hospitalizations was 4.0 [range 0-18]. 33.2% of patients underwent stem cell transplantation. The most common primary reasons for hospitalizations were: fever/infection (38.3%), planned hospitalizations for chemotherapy or transplantation (35.9%), and uncontrolled symptoms (10.5%). We identified 108/627 hospitalizations (17.2%) as potentially avoidable. Among potentially avoidable hospitalizations, 40.7% were due to premature hospital discharge, 22.2% could have been managed in the outpatient setting, 13.9% failed to have timely outpatient follow-up, and 13% were due to patients’ medication non-adherence. There were no differences in potentially avoidable hospitalizations between patients receiving intensive vs. non-intensive chemotherapy (16.9% vs. 17.8%, P = 0.83). Conclusions: Most hospitalizations in older patients with AML are unavoidable and driven by the illness course and its treatments. However, a minority of hospitalizations is potentially avoidable and should be the focus of future interventions to reduce health care utilization and the burden of AML on this population.
A phase I dose-escalation study of NK012
Authors: H. A. Burris, J. R. Infante, D. R. Spigel, F. A. Greco, D. S. Thompson, S. Matsumoto, S. Kawamura, S. F. Jones
Journal: Journal of Clinical Oncology (2008)

2538 Background: NK012 is a micelle-forming macromolecular prodrug of EHC (7-ethyl-10-hydroxycamptothecin), also known as SN-38 the active metabolite of irinotecan, bound to an amphiphilic block copolymer. NK012 accumulates as nanoparticles in tumors where it gradually releases EHC by chemical hydrolysis under neutral conditions. Accumulation and sustained release of EHC could result in increased efficacy of the drug. Methods: Patients with previously treated advanced solid tumors and acceptable organ function were administered NK012 as a 30-minute infusion every 21 days without premedications. UGT1A1 genotype screening was performed prior to enrollment, and UGT1A1*28/*28 homozygotes were treated at a reduced dose level with the potential for dose escalation based on toxicities. At least three patients were treated and evaluated for dose-limiting toxicities at each dose level prior to dose escalation. Pharmacokinetic samples were obtained during cycles 1 and 2 of treatment. Results: Eighteen patients have received 54 cycles of treatment across 5 dose levels ranging from 9 - 28 mg/m2. Four homozygous patients have also been enrolled at dose levels ranging from 4.5 - 10.5 mg/m2 and received a total of 16 cycles. Three of the 22 patients previously received irinotecan. No dose-limiting toxicities were reported at dose levels 1–4. One patient at dose level 5 (28 mg/m2) experienced uncomplicated grade 4 neutropenia lasting > 7 days, which was a dose-limiting toxicity per protocol. As a result, this level has been expanded to a total of 6 patients. Hematologic toxicities have consisted of transient grade 3 neutropenia (1 pt), grade 4 neutropenia (4 pts), and grade 3 thrombocytopenia (1 pt) with 3 patients requiring dose delays due to neutropenia. Nonhematologic toxicities have been minimal. Two partial responses have been reported in patients with previously treated breast cancer and small cell lung cancer, respectively. Ten patients have experienced stable disease as best response (range 3–10 cycles), four patients experienced disease progression, two were inevaluable, and 4 are too early to evaluate. Conclusions: NK012 is well tolerated and has demonstrated antitumor activity in patients with refractory tumors. Phase II trials are warranted in patients with tumor types demonstrating sensitivity to irinotecan. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Nippon Kayaku Co, Ltd Nippon Kayaku
Aryl Hydrocarbon (Benzo[a]pyrene) Hydroxylase in Guinea Pig Lymphoid Tissue&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. C. Bast, Jr.
 4, H. Miller, H. J. Rapp, H. V. Gelboin
Journal: JNCI Journal of the National Cancer Institute (1981)

Aryl hydrocarbon hydroxylase (AHH) activity was detected in a variety of guinea pig lymphoid tissues and was increased by intradermal or ip administration of 3-methylcholanthrene AHH levels were generally greater in spleen than in lymph node, bone marrow, or thymus. Similar AHH activities were observed in lymphoid tissues from Sewall-Wright inbred strain 2 and strain 13 guinea pigs. Greater AHH activities were associated with peritoneal and alveolar macrophages than with lymph nodes lymphocytes in the absence of mitogens.
The liver-first approach for patients with locally advanced rectal cancer and synchronous liver metastases: Long-term results.
Authors: A. E. van der Pool, J. H. de Wilt, J. J. Nuytens, A. M. Eggermont, C. Verhoef
Journal: Journal of Clinical Oncology (2010)

e14027 Background: A previous study has shown that the reversed approach is possible in patients with locally advanced rectal cancer and synchronous liver metastases. In summary, the optimal strategy for locally advanced rectal cancer is pre-operative chemoradiation therapy. The morbidity of rectal cancer surgery after chemoradiation therapy is considerable. Treatment of the liver disease that is decisive for survival maybe postponed for over months. To avoid this delay in treatment, we started the “liver first approach” in patients with locally advanced rectal cancer and synchronous liver metastases. We herein present the long-term results. Methods: Patients presented with locally advanced rectal cancer and synchronous liver metastases were primarily given systemic chemotherapy (CTx) followed by liver resection. After a successful liver resection, patients were treated with chemoradiation therapy for the primary rectal tumor. If thoracic and abdominal imaging did not reveal unresectable metastases, surgery of the rectal cancer was performed. Results: Twenty-two patients were included and underwent liver surgery after CTx. Six patients were not following protocol due to extensive metastatic disease and died after a median of 22 (range, 10-34) months. Three out of these six patients (50%) did not need to undergo a palliative resection of the rectal primary. Sixteen patients (73%) completed the full treatment protocol. With a median follow-up of 37 (range, 17-77) months, 11 patients are showing no evidence of disease, one patient developed a recurrence and is treated with palliative CTx and four patients died after 17, 23, 42 and 70 months. The estimated 5-year overall survival of the 16 patients who fulfilled the protocol was 74% with a median survival of 70 months. Conclusions: The “liver first approach” is a strategy in patients with locally advanced rectal cancer and synchronous liver metastases with promising long-term results . With this strategy, the majority of patients could undergo curative resection of both the metastatic and primary disease. Moreover, needless radical rectal surgery could be avoided in patients who have incurable metastatic disease. No significant financial relationships to disclose.
SP0026 A Fairy Tale from the Land of Andersen – Enabling Patients to Contribute to Arthritis Research
Authors: J. Primdahl
Journal: Annals of the Rheumatic Diseases (2015)

This lecture will describe and discuss the first experiences with user involvement in Danish Rheumatology research and will take its departure at King Christian 10th Hospital for Rheumatic diseases in Denmark. The examples and experiences shared will concern the first experiences from involving users in the AMBRA-study where patient initiated follow-up for outpatients with Rheumatoid Arthritis was explored; the results from a study on what type of information the patients want when participating in research; the experiences from involving users in the development of a new education programme for persons with rheumatoid arthritis; an interview study on patients and researchers thoughts about user involvement in rheumatology research and finally our first experiences with a user-board in our research department. <h3>Disclosure of Interest</h3> None declared