tbuckley/cabot-search huggingface dataset:
Ruxolitinib For Patients With Primary Or Secondary Myelofibrosis before Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT): A Retrospective Study Of The Société Française De Greffe De Moelle Et De Thérapie Cellulaire (SFGM-TC)
Authors: Delphine Lebon, Marie T Rubio, Faezeh Legrand, Jean-Jacques Kiladjian, Mohamad Mohty, Jean-Yves Cahn, Laure Vincent, Amandine Charbonnier, Nicole Raus, Gérard Socié, Marie Robin
Journal: Blood (2013)
Simultaneous and quantitative detection of cell signaling phosphoproteins with a multiplex kinase immunoassay
Authors: Yu-Xin Yan, Scott Van Arsdell, Christine Burns
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2828 

Cell signaling networks regulate many biological processes, such as cell proliferation, differentiation, apoptosis, immune response and gene transcription. Kinases play central roles in these diverse cellular functions. They mediate extracellular signals via phosphorylation to regulate downstream events. By monitoring phosphorylation levels, researchers can discover new signaling pathways, and establish relationships between different signal transduction networks. We have developed a new multiplex kinase immunoassay by using the SearchLight® protein array platform to simultaneously and quantitatively detect multiple activated kinases in a single sample. Mouse cell line NIH/3T3 was stimulated with 50 ng/ml of platelet derived growth factor (PDGF) and 10 μg/ml of anisomycin for 30 minutes. Cells were then lysed with RIPA buffer containing various protease inhibitors and phosphatase inhibitors. The whole cell lysate was applied to a 96-well microtiter plate containing antibody arrays directed to phospho-kinases such as phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-ERK1/2, and phospho-p38 MAPK. The assay was carried out as a typical sandwich ELISA assay until the last step. After adding streptavidin-horseradish peroxidase (SA-HRP) conjugate and a chemiluminescent substrate, the image of the protein array was captured with a CCD camera and analyzed with SearchLight Array Analyst software. Induction of phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-ERK1/2, and phospho-p38 in lysates from stimulated NIH/3T3 cells was observed. The quantitative results of multiplex kinase immunoassay have shown comparable induction trends to that shown in the Western blots for multiple phosphorylated kinases. The increased level of phospho-kinases from our assay was also similar to the level measured by single-plex ELISA results. Similar results were observed in the human monocytic leukemia cells, THP-1. The multiplex kinase assay is rapid, high-throughput, and provides a large amount of data with minimal sample volume. With the multiplex kinase assay, we could detect and monitor the cellular signal transduction activities within the same signal pathway as well as cross-pathways (cross-networks) at same time in the same sample.
Isoniazid Prophylaxis against Tuberculosis in Children
Authors: Heather J Zar, Carl Lombard
Journal: New England Journal of Medicine (2011)

To the Editor: The results of the study by Madhi et al. (July 7 issue)1 contradict those of a study in which isoniazid prophylaxis reduced mortality and the incidence of tuberculosis by 54% and 79%, respectively,2 in children infected with the human immunodeficiency virus (HIV). The authors suggest that the findings reported in the 2007 study may have resulted from the response of patients with undiagnosed pulmonary tuberculosis to isoniazid monotherapy. This suggestion may be plausible, since childhood tuberculosis is difficult to diagnose. However, all children were carefully screened for tuberculosis at enrollment, at which time 13% received a diagnosis of pulmonary tuberculosis.3 In addition, the results of our recently published long-term study indicate that pulmonary tuberculosis occurred throughout the 5-year study period and further support the efficacy of isoniazid with antiretroviral therapy for the prevention of tuberculosis.3 Differences in patient populations and methods, particularly the use of prophylaxis after exposure to an adult with tuberculosis (a practice rigorously followed by Madhi et al.), may explain the differences. However, the tracing of contacts is poorly conducted in tuberculosis programs, and this strategy is unlikely to be feasible in countries with a high prevalence of tuberculosis. We concur that for HIV-exposed children who have excellent follow-up, prophylaxis is ineffective; however, for HIV-infected symptomatic children receiving care through the public health system in developing countries, isoniazid prophylaxis can offer substantial benefit and protection against tuberculosis.2,3
Pharmacogenetics, molecular correlates and multiparameter high throughput evaluation of the response of inflamatory breast cancer cells to anticancer agents
Authors: Simendra Singh, Gamil Antoun, Bartley Adams, Gayathri Devi, Neil Spector, Kim Blackwell, Mark Dewhirst, Herbert K. Lyerly, Francis Ali-Osman
Journal: Cancer Research (2006)

4637   Inflammatory breast cancer (IBC) is an aggressive, fast-growing and highly invasive tumor, and therapeutically has the worst outcome among breast cancers. Understanding the molecular and genetic determinants of IBC therapeutic response and the identification of novel agents and strategies for treating IBC are thus urgently needed. Using two IBC cell lines, SUM 149 and SUM 159, we optimized a multi-parameter high throughput system for both cell- and target-based screening of anticancer agents against IBC cells. The target-based screen utilizes either IBC cell extracts or the purified target, while the cell-based screening simultaneously evaluates cell viability and apoptotic response in a single assay. We used the system to determine the growth kinetics and to characterize the differential sensitivity of mechanistically different anticancer agents (cisplatin, carboplatin, adriamycin, paclitaxel and vinorelbine) against the two IBC cell lines. The growth rate of SUM 159 (8.5 x 10-2.Hr-1) was approximately 2-fold that of SUM 149. At clinically relevant concentrations, both cell lines showed the highest sensitivity to cisplatin and the highest resistance to vinorelbine, when tested as single agents. Overall, the IC50 of all five agents were higher for SUM 159 than SUM 149. Because previous studies have shown that expression of GSTP1, a phase II metabolizing enzyme and regulator of cellular signaling in response to stress, is a strong determinant of therapeutic outcome and survival in breast and other cancers, we examined the expression of the GSTP1 gene by real time quantitative PCR and western blotting. Single nucleotide polymorphisms in GSTP1 and three other GST genes (GSTM1, GSTM3 and GSTT1) were determined using an allele-specific TaqMan RT-PCR assay. The results showed SUM149 to have a lower level of GSTP1 expression and to lack the Ala‡Val transition in exon 6 of the GSTP1 gene. In addition, unlike SUM159, which is homozygous for GSTM1*B, the GSTM1 gene was deleted in SUM149. These genotypes and phenotype are consistent with the higher drug sensitivity of SUM149 compared to SUM 159. The pharmacogenetic differences between the cell lines correlated with differential effects of siRNA-mediated GSTP1 suppression on their drug sensitivity. Screening of the cell lines against GSTP1 inhibitors is ongoing. Our data and the high throughput target- and cell-based screening system we describe provide a useful tool for the discovery of novel targeted agents and for rapidly evaluating novel combination therapy strategies for IBC. The system is suitable for screening engineered cells and cells with specific molecular defects and should complement in vivo systems in the rational drug discovery of novel IBC therapeutics. Supported by RO1 CA90462, P50 CA69438 and the Cancer Center Core Grant P30 CA124322.
Increased Rectal Wall Thickness May Predict Relapse in Ulcerative Colitis: A Pilot Follow-Up Study by Ultrasonographic Colonoscopy
Authors: S. Higaki, H. Nohara, Y. Saitoh, A. Akazawa, H. Yanai, T. Yoshida, K. Okita
Journal: Endoscopy (2002)

Ulcerative colitis is a chronic inflammatory bowel disease with repeated remission and relapse, although the occurrence of relapse is difficult to predict. We performed a prospective study to determine whether there is a relationship in ulcerative colitis between the inflammatory changes identified by endoscopic ultrasonography (EUS) and relapse.Participants were 23 ulcerative colitis patients who had not suffered a relapse for 1 month, with a Seo activity index less-than-or-equal 150 and Baron grade 1 at colonoscopy. The thickness of the first to the third layer of the rectal wall in these patients was measured by EUS at the start of the study. They were subsequently followed up for 1 year to record any relapses, defined as having a Seo activity index > 150 and Baron grade greater-than-or-equal 2 at colonoscopy.Relapse occurred in eight patients. The mean activity index of the relapsed patients was 187.3 (95 % confidence interval (CI), 166.4 - 208.2) at the end of the study. The thickness of the first to the third layer of the rectal wall, as evaluated by EUS at the beginning of the study, was significantly larger in the relapse group (mean 2.73 mm, 95 % CI 2.13 - 3.33 mm) than in the non-relapse group (1.79 mm; 1.56 - 1.99 mm; P = 0.0001).Catheter probe-assisted endoluminal ultrasonography may predict the occurrence of relapse of ulcerative colitis.
Noninvasive assessment of benign pigmented genital lesions using reflectance confocal microscopy
Authors: M. Agozzino, P. Buccini, C. Catricalà, R. Covello, C. Donadio, A. Ferrari, C. Franceschini, I. Sperduti, M. Ardigò
Journal: British Journal of Dermatology (2015)

Funding sources: M. Agozzino is a clinical researcher financially supported by Banca d'Italia. Conflicts of interest: none declared. Dear Editor, Pigmented genital lesions include a wide variety of disorders such as melanocytic tumours (naevi, melanoma), epithelial hyperpigmentation without prominent melanocytic hyperplasia (genital melanosis, lentigo and postinflammatory pigmentation) and nonmelanocytic lesions (vulvar intraepithelial neoplasia, seborrhoeic keratosis, angiokeratoma).1 Genital melanosis presents as single or multiple macules with variable size and colour, and arises commonly on the labia minora, or on the glans penis in male subjects. The possibility of malignant transformation of genital melanosis remains unclear. Generally, genital naevi are pigmented and show typical dermoscopic and histopathological features.2 However, atypical melanocytic naevus of the genital type (AMNGT), a small subset of melanocytic lesions, shares clinical and histological features overlapping those of melanoma.3 Melanomas of the glans penis and vulva are rare (1–7% of all melanomas), and the only curative treatment is immediate surgery after early detection.4 5 Genital melanomas are usually asymptomatic in the early stage and are discovered during routine gynaecological and dermatological examination, as well as self‐examination.
Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-Münster Group.
Authors: A Reiter, M Schrappe, R Parwaresch, G Henze, S Müller-Weihrich, S Sauter, K W Sykora, W D Ludwig, H Gadner, H Riehm
Journal: Journal of Clinical Oncology (1995)

PURPOSE To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL). PATIENTS AND METHODS From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression. RESULTS The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure. CONCLUSION This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.
Left Ventricular Performance in Ischemic Right Ventricular Dysfunction
Authors: Yoichi Goto
Journal: Circulation (2000)

To the Editor:Brookes et al 1 reported decreased left ventricular (LV) systolic performance during right ventricular (RV) ischemia in the pig and concluded that "The hemodynamic compromise seen in association with acute RV dilatation within an intact pericardium is partly attributable to impaired LV systolic performance and cannot be wholly ascribed to changes in either LV preload or compliance."They also stated that ". . .no studies to date have examined LV systolic performance in this context."However, my colleagues and I reported LV systolic and diastolic performance during ischemic RV dysfunction in the dog. 2 This study was unfortunately ignored by Brookes et al. 1 We demonstrated that ischemic RV dysfunction induced by right coronary artery (RCA) occlusion resulted in a significant leftward shift of the LV end-diastolic pressure-volume relation, which was markedly exaggerated by the presence of an intact pericardium.This finding agrees with that of Brookes et al. 1 More important, when we compared the indexes of LV systolic performance (ie, cardiac output, LV systolic pressure, peak LV dP/dt, and percent systolic shortening) during RCA occlusion with those during inferior vena caval occlusion at a matched LV end-diastolic volume, they were the same.This indicates that the primary mechanism of decreased cardiac output during RCA occlusion is caused by decreased LV preload (ie, end-diastolic volume) due to decreased LV chamber compliance rather than by decreased LV contractility.Because RCA occlusion in the dog causes isolated RV free wall ischemia, 2 our results represent a pure RV ischemia model.In contrast, because occlusion of a dominant RCA in the pig probably causes ischemia in the inferior interventricular septum, the decreased LV contractility (ie, decreased slopes of both the preloadrecruitable stroke work and end-systolic pressure-volume relation) seen in Brookes et al's study 1 may be explained by concomitant LV myocardial ischemia.Thus, the hemodynamic compromise seen in Brookes et al's study 1 is attributable to the combined mechanisms of decreased LV preload and acute LV ischemia.
Soundings: Aristotle, the NHS, and Davie's henhouse
Authors: Colin Douglas
Journal: BMJ (2005)

In the village in which I grew up there was a little band of first world war veterans already far outnumbered by the names of their old comrades on the war memorial beside the church. Once, walking slowly past the bench on which they always sat, I overheard a conversation among them about another who had died only the week before.

“D'ye remember yon time we built Davie's henhouse?” one asked. There was a thoughtful silence. Someone nodded and said, “He was an awful man for square corners,” then they all laughed.

I wondered about that, as one does at the age of 10. They might well have described my father, whom they knew, as a terrible man for square corners; and I thought then that I would probably never settle for less myself. But more recently, and in a variety of contexts, I have had cause to recall their wisdom. Need every henhouse in every village backyard have perfectly square corners?

A long time ago I presented, at what in geriatric medicine circles passes for a scientific meeting, some work that I thought was a reasonably robust piece of health service research. People seemed to like it, and questions were generally supportive, but over coffee a senior colleague sought me out to put me right about the squareness of the corners: “That's all very well so far as it goes, Colin, but where's your perfect randomised controlled trial?”

He's still waiting for it. Geriatric medicine remains uncomfortable territory for perfectionists, and health service research in the care of older people if anything more so. But the concept that I and others were working on then has since progressed, via various imperfect evaluations and still in the absence of any perfect trials, from the status of interesting idea to that of policy—in NHS Scotland at least. And people do it because it works.

Davie might not have approved, though in certain circumstances he might have benefited from our rough efforts to improve the care of older people. But Aristotle would be with us. A quote of his was pinned on the notice board of the little department where I learned my trade: “It is the mark of a civilised man, and a hallmark of his culture, that he applies no more precision to a problem than its nature permits, or its solution demands.”
Smoking by parents of asthmatic children
Authors: J. Kemm, L. Irvine, I. K Crombie, R. A Clark, P. W Slane
Journal: BMJ (1999)

Editor—Reducing exposure of asthmatic children to parental smoking is important, but without more information the paper by Irvine et al provides no foundation for evidence based practice.1 The reader can safely conclude that something made no difference but is given no useful description of what that something was. The paper supplies only two of the five elements that Windsor et al suggest as an adequate description of an intervention—namely, counselling content, theoretical framework from which methods are derived, duration of each patient contact, frequency of intervention components, and training of intervention counsellors.2 It is sad that journals which take commendable steps to ensure that the outcomes are adequately reported still do not apply similar standards to the reporting of the intervention.3

A further cause for concern is the context of the study. What was the nature of the families’ consent? If they were given adequate information it is likely that the control group was appreciably contaminated, and if they were not the ethics of the study are debatable. What previous advice and support had been given to these families? I hope we can assume that all practices in the study routinely advised all such parents of the possible connection between their smoking and their child’s asthma, in which case the additional intervention sounds marginal.

I would also question whether the intervention was in accord with best practice. The use of a research nurse unknown to the family and apparently unconnected with the patient’s practice does not use the practice-patient relationship. The use of the phrase “telling patients what to do” in the discussion raises concern about the counselling style.

Certainly we need more effective methods of helping smokers cut back or quit, and the intervention used in this study was apparently ineffective. However, this paper should not be interpreted as indicating that sensitive counselling by primary care teams of parents who smoke and have asthmatic children is not worth while.
Abstract 4963: Prognostic significance of the expression of nuclear EIF5A2 in human melanoma
Authors: Shahram Khosravi, Magdalena Martinka, Christopher J Ong
Journal: Cancer Research (2015)

Abstract Eukaryotic translation initiation factor 5A2 (EIF5A2) is an oncogene that is upregulated in several different cancers. We previously showed that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with melanoma patient survival. In this study, we used immunohistochemistry and tissue microarray (TMA) using a large number of melanocytic lesions (n = 459) to examine the expression profile of nuclear EIF5A2 in melanoma progression in addition to the correlation between nuclear EIF5A2 expression and melanoma patient survival. We found that nuclear EIF5A2 expression was significantly upregulated in primary melanomas compared with normal nevi and dysplastic nevi, as well as in metastatic melanomas compared with primary melanomas, normal nevi and dysplastic nevi. Nuclear EIF5A2 expression had a significant inverse correlation with overall and disease-specific 5-year survival of all and primary melanoma patients. Nuclear EIF5A2 expression was also significantly correlated with melanoma thickness and AJCC stages, suggesting the possible role of nuclear EIF5A2 in melanoma cell invasion. We then investigated the correlation between the expression of nuclear EIF5A2 and MMP-2 which is one of the important factors for promoting cancer cell invasion. Nuclear EIF5A2 expression and strong MMP-2 expression were directly correlated as well, and their concurrent expression was significantly associated with worse overall and disease-specific 5-year survival of all and primary melanoma patients. We also studied the correlation between nuclear and cytoplasmic EIF5A2 expression and found that they were significantly correlated, and simultaneous expression of both was significantly associated with poor overall and diseases-specific 5-year survival of all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear expression of EIF5A2 was an adverse independent prognostic factor for melanoma patients. In conclusion, we for the first time demonstrated the nuclear expression of EIF5A2 as an independent prognostic marker in melanoma and its role in melanoma progression and patient survival. As a result, nuclear EIF5A2 may have the potential to serve as a therapeutic marker for melanoma. Citation Format: Shahram Khosravi, Magdalena Martinka, Christopher J Ong. Prognostic significance of the expression of nuclear EIF5A2 in human melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4963. doi:10.1158/1538-7445.AM2015-4963
Practical Considerations in the Radionuclide Imaging of Children
Authors: D. S. Levine, H. R. Nadel
Journal: Clinical Nuclear Medicine (2008)

Although many types of diagnostic nuclear medicine studies are common to both adult and paediatric practice, certain studies are performed much more commonly for children. These include examinations of the urinary, hepatobiliary, gastrointestinal, cardiovascular and endocrine systems, together with those utilized in tumour imaging. The radiotracer biodistributions, common clinical indications, recommended imaging protocols and typical effective radiation doses are described for this range of procedures.