tbuckley/cabot-search huggingface dataset:
TEMOZOLOMIDE FOR RECURRENT INTRACRANIAL EPENDYMOMA OF THE ADULT: PATTERNS OF RESPONSE, SURVIVAL AND CORRELATIONS WITH MGMT PROMOTER METHYLATION
Authors: R. Soffietti, C. Bosa, L. Bertero, E. Trevisan, P. Cassoni, I. Morra, R. Ruda
Journal: Neuro-Oncology (2014)

BACKGROUND: A variety of agents have been investigated with modest results in recurrent grade II and III ependymomas failing surgery and/or radiotherapy. Few data are available on the role of temozolomide (TMZ). We investigated patterns of response, outcome and correlations with MGMT promoter methylation in a cohort of patients with recurrent ependymomas of the adult receiving temozolomide as salvage therapy. METHODS: We retrospectively studied all patients aged ≥18 years with recurrent intracranial ependymoma, who received as part of their treatment standard temozolomide between 1999 and 2011. Clinical information were retrieved from the database and follow-up visits, while MRI images were reviewd by an investigator blind to patients' outcome. Response to TMZ on MRI was evaluated according to Macdonald Criteria. An analysis of MGMT gene promoter methylation by PCR was performed. RESULTS: We found 18 evaluable patients of whom 12 were males and 6 females, and 10 (56%) were of grade III and 8 (44%) of grade II. Tumor location at initial surgery was supratentorial in 11 (61%) patients and infratentorial in 7 (39%), and type of progression before TMZ was local in 10 (56%), local and spinal in 6 (33%) and spinal alone in 2 (11%). Median age was 42 years (18-61) and median KPS 70 (60-90). Previous treatments consisted of radiotherapy (either adjuvant or at relapse) in 17/18 (94%) patients, and chemotherapy (cisplatin + VP16, PCV, BCNU) in 6/18 (33%). A median of 8 cycles of TMZ (1-24) were administered. Best response to TMZ was as follows: CR 1/18 (5%) and PR 3/18 (17%), with an overall RR of 22%; SD 7/18 (39%) and PD 7/18 (39%). Maximum reponse in 3 out of 4 patients was observed after 10, 14 and 15 cycles, respectively. All 4 responding patients were chemotherapy-naive. Responses occurred in both anaplastic (2) and low grade (2) tumors. Median PFS was 9 months (1 month-13 years), while PFS 6 and 12 were 72% and 39%, respectively. Median OS was 31 months (3 months-14 years), and 4/18 (22%) patients are alive. MGMT analysis was available in 10 patients, of whom 6 were unmethylated and 4 methylated. There were no correlations between MGMT methylation and response to TMZ or survival. CONCLUSIONS: Temozolomide has activity in recurrent ependymomas, regardless of tumor grade. Responses are often delayed and prevail in chemo-naive patients. MGMT promoter methylation does not influence neither response nor survival. SECONDARY CATEGORY: n/a.
Membrane-bound and soluble IL-15/IL-15Rα complexes display differential signaling and functions on human hematopoietic progenitors
Authors: Julien Giron-Michel, Massimo Giuliani, Manuela Fogli, Danièle Brouty-Boyé, Silvano Ferrini, Florence Baychelier, Pierre Eid, Caroline Lebousse-Kerdilès, Deniz Durali, Roberto Biassoni, Bernard Charpentier, Aimé Vasquez, Salem Chouaib, Anne Caignard, Lorenzo Moretta, Bruno Azzarone
Journal: Blood (2005)
Circadian dynamics of tumor necrosis factor alpha (cachectin) lethality.
Authors: W J Hrushesky, T Langevin, Y J Kim, P A Wood
Journal: The Journal of Experimental Medicine (1994)

Recombinant human tumor necrosis factor-alpha (TNF-alpha) has demonstrable antitumor activity in transplantable murine tumor models and patients with cancer but is highly toxic to both animals and human beings. The narrow therapeutic index of TNF-alpha has limited its anticancer utility. Toxicity associated with many standard anticancer drugs is highly dependent upon the circadian timing of their administration. The effect of time of day of TNF-alpha administration on lethal toxicity was examined in 238 BALB/c female mice in two studies. Each mouse received a single intravenous injection of human TNF-alpha at one of six equispaced times within the first contiguous 24-h cycle. The probability of dying across all times of day of TNF-alpha treatment was not equal (p < 0.01) and varied up to ninefold. Significant time of day dependence of TNF-alpha toxicity was present over a full order of magnitude of TNF-alpha dose. The frequency of TNF-alpha-induced lethality was greatest and the time to death was most brief when TNF-alpha was administered just before awakening. The survival probability was highest when TNF-alpha was administered in the second half of the daily activity span corresponding roughly to late afternoon and evening hours for human beings. The optimization of TNF-alpha administration timing is a strategy that warrants further investigation for improving the toxic/therapeutic ratio of this important cytokine. From a more fundamental perspective, these data may be essential for achieving a fuller understanding of TNF-alpha in vivo biology.
Lessons from an Aggressive Cancer: Evolutionary Dynamics in Esophageal Carcinoma
Authors: Christoph A. Klein, Nikolas H. Stoecklein
Journal: Cancer Research (2009)

Abstract Rapid progression to metastatic disease and an intrinsic resistance to any type of systemic therapy are hallmarks of aggressive solid cancers. The molecular basis for this phenotype is not clear. A detailed study of the somatic progression from local to early systemic esophageal cancer revealed rapid diversification of cancer cells isolated from various sites, but also evidence for early clonal expansion. These findings have implications for diagnostic pathology and therapeutic decision making. [Cancer Res 2009;69(13):5285–8]
Concussion tests: clarifying potential confusion regarding sideline assessment and cognitive testing
Authors: Gavin A Davis, Michael Makdissi
Journal: British Journal of Sports Medicine (2012)

The management of concussion has evolved significantly over the past decade, and more recently has received significant media attention, particularly as it relates to professional football codes. Many of the concussion guidelines published 30 years ago were predominantly opinion-based, and favoured mandated periods of abstinence from sport, without consideration of individual athlete recovery times. As the science of concussion has developed, significant new data have enabled the formulation of evidence-based guidelines for the management of concussion in sport, culminating in the guidelines published after each International Symposium on Concussion in Sport meeting in Vienna (2001), Prague (2004) and Zurich (2008).1 Current guidelines focus on clinical assessment of recovery to allow graded return to sport. In the absence of a single gold standard direct measure of recovery, combined clinical measures are used (ie, symptoms, balance and cognitive function).

The paper by Price et al 2 examines the extent of practical application of these guidelines into professional football in the UK. They found that there was a …
Nuclear Factor κb Is Required for the Development of Marginal Zone B Lymphocytes
Authors: Annaiah Cariappa, Hsiou-Chi Liou, Bruce H. Horwitz, Shiv Pillai
Journal: The Journal of Experimental Medicine (2000)

Although immunoglobulin (Ig)MhiIgDlo/−CD21hi marginal zone B cells represent a significant proportion of naive peripheral splenic B lymphocytes, few of the genes that regulate their development have been identified. This subset of peripheral B cells fails to emerge in mice that lack nuclear factor (NF)-κBp50. Less drastic reductions in marginal zone B cell numbers are also seen in the spleens of recombination activating gene (Rag)-2−/− mice reconstituted with NF-κBp65−/− fetal liver cells and in c-Rel−/− mice. In contrast, steady-state levels of IgDhi splenic follicular B cells are not significantly reduced in the absence of NF-κBp50, NF-κBp65, or c-Rel. Reconstitution of B cells in Rag-2−/− mice with a mixture of p50−/−/p65−/− fetal liver cells and Rag-2−/− bone marrow cells revealed that the generation of marginal zone B cells requires the expression of NF-κB in developing B cells, as opposed to supporting cells.
Dietary fats and breast cancer risk
Authors: K.-T. Khaw
Journal: BMJ (2013)

Marine n-3 polyunsaturated fatty acids are associated with reduced breast cancer risk 

The more than 10-fold international variation in the incidence of breast cancer and changing rates of breast cancer in migrants from low to high risk countries suggest that a substantial proportion of breast cancers could be prevented through modifiable environmental factors.1 Armstrong and Doll showed a strong international correlation between national per capita fat consumption and breast cancer rates.2 This stimulated a plethora of epidemiological and laboratory studies, which culminated in the largest and most ambitious randomised trial of dietary fat reduction to prevent breast cancer, the Women’s Health Initiative (WHI).3 

However, nearly four decades after Armstrong and Doll’s publication, the role of dietary fat in breast cancer is still unclear. In the linked meta-analysis (doi:10.1136/bmj.f3706), Zheng and colleagues investigate the association between intake of fish and n-3 polyunsaturated fatty acids (n-3 PUFAs) and the risk of breast cancer.4 Associations between dietary total or saturated fat and breast cancer have been inconsistent in prospective studies.5 6 WHI, which reduced total fat intake by 9% rather than the target 14%, reported a relative risk of 0.91 (95% confidence interval …
Micro-NMR for Rapid Molecular Analysis of Human Tumor Samples
Authors: Jered B. Haun, Cesar M. Castro, Rui Wang, Vanessa M. Peterson, Brett S. Marinelli, Hakho Lee, Ralph Weissleder
Journal: Science Translational Medicine (2011)

A portable micro-NMR device enables rapid molecular diagnosis from scarce cancer cells in fine-needle aspirates from human tumors.
Hepatitis-associated-antigen-positive hepatitis in a tuberculosis unit.
Authors: G R Fitzgerald, H Grimes, M Reynolds, H Hitchcock, C F McCarthy
Journal: Gut (1975)

An outbreak of hepatitis-associated-antigen-(HB Ag)-positive hepatitis in a hospital unit for the care of male patients with pulmonary tuberculosis is described. Sixty-four patients were studied of whom 37 were HB Ag positive. Hepatitis developed in at least 20 and was icteric in 11. The illness was mild, without fatality due to hepatitis and persistent jaundice did not occur. A carrier state developed in 15 of 24 HB Ag-positive patients followed up for more than six months and was unrelated to the presence or absence of initial hepatitis. Spread of HB Ag to domestic and medical staff occurred and following the discharge of the patients, household contacts became positive. Five, all wives of patients, developed jaundice. Faeces and sputum were HB Ag negative in seropositive cases. The origin of the outbreak remains undetected. The probability of non-parenteral transmission of HB Ag in this outbreak is discussed. Closure of the unit, isolation of HB Ag-positive cases with separate toilet and kitchen facilities, and discharge of patients when their respiratory condition allowed, resulted in prevention of further spread and eventually all patients were discharged from the unit.
Clinical Uses of Insulin-like Growth Factor I
Authors: C A Bondy, L E Underwood, D R Clemmons, H P Guler, M A Bach, M Skarulis
Journal: Annals of Internal Medicine (1994)

Insulin-like growth factor I (IGF-I) has acute insulin-like metabolic effects and long-term anabolic actions. The therapeutic potential of recombinant human IGF-I treatment is being investigated in various growth hormone-resistant and insulin-resistant disorders. Recent studies have shown that IGF-I may substitute for growth hormone in promoting linear growth in children with growth hormone insensitivity. The anabolic, protein-sparing action of IGF-I is being evaluated as a potential therapy for adults with catabolic diseases. Patients with insulin-dependent diabetes mellitus have reduced endogenous IGF-I production, and studies are in progress to determine whether treatment with IGF-I in addition to insulin may improve their metabolic/anabolic status. Insulin-like growth factor I treatment may reduce glucose and triglyceride levels in adults with non–insulin-dependent diabetes mellitus and in some patients with extreme insulin resistance. Further studies are needed to evaluate the efficacy and safety of IGF-I treatment in these and other conditions and to provide a better understanding of this hormone's normal physiologic role(s) and complex relations with growth hormone and insulin.
BAL fluid LDH activity and LDH isoenzyme pattern in lipoid pneumonia caused by an intravenous injection of lamp oil
Authors: M Drent, NA Cobben, RF Henderson, JA Jacobs, EF Wouters, MP van Dieijen-Visser
Journal: European Respiratory Journal (1996)

A 30 year old man developed lipoid pneumonia after an injection of lamp oil. In addition to "foamy" alveolar macrophages, bronchoalveolar lavage (BAL) fluid analysis showed an increased number of neutrophils. Moreover, lactate dehydrogenase (LDH) and alkaline phosphatase activities were elevated. The increase seen in LDH activity both in serum and BAL fluid was accompanied by shifts in the isoenzyme pattern in similar directions for both fluids. These findings suggest a pulmonary source for the temporary serum as well as BAL fluid LDH increase. This case indicates the usefulness of bronchoalveolar lavage fluid analysis as a probe to detect pulmonary injury caused by a pneumotoxicant and, probably, to monitor recovery or deterioration.
Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study
Authors: Sudhin Thayyil, Neil J Sebire, Lyn S Chitty, Angie Wade, WK Chong, Oystein Olsen, Roxana S Gunny, Amaka C Offiah, Catherine M Owens, Dawn E Saunders, Rosemary J Scott, Rod Jones, Wendy Norman, Shea Addison, Alan Bainbridge, Ernest B Cady, Enrico De Vita, Nicola J Robertson, Andrew M Taylor
Journal: The Lancet (2013)
Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro.
Authors: C N Serhan, K A Sheppard
Journal: Journal of Clinical Investigation (1990)

Human neutrophils from peripheral blood may physically interact with platelets in several settings including hemostasis, inflammation, and a variety of vascular disorders. A role for lipoxygenase (LO)-derived products has been implicated in each of these events; therefore, we investigated the formation of lipoxins during coincubation of human neutrophils and platelets. Simultaneous addition of FMLP and thrombin to coincubations of these cells led to formation of both lipoxin A4 and lipoxin B4, which were monitored by reversed-phase high pressure liquid chromatography. Neither stimulus nor cell type alone induced the formation of these products. When leukotriene A4 (LTA4), a candidate for the transmitting signal, was added to platelets, lipoxins were formed. In cell-free 100,000 g supernatants of platelet lysates, which displayed 12-LO activity, LTA4 was also transformed to lipoxins. Platelet formation of lipoxins was inhibited by the LO inhibitor esculetin and partially sensitive to chelation of Ca2+, while neither acetylsalicylic acid nor indomethacin significantly inhibited their generation. In contrast, neutrophils did not transform LTA4 to lipoxins. Cell-free 100,000 g supernatants of neutrophil lysates converted LTA4 to LTB4. These results indicate that neutrophil-platelet interactions can lead to the formation of lipoxins from endogenous sources and provide a role for platelet 12-LO in the formation of lipoxins from LTA4.
Challenge of Managing Cancer-Related Fatigue
Authors: Eduardo Bruera, Sriram Yennurajalingam
Journal: Journal of Clinical Oncology (2010)

Fatigue is the most common, and one of the most devastating, symptoms in patients with cancer. 1 It has been defined as "a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatments that is not proportional to recent activity and interferes with usual functions." 2 Unfortunately, there are limited treatment options to alleviate this distressing symptom. 3,4This is partly because fatigue is a complex, multidimensional syndrome.In recent years, there has been a much better understanding of the multiple mechanisms contributing to the expression of fatigue by patients with cancer.Tumor byproducts and host cytokines, direct effects of radiation therapy and chemotherapy, cachexia, deconditioning, opioids and other drugs, hypogonadism, metabolic abnormalities, chronic infection, mood abnormalities such as anxiety and depression, cognitive changes, and severe anemia are all contributors to the intensity of fatigue in patients with cancer. 4,5In a given patient, it is quite likely that multiple mechanisms coexist at any given time and that the main contributors change as the disease progresses or as patients reach the completion of therapy. 6ltimately, fatigue is a symptom, and therefore, it is perceived in the brain.For this reason, centrally acting agents have been among the most commonly tried for the management of fatigue.A recent systematic review concluded that methylphenidate was the agent for which the most research and supportive evidence exists. 4In this issue of Journal of Clinical Oncology, Moraska et al 7 publish the results of a randomized, controlled trial, comparing a long-acting methylphenidate preparation versus a placebo in patients with cancer-related fatigue (CRF).The authors found no significant differences in usual fatigue, current fatigue, or worse fatigue during the course of the 4-week study.They did observe that patients with more advanced disease showed a significant response to methylphenidate as well as a trend for patients with more severe fatigue to improve more when receiving methylphenidate than when receiving placebo.Our group recently conducted a secondary review of patients who received methylphenidate in our clinical trials.Consistent with the results reported by Moraska et al, we observed that higher levels of fatigue were predictors of response to methylphenidate in patients with advanced cancer. 8he results of this study are consistent with those of a previous randomized, controlled trial by our group using an immediate-release methylphenidate preparation. 9However, there are some differences in the findings between our study and that of Moraska et al.Our study found a dramatic improvement in fatigue in both the methylphenidate and placebo groups, with no significant difference between the two arms. 8Moraska et al 7 saw a less dramatic improvement in fatigue
Characterizing the genetic basis of bacterial phenotypes using genome-wide association studies: a new direction for bacteriology
Authors: Timothy D Read, Ruth C Massey
Journal: Genome Medicine (2014)

Abstract Genome-wide association studies (GWASs) have become an increasingly important approach for eukaryotic geneticists, facilitating the identification of hundreds of genetic polymorphisms that are responsible for inherited diseases. Despite the relative simplicity of bacterial genomes, the application of GWASs to identify polymorphisms responsible for important bacterial phenotypes has only recently been made possible through advances in genome sequencing technologies. Bacterial GWASs are now about to come of age thanks to the availability of massive datasets, and because of the potential to bridge genomics and traditional genetic approaches that is provided by improving validation strategies. A small number of pioneering GWASs in bacteria have been published in the past 2 years, examining from 75 to more than 3,000 strains. The experimental designs have been diverse, taking advantage of different processes in bacteria for generating variation. Analysis of data from bacterial GWASs can, to some extent, be performed using software developed for eukaryotic systems, but there are important differences in genome evolution that must be considered. The greatest experimental advantage of bacterial GWASs is the potential to perform downstream validation of causality and dissection of mechanism. We review the recent advances and remaining challenges in this field and propose strategies to improve the validation of bacterial GWASs.
In situ detection of enterocytic apoptosis in normal colonic mucosa and in familial adenomatous polyposis.
Authors: J Strater, K Koretz, A R Gunthert, P Moller
Journal: Gut (1995)

Physiological regeneration of colonic epithelium entails proliferation at the crypt base and cell loss by shedding or cell death. The aim of this study was to localise and assess the rate of apoptosis in normal and neoplastic colonic epithelium with respect to zones of proliferation. Familial adenomatous polyposis (FAP) was chosen as a model to study neoplastic transformation of colonic mucosa at an early stage. Apoptotic cells were detected in situ by TdT-mediated biotin-dUTP nick end labelling (TUNEL) in parallel to cells in cycle determined by Ki-67 immunohistochemistry using the monoclonal antibody MiB-1. By detection of genomic fragmentation, two different patterns of enterocytic apoptosis emerged: (a) apoptotic bodies being engulfed by adjacent epithelial cells, and (b) apoptotic cells with only subtle morphological changes being extruded into the gut lumen. The engulfment pattern was seen predominantly in the crypts of the normal colonic mucosa and, although very rare, was clearly confined to the basal proliferation compartment. The extrusion pattern was restricted to the luminal mucosal surface. Adenomas of FAP showed highly increased numbers of apoptotic bodies, which were scattered throughout the transformed mucosa. Both patterns of apoptosis were topographically intermingled although the extrusion pattern prevailed at the luminal adenoma surfaces. Whereas cells in cycle were somewhat more numerous in the upper parts of the crypts, apoptosis occurred with increased frequency at sites beneath the proliferation maximum suggesting an inverted direction of epithelial cell migration in adenomas. These results suggest two distinct routes towards enterocytic apoptosis in the colonic mucosa leading to engulfment or extrusion of dying cells. Adenomatous transformation of colon epithelium is associated with a considerable increase of the cellular turnover rate and with a severe disturbance of the microtopographical localisation of birth and death of enterocytes.
Sympathetic Control of Canine Abdominal Aorta
Authors: MÁria GEROVÁ, JÁN GERO, SVATOPLUK DOLEŽEL, IDA BLAŽKOVÁ-HuzulÁKOVÁ
Journal: Circulation Research (1973)

In anesthetized dogs the peripheral ends of the cut sympathetic chains (LG 1 -LG 2 level) were stimulated while blood pressure was held constant artificially, and the diameter of the abdominal aorta was monitored. Bilateral stimulation induced a reduction in diameter that was directly related to the stimulation frequency. Maximal diameter reduction of the aorta above the iliac bifurcation averaged 8.01±0.74% of resting diameter. The half-time of contraction (36.5±2.1 to 51.5±3.6 seconds) was indirectly related to the stimulation frequency. The effects of right or left sympathetic chain stimulation were quantitatively similar to each other (51.3±4.4% and 46.7±4.5%, respectively), and the response to bilateral stimulation (92.8±6.1%) did not differ from the calculated value for paired unilateral stimulation (100%). A significant proximo-distal gradient of response (below the branching off of the renal arteries 2.97±0.28%, at the midpoint 5.15±0.52%, and above the iliac bifurcation 8.56±0.79% of resting diameter) along the abdominal aorta was established during bilateral stimulation. Histochemical examination showed no corresponding differences in the density or the distribution of monoaminergic terminals. Dose-response relations for spiral strips taken from analogous aortic segments, however, displayed sensitivity to norepinephrine in the same order as the gradient in the in vivo experiments.