tbuckley/cabot-search huggingface dataset:
The role of genetic diversity in cancer
Authors: Lauren M.F. Merlo, Carlo C. Maley
Journal: Journal of Clinical Investigation (2010)

The role of genetic heterogeneity within neoplasms is increasingly recognized as important for understanding the dynamics of cancer progression, cancer stem cells, and therapeutic resistance, and there is interest in intratumoral heterogeneity measurements as potential biomarkers for risk stratification. In this issue of the JCI, Park et al. characterize this genetic diversity in carcinoma in situ and in invasive regions from 3 types of human breast cancers and lay the groundwork for translation of these measures to the clinic.
Subcutaneous Alemtuzumab in Fludarabine-Refractory Chronic Lymphocytic Leukemia: Clinical Results and Prognostic Marker Analyses From the CLL2H Study of the German Chronic Lymphocytic Leukemia Study Group
Authors: Stephan Stilgenbauer, Thorsten Zenz, Dirk Winkler, Andreas Bühler, Richard F. Schlenk, Silja Groner, Raymonde Busch, Manfred Hensel, Ulrich Dührsen, Jürgen Finke, Peter Dreger, Ulrich Jäger, Eva Lengfelder, Karin Hohloch, Ulrike Söling, Rudolf Schlag, Michael Kneba, Michael Hallek, Hartmut Döhner
Journal: Journal of Clinical Oncology (2009)

The phase II CLL2H trial evaluated safety and efficacy of subcutaneous alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). Clinical and biologic markers were evaluated for their impacts on outcome.One hundred nine patients were enrolled, and 103 received at least one dose of alemtuzumab. After dose escalation, alemtuzumab was administered subcutaneously at 30 mg three times weekly for up to 12 weeks. Response was assessed every 4 weeks during treatment and quarterly thereafter.The overall response rate was 34% (complete response, 4%; partial response, 30%). The median progression-free survival was 7.7 months, and the median overall survival (OS) was 19.1 months. Grades 3 to 4 neutropenia, thrombocytopenia, and anemia occurred in 56%, 57%, and 49% of patients, respectively. Grades 3 to 4 noncytomegalovirus and cytomegalovirus infections occurred in 29% and 8% of patients, respectively. Injection-site skin reactions were generally mild. Efficacy did not vary significantly in subgroups defined by genetic parameters (in particular, in 17p deletion, 11q deletion, mutated TP53, and unmutated VH), but efficacy was inferior in patients with increased beta2-microglobulin (beta2-MG) and thymidine kinase (TK). In multivariate analysis of clinical and biologic variables, age, performance status, beta2-MG, and TK were independent prognostic factors for OS.Subcutaneous alemtuzumab appears as effective and safe as intravenous alemtuzumab in fludarabine-refractory CLL. Subcutaneous administration should be the preferred delivery route because of its efficacy, convenience, improved adverse effect profile, and cost savings. In contrast to chemotherapy-based therapy, alemtuzumab treatment overcomes the adverse prognostic impact of VH mutation status, TP53 mutation, and genomic aberrations.
α-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity
Authors: Aaron D Gitler, Alessandra Chesi, Melissa L Geddie, Katherine E Strathearn, Shusei Hamamichi, Kathryn J Hill, Kim A Caldwell, Guy A Caldwell, Antony A Cooper, Jean-Christophe Rochet, Susan Lindquist
Journal: Nature Genetics (2009)
Abstract P4-02-08: Quantitative Characterization of 3D Vasculature Spatial Patterns Within Tumor Microenvironment of Breast Cancer Stem Cells
Authors: M Zhan, F Li, Y Zhu, J Ma, J Landua, W Wei, T Vadakkan, M Zhang, M Dickinson, M Lewis, J Rosen, S Wong
Journal: Cancer Research (2012)

Abstract The sustainment characters of cancer stem cells (CSCs) such as self-renew and differentiation to other tumor cells greatly depend on the tumor microenvironment, which is composed of many components, e.g. vasculature, extracellular matrix, epithelial cells, stromal cells, as well as nutrients and oxygen. As vasculature is an important factor for the CSC and tumor development, the understanding of their spatial patterns is essential for calibrating the CSC-microenvironment interactions in mathematical modeling. In this study, we acquired the vasculature in side tumors and normal breast tissues by using two-photon fluorescence microscopy, which enables 3D in vivo imaging. We developed an advanced vasculature segmentation approach for an objective and accurate quantification of the vasculature in 3D image volumes. The approach integrates supervoxel analysis and the orientation guided hidden Markov random field (ori-HMRF) modeling together to compensate for low quality images, e.g., low signal-to-noise ratio (SNR) and uneven background. By constructing a new feature space that combines the CIELAB color space and the coordinates space, the supervoxel analysis divides an image volume into subregions with local similar intensity and restricted regular shape, boundaries of which can delineate the vasculature boundaries accurately even in low intensity contrast regions. We further designed a set of features for the separation of blood vessel regions from the background. To make use of the context information, i.e. the continuity of vasculature, the ori-HMRF model is used to incorporate the consistency of vasculatures' orientation in order to reduce the false positives and negatives. Experimental results on image volumes from both breast cancer and normal breast tissues show that the proposed method can effectively reconstruct the vasculature structure with the CSC embedded tumor microenvironment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-08.
Association of Chromosomal Alterations with Arsenite-Induced Tumorigenicity of Human HaCaT Keratinocytes in Nude Mice
Authors: Chia-Wen Chien, Ming-Chang Chiang, I-Ching Ho, Te-Chang Lee
Journal: Environmental Health Perspectives (2004)

Inorganic arsenic is a well-documented human carcinogen. Chronic low-dose exposure to inorganic arsenic is associated with an increased incidence of a variety of cancers, including skin, lung, bladder, and liver cancer. Because genetic alterations often occur during cancer development, the objective of this study was to explore what types of genetic alterations were induced by chronic exposure of human HaCaT cells to arsenic. After 20 passages in the presence of inorganic trivalent arsenite at concentrations of 0.5 or 1 microM, HaCaT cells had higher intracellular levels of glutathione, became more resistance to arsenite, and showed an increased frequency of micronuclei. Furthermore, the previously nontumorigenic HaCaT cells became tumorigenic, as shown by subcutaneous injection into Balb/c nude mice. Cell lines derived from the tumors formed by injection of arsenite-exposed HaCaT cells into nude mice expressed higher levels of keratin 6, a proliferation marker of keratinocytes, than did parental HaCaT cells, whereas the expression of keratins 5, 8, and 10 was significantly decreased. Comparative genomic hybridization demonstrated chromosomal alterations in the 11 cell lines derived from these tumors; all 11 showed significant loss of chromosome 9q, and seven showed significant gain of chromosome 4q. The present results show that long-term exposure to low doses of arsenite transformed nontumorigenic human keratinocytes to cells that were tumorigenic in nude mice and that chromosomal alterations were observed in all cell lines established from the tumors.
Kinetic Constants of the Human Renin and Human Angiotensinogen Reaction
Authors: ERWIN HAAS, HARRY GOLDBLATT, C. Gipson Edwin, LeWis Lavera
Journal: Circulation Research (1967)

The rate of formation of angiotensin was investigated for the reaction of angiotensinase-free human renin, at various states of purity, with angiotensinogen, in pooled, angiotensinase-free human serum. The velocity constant of this reaction and the Michaelis constant of the renin-substrate complex were determined. The concentration of angiotensinogen and of endogenous renin in human serum was also determined and, on the basis of these results, a procedure was designed for the indirect assay of human renin. This was carried out under a wide range of experimental conditions, for periods of incubation ranging from 10 min to 18 hours, for various concentrations of substrate, and for renin concentrations varying from 0.000025 to 0.20 unit/ml. The absence of angiotensinase made possible the prolonged incubation (18 hours) of a minute quantity of renin with a large amount of the renin substrate. The resultant formation of large amounts of angiotensin permitted its accurate assay in the dog.
Trichophyton tonsurans Tinea Capitis
Authors: Elena Prevost
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In regard to my article in<i>JAMA</i>(242:1765, 1979) and the accompanying editorial by Andrew H. Rudolph, MD (242:1770, 1979), concerning<i>Trichophyton tonsurans</i>tinea capitis, I recently had the opportunity to review the charts of 40 children with culturally proved<i>T tonsurans</i>scalp infections. Of these, 30 (75%) were originally misdiagnosed by the primary care physician (pediatrician, family practitioner) as chronic dandruff, impetigo, and seborrhea. After various prescribed treatments (dandruff and medicated shampoos, erythromycin, and tetracycline) with little or no improvement (in one case as long as two years of chronic flaking and hair loss), a culture was finally taken, and the problem resolved with griseofulvin therapy. This finding illustrates the difficulty in diagnosing these infections. Our dermatologists have suggested that all scalp problems in children should be considered tinea capitis until culturally proved otherwise.
Lentivirus-mediated RNA interference targeting enhancer of zeste homolog 2 inhibits hepatocellular carcinoma growth through down-regulation of stathmin
Authors: Yangchao Chen, Marie C. Lin, Hong Yao, Hua Wang, Ai-Qun Zhang, Jun Yu, Chee-kin Hui, George K. Lau, Ming-liang He, Joseph Sung, Hsiang-fu Kung
Journal: Hepatology (2007)

Abstract Enhancer of zeste homolog 2 (EZH2) has been shown to be overexpressed in hepatocellular (HCC). We investigated the potential role of EZH2 in HCC tumorigenesis and examined the usefulness of RNA interference (RNAi) targeting EZH2 as a form of HCC treatment. Lentivirus-mediated RNAi was employed to knock-down EZH2 expression in human hepatoma cells to study the function of EZH2 in tumorigenesis and evaluate the treatment efficacy. Lentivirus-mediated RNAi effectively reduced EZH2 expression. Suppression of EZH2 in HCC cells significantly reduced their growth rate in vitro and markedly diminished their tumorigenicity in vivo. Moreover, in a mice model of established large-sized HCC, we showed that intratumor injection of lentiviral (Lenti)-shRNA (short hairpin RNA) or siRNA (small interfering RNA) targeting EZH2 produced significant tumor regression. To understand its molecular mechanism of action, we employed proteomic profiling technique and found that stathmin 1 is the downstream target of EZH2, as Lenti-shEZH2 treatment decreased stathmin protein expression, and ectopic overexpression of stathmin prevented Lenti-shEZH2 mediated tumor growth inhibition. Conclusion: Results from our study suggested for the first time that EZH2 plays a key role in HCC tumorigenesis, and is a novel therapeutic target for HCC. (HEPATOLOGY 2007;46:200–208.)
National Prevalence and Exposure Risk for Cockroach Allergen in U.S. Households
Authors: Richard D. Cohn, Samuel J. Arbes, Renee Jaramillo, Laura H. Reid, Darryl C. Zeldin
Journal: Environmental Health Perspectives (2005)

We characterized the prevalence of cockroach allergen exposure in a nationally representative sample of U.S. homes and assessed risk factors for elevated concentrations.We used data from the National Survey of Lead and Allergens in Housing, a population-based cross-sectional survey.Participants were residents of 831 U.S. homes in the survey.We analyzed allergen, questionnaire, and observational data of 831 U.S. homes.Cockroach allergen (Bla g 1) concentrations exceed 2.0 U/g, a level associated with allergic sensitization, in 11% of U.S. living room floors and 13% of kitchen floors. Concentrations exceed 8.0 U/g, a level associated with asthma morbidity, in 3% of living room floors and 10% of kitchen floors. Elevated concentrations were observed in high-rise apartments, urban settings, pre-1940 constructions, and households with incomes < $20,000. Odds of having concentrations > 8.0 U/g were greatest when roach problems were reported or observed and increased with the number of cockroaches observed and with indications of recent cockroach activity.Household cockroach allergen exposure is characterized in a nationally representative context. The allergen is prevalent in many settings, at levels that may contribute to allergic sensitization and asthma morbidity.Likelihood of exposure can be assessed by consideration of demographic and household determinants.
THE POSTERIOR HYPOPHYSIS
Authors: E. M. K. Geiling
Journal: JAMA (1935)

Note.  — This article and the articles in the previous issues of The Journal are part of a series published under the auspices of the Council on Pharmacy and Chemistry. Other articles will appear in succeeding issues of The Journal. When completed, this series will be published in book form .—Ed.  The primary structural elements of the posterior lobe of the hypophysis are the neuroglial cells, the pituicytes and the nerve fibers. The neuroglial cells resemble those found elsewhere in the central nervous system. In the pituitary some of them have become differentiated to form pituicytes, 1 highly branched cells that have granules in the cytoplasm. The presence and significance of nerve fibers in the posterior lobe are still an open question.  ORIGIN AND PATH OF ESCAPE OF THE SECRETION  None of these structures, with the exception perhaps of the pituicytes, are regarded as secreting elements in the ordinary sense.
Effect of <i>Helicobacter pylori</i>infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis
Authors: G Nardone, S Staibano, A Rocco, E Mezza, F P D’Armiento, L Insabato, A Coppola, G Salvatore, A Lucariello, N Figura, G De Rosa, G Budillon
Journal: Gut (1999)

Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability.To evaluate the effect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression.Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients with H pylori negative chronic gastritis, 53 with H pylori positive chronic gastritis, and 11 with gastric cancer.All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pylori infection. Atrophy was present in three of 10 patients with H pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients with H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whom H pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged.Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication of H pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability.
Effects of Anabolic-Androgenic Steroids on Muscular Strength
Authors: Janet D. Elashoff, Alan D. Jacknow, Sara G. Shain, Glenn D. Braunstein
Journal: Annals of Internal Medicine (1991)

Objective: To assess the effects of anabolic-androgenic steroids on human muscle strength. Data Sources: A MEDLINE search for the period from January 1966 to April 1990, supplemented by manual searches of previous reviews, produced 30 studies in which subjects received more than one dose of the study steroid and in which changes in muscular strength were measured. Study Selection: Of the 30 studies, 14 were not included in the detailed data summary because they did not use a placebo control, did not randomize subjects to groups, or did not make objective strength measurements, or because percent change in strength data could not be abstracted. Data Extraction: Details of study design, reporting of results, and the adequacy and correctness of statistical methods were tabulated. Percent improvement in strength for the largest muscle group studied was computed, using the difference between results for the placebo and for the steroid-treated groups. Data Synthesis: Previously trained athletes show slightly greater improvements in strength in the anabolic-androgenic steroid-treated group than in the placebo group, with a median difference of 5% across the nine studies (range, 1.2% to 18.7%). A meta-analysis of the three studies with enough information to compute effect size showed a mean difference of 1.0 standard deviations (95% Cl, 0.49 to 1.5). However, the poor overall quality of the studies in terms of design, sample size, and analysis; the lack of a dose-response effect across the narrow range of dosages tested; and the tendency for differences to be smaller in the larger studies throw these results into question. No evidence was found to support enhanced muscle strength with steroid use in eight studies in untrained normal volunteers. Conclusions: Anabolic steroids may slightly enhance muscle strength in previously trained athletes. No firm conclusion is possible concerning the efficacy of anabolic steroids in enhancing overall athletic performance. Results for the low steroid dosages studied in the published reports cannot be generalized to steroid-using athletes taking megadose regimens.
Cc‐chemokine eotaxin as a marker of efficacy of specific immunotherapy in patients with intermittent IgE‐mediated allergic rhinoconjunctivitis
Authors: K. Jahnz‐Różyk, T. Targowski, E. Głodzinska‐Wyszogrodzka, T. Płusa
Journal: Allergy (2003)

Background: Allergen‐specific immunotherapy (SIT) is believed to be a valuable remedy in several allergic diseases; however, an accurate immunological marker of the efficacy of this treatment method has not been found yet. Cc‐chemokine eotaxin, owing to its selective action on eosinophils, seems to play an important role in the pathophysiology of allergic response. The purpose of this study was to assess the usefulness of eotaxin in monitoring of SIT efficacy in patients with IgE‐mediated allergic rhinoconjunctivitis. Methods: One hundred and twenty‐two patients with seasonal IgE‐mediated allergic rhinoconjunctivitis due to tree‐ (birch, n = 42; hazel/alder, n = 14) or grass/cereal‐ ( n = 66) pollen received allergen‐specific immunotherapy.Serum eotaxin levels were determined four times in every patient, shortly before immunotherapy (Evaluation 0), immediately after the treatment (Evaluation 1), in the height of pollen season (Evaluation 2) and at least 2 weeks after the pollen season (Evaluation 3). Serum eotaxin levels were simultaneously measured in 59 healthy people from the control group. Changes in serum eotaxin levels were assessed in the healthy and allergic groups. Clinical symptoms of IgE‐mediated rhinoconjunctivitis were evaluated and compared with serum eotaxin concentration changes. Results: Mean values of eotaxin concentrations in serum during Evaluations 0–3 did not significantly differ in the healthy subjects and the patients with IgE‐mediated rhinoconjunctivitis ( P &gt; 0.05). Moreover, no statistically significant differences in the serum eotaxin levels between the visits were observed in the patients who received immunotherapy ( P &gt; 0.05); however, immediately after immunotherapy (Evaluation 1) the mean serum level of eotaxin was lowest and closest to the serum eotaxin concentration in the control group at the same visit. No significant correlation between the mean value of the serum eotaxin level in the height of pollen season ( r = −0.12, P &gt; 0.05) or mean changes of the eotaxin levels between Evaluations 2 and 1 ( r = −0.03, P &gt; 0.05), on the one hand, and the cumulative score of symptoms and drug, on the other, were found. Conclusions: The results allow to conclude that although eotaxin plays a significant role in the mechanism of antigen‐specific immunotherapy, its serum expression remains a poor marker of SIT efficacy.
Tissue eosinophilia in acute and chronic atopic dermatitis: a morphometric approach using quantitative image analysis of immunostaining
Authors: P. Kiehl, K. Falkenberg, M. Vogelbruch, A. Kapp
Journal: British Journal of Dermatology (2001)

The frequency and amount of tissue eosinophilia in spontaneous lesions of acute and chronic atopic dermatitis (AD) are still a matter of controversy, and little is known about the distribution of eosinophilia in skin.To give a quantitative description of tissue eosinophilia in spontaneous lesions of acute and chronic AD based on morphometric data.Thirty-one lesional skin biopsies of AD were evaluated using our recently described method for the quantitative assessment of eosinophilic granule protein (EGP) deposition by image analysis of immunostaining using the antibodies EG1, EG2, MBP, EPO and neutrophil elastase (NE). The frequency, amount and distribution of protein deposition including extracellular EGP deposition as an indicator of complete activation and degranulation of eosinophils were determined. Eosinophil count was performed in addition. Histopathological parameters of acute dermatitis (spongiosis) and chronic dermatitis (epidermal hyperplasia) were scored to look for a correlation with tissue eosinophilia.Tissue eosinophilia was found in nearly all biopsies (30 of 31). The most protein was detected by EG2, followed by EG1, MBP and EPO, with very small amounts of NE. A superficial tissue distribution of eosinophilia was found, with < 10% of total EGP deposition below a depth of 1.39 mm from the epidermis. Eosinophils were involved in acute, spongiotic dermatitis, but more tissue eosinophilia including EGP deposition was detected in lesions with pronounced epidermal hyperplasia than in biopsies without.These data provide further evidence for the involvement of activated eosinophils in acute and chronic AD by a new quantitative in situ approach. Pronounced tissue eosinophilia, especially EGP deposition as the result of complete activation of eosinophils, is found in chronic AD and may be involved in the development or maintenance of chronicity.