tbuckley/cabot-search huggingface dataset:
Abstract CT154: Phase I dose-escalating PoC study to evaluate the safety and tolerability of LiPlaCis (liposomal cisplatin formulation) in patients with advanced or refractory tumors
Authors: Ulrik Lassen, Morten Mau-Sørensen, Ulla Hald Buhl, Mogens W. Madsen, Eva Balslev, Dick Pluim, Jan H. M. Schellens, Steen Knudsen, Peter B. Jensen
Journal: Cancer Research (2016)

Abstract LiPlaCis is a novel liposomal formulation of cisplatin, designed to be specifically degraded by secretory phospholipase A2 (sPLA2) which is over-expressed in tumor tissue. sPLA2 has been shown to be present in a number of different tumor tissues - e.g. prostate, lung, ovarian, breast etc. (T. Abe 1997). Thus, LiPlaCis is intended to improve the therapeutic index due to an improved therapeutic efficacy and possibly also an improved safety and tolerability profile. Objectives: The primary objectives were safety and determination of MTD. Secondary objectives were evaluation of PK, clinical activity, and PD. This included two PoC cohorts to study platinum-DNA adducts in tumor compared to normal tissue following administration of LiPlaCis. Methods: A standard 3+3 design was used to include patients with advanced solid tumors and PS 0-1. LiPlaCis was administered weekly on day 1, day 8 and possibly day 15 every 3 wks. CTCAE v4.03 and RECIST were used to assess safety and tumor activity. Paired tumor and normal tissue biopsies obtained pre-treatment and on day 2 were used to assess sPLA2-IIA protein levels and platinum-DNA adducts (by 32P-postlabeling assay) in two PoC cohorts of 60 and 90 mg LiPlaCis. Results: A total of 16 patients were included at dose levels of 60, 90 and 120 mg. At 120 mg two DLTs were observed and an intermediate dose level of 90 mg Day 1 and 8 and 45 mg Day 15 was explored. After 1 DLT, this dose level was halted and the PoC cohorts were initiated sequentially. The observed DLTs included renal toxicity and infusion reactions. Most frequent AEs of all grades were fatigue, hypomagnesemia and vomiting. The most common (&amp;gt;10%) grade 3-4 AEs were hypomagnesemia, hypokalemia and anemia. Clinical activity was observed in a patient with H&amp;N cancer; 60 mg (PR), SCC skin;120 mg (PR), BC; 60 mg (SD-ongoing), CRC; 90 mg (SD -18 wks) and gastric cancer; 90 mg (SD-21 wks). In the 60 mg PoC cohort of 3 pts the tumor- to normal tissue ratio of platinum-DNA adducts was from 5.7 to 8.3 fold. Conclusion: MTD has not yet been determined, but ongoing PoC cohorts indicate that LiPlaCis is preferably released in tumor by sPLA2 compared to normal tissue which potentially could improve the therapeutic index of cisplatin. Citation Format: Ulrik Lassen, Morten Mau-Sørensen, Ulla Hald Buhl, Mogens W. Madsen, Eva Balslev, Dick Pluim, Jan H. M. Schellens, Steen Knudsen, Peter B. Jensen. Phase I dose-escalating PoC study to evaluate the safety and tolerability of LiPlaCis (liposomal cisplatin formulation) in patients with advanced or refractory tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT154.
Story behind meldonium–from pharmacology to performance enhancement: a narrative review
Authors: Wolfgang Schobersberger, Tobias Dünnwald, Günther Gmeiner, Cornelia Blank
Journal: British Journal of Sports Medicine (2016)

Recent reports from the World Anti-Doping Agency (WADA) indicate an alarming prevalence in the use of meldonium among elite athletes. Therefore, in January 2016, meldonium was added to WADA's prohibited list after being monitored since 2015. Meldonium has been shown to have beneficial effects in cardiovascular, neurological and metabolic diseases due to its anti-ischaemic and cardioprotective properties, which are ascribed mainly to its inhibition of ß-oxidation and its activation of glycolysis. Despite its widespread use, there are only a few clinical studies or clinical trials available. Meldonium is registered in most Baltic countries and is easily accessible through the internet with no serious adverse effects reported by the manufacturer so far. Among athletes, meldonium is used with the purpose of increasing recovery rate or exercise performance. The benefit of taking meldonium in view of performance enhancement in athletes is quite speculative and is discussed without sound scientific evidence. This narrative review provides a detailed overview of the drug meldonium, focusing on the main topics pharmacology and biochemical actions, clinical applications, pharmacokinetics, methods of detection and potential for performance enhancement in athletes.
The Globally Synchronized Switch—Another Milestone Toward Achieving Polio Eradication
Authors: Steven G. F. Wassilak, John F. Vertefeuille, Rebecca M. Martin
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 171: Comparative genomic analyses of synchronous colorectal cancers by exome sequencing
Authors: Ulrika A. Hänninen, Tomas Tanskanen, Riku Katainen, Jan Böhm, Minna Taipale, Jussi Taipale, Jukka-Pekka Mecklin, Netta Mäkinen, Lauri A. Aaltonen
Journal: Cancer Research (2016)

Abstract Colorectal cancer (CRC) is the third most common cancer type and the second leading cause for cancer deaths in the Western world. Around 3.5% of CRC patients have more than one primary colorectal carcinoma at the time of diagnosis. These so-called synchronous colorectal cancers (SCRC) are more common in men and have been associated with predisposing conditions, such as hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatosis polyposis (FAP) and inflammatory bowel disease. Such conditions account for slightly more than 10% of SCRC cases. The pathological and clinical features of the tumors have been widely studied. The underlying molecular mechanisms in SCRC have not been well described, though. The research has mainly focused on single factors such as microsatellite instability (MSI) status or APC-, KRAS-, and p53-mutations. By exome sequencing a tumor pair and corresponding normal sample from 23 patients, we aim to study the extent of genetic overlap between the synchronous tumors to assess if they derive from a common progenitor. The tumor data will be filtered against the normal tissue data to verify the somatic origin of the observed mutations. The comparison of the mutation profiles in each tumor pair will take into account the number of shared variants that occur in the exact same positions in the coding region. If the tumors share a high number of changes in exactly the same base it would suggest they have a common origin. Different mutation patterns, with possibly a few coincidental shared mutations, may support a stochastic process in the genesis of the two tumors. We will also identify commonly mutated genes - those that are mutated in both tumors of a synchronous pair or among synchronous pairs of different patients. The patient material derives mainly from a consecutive, population-based colorectal cancer collection “Suolisyöpä Keski-Suomi 2000-2010” from Jyväskylä, Finland. In addition three SCRC-cases were included from our in-house collections. Knowledge on the molecular basis of SCRC, which haven't been studied to this extent before, provides insight on how these tumors arise and allows for development of more personalized treatments. Citation Format: Ulrika A. Hänninen, Tomas Tanskanen, Riku Katainen, Jan Böhm, Minna Taipale, Jussi Taipale, Jukka-Pekka Mecklin, Netta Mäkinen, Lauri A. Aaltonen. Comparative genomic analyses of synchronous colorectal cancers by exome sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 171.
A Phase 1 Study of Prasugrel in Subjects with Sickle Cell Disease: Effects on In Vivo Markers of Platelet Activation and of Coagulation
Authors: Joseph A. Jakubowski, Chunmei Zhou, David S. Small, Kenneth J. Winters, D. Richard Lachno, Andrew L. Frelinger, Jo Howard, Stipo Jurcevic, Christopher D. Payne
Journal: Blood (2011)
Abstract 615: Scaffold-based perfusion bioreactor system for in vitro maintenance of primary breast cancer tissue microenvironment suitable for personalized medicine
Authors: Manuele Giuseppe Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Alexandar Tzankov, Walter P. Weber, Giulio C. Spagnoli, Savas D. Soysal
Journal: Cancer Research (2016)

Abstract INTRODUCTION Two-dimensional (2D) in vitro culture systems and in vivo animal models are the primary tools used to test cancer cell responses to drugs but they are not suited for the development of immune-mediate therapies. Here we present an innovative method for in vitro culture primary breast cancer (BrCa) tissues in porous 3D scaffolds by using a perfusion-based bioreactor system (U-CUP). MATERIALS &amp; METHODS Freshly excised breast cancer specimens were fragmented and cultured in a 3D “sandwich-like format” between collagen porous scaffolds under perfusion flow. DMEM/F12, supplemented with 10% autologous human serum, was used as a culture medium. Malignant and non-malignant cells survival, expansion into the scaffold and the ability to recapitulate features of the original BrCa specimens were histologically assessed. For estrogen receptor (ER) positive tissues we tested the response to hormonal therapy by adding the anti-ER drug Fulvestrant. Furthermore, the maintenance of immune-infiltrating cells allowed testing immune blockade therapy in vitro using anti PD-L1 on PD-L1 positive samples. Response to treatment was evaluated by histology and qRT-PCR for markers of immune-response. RESULTS By culturing BrCa using the U-CUP we were able to preserve viability and to promote the expansion of breast cancer cells from surgical specimens together with accompanying stromal and immune cells into the porous scaffold. Expanding cancer cells were viable after 21 days and recapitulating the initial histology with formation of glands. Administration of anti-ER treatment was associated with decreased expansion of cancer tissue into the scaffold after 21 days. After 7 days of anti PD-L1 antibody treatment we observed a reduced number of tumor cells due to the activation of infiltrating lymphocytes, as shown by increased expression of IFNg and decreased expression of IL10. CONCLUSIONS The scaffold-based perfusion bioreactor represents a successful organotypic tumor model allowing in vitro long-term culture of breast cancer specimens. Our findings shed the light on a promising system for selecting personalized treatment based on a patient's tumor specific microenvironment. Citation Format: Manuele Giuseppe Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Alexandar Tzankov, Walter P. Weber, Giulio C. Spagnoli, Savas D. Soysal. Scaffold-based perfusion bioreactor system for in vitro maintenance of primary breast cancer tissue microenvironment suitable for personalized medicine. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 615.
Abstract 3457: Social support as emotional adjustment determinant of breast cancer patients after surgery in selected hospitals in Nigeria
Authors: Christiana Oluseun Oyewusi, Samuel Oyebode Oyewusi
Journal: Cancer Research (2016)

Abstract Breast cancer is the most common invasive cancer and a leading cause of premature mortality for females worldwide. It accounts for 16% of all female cancers; 18.2% of all cancer deaths globally are from breast cancer. Social support plays a major role in modifying negative effect of this disease on affected individuals. It is an important psychosocial resource for coping with stressful life events. This study was carried out to examine social support as determinant of emotional adjustment of breast cancer patients after surgery in selected hospitals in Ibadan, Nigeria. This cross-sectional descriptive survey utilized a quantitative approach. A sample of two hundred and eighteen patients was randomly selected from hospitals in Ibadan. The respondents were reassured of confidentiality of the data. The instrument used basically was self-structured questionnaire. Data were collected, coded and analyzed using Pearson correlation coefficient. The respondents’ ages were between 21- 51 years; 87.2% were females, majority of them (81.6%) were Christians, more than half (62.4%) were married, about one third (31.2%) had higher qualifications, 55.0% were civil servants and 74.3% were living with other family members. Result findings show that instrumental support had significant effect on emotional adjustment of the breast cancer patients after surgery. Family and friends helping the patients had a positive effect on their emotional adjustment. Therefore, it was revealed that instrumental support had a positive effect on emotional adjustment of the patients (r.cal = .217, r. critical = .195, P &amp;lt; 0.05). Also, emotional support had a significant effect on emotional adjustment of the patients after surgery. Having family members and friends to talk to and help with personal problems was helpful to emotional adjustment. Thus it was evident that emotional support had a positive effect on emotional adjustment (r. cal = .250, r. critical = .195, P &amp;lt; 0.05) The patients admitted that they had friends and family members who helped them and were a source of comfort to them. This helped them to show a better psychological and emotional adjustment to breast cancer than those who did not have support. It is recommended that adequate attention be given to financial, material and emotional needs of the breast cancer patient. Keywords: Social support, determinant, emotional adjustment, breast cancer patients. Citation Format: Christiana Oluseun Oyewusi, Samuel Oyebode Oyewusi. Social support as emotional adjustment determinant of breast cancer patients after surgery in selected hospitals in Nigeria. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3457.
Abstract 1778: A comparison study of the disparities of cervical cancer excess mortality between Black and Caucasian women in Alabama and the US
Authors: Ehsan M. Abdalla
Journal: Cancer Research (2016)

Abstract Background: The main purpose of this study was to assess the disparity of cervical cancer (CerCancer) mortality rates change through time between Black and Caucasian women residing in Alabama and the US. Methods: The CerCancer behavioral risk factors and utilization of screening tests data were obtained from CDC's Behavioral Risk Factor Surveillance System (BRFSS) database. Baseline data and target objectives of utilization of CerCancer screening and mortality rates were obtained from Healthy People 2020. The CerCancer mortality rates data were obtained from the Surveillance, Epidemiology, and End Results (SEER). Mortality rates, percentage difference, percentage change and annual percentage change for trends were calculated and compared with the US baseline. Data were stratified by age, gender, race, and geography, using SEER*Stat version 8.4.1 in conjunction with Linear Trendlines analysis to model the racial changes of CerCancer mortality rates through time in Alabama and the US. Results: Our results depicted in general, that although Blacks had higher CerCancer mortality rates at all times, a decreasing trend in CerCancer mortality rates was noted for both races. However, the degree of disparities in mortality rates fluctuated over time and differed by age. In Alabama, Blacks aged 65 years and older have not experienced significant decline in CerCancer mortality rates in recent years, despite a high screening rate compared to Whites. In contrast, between 2002 and 2012, Whites in Alabama and the US made a significant progress toward the Healthy People 2020 goal. Conclusions: Conclusively in Alabama, a disparity still exists for the high CerCancer mortality rates in Blacks despite the higher rates of screening for CerCaner as would otherwise be expected. Additionally, the state has not yet achieved the Healthy People 2020 goal. Thus, although the gap in mortality rates in Alabama has narrowed, however the disparity remains, but if the dismal narrowing is sustained, it will reduce the racial disparities in CerCancer mortality though at a very slow rate. Therefore, Public health officials should monitor progress toward reduction and/or elimination of these disparities. Citation Format: Ehsan M. Abdalla. A comparison study of the disparities of cervical cancer excess mortality between Black and Caucasian women in Alabama and the US. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1778.
Abstract 20: Outlier overexpression of genes involved in fatty acid metabolism and processing define two aggressive prostate cancer phenotypes
Authors: Sandra M. Gaston, Kerry Dehimer, James Kearns, Kyle-Ravi Chinsky, Dennis Otali, Denise Oelschlager, Soroush Rais-Bahrami, Jeffrey W. Nix, Peter Kolettis, George W. Adams, William E. Grizzle
Journal: Cancer Research (2016)

Abstract Major shifts in fatty acid metabolism are part of the malignant phenotype of many types of cancer, including prostate cancer. We have used a biopsy based approach to characterize high grade prostate cancers in both African American and European American patients. This approach allows us to analyze prostate cancers from patients whose disease is too advanced for radical prostatectomy and who are thus not represented in the study specimens available from conventional biorepositories. mRNA gene expression profiling of high grade prostate cancers from biopsies revealed cancer subtypes with very high (&amp;gt;10 fold) levels of overexpression of fatty acid binding protein 5 (FABP5) and fatty acid synthase (FASN). Interestingly, these prostate cancer subtypes showed an either-or phenotype, with “super-overexpression” of either FABP5 or FASN but not both. These findings suggest two “outlier” prostate cancer subtypes with striking differences in the pathways that drive a shift in tumor fatty acid metabolism; one is a fatty acid synthase (FASN) dominant phenotype and the other a previously unrecognized fatty acid binding protein (FABP5) dominant phenotype. In contrast, prostate cancers with lower levels of FABP5 and/or FASN overexpression (2-4 fold) often co-overexpressed both of these genes. Immunohistochemical analyses confirmed prostate cancer FABP5 and FASN overexpression; both showed strong cytoplasmic staining. FABP5 also showed robust nuclear staining consistent with its proposed role in regulating fatty acid mediated gene expression. At both the mRNA and protein levels, the high grade prostate cancers with the highest levels of FABP5 over-expression were more common in African Americans, while the highest levels FASN overexpression were more common in prostate cancers from European Americans. These findings may provide the basis for more effective dietary interventions and targeted therapies for African American and European American patients with these two different subtypes of high grade prostate cancer. Citation Format: Sandra M. Gaston, Kerry Dehimer, James Kearns, Kyle-Ravi Chinsky, Dennis Otali, Denise Oelschlager, Soroush Rais-Bahrami, Jeffrey W. Nix, Peter Kolettis, George W. Adams, William E. Grizzle. Outlier overexpression of genes involved in fatty acid metabolism and processing define two aggressive prostate cancer phenotypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 20.
Teaching Medical Students to Engage Meaningfully and Judiciously With Patient Data
Authors: Rachel J. Stern
Journal: JAMA Internal Medicine (2016)

virulent health risk factor for AA men.Our findings at 125% of the poverty line suggest that revision of poverty thresholds triggering eligibility for federal programs that influence quality of life, health, and equal opportunity should take into account premature mortality driven by poverty as a first step to address the vulnerability of poor AA men.