tbuckley/cabot-search huggingface dataset:
<i>Circulation</i> : The Beat Goes On
Authors: Eugene Braunwald
Journal: Circulation (2016)

wrote of "the truly revolutionary advances made in our knowledge of the normal and pathological physiology of the heart and its beat, along with the advances in understanding of its diseases and their management" and of "the conviction on the part of the AHA that such a journal might be a potent factor in the furtherance of its purposes -the better education of the medical profession in matters relating to the diagnosis, treatment and prevention of heart diseases." 1 In 1948, the AHA was transformed from what then-president of the association H.M. Marvin described as a relatively "small organization of doctors interested in the purely scientific aspects of cardiovascular disease into a large, national voluntary health agency with wide interests and broad responsibilities." 2 This "new" AHA needed a new journal, and in 1950, Circulation was born.
Surface Expression of Mpl: Aberrant Mpl Trafficking In Myeloproliferative Neoplasms Is Linked to Insufficient Expression of Wild Type Jak2
Authors: Cédric Cleyrat, Mathias Vilaine, Marjorie Boissinot, Francois Girodon, Mara P. Steinkamp, Irène Dobo, Éric Lippert, Isabelle Corre, Bridget S. Wilson, Sylvie Hermouet
Journal: Blood (2011)
Reinforcing the Ability of 99mTcO4 Scintigraphy for Identifying Differentiated Thyroid Cancer by TSH Stimulation
Authors: Byeong-Cheol Ahn
Journal: Clinical Nuclear Medicine (2016)

Although radioiodines are widely used to localize metastatic differentiated thyroid cancer (DTC), TcO4 also can be used because it is a substrate for the sodium-iodide symporter protein. The use of TcO4 has advantages over radioiodine, namely, easy availability, dispensability of iodine restriction, and early imaging time. However, its low sensitivity precludes its practical application. Scintigraphic detectability of DTC using sodium-iodide symporter substrates is related to the serum TSH levels. Here, I report a case with multiple metastatic lesions of DTC that were detected upon TSH-stimulated TcO4 scintigraphy, but not with non-TSH-stimulated scintigraphy using the same tracer.
Surreptitious drug use by patients in a panic disorder study
Authors: D B Clark, C B Taylor, W T Roth, C Hayward, A Ehlers, J Margraf, W S Agras
Journal: American Journal of Psychiatry (1990)

In a double-blind, placebo-controlled trial comparing alprazolam and imipramine for panic disorder, serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication. Excluding these patients changed the results.
Blood serum albumin as prognostic factor in patients with colorectal carcinoma.
Authors: Luis F. Onate-Ocana, Sagrario Gonzalez-Trejo, Gloria Nunez, Roberto Herrera-Goepfert, Jose F. Carrillo, Francisco J. Ochoa-Carrillo, Vincenzo Aiello-Crocifoglio
Journal: Journal of Clinical Oncology (2016)

740 Background: During the las decades, Colorectal carcinoma (CRC) has become the commonest gastrointestinal neoplasm in Mexico, being stages III and IV the most frequent, reaching thus,, diagnosed by colonoscopy and biopsyand a dismal prognosis. Basal blood serum albumin has been reported as significant prognostic factor in several diseases and in several cancers. Therefore, our aim is to define the role of the basal measurement of blood serum albumin at diagnosis as prognostic factor. Methods: Consecutive cases with CRC diagnosed by colonoscopy and biopsy and treated at a single cancer center in Mexico City from January 2010 to December 2014, were included in this cohort. Clinical history and laboratory data were registered, and patients were treated according to standard guidelines. Follow-up continued until September 2015; the Kaplan-Meier method and the Cox model were used to analyze the association of prognostic factors and overall survival (OS). Results: There were 567 patients with CRC: 258 women (45.5%) and 309 males (55.5%); mean age was 60.04 years (SD 15.6). Fifty-seven, 155, 113 and 242 were stages I, II, III and IV, respectively; 132 were located in right colon, 33 in transverse, 35 in left, 114 in sigmoid, 239 in rectum and 14 in anal canal. Neither gender, age, blood hemoglobin, lymphocyte count, albumin-lymphocyte interaction, nor Nutritional prognostic index were significantly associated with OS. Serum albumin was associated to OS, by bivariate and by multivariate analysis. This association remainded significant after adjustment for TNM stages, locations, and other clinically relevant factors. Conclusions: Serum albumin at diagnosis is an independent, significant, simple, cheap and widely available prognostic factor in patients with CRC in Mexico, adding significant prognostic information to TNM classification. Feasibly, it can be used to develop multivariate prognostic models with clinical impact.
Global Proteomic Profiling of Endemic Versus Sporadic Epstein-Barr Virus (EBV) Positive Burkitt Lymphoma (BL).
Authors: Nader El-Mallawany, Janet Ayello, Nancy Day, Carmella van de Ven, Kevin P Conlon, Damian Fermin, Venkatesha Basrur, Kojo S.J. Elenitoba-Johnson, Megan S Lim, Mitchell S. Cairo
Journal: Blood (2009)
Innovations in American Society of Clinical Oncology Practice Guideline Development
Authors: Mark R. Somerfield, Kari Bohlke, George P. Browman, Neelima Denduluri, Kaitlin Einhaus, Daniel F. Hayes, Alok A. Khorana, Robert S. Miller, Supriya G. Mohile, Thomas K. Oliver, Eduardo Ortiz, Gary H. Lyman
Journal: Journal of Clinical Oncology (2016)

Since the beginning of its guidelines program in 1993, ASCO has continually sought ways to produce a greater number of guidelines while maintaining its commitment to using the rigorous development methods that minimize the biases that threaten the validity of practice recommendations. ASCO is implementing a range of guideline development and implementation innovations. In this article, we describe innovations that are designed to (1) integrate consideration of multiple chronic conditions into practice guidelines; (2) keep more of its guidelines current by applying evolving signals or (more) rapid, for-cause updating approaches; (3) increase the number of high-quality guidelines available to its membership through endorsement and adaptation of other groups' products; (4) improve coverage of its members' guideline needs through a new topic nomination process; and (5) enhance dissemination and promote implementation of ASCO guidelines in the oncology practice community through a network of volunteer ambassadors. We close with a summary of ASCO's plans to facilitate the integration of data from its rapid learning system, CancerLinQ, into ASCO guidelines and to develop tactics through which guideline recommendations can be embedded in clinicians' workflow in digital form. We highlight the challenges inherent in reconciling the need to provide clinicians with more interactive, point-of-care guidance with ASCO's abiding commitment to methodologic rigor in guideline development.
High dose rate brachytherapy as monotherapy for localized prostate cancer: Our initial experience.
Authors: Amarnath Challapalli, Susan Masson, Pauline Humphrey, Frances Bamisaye, Petra Jacobs, Chris French, Amit Bahl
Journal: Journal of Clinical Oncology (2016)

e626 Background: High dose rate (HDR) brachytherapy is an attractive treatment option for localized prostate cancer (CaP) as it allows for safe dose escalation and exploits the radiobiological advantage of using a high dose/fraction. We evaluate our early experience in using HDR monotherapy for localized CaP. Methods: Forty patients with low- to intermediate-risk CaP were treated from October 2013-July 2015. Patients had catheters placed transperineally under spinal anaesthesia, using transrectal ultrasound guidance. The clinical target volume [CTV: prostate ± seminal vesicles base] was outlined on a planning CT scan with the catheters and template in-situ. The CTV was grown by 3mm isotropically to obtain the planning target volume (PTV). The catheters were reconstructed and plan optimised according to pre-set dose constraints [DC]. Dose delivered was 19Gy/one fraction. Toxicity was assessed using RTOG criteria. Results: A range of volumes were implanted (20–120 cc, median: 37.5), using a median of 17 needles (range 13–20). Satisfactory implants were achieved in patients with volumes&gt;60cc by excluding pubic arch interference on the pre-implant MRI pelvis. All patients were discharged home within 24 hours, with two patients (5%) requiring re-catheterisation. Good dose coverage to the PTV was achieved: median D90 of 20.4Gy (DC&gt;19Gy), V100 of 95.1% (DC≥95%). Urethral and rectal sparing was satisfactory: urethral D10 of 21.23Gy (DC&lt;22Gy), rectal D2cc of 14Gy (DC&lt;15Gy). The median follow-up was 8 (1-22.6) months. Twenty-five patients, with at least 6 months follow-up showed a median PSA reduction of 80%. Thus far, one had biopsy proven recurrence. Only two patients had grade 3 urinary toxicity and one had grade 3 bowel toxicity at 2 weeks, which returned to baseline at 12 weeks. The IPSS score increased at 2-4 weeks after treatment, but returned to baseline after 3 months. Conclusions: Our initial experience with HDR monotherapy for localized CaP confirms this to be safe, with minimal acute complications. It is possible to implant volumes higher than 60cc, if adequate measures are taken. The early efficacy data for 19Gy is also promising.
Relationships between DNA Adduct Formation and Carcinogenesis
Authors: James A. Swenberg, Frank C. Richardson, Joyce A. Boucheron, Martin C. Dyroff
Journal: Environmental Health Perspectives (1985)

An impressive array of evidence has been obtained during the past decade establishing correlations between specific DNA adducts and carcinogenesis. Many of the studies utilized organ specific differences in carcinogenesis to establish the correlations. More recently, we have investigated similar relationships between target and nontarget cell populations within the liver. Chronic exposure to methylating hepatocarcinogens predominantly induces hemangiosarcomas, whereas exposure to ethylating agents causes hepatocellular carcinomas. This cell specificity in carcinogenesis correlates well with the presence of promutagenic DNA adducts. In the case of methylating agents, the nonparenchymal cells accumulate O6-methylguanine whereas the hepatocytes do not. Exposure to ethylating agents leads to accumulation of O4-ethyldeoxythymidine, but not O6-ethyldeoxyguanosine in hepatocytes. These differences reflect the ability of the two cell populations to repair O6-alkylguanine and the extent of purine and pyrimidine alkylation with methylating and ethylating agents. Hepatocytes of rats exposed to diethylnitrosamine for 28 days have four to five times more promutagenic DNA adducts (O6-alkyldeoxyguanosine and O4-alkyldeoxythymidine) than hepatocytes of rats exposed to nearly equimolar doses of dimethylhydrazine. Both O6-methylguanine and O4-methyldeoxythymidine are rapidly repaired by rat hepatocytes, while only O6-ethyldeoxyguanosine is rapidly repaired. Studies comparing the relationship between the induction of gamma-glutamyl transpeptidase-positive foci, hepatocellular carcinoma and promutagenic lesions such as O4-ethyldeoxythymidine will be useful in understanding associations between the molecular dosimetry of DNA adducts, initiation, and progression of hepatocarcinogenesis.
Early diagnosis program for cervical cancer in Tanzania: The “Vanda Project”.
Authors: Patrizia Serra, Dino Amadori, Oriana Nanni, Alessandra Gennari, Sara Bravaccini, Maurizio Puccetti, Rosario Tumino, Jackson Kahima, Nestory Andrew Masalu
Journal: Journal of Clinical Oncology (2013)

5594 Background: In Sub-Saharan Africa cervical cancer represents 24% of all cancers and accounts for 23% of all cancer deaths in women. An early diagnosis program for breast and cervical cancer (Vanda Project) is ongoing in Mwanza and the surrounding lake area (12 districts with a population of 14,000,000). The aim of this project was to screen women aged 15-64 years living in the 12 districts. Methods: Women were invited to participate through local media and a mobile unit operating within the districts. A multidisciplinary team including medical oncologists was involved. Interventions consisted in Pap smear, clinical breast examination, breast self-examination training and training of district physicians to perform Pap smear and breast examination. Results: From May to December 2012, 2155 women from the districts of Shinyanga, Bukumbi, Kibara, Serengema and Musoma took part in the program: of these 91 (4%) had clinically evident cervical cancer. Age distribution classes were: &lt; 18 years, 12% ; 18-35, 38%; 36-50, 41%; &gt; 50, 9%. As expected a high stage distribution at diagnosis was observed: 30% stage III and 20% stage IV. Among the women with no clinical evidence of cancer, 408 samples were analyzed by cytology and 4% consisted of inadequate material. Of the remaining 392 samples, 85 (22%) were normal, 216 (55%) were infections (chiefly mycotic), 72 (18%) were precancerous lesions (50% H-SIL according to Bethesda classification) and 19 (5%) were positive for cancer (mainly stages III-IV). Precancerous lesions turned out to be cancer at histology in 44% of cases. 22% of precancerous lesions and 8% of clinically evident cancer were HIV-positive. Conclusions: This experience shows the high feasibility, good compliance and usefulness of a screening program for the early detection of cervical cancer in this high-risk population. [Table: see text]
Nutritional strategies to optimise cognitive function in the aging brain
Authors: Devin Wahl, Victoria C. Cogger, Samantha M. Solon-Biet, Rosilene V.R. Waern, Rahul Gokarn, Tamara Pulpitel, Rafael de Cabo, Mark P. Mattson, David Raubenheimer, Stephen J. Simpson, David G. Le Couteur
Journal: Ageing Research Reviews (2016)
IG Heavy and Light Chain Variable Genes in Chronic Lymphocytic Leukemia Exhibit Distinct Somatic Mutation Patterns and a Comparable Imprint of Antigen Selection.
Authors: Kostas Stamatopoulos, Chrysoula Belessi, Anastasia Hadzidimitriou, Katerina Hatzi, Niki Stavroyianni, Evangelia Kalagiakou, Theodora Papadaki, Fotini Marantidou, Eleni Manioudaki, Anastasia Athanasiadou, Vassiliki Douka, Ioanna Athanasiadou, Varvara Tachynopoulou, Riad Saloum, Nikolaos Laoutaris, Athanasios Fassas, Achilles Anagnostopoulos
Journal: Blood (2004)
Frequency of HER2 mutations and amplification in GI malignancies and ability of pertuzumab to overcome neuregulin1 mediated drug resistance to a HER2 tyrosine kinase inhibitor in colon cancer.
Authors: Ron Bose, Siraj Ali, Naveen Jain, Kyle Gowen, Andrea Bertotti, Elisa Murray, Jeffrey S. Ross, Mary Stanley Beattie, Herbert Hurwitz, John D. Hainsworth
Journal: Journal of Clinical Oncology (2016)

630 Background: HER2 amplifications and activating mutations are an emerging drug target in the treatment of colorectal cancer (CRC). Ongoing studies, such as MyPathway (Clinicaltrials.gov NCT02091141), include basket trials of targeted therapies for multiple solid tumor types. The frequency of HER2 mutations in GI cancers and a drug resistance mechanism to the HER2 kinase inhibitor, afatinib, are presented here. Methods: The Foundation Medicine database of 53,126 cases was searched and clinical data from patients with GI tumors enrolled in the HER2 basket of MyPathway was included. Results: 10,358 patients with GI cancers and FoundationOne (FO) testing were identified and compared to the HER2 mutation frequency reported by The Cancer Genome Atlas (TCGA). In MyPathway, 28 GI tumors with HER2 alterations are enrolled: CRC (n = 13, all amplified), liver/biliary (n = 5), pancreatic (n =4), small intestine (n = 3), and esophageal (n = 2). Several CRC patients demonstrated responses to trastuzumab/pertuzumab (reported separately). The HER2 mutant CRC cell lines, CW-2 and CCK-81, are highly sensitive to afatinib (IC 50 =7-20 nM). Addition of the HER3 ligand, neuregulin1 caused afatinib resistance, but pertuzumab prevented HER3/HER2 activation and reversed this drug resistance. Conclusions: HER2 mutations or amplifications are commonly found in a wide range of GI cancers. Pre-clinical data provide rationale for inclusion of pertuzumab in the treatment strategy for these cancers. The MyPathway Trial is testing this approach. [Table: see text]
An Evaluation of Recurrent Diabetic Ketoacidosis, Fragmentation of Care, and Mortality Across Chicago, Illinois
Authors: James A. Mays, Kathryn L. Jackson, Teresa A. Derby, Jess J. Behrens, Satyender Goel, Mark E. Molitch, Abel N. Kho, Amisha Wallia
Journal: Diabetes Care (2016)

A portion of patients with diabetes are repeatedly hospitalized for diabetic ketoacidosis (DKA), termed recurrent DKA, which is associated with poorer clinical outcomes. This study evaluated recurrent DKA, fragmentation of care, and mortality throughout six institutions in the Chicago area.A deidentified Health Insurance Portability and Accountability Act-compliant data set from six institutions (HealthLNK) was used to identify 3,615 patients with DKA (ICD-9 250.1x) from 2006 to 2012, representing 5,591 inpatient admissions for DKA. Demographic and clinical data were queried. Recurrence was defined as more than one DKA episode, and fragmentation of health care was defined as admission at more than one site.Of the 3,615 patients, 780 (21.6%) had recurrent DKA. Patients with four or more DKAs (n = 211) represented 5.8% of the total DKA group but accounted for 26.3% (n = 1,470) of the encounters. Of the 780 recurrent patients, 125 (16%) were hospitalized at more than one hospital. These patients were more likely to recur (odds ratio [OR] 2.96; 95% CI 1.99, 4.39; P < 0.0001) and had an average of 1.88-times the encounters than nonfragmented patients. Although only 13.6% of patients died of any cause during the study period, odds of death increased with age (OR 1.06; 95% CI 1.05, 1.07; P < 0.001) and number of DKA encounters (OR 1.28; 95% CI 1.04, 1.58; P = 0.02) after adjustment for age, sex, insurance, race, fragmentation, and DKA visit count. This study was limited by lack of medical record-level data, including comorbidities without ICD-9 codes.Recurrent DKA was common and associated with increased fragmentation of health care and increased mortality. Further research is needed on potential interventions in this unique population.
Purification of human marrow progenitor cells and demonstration of the direct action of macrophage colony-stimulating factor on colony-forming unit-macrophage
Authors: N Sato, K Sawada, M Kannonji, T Tarumi, N Sakai, M Ieko, S Sakurama, S Nakagawa, T Yasukouchi, SB Krantz
Journal: Blood (1991)
Cytokines and chemokines released from the interaction of anti-HER2/anti-CD3 bispecific antibody armed activated T cells (ATC) with the tumor microenvironment can induce efficient antigen presentation and induce an adaptive immune response
Authors: Z. Al-Kadhimi, E. Paul, O. Norkina, L. G. Lum
Journal: Journal of Clinical Oncology (2008)

3072 Background: The tumor microenvironment has a complexes network of soluble factors, and cell surface signals which can induce a significant state of immune tolerance. Several immunotherapy strategies attempted to break this tolerance aiming to re-activate and expand tumor specific adaptive immune responses. Our approach uses ATC armed with chemically heteroconjugated bispecific antibodies (AATC) that bind and activate T cells while targeting Her2/neu on tumor targets. This creates non-HLA restricted cytotoxic/cytokine producing-T lymphocytes. Methods: Coculture experiments were perform by mixing AATC with Her2/neu+ SKBR3 target cell lines and fresh autologous peripheral blood mononuclear cells (PBMC) to induce cytotoxic activity directed at SKBR3 after 7 days. The ability of PBMCs to develop an adaptive response towards SKBR3 at the end of 7 days was studied using standard 51Cr release assay. Chemokines and cytokines released form the above interaction were studied. Results: In the presence of PBMC and SKBR3 cells, armed ATC induced the secretion of IFNγ, GM-CSF, IL-12, and MIP1α after 96 hrs of co-culture compared to unarmed ATC co- cultured with SKBR3 and PBMC. When we irradiated AATC so that they can induce initial tumor cell kill and die shortly after, we noticed the emergence of SKBR3 specific CD8 CTL response 7 days later. Depletion of CD14+ cells from the co-culture at day 0 reduced the SKBR3 CTL response at day 7 as well as the amounts of the cytokines generated (96 hrs) significantly. When supernatants from a 24 h co-culture of armed ATC+ PBMC+ SKBR3 were mixed with fresh CD14+ monocytes and autologous CD3+ T cells for 7 days, there was a significant increase in SKBR3 specific CTL activity compared to supernatants from co-cultures of unarmed ATC, PBMC, and SKBRR3. Studies are on there way to evaluate the impact of these cytokines on the phenotype CD14+ monocytes. Conclusions: These results suggest that cytokines and chemokines released from the interaction of AATC with the tumor microenvironment can induce an efficient maturation of immature antigen presenting cells and may lead ultimately to breaking tolerance. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Transtarget Inc. Transtarget Transtarget
Intravaginal Administration of Fc-Fused IL7 Suppresses the Cervicovaginal Tumor by Recruiting HPV DNA Vaccine-Induced CD8 T Cells
Authors: Young Woo Choi, Moon Cheol Kang, Yong Bok Seo, Hong Namkoong, Yunji Park, Dong-Hoon Choi, You Suk Suh, Seung-Woo Lee, Young Chul Sung, Hyun-Tak Jin
Journal: Clinical Cancer Research (2016)

The induction of tissue-localized virus-specific CD8 T-cell response is essential for the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. Here, we aimed to elucidate the immunologic role of IL7 in the induction of mucosal cellular immunity.IL7 was engineered through Fc fusion to enhance mucosal delivery across the genital epithelial barrier. The immunomodulatory role of IL7 was evaluated by monitoring the kinetics of various immune cells and measuring the expression of chemokines and cytokines after intravaginal administration of Fc-fused IL7 (IL7-Fc). The antitumor effects of intramuscular human papillomavirus (HPV) DNA vaccine or topical IL7-Fc alone or in a combinational regimen on mice survival were compared using a orthotopic cervical cancer model.Intravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFNγ, TNFα, IL6, and IL1β), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, γδ T cells, and dendritic cells. Importantly, in this murine cervical cancer model, topical administration of IL7-Fc after intramuscular HPV DNA vaccination increases the number of HPV-specific CD8 T cells in the genital mucosa, but not in the spleen, leading to stronger antitumor activity than the HPV DNA vaccine alone.Our findings provide an important insight into the immunomodulatory role of IL7-Fc via topical application and the design of therapeutic vaccine regimen that induces effective genital-mucosal CD8 T-cell responses. Clin Cancer Res; 22(23); 5898-908. ©2016 AACR.