tbuckley/cabot-search huggingface dataset:
Targeting the SMO oncogene by miR-326 inhibits glioma biological behaviors and stemness
Authors: Wenzhong Du, Xing Liu, Lingchao Chen, Zhijin Dou, Xuhui Lei, Liang Chang, Jinquan Cai, Yuqiong Cui, Dongbo Yang, Ying Sun, Yongli Li, Chuanlu Jiang
Journal: Neuro-Oncology (2014)

Few studies have associated microRNAs (miRNAs) with the hedgehog (Hh) pathway. Here, we investigated whether targeting smoothened (SMO) with miR-326 would affect glioma biological behavior and stemness. To investigate the expression of SMO and miR-326 in glioma specimens and cell lines, we utilized quantitative real-time (qRT)-PCR, Western blot, immunohistochemistry, and fluorescence in situ hybridization. The luciferase reporter assay was used to verify the relationship between SMO and miR-326. We performed cell counting kit-8, transwell, and flow cytometric assays using annexin-V labeling to detect changes after transfection with siRNA against SMO or miR-326. qRT-PCR assays, neurosphere formation, and immunofluorescence were utilized to detect the modification of self-renewal and stemness in U251tumor stem cells. A U251-implanted intracranial model was used to study the effect of miR-326 on tumor volume and SMO suppression efficacy. SMO was upregulated in gliomas and was associated with tumor grade and survival period. SMO inhibition suppressed the biological behaviors of glioma cells. SMO expression was inversely correlated with miR-326 and was identified as a novel direct target of miR-326. miR-326 overexpression not only repressed SMO and downstream genes but also decreased the activity of the Hh pathway. Moreover, miR-326 overexpression decreased self-renewal and stemness and partially prompted differentiation in U251 tumor stem cells. In turn, the inhibition of Hh partially elevated miR-326 expression. Intracranial tumorigenicity induced by the transfection of miR-326 was reduced and was partially mediated by the decreased SMO expression. This work suggests a possible molecular mechanism of the miR- 326/SMO axis, which can be a potential alternative therapeutic pathway for gliomas.
Effect of Glucagon-Like Peptide 1 (7-36 Amide) on Insulin-Mediated Glucose Uptake in Patients With Type 1 Diabetes
Authors: Graydon S. Meneilly, Christopher H.S. McIntosh, Raymond A. Pederson, Joel F. Habener, Mario R.W. Ehlers, Josephine M. Egan, Dariush Elahi
Journal: Diabetes Care (2003)

To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type 1 diabetic patients.We used the hyperinsulinemic-euglycemic clamp (480 pmol. m(-2) x min(-1)) in paired randomized studies of six women and five men with type 1 diabetes. In the course of one of the paired studies, the subjects also received GLP-1 at a dose of 1.5 pmol. kg(-1) x min(-1). The patients were 41 +/- 3 years old with a BMI of 25 +/- 1 kg/m(2). The mean duration of diabetes was 23 +/- 3 years.Plasma glucose was allowed to fall from a fasting level of approximately 11 mmol/l to 5.3 mmol/l in each study and thereafter was held stable at that level. Plasma insulin levels during both studies were approximately 900 pmol/l. Plasma C-peptide levels did not change during the studies. In the GLP-1 study, plasma total GLP-1 levels were elevated from the fasting level of 31 +/- 3 to 150 +/- 17 pmol/l. Plasma glucagon levels fell from the fasting levels of approximately 14 pmol/l to 9 pmol/l during both paired studies. Hepatic glucose production was suppressed during the glucose clamps in all studies. Glucose uptake was not different between the two studies ( approximately 40 micromol. kg(-1) x min(-1)).GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients.
Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose Chemotherapy
Authors: Daniela Cardinale, Maria T. Sandri, Alessandro Colombo, Nicola Colombo, Marina Boeri, Giuseppina Lamantia, Maurizio Civelli, Fedro Peccatori, Giovanni Martinelli, Cesare Fiorentini, Carlo M. Cipolla
Journal: Circulation (2004)

In patients with aggressive malignancies who are undergoing high-dose chemotherapy, even minimal elevation of troponin I (TnI) is associated with late left ventricular dysfunction. The time course of the subclinical myocardial damage and its impact on the clinical outcome have never been investigated previously.In 703 cancer patients, we measured TnI soon after chemotherapy (early TnI) and 1 month later (late TnI). Troponin was considered positive for values > or =0.08 ng/mL. Clinical and left ventricular ejection fraction evaluation (echocardiography) were performed before chemotherapy, 1, 3, 6, and 12 months after the end of the treatment, and again every 6 months afterward. Three different TnI patterns were identified, and patients were grouped accordingly. In 495 patients, both early and late TnI values were <0.08 ng/mL (TnI-/- group); in 145, there was only an early increase (TnI+/- group); and in 63 patients, both values increased (TnI+/+ group). In the TnI-/- group, no significant reduction in ejection fraction was observed during the follow-up, and there was a very low incidence of cardiac events (1%). In contrast, a greater incidence of cardiac events occurred in TnI-positive patients, particularly in the TnI(+/+) group (84% versus 37% in the TnI+/- group; P<0.001).TnI release pattern after high-dose chemotherapy identifies patients at different risks of cardiac events in the 3 years thereafter. This stratification allows us to differentiate the monitoring program and to plan, in selected patients, preventive strategies aimed at improving clinical outcome.
NUTRITIONAL DISORDERS OF THE SKIN AMONG PRISONERS OF WAR IN THE FAR EAST
Authors: R. D. G. Ph. SIMONS
Journal: British Journal of Dermatology (1949)

Journal Article NUTRITIONAL DISORDERS OF THE SKIN AMONG PRISONERS OF WAR IN THE FAR EAST Get access R. D. G. Ph. SIMONS R. D. G. Ph. SIMONS Consulting Dermatologist, Civilian Hospital, Amsterdam; Lecturer, University of Leiden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 61, Issue 6, 1 June 1949, Pages 210–215, https://doi.org/10.1111/j.1365-2133.1949.tb11086.x Published: 01 June 1949
Autophagy in Multiple Myeloma: What Makes You Stronger Can Also Kill You
Authors: Richard G. Carroll, Seamus J. Martin
Journal: Cancer Cell (2013)

Autophagy, a process for recycling cellular constituents, is normally associated with cell survival and is thought to be beneficial for tumor maintenance. However, in this issue of Cancer Cell, Lamy and colleagues report that multiple myeloma utilizes caspase-10 to restrain autophagy and undergoes autophagic cell death upon its removal or inhibition.
T<scp>HE</scp>R<scp>OLE OF</scp>V<scp>ITAMIN</scp>A<scp>IN</scp>M<scp>AMMALIAN</scp>R<scp>EPRODUCTION AND</scp>E<scp>MBRYONIC</scp>D<scp>EVELOPMENT</scp>
Authors: Margaret Clagett-Dame, Hector F. DeLuca
Journal: Annual Review of Nutrition (2002)

▪ Abstract Since the late 1980s, there has been an explosion of information on the molecular mechanisms and functions of vitamin A. This review focuses on the essential role of vitamin A in female reproduction and embryonic development and the metabolism of vitamin A (retinol) that results in these functions. Evidence strongly supports that in situ–generated all-trans retinoic acid (atRA) is the functional form of vitamin A in female reproduction and embryonic development. This is supported by the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency with atRA, the block in embryonic development that occurs in retinaldehyde dehydrogenase type 2 null mutant mice, and the essential roles of the retinoic acid receptors, at least in embryogenesis. Early studies of embryos from marginally vitamin A–deficient (VAD) pregnant rats revealed a collection of defects called the vitamin A–deficiency syndrome. The manipulation of all-trans retinoic acid (atRA) levels in the diet of VAD female rats undergoing a reproduction cycle has proved to be an important new tool in deciphering the points of atRA function in early embryos and has provided a means to generate large numbers of embryos at later stages of development with the vitamin A–deficiency syndrome. The essentiality of the retinoid receptors in mediating the activity of atRA is exemplified by the many compound null mutant embryos that now recapitulate both the original vitamin A–deficiency syndrome and exhibit a host of new defects, many of which can also be observed in the VAD-atRA-supported rat embryo model and in retinaldehyde dehydrogenase type 2 (RALDH2) mutant mice. A major task for the future is to elucidate the atRA-dependent pathways that are normally operational in vitamin A–sufficient animals and that are perturbed in deficiency, thus leading to the characteristic VAD phenotypes described above.
How much inhaled steroid is sufficient? Assessing the relationship between adherence rate to beclomethasone dipropionate and the level of asthma control
Authors: Paulo Camargos, Nulma Jentzsch
Journal: European Respiratory Journal (2011)

Aims:  To verify the relationship between adherence rate to beclomethasone diproprionate (BDP) and the level of asthma control.   Methods:  In this prospective cohort study, 102 randomly selected subjects with persistent asthma, aged 4-14 years, were treated according to GINA recommendations and followed for one year. Adherence rate to BDP was measured through Doser CT® (Medtrack Products, USA), during each of the three follow-up visits taking place in the 4th, 8th and 12th month. Based on modified GINA categories, the level of asthma control was classified as either controlled or uncontrolled.   Results:  Mild (36.2%) and moderate (56.9%) predominate over severe persistent asthma. The median adherence rate was higher in patients with controlled asthma during follow-up, but went down from 54.0% in the 4th month to 47.0% in the 12th month (p=0.038). Conversely, among patients with uncontrolled asthma, the median adherence rate reduced from 43.8% (4th month) to 31.2% (12th month, p=0.001). Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all three visits (p-values ≤ 0.005).   Conclusion:  In this study, level of asthma control was directly proportional to adherence rate. However, our results suggest that to gain control over mild and moderate persistent asthma, an optimal BDP adherence rate to currently recommended therapeutic regimens seems to be unnecessary.  Paulo Camargos is supported by FAPEMIG- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais, Brazil (Grant PPM-00230-10).
Vascular Endothelial Growth Factor Expression is Up-Regulated by EWS-ETS Oncoproteins and Sp1 and May Represent an Independent Predictor of Survival in Ewing’s Sarcoma
Authors: Bruno Fuchs, Carrie Y. Inwards, Ralf Janknecht
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Tumor markers ideally allow monitoring and prediction of disease progression. In Ewing’s sarcoma, a devastating childhood cancer, only a few reliable prognostic markers have been identified. To this end, we analyzed the expression of four tumor-promoting proteins, cyclin D1, HER2/Neu, Mdm2, and vascular endothelial growth factor (VEGF), in Ewing’s sarcoma. Experimental Design and Results: Thirty-one tissue samples from patients with Ewing’s sarcoma were stained with antibodies against cyclin D1, HER2/Neu, Mdm2, or VEGF. Whereas no significant expression of HER2/Neu and Mdm2 was detected, positive cyclin D1 and VEGF staining was observed in 42% and 55% of all tumors, respectively. Importantly, VEGF expression was found to be an independent negative predictor of survival in Ewing’s sarcoma patients, whereas cyclin D1 expression did not correlate with survival in these patients. Consistently, the Ewing’s sarcoma-specific EWS-ETS oncoproteins were capable of activating both the cyclin D1 and VEGF promoters in transient transfections of tissue culture cells. Furthermore, this activation was enhanced by coexpression of the Sp1 transcription factor. Using a mammalian two-hybrid system, some evidence was obtained that this may involve a physical interaction between EWS-ETS and Sp1 proteins. Conclusions: Our data reveal that VEGF may serve as a prognostic marker in Ewing’s sarcoma patients and provide a molecular mechanism by which VEGF and cyclin D1 expression is up-regulated in approximately half of all Ewing’s sarcomas.
THE RESPIRATION MECHANISM OF PNEUMOCOCCUS. III
Authors: M. G. Sevag, Lore Maiweg
Journal: The Journal of Experimental Medicine (1934)

From an examination of Tables I to III, and Figs. 1 to 4 and the consideration of various observations, the following facts are evident. A virulent pneumococcus on being transformed into its-avirulent form consumes many times more oxygen than the parent organism; but this gain of activity is a temporary property. After a time it degenerates into a form which consumes very much less oxygen than either the virulent or the recently derived avirulent form. In a comparative study of the metabolic functions, and oxidation products of various virulent and avirulent pneumococci, these phenomena should receive consideration. The change that takes place in the structure of the enzyme responsible for carbohydrate biosynthesis during the shift from the virulent to the avirulent form may be associated with the changes in the enzyme structure already demonstrated in connection with these metabolic studies.
The Possible Involvement of Micro-Organisms Other Than Helicobacter pylori in the Development of Rectal MALT Lymphoma in H. Pylori-Negative Patients
Authors: H. Nakase, K. Okazaki, M. Ohana, K. Ikeda, K. Uchida, S. Uose, T. Itoh, M. Iwano, N. Watanabe, S. Yazumi, C. Kawanami, F. Inoue, T. Chiba
Journal: Endoscopy (2002)

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.
Haploinsufficiency for <i>Odc</i> Modifies Mouse Skin Tumor Susceptibility
Authors: Yongjun Guo, John L. Cleveland, Thomas G. O'Brien
Journal: Cancer Research (2005)

Abstract Numerous studies have linked overexpression of ornithine decarboxylase (Odc) gene with enhanced susceptibility to mouse skin tumorigenesis. However, there is little experimental evidence suggesting that modest reductions in Odc expression might reduce tumor susceptibility. To address this issue, here we report the use of the Odc+/− haploinsufficiency model, in which one copy of the murine Odc gene has been inactivated by a homologous recombination. Compared with Odc+/+ mice, Odc+/− mice exhibit reduced epidermal ODC enzyme activity and polyamine accumulation following treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, following chronic TPA treatment, the characteristic hyperplastic response of the epidermis was diminished in Odc+/− mice. Finally, when subjected to a two-stage initiation-promotion protocol, substantially fewer skin papillomas developed in Odc+/− mice compared with wild-type littermates. These results support the concept that differences in tissue polyamine levels, resulting from either overexpression or reductions in ODC, are important modifiers of tumor susceptibility.
Gene Expression Profiling of Breast, Prostate, and Glioma Cells following Single versus Fractionated Doses of Radiation
Authors: Mong-Hsun Tsai, John A. Cook, Gadisetti V.R. Chandramouli, William DeGraff, Hailing Yan, Shuping Zhao, C. Norman Coleman, James B. Mitchell, Eric Y. Chuang
Journal: Cancer Research (2007)

Abstract Studies were conducted to determine whether gene expression profiles following a single dose of radiation would yield equivalent profiles following fractionated radiation in different tumor cell lines. MCF7 (breast), DU145 (prostate), and SF539 (gliosarcoma) cells were exposed to a total radiation dose of 10 Gy administered as a single dose (SD) or by daily multifractions (MF) of 5 × 2 Gy. Following radiation treatment, mRNA was isolated at 1, 4, 10, and 24 h and processed for cDNA microarray analysis. To determine the influence of the tumor microenvironment on gene expression, one cell type (DU145) was evaluated growing as a solid tumor in athymic nude mice for both radiation protocols. Unsupervised hierarchical cluster map analysis showed significant differences in gene expression profiles between SD and MF treatments for cells treated in vitro, with MF yielding a more robust induction compared with SD. Several genes were uniquely up-regulated by MF treatment, including multiple IFN-related genes (STAT1, G1P2, OAS1, OAS3, G1P3, IFITM1) and TGF-β–associated genes (EGR1, VEGF, THBS1, and TGFB2). DU145 cells grown in vivo exhibited a completely different set of genes induced by both SD and MF compared with the same cells exposed in vitro. The results of the study clearly show distinct differences in the molecular response of cells between SD and MF radiation exposures and show that the tumor microenvironment can significantly influence the pattern of gene expression after radiation exposures. [Cancer Res 2007;67(8):3845–52]
CRR9/CLPTM1L Regulates Cell Survival Signaling and Is Required for Ras Transformation and Lung Tumorigenesis
Authors: Michael A. James, Haris G. Vikis, Everett Tate, Amy L. Rymaszewski, Ming You
Journal: Cancer Research (2013)

The transmembrane protein CLPTM1L is overexpressed in non-small cell lung cancer, where it protects tumor cells from genotoxic apoptosis. Here, we show that RNA interference-mediated blockade of CLPTM1L inhibits K-Ras-induced lung tumorigenesis. CLPTM1L expression was required in vitro for morphologic transformation by H-RasV12 or K-RasV12, anchorage-independent growth, and survival of anoikis of lung tumor cells. Mechanistic investigations indicated that CLPTM1L interacts with phosphoinositide 3-kinase and is essential for Ras-induced AKT phosphorylation. Furthermore that the anti-apoptotic protein Bcl-xL is regulated by CLPTM1L independently of AKT activation. Constitutive activation of AKT or Bcl-xL rescued the transformed phenotype in CLPTM1L-depleted cells. The CLPTM1L gene lies within a cancer susceptibility locus at chromosome 5p15.33 defined by genome-wide association studies. The risk genotype at the CLPTM1L locus was associated with high expression of CLPTM1L in normal lung tissue, suggesting that cis-regulation of CLPTM1L may contribute to lung cancer risk. Taken together, our results establish a protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization.
Cardiovascular Overexpression of Transforming Growth Factor-β <sub>1</sub> Causes Abnormal Yolk Sac Vasculogenesis and Early Embryonic Death
Authors: Ramtin Agah, K. S. Srinivasa Prasad, Ruth Linnemann, Meri T. Firpo, Thomas Quertermous, David A. Dichek
Journal: Circulation Research (2000)

Abstract —Transforming growth factor-β 1 (TGF-β 1 ) is expressed in the adult and embryonic vasculature; however, the biological consequences of increased vascular TGF-β 1 expression remain controversial. To establish an experimental setting for investigating the role of increased TGF-β 1 in vascular development and disease, we generated transgenic mice in which a cDNA encoding a constitutively active form of TGF-β 1 is expressed from the SM22α promoter. This promoter fragment directs transgene expression to smooth muscle cells of large arteries in late-term embryos and postnatal mice. We confirmed the anticipated pattern of SM22α-directed transgene expression (heart, somites, and vasculature of the embryo and yolk sac) in embryos carrying an SM22α–β-galactosidase transgene. SM22α– β-galactosidase transgenic mice were born at the expected frequency (13%); however, nearly all SM22α–TGF-β 1 transgenic mice died before E11.5. SM22α–TGF-β 1 transgenic embryos identified at E8.5 to E10.5 had growth retardation and both gross and microscopic abnormalities of the yolk sac vasculature. Overexpression of TGF-β 1 from the SM22α promoter is lethal at E8.5 to E10.5, most likely because of yolk sac insufficiency. Investigation of the consequences of increased vascular TGF-β 1 expression in adults may require a conditional transgenic approach. Moreover, because the SM22α promoter drives transgene expression in the yolk sac vasculature at a time when embryonic survival is dependent on yolk sac function, use of the SM22α promoter to drive expression of “vasculoactive” transgenes may be particularly likely to cause embryonic death.
Implications of Postprandial Glucose and Weight Control in People With Type 2 Diabetes
Authors: Baptist Gallwitz
Journal: Diabetes Care (2009)

The International Diabetes Federation (IDF) recently published guidelines for the management of postmeal hyperglycemia. These guidelines were established in view of the risk of postmeal hyperglycemia for vascular events. Because of the rising incidence and prevalence of diabetes and its complications, the IDF took action to state useful strategies for the treatment of diabetes, focusing on the detection and therapy of postprandial hyperglycemia. Besides nonpharmacological measures (blood glucose self-control and diet), drugs such as short-acting insulinotropic agents (sulfonylureas and glinides), glucosidase inhibitors, insulin, and incretin-based therapies can specifically be used to act on postmeal glucose elevations. The specific action profiles of these agents are shown and discussed with respect to the IDF guidelines.

Type 2 diabetes is a chronic and progressive disease that affects ∼250 million people worldwide today, with an increasing incidence in the years to come (1). With this epidemic dimension, type 2 diabetes is of global concern. Poor control of the disease is a leading cause of death in most developed countries and is associated with microvascular complications (renal failure and blindness due to retinopathy) and macrovascular complications (cardiovascular disease and stroke) as well as neurological complications such as diabetic neuropathy. Macrovascular complications are the major cause of death in type 2 diabetic patients (2–7).

Numerous epidemiological studies have shown that postprandial hyperglycemia substantially adds to the micro- and macrovascular risk not only in type 1 and type 2 diabetes, but already in impaired glucose tolerance (2–4,8). The associations between postmeal hyperglycemia and markers of cardiovascular disease such as oxidative stress, inflammation, endothelial dysfunction, and carotid IMT have been well characterized. In addition, postprandial hyperglycemia has also been connected with the incidence of carcinomas and cognitive dysfunction in elderly type 2 diabetic patients (9–11).

Large intervention trials …