tbuckley/cabot-search huggingface dataset:
Elucidation of the role of dyclin dependent kinase 11p58 in mitosis
Authors: Amber C. Kahle, Jiaqi Shi, Mark A. Nelson
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4434 

Cyclin dependent kinase 11 (CDK11, formerly known as PITSLRE) belongs to the p34cdc2 family of proteins. CDK11 has several isoforms with different functions, including RNA processing and apoptosis. The CDK11p58 isoform is generated by an internal ribosome entry site (IRES) during the G2/M phase of the cell cycle. CDK11p58 may play a role in the cell cycle. However the function of CDK11p58 remains to be determined. In the present study, we confirm that CDK11p58 is produced during the G2/M phase of the cell cycle in A375 melanoma cells. We show that ectopic expression of CDK11p58 in A375 cells delays the cell cycle at the G2/M phase. We also demonstrate that over expression of CDK11p58 decreases tumor cell growth in colony formation assays. The growth inhibitory activity of CDK11p58 appears to be due to increased apoptosis. We have utilized an immunoprecipitation and proteomic approach in order to identify proteins that are associated with CDK11p58. Using mass spectrometry, we were able to identify that CDK11p58 associates with the RNA helicase, DDX15 as well as other proteins. Confirmation of these specific protein interactions is currently under investigation in our laboratory. Collectively, these studies suggest that CDK11p58 may regulate RNA processing during mitosis. (Supported by NIH CA-70145 and Cancer Biology Training Grant T32CA-09213)
Neoplasms in Children Treated With X rays for Thymic Enlargement. III. Clinical Description of Cases&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Edward T. Toyooka, James W. Pifer, Louis H. Hempelmann
Journal: JNCI Journal of the National Cancer Institute (1963)

Detailed clinical and pathological descriptions of 69 neoplasms occurring in a group of 2,809 children treated with X rays for thymic enlargement in infancy are presented. Complete radiation treatment factors are also given. Thyroid neoplasms were emphasized as they comprised 43 percent of the tumors.
Committee lacks "shop floor" support
Authors: C. Davies
Journal: BMJ (1995)

the reduction was to only 83 hours a week.Furthermore, although we included some of the more benign comments of the trainees in our article, many of them, though entertaining, were unprintable.We agree that the Junior Doctors Committee (which allegedly disbelieved our data) is out of touch with the wishes of many junior staff, particularly surgical trainees.Perish the thought that we should shorten our hours to the levels in Europe.For example, in Denmark (where they have a 37 hour week), on a urological unit a little bigger than ours there are eight senior registrars.The trainee who covers a weekend has to have the whole of the next week off.Surely even the Junior Doctors Committee cannot believe that this is compatible with an adequate training programme.One of the great advantages of consultant practice in Britain is personal autonomy (though this also is under threat).This requires a higher level of exposure and experience than is needed by our counterparts in Europe, who are more protected.
Survival rates after bowel cancer surgery rise in England and Wales
Authors: Jacqui Wise
Journal: BMJ (2015)

More patients than ever are surviving colorectal cancer after surgery in England and Wales, the National Bowel Cancer Audit report 2015 has found.1

The audit, published by the Royal College of Surgeons, found that 96.2% of patients were alive 90 days after bowel cancer surgery in 2013-14, up from 94.2% in 2009-10. Although patients who have an emergency operation are known to be more likely to die within 90 days of their operation, survival after emergency surgery has also improved over the past five years …
Synergistic activity of PHY906 with capecitabine in pancreatic carcinoma
Authors: M. W. Saif, S. Liu, A. Elfiky, Z. Jiang, Y. Cheng
Journal: Journal of Clinical Oncology (2007)

15116 Background: Preclinical data indicates that PHY906, a traditional Chinese botanical formulation, can reduce chemo-induced gastrointestinal toxicity while simultaneously enhancing therapeutic efficacy of a broad-spectrum of common anticancer agents. Methods: Male NCR athymic nude mice were transplanted with human PANC-1 cells. To determine the best dose of combinational regimen, two dose ranges of capecitabine, 60 and 180 mg/kg bid for 14 consecutive days with two dose ranges of PHY906, 300 and 900 mg/kg bid on days 1–4 and days 8–11 were administered by gavage in the first experiment. In the second experiment, PHY906 was fixed at 500 mg/kg bid at days 1–4 and 8–11 while dose of capecitabine was increased to 360 mg/kg bid for 14 consecutive days. A dose of 180 mg/kg of capecitabine was also included for comparison with previous experiments. In the third experiment, capecitabine at 360 mg/kg was selected to evaluate effect of different doses of PHY906 ranging from 100 mg/kg to 500 mg/kg on enhancement of antitumor activity of capecitabine. PHY906 was always administered 30 minutes prior to capecitabine. Tumor size, body weight and mortality were monitored daily and mice were sacrificed when tumor size reached 10% of body weight or on Day 21. Results: PHY906 showed enhancement of antitumor activity of capecitabine when both doses of PHY906 were co-administered with both doses of capecitabine in first experiment. In second experiment, increase of capecitabine dose from 180 mg/kg to 360 mg/kg significantly increased disparity of tumor growth rates between capecitabine alone and concomitant use of both PHY906 and capecitabine. Similar results were obtained in third experiment using a dose of 360 mg/kg of capecitabine and 500 mg/kg of PHY906 (p= 0.0018) as compared with control, capecitabine or PHY906 alone. Similar observation was found in mice bearing PAN-2 murine pancreatic cancer. Conclusions: The studies demonstrate that PHY906 potentiates antitumor activity of capecitabine in human pancreatic carcinoma xenograft mouse model in all capecitabine and PHY906 dosing regimens examined. Observed effect appeared to be dependant on dosage of capecitabine. Therefore, we are employing a dose intense weekly schedule for capecitabine with PHY906 in a phase I/II study in patients with advanced pancreatic cancer. No significant financial relationships to disclose.
The optimal dose of ondansetron as premedication for moderately or highly emetogenic chemotherapy
Authors: S. M. Abo, A. Sengar, K. Ryan, J. Malinowski, D. Randhawa, G. Guron
Journal: Journal of Clinical Oncology (2005)

8209 Background: Anti-emetic guidelines recommend the use of a serotonin-receptor antagonist for the prevention of acute emesis prior to the administration of highly or moderately emetogenic chemotherapy. However, dosages of these agents, such as ondansetron, vary throughout the literature. Our trial was undertaken to determine the optimal dosage of ondansetron in terms of anti-emetic efficacy and safety while keeping in mind a cost-conserving perspective. Methods: In this single institution study, all patients scheduled to receive moderately or highly emetogenic chemotherapy (Hesketh criteria ≥ 3) in a six month period for various cancer types were eligible. Ondansetron 32mg I.V. was administered prior to the first cycle of chemotherapy. De-escalation of the dosage to 24mg and 16mg I.V. occurred with cycles two and three, respectively. Acceptable response was defined as no emesis or mild nausea. Failure was defined as ≥1 episodes of emesis or nausea lasting more than 30 minutes. Efficacy and side effects were monitored for 24 hrs. McNemar test for repeated measures was used to compare dosage responses. Results: A total of 52 patients were properly enrolled. 35 patients received a Hesketh 5 regimen, 16 patients received a Hesketh 4 regimen, and 1 patient received a Hesketh 3 regimen. Acceptable response rates were 86.5% in the 32mg group, 78.8% in the 24mg group, and 63.5% in the 16mg group. When we compared the 32mg vs. the 24mg group in terms of acceptable versus failed response there was no statistical difference (p= 0.22). However, statistical differences were significant when comparing the 24mg vs. the 16mg group (p=0.02) and the 32mg vs. the 16mg group (p=0.001). All three doses of ondansetron were well tolerated with no unexpected drug-related adverse effects. Headache was the most commonly reported side effect and occurred in 23% of the patients. Conclusions: Despite our small sample size, differences in efficacy became apparent once the dosage was de-escalated below 24mg. Although lower dosages are more cost efficient, 24mg should be the minimal dosage of ondansetron administered prior to moderately or highly emetogenic chemotherapy. No significant financial relationships to disclose.
Role of genotyping in risk factor assessment for sudden death in hypertrophic cardiomyopathy**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: William J McKenna, Jens Mogensen, Perry M Elliott
Journal: Journal of the American College of Cardiology (2002)
CT Defined Atherosclerotic Plaque Type and Severity
Authors: John A. Rumberger
Journal: JACC. Cardiovascular imaging (2012)

In the 1960s hit television show The Outer Limits , the following (paraphrased) introduction was meant to focus our minds on what we see and then make an interpretation: There is nothing wrong with your television set … . We are controlling the transmission. We will control the horizontal. We
Brain Disorders Due to Lysosomal Dysfunction
Authors: Alessandro Fraldi, Andrés D. Klein, Diego L. Medina, Carmine Settembre
Journal: Annual Review of Neuroscience (2016)

Recent studies of autophagic and lysosomal pathways have significantly changed our understanding of lysosomes; once thought to be simple degradative and recycling centers, lysosomes are now known to be organelles capable of influencing signal transduction, via the mammalian target of rapamycin complex 1 (mTORC1), and regulating gene expression, via transcription factor EB (TFEB) and other transcription factors. These pathways are particularly relevant to maintaining brain homeostasis, as dysfunction of the endolysosomal and autophagic pathways has been associated with common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, and lysosomal storage disorders, a group of inherited disorders characterized by the intralysosomal buildup of partially degraded metabolites. This review focuses on the cellular biology of lysosomes and discusses the possible mechanisms by which disruption of their function contributes to neurodegeneration. We also review and discuss how targeting TFEB and lysosomes may offer innovative therapeutic approaches for treating a wide range of neurological conditions.
Pretreatment d-2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia
Authors: J Balss, C Thiede, T Bochtler, J G Okun, M Saadati, A Benner, S Pusch, G Ehninger, M Schaich, A D Ho, A von Deimling, A Krämer, C E Heilig
Journal: Leukemia (2015)
Abstract P221: Plasma Triglyceride/High Density Lipoprotein Cholesterol Ratio and Subclinical Cardiovascular Disease Parameters in a South Asian Population
Authors: Mohan Thanikachalam, Jahnavi Sunderarajan, Shravanti Shankar, Vijaykumar Harivanzan, Sadagopan Thanikachalam
Journal: Circulation (2015)

Background: There is increasing focus on biomarkers for early detection of cardiovascular disease (CVD). Studies suggest that the ratio of triglyceride (TG)/high density lipoprotein (HDL) could be a simple marker for insulin resistant and increased cardiometabolic risk, but the association between TG/HDL ratio and CVD is not fully defined. In the current study we assess the relationship between TG/HDL ratio and subclinical CVD parameters in a South Asian population. Methods: In the cross-sectional analysis of 8080 South Indians, the assessments included left ventricular mass indexed (LVMI) to body surface area by echocardiograph, carotid intimal medial thickness (IMT), arterial stiffness by carotid-femoral pulse wave velocity (PWV) and endothelial function by brachial artery flow mediated dilatation (FMD). Generalized linear regression models were used to test the association of TG/HGL ratio with subclinical parameters. All models were adjusted for age, gender, BMI, physical activity, LDL, blood sugar, smoking, stress, and anxiety status. Results: After the exclusion of people with evidence of coronary artery disease, 7164 subjects (mean age 43 years, 58% women) constituted the study sample. The value of subclinical parameters by TG/HDL quartiles is shown in the Table. In univariate analysis, TG/HDL ratio was associated with subclinical parameters [PWV (r = 0.14), LVMI (r = 0.11), FMD (r = -0.06); IMT (r = 0.103; p &lt;0.01]. In adjusted linear regression models, TG/HDL ratio was independently associated with PWV (β = 0.029, p = 0.014) and IMT (β = 0.051, p &lt;0.01). Subsequently, in gender specific models, TG/HDL ratio was independently associated PWV and IMT only in women [PWV (β = 0.042, p = 0.006); IMT (β = 0.067, p = 0.01)] and in subgroup analysis in healthy participants below 40 years of age [PWV (β = 0.082, p &lt;0.01); IMT (β= 0.067, p = 0.01)]. Conclusion: TG/HDL ratio was independently associated with PWV and IMT in South Asian women, including apparently health young individuals.
Abstract 18870: Adjudicated versus “Administrative” Heart Failure With Preserved Ejection Fraction
Authors: Andreas P Kalogeropoulos, Akash Patel, Song Li, Gregory Burkman, Lampros Papadimitriou, Lane Zhang, Taylor A Lebeis, Kanwal Farooq, Vasiliki V Georgiopoulou, Javed Butler
Journal: Circulation (2014)

Introduction: The proportion of heart failure (HF) with preserved ejection fraction (HFpEF) is reported to be as high as 40%-60% based on administrative data, but these estimates have not been clinically validated. Methods: We evaluated 1752 consecutive patients who received outpatient care during the first quarter of 2012 for an encounter ICD-9 code of 402.X1, 404.X1, 404.X3, or 428.XX. Medical records were reviewed for HF symptoms, signs, and treatment; last reported ejection fraction (EF); all previous EF documentations; and special causes of HF (congenital heart disease or specific cardiomyopathies). We classified confirmed HF cases not due to special causes into 3 mutually exclusive categories: (1) HFpEF: current EF &gt;40% without any previous EF ≤40%; (2) HF with recovered EF (HFrecEF): current EF &gt;40% but previous EF ≤40%; and (3) HF with reduced EF (HFrEF): current EF ≤40%. Results: HF was confirmed in 1652 cases (94.3%). Among these, 321 had HFpEF (19.4%; 95%CI 17.6-21.4); 268 had HFrecEF (16.2%; 95%CI 14.5-18.1); and 992 had HFrEF (60.0%; 95%CI 57.7-62.4); the remaining 71 cases (4.3%) had HF due to special causes. In comparison, the proportion of HFpEF on the basis of ICD codes and last EF without further adjudication would have been 39.0%. Patient characteristics are summarized in Table 1. After 2 years of follow up, age- and gender- adjusted mortality was 10.2% in HFrEF, 8.6% in HFpEF, and 4.4% in HFrecEF patients (stratified log-rank P=0.005), Fig. 1 . Conclusions: The proportion of clinically verified HFpEF is considerably lower compared to estimates from administrative data. Many patients with preserved EF actually represent HFrecEF, which has a more favorable prognosis.
Recognizing the Limitations of Cancer Overdiagnosis Studies: A First Step Towards Overcoming Them
Authors: R. Etzioni, R. Gulati
Journal: JNCI Journal of the National Cancer Institute (2015)

Numerous studies have attempted to quantify the number of breast cancers that would never have been diagnosed in the absence of screening. Unfortunately, results are highly variable across studies and there is considerable disagreement about both the frequency of overdiagnosis and the validity of different methodologic approaches. In this Commentary, we review limitations of the two major approaches used in existing studies. Studies that use excess incidence as a proxy for overdiagnosis require a valid estimate of incidence in the absence of screening and sufficient follow-up to ensure the excess excludes relevant (ie, nonoverdiagnosed) cancers detected early. The requirement of sufficient follow-up applies to both population studies and clinical trials, but only certain clinical trial designs have the potential to yield unbiased results. Studies that model disease natural history to infer overdiagnosis must, in addition, examine whether their models produce valid estimates in the presence of nonprogressive cases. In this setting, limited follow-up could lead to a lack of identifiability of the parameters needed to accurately infer overdiagnosis. In a polarized research community, the excess incidence and modeling approaches are generally viewed as competitors, but we argue that they are complementary, with models being more complex but having greater potential to inform about disease natural history and the outcomes of candidate screening policies. Rather than arguing why one approach should be preferred to another, investigators should focus on developing studies that generate reliable estimates of overdiagnosis. Recognizing that both approaches have limitations, which existing studies rarely overcome, is a first step towards reconciling methodologic perspectives and achieving consensus about the real magnitude of the overdiagnosis problem.
M10-01: Molecular pathogenesis of lung cancer with translation to the clinic
Authors: John D. Minna, Luc Girard, Mitsuo Sato, Michael Peyton, Woochang Lee, David Shames, Sofia Honorio, Yang Xie, Xian-Jin Xie, David Lam, Will Lockwood, Wan Lam, Yuzhuo Wang, Stephen Lam, Edward Kim, Jonathan Pollack, Rachel Greer, Robin Frink, James Sullivan, Boning Gao, Monica Spinola, Ignacio Wistuba, Kevin Coombes, John Heymach, Meera Nanjundan, Li Mao, Christopher Amos, Bingliang Fang, Jack A. Roth, Alex Pertsemlidis, Chaitanya Nirodi, Michael Story, Harold Garner, Michael White, Jef De Brabander, Patrick Harran, Xiaodong Wang, Yangsik Jeong, David Mangelsdorf, J Michael DiMaio, Joan Schiller, Jerry Shay, Adi F. Gazdar
Journal: Journal of Thoracic Oncology (2007)
Vocal communication is multi-sensorimotor coordination within and between individuals
Authors: Daniel Y. Takahashi, Asif A. Ghazanfar
Journal: Behavioral and Brain Sciences (2014)

Abstract Speech is an exquisitely coordinated interaction among effectors both within and between individuals. No account of human communication evolution that ignores its foundational multisensory characteristics and cooperative nature will be satisfactory. Here, we describe two additional capacities – rhythmic audiovisual speech and cooperative communication – and suggest that they may utilize the very same or similar circuits as those proposed for vocal learning.
Personal paper: Late onset genetic disease: where ignorance is bliss, is it folly to inform relatives?
Authors: J T Wilcke
Journal: BMJ (1998)

One aspect of the rapid advances in molecular genetics is the capacity to identify genetic predispositions in a particular individual, where previously we made risk assessments based on aggregate or population observations. 1 2

Specific genetic data on one person unavoidably involve the family. They reveal information not only about the person examined but about their relatives and future children, who may be sick or carriers of the disease or trait. The proband, the family, and the genetic counsellor are faced with the problem of communicating news of the high risk for a genetic disease to healthy (asymptomatic) family members. They are also faced with making a moral choice between the right of family members to be privy to this information and their right to “blissful ignorance.”

#### Summary points

Most genetic counsellors believe that family members have a moral obligation to share genetic information with each other.3 Many counsellors also believe that an uninvited approach to relatives at risk for a genetic disease is ethically questionable, irrespective of the disease. The Danish Ethics Council recently stated that “no unsolicited approach may be made by the health authorities in the case of an examination that may show any hereditary disease in the family. This should also be the case in situations where it can …
Mutational dynamics between primary and relapse neuroblastomas
Authors: Alexander Schramm, Johannes Köster, Yassen Assenov, Kristina Althoff, Martin Peifer, Ellen Mahlow, Andrea Odersky, Daniela Beisser, Corinna Ernst, Anton G Henssen, Harald Stephan, Christopher Schröder, Lukas Heukamp, Anne Engesser, Yvonne Kahlert, Jessica Theissen, Barbara Hero, Frederik Roels, Janine Altmüller, Peter Nürnberg, Kathy Astrahantseff, Christian Gloeckner, Katleen De Preter, Christoph Plass, Sangkyun Lee, Holger N Lode, Kai-Oliver Henrich, Moritz Gartlgruber, Frank Speleman, Peter Schmezer, Frank Westermann, Sven Rahmann, Matthias Fischer, Angelika Eggert, Johannes H Schulte
Journal: Nature Genetics (2015)
Risks of Thrombosis and Rehemorrhage During Early Management of Intracranial Hemorrhage in Patients With Mechanical Heart Valves
Authors: Alexander C. Flint, Ramesh Lingamneni, Vivek A. Rao, Sheila L. Chan, Xiushui Ren, Jasmeen Pombra, J. Claude Hemphill, Robert O. Bonow
Journal: Journal of the American College of Cardiology (2015)
Targeting KIT on innate immune cells enhances the antitumor activity of checkpoint inhibitors in vivo
Authors: Richard Gedrich, Scott Seibel, Theresa LaVallee, Joseph Paul Eder
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Mast cell infiltrates are associated with tumors, though their role in the tumor microenvironment remains unclear. Mast cells express high levels of KIT throughout differentiation and as mature cells. Mast cells in tumors have been shown to release proinflammatory cytokines and
Molecular profiling of small cell bladder cancer.
Authors: Jue Wang, David Arguello, Zoran Gatalica, Sandeep K. Reddy
Journal: Journal of Clinical Oncology (2015)

338 Background: Small cell bladder cancer (SCBC), a malignancy indistinguishable from small cell lung cancer (SCLC), is a rare and aggressive subtype of bladder cancer. Response to chemotherapy in SCBC is poor, yet the standard therapy remains cisplatin and etoposide. Novel therapies based on a better understanding of the underlying mechanisms of transformation are needed. The purpose of this study is to identify potential targets and therapeutic options for this disease, using multiplatform tumor profiling. Methods: In total, 19 small cell bladder cancer specimenswere tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (CISH or FISH). Results: Loss of RRM1 (22.2%, 4/18), MGMT (83.3%, 15/18), and TS (26.3%, 5/19) by IHC are associated with potential benefit to traditional chemotherapy. High expression of ERCC1, associated with resistance to platinum-based therapy, was 37.5% (3/8). MRP1, a drug pump associated with resistance to various chemotherapies, was present in 100% (5/5) of specimens. PD-L1 (0%, 0/6) was not expressed. EGFR amplification was detected in 25.0% of patients (1/4). NGS aberrations included TP53 (90.0%), cMET (20.0%, 2/10), RB1 (11.1%), FBXW7 (10%, 1/10), PTEN (10%, 1/10). Sanger sequencing also detected KRAS (100%, 1/1) and PIK3CA (33.3%, 1/3) mutations. Conclusions: Multiplatform tumor profiling identified biomarkers which may clarify treatment dilemmas with this rare cancer. MRP1 overexpression and TP53 loss help explain this cancer’s resistance to traditional chemotherapy and its aggressive course. This approach identified potential therapies, some of which are not typically considered, like temozolomide. Immunotherapy may not be as beneficial in SCBC based on absent PD-L1 expression. NGS and Sanger sequencing identified cell surface receptors and downstream molecules that could be candidates for therapeutic strategies.