tbuckley/cabot-search huggingface dataset:
Abstract 2266: Pioglitazone increases tumor progression and metastasis in an orthotopic mouse model of non-small cell lung cancer
Authors: Howard Y. Li, Amber Sorenson, Jay Amin, Deryck Middleton, Mary Weiser-Evans, Raphael A. Nemenoff
Journal: Cancer Research (2010)

Abstract RATIONALE: Pathways regulating lung cancer metastasis are not well understood. As with most cancers, metastasis depends on critical interactions between tumor cells and the surrounding tumor microenvironment. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. In humans, a retrospective study of patients treated with thiazolidinediones (TZDs), which are ligands for PPARγ, demonstrated a 33% reduction in risk of developing lung cancer. However, the effect of PPARγ activation on progression and metastasis of established lung tumors has not been clearly established. Our laboratory has developed a mouse model in which murine lung cancer cells directly injected into the lung of syngeneic mice develop secondary pulmonary tumors and metastasize to the mediastinal lymph nodes, the liver, and the brain. The goal of this study was to assess the effects of the TZD pioglitazone on lung cancer progression using this model. METHODS: Murine non-small cell lung cancer cells stably transfected with firefly luciferase were implanted in the left lung of C57BL/6 wild-type mice. Mice were fed either chow impregnated with pioglitazone (0.05%) or control chow. At various time points following injection, animals were sacrificed and organs were assessed for tumors using ex vivo bioluminescence imaging. Primary tumors were measured with digital calipers, and the number of secondary tumors in the other lung lobes, liver and brain were quantified. RESULTS: There was no significant difference in the size of the primary tumor between pioglitazone-treated and control mice at one week. However, primary tumors were significantly larger in pioglitazone-treated animals both 16 and 22 days after implantation of cancer cells. The differences in pulmonary metastases were even more impressive. At both 7 and 16 days, pioglitazone-treated mice showed 2-3 times more secondary pulmonary tumors compared to control animals. By day 25-30, 37.5% of mice fed pioglitazone-impregnated chow developed liver metastases, whereas only 17.6% of mice fed normal chow developed liver metastases. Brain metastases were only detected in mice fed chow impregnated with pioglitazone. CONCLUSION: Treatment of mice with the PPARγ activator pioglitazone unexpectedly accelerates metastasis of established pulmonary tumors. Since selective activation of PPARγ in tumor cells has been shown to inhibit transformed growth and invasiveness, we hypothesize that the metastasis-promoting effects of pioglitazone are mediated through effects on the tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2266.
A6.34 The role of the costimulatory receptor herpes virus entry mediator (HVEM) in B-cell activation and differentiation. implications for SLE pathogenesis
Authors: A Seretis, A Zampoulaki, C Choulaki, I Gergianaki, P Sidiropoulos, D Boumpas, G Bertsias
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background/objectives</h3> B-cells are key players in immune responses and autoimmunity through antibody production, antigen presentation and cytokine production. Fine tuning of B-cell activation depends on convergent signals from the B-cell receptor (BCR) and costimulatory membrane receptors. We studied the expression and function of the recently characterised costimulator HVEM and its receptors, and investigated its role in B-cell activation and differentiation in healthy individuals and patients with systemic lupus erythematosus (SLE). <h3>Materials/methods</h3> Peripheral blood mononuclear cells were isolated from healthy volunteers and patients with active SLE. Expression of HVEM and its ligands, BTLA and LIGHT, were assessed by flow cytometry at basal conditions and following activation. Immunomagentically-sorted CD19<sup>+</sup>total, CD19<sup>+</sup>CD27<sup>-</sup>naïve, or CD19<sup>+</sup>CD27<sup>+</sup>memory B-cells were stimulated with anti-IgM±IL-21 in presence or not of plate-bound HVEM. Fc chimeric protein to evaluate effects on cell proliferation (CFSE assay), apoptosis (Annexin/7AAD assay), activation (CD80/86, CD40), cytokine production (IL-6) and differentiation (CD38, Ig secretion). <h3>Results</h3> Active SLE patients had significantly higher proportion of circulating HVEM-expressing CD4<sup>+</sup>T-cells than healthy individuals (95.4 ± 1.3% vs. 85.4 ± 3.9%, p = 0.013). Both patients and controls demonstrated high-level expression of BTLA on freshly isolated peripheral blood B-cells, whereas LIGHT had minimal basal expression and was induced following BCR activation. HVEM. Fc crosslinking on B-cells activated with anti-IgM±IL-21 led to significantly reduced cell proliferation (by 72 ± 3%) and membrane CD80/CD86 expression (by 29 ± 4%). Notably, in 5–8 days cell cultures, HVEM. Fc induced the differentiation of both CD27<sup>-</sup> and CD27<sup>+</sup> B-cells, as evidenced by the increased expression of CD27/CD38 (CD27<sup>+</sup>: 27.9% vs. 18.4%; CD38<sup>+</sup>: 25.0% vs. 21.5%) and CD38/CD138, respectively (CD38<sup>+</sup><sup>+</sup>: 6.0% vs. 3.8%). This finding was accompanied by strong anti-apoptotic effect of HVEM. Fc treatment. Further experiments are underway to elucidate the molecular mechanisms of HVEM. Fc-mediated effects on B-cells and the potential therapeutic use of HVEM/BTLA manipulation in SLE. <h3>Conclusions</h3> HVEM exerts significant B-cell co-stimulatory effects through regulation of proliferation, apoptosis and differentiation. Increased HVEM expression on SLE CD4<sup>+</sup>T-cells might contribute to enhanced memory and plasma cell differentiation observed in the disease.
Pancreatic and Islet Transplantation for Diabetes — Cures or Curiosities?
Authors: Jeffrey S. Flier, Lisa H. Underhill, R. Paul Robertson
Journal: New England Journal of Medicine (1992)

A PRESSING question in diabetes research is whether transplanting a pancreas or pancreatic islet cells can be used as successful therapy. In animals with insulin-dependent diabetes, pancreatic and islet transplantation has repeatedly been successful in establishing euglycemia. In humans with diabetes, successful transplantation of the pancreas maintains euglycemia, but at considerable cost in terms of morbidity and health care funds. Success with the less costly procedure of islet transplantation remains elusive. Resolution of the remaining technical difficulties with both these procedures is all the more urgent because, if pancreatic or islet transplantation or both are completely successful, they could provide . . .
US drug makers have imposed big price rises for top selling drugs, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

From 2011 to 2014 drug companies have increased the prices of four of the top 10 drugs sold in the United States by more than 100% and the prices of the remaining six by more than 50%, an analysis by Reuters has found.1

According to the news agency, the biggest increase was by AbbVie Inc, which raised the price of arthritis drug Humira (adalimumab) by more than 126%. The next highest price increases were by Amgen, maker of the arthritis drug Enbrel (etanercept), and Teva Pharmaceuticals, maker of the multiple sclerosis drug Copaxone (glatiramer acetate). Both companies raised the prices of their drugs by 118%. AstraZeneca came in fourth with a 113% price increase for its cholesterol drug Crestor (rosuvastatin).

Of …
Appearance of Extraosseous Pelvic Ewing Sarcoma on Triphasic Bone Scan
Authors: Marianne Muckle, Elham Habibi, Birgit Simon, Matthias Zipfel, Hans Jürgen Biersack, Hojjat Ahmadzadehfar
Journal: Clinical Nuclear Medicine (2014)

A 24-year-old man with extraosseous Ewing sarcoma in the pelvis underwent a triphasic bone scintigraphy to rule out bone metastases and local bone infiltration before chemotherapy. The bone scintigraphy showed tracer uptake in the tumor in all 3 phases.
Abstract 563: Chemoprevention of mammary cancer in MMTV-neutransgenic mice by dietary administration of cruciferous vegetable constituent phenethyl isothiocyanate
Authors: Julie A. Arlotti, Su-Hyeong Kim, Anuradha Sehrawat, Eun-Ryeong Hahm, Anna A. Powolny, Joomin Lee, Jan H. Beumer, Kozue Sakao, Shivendra V. Singh
Journal: Cancer Research (2012)

Abstract We have shown previously that phenethyl isothiocyanate (PEITC), which is a highly promising cancer chemopreventive constituent of edible cruciferous vegetables (e.g., watercress), inhibits growth of cultured breast cancer cells in association with apoptosis induction. The present study was undertaken to determine the efficacy of PEITC for prevention of breast cancer using MMTV-neu mouse model. PEITC administration in the diet (3 mmol PEITC/kg AIN76A diet) for 29 weeks caused an approximate 27% decrease in incidence of mammary hyperplasia compared with control, but the difference between control and PEITC treatment groups did not reach statistical significance. On the other hand, incidence of palpable tumors was reduced by about 53% by PEITC administration (P= 0.07 by two-sided Fisher's exact test). Moreover, size of microscopic carcinoma lesions was significantly lower in mice fed PEITC-supplemented diet compared with those fed basal diet (P= 0.05 by two-sided Fisher's exact test). Average body weight of the PEITC-fed mice was modestly but significantly higher than that of control mice at earlier time points (weeks 1-7) but this differential was not observed at later time points (weeks 8-29). Diet consumption was comparable for mice placed on basal diet and PEITC-supplemented diet. Mean PEITC concentration in the plasma and tumor tissue was 901 nM (95% confidence interval- 741-1060 nM) and 87 nmol/kg (95% confidence interval- 67-107 nmol/kg), respectively. Expression of HER-2 oncoprotein as well as number of CD31-positive blood vessels in the tumor did not differ between control and PEITC treatment groups. On the other hand, tumors from PEITC treatment group exhibited about 46% decrease in Ki-67 expression in comparison with control (P= 0.01). Consistent with cellular observations, number of TUNEL-positive apoptotic bodies was about 4.4-fold higher in the tumors of PEITC-fed mice as compared with controls (P= 0.01). Pulmonary metastasis was evident in 3/35 control mice but only 1/32 mice placed on PEITC-supplemented diet exhibited microscopic evidence of metastasis. Size of pulmonary metastasis was also smaller in the PEITC treatment group compared with control. The results indicate that PEITC administration in the diet inhibits carcinoma development in MMTV-neu mice without any signs of overt toxicity. This investigation was supported in part by the US PHS grants CA101753 and CA129347 awarded by the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 563. doi:1538-7445.AM2012-563
Fan-Beam Tc-99m HMPAO Brain SPECT in Acute Carbon Monoxide Poisoning
Authors: CHIA-HUNG KAO
Journal: Clinical Nuclear Medicine (1998)

Carbon monoxide intoxication causes a wide variety of neurologic and psychiatric disorders. Presented is the case of a 20-year-old patient with acute carbon monoxide poisoning. This report compares the findings of brain SPECT and CT images and emphasizes the benefit of Tc-99m HMPAO fan-beam brain SPECT.
HIGH INTERSTITIAL FLUID PRESSURE REGULATES TUMOR GROWTH AND DRUG UPTAKE IN HUMAN GLIOBLASTOMA
Authors: A. I. Persson, S. Ilkhanizadeh, Y. A. Miroshnikova, A. Frantz, J. N. Lakins, C. D. James, T. R. McKnight, M. S. Berger, G. Bergers, W. A. Weiss, V. M. Weaver
Journal: Neuro-Oncology (2014)

BACKGROUND: (blind field). METHODS: We developed methodology to measure IFP in human GBM xenografts and mechanical compression in 3D-cultures. We used a cell counter and calcein-AM-loaded cells to measure cell volume following treatment with temozolomide and/or blockade of NKCC1 activity. Fluorescent MQAE-loaded cells were recorded to measure intracellular chloride levels. To study uptake of chemotherapy following IFP-reduction in GBM xenografts following AF-induction or treatment with bumetanide, we injected doxorubicin and measured fluorescent doxorubicin levels in tissue sections. RESULTS: Elevated compression increased proliferation in GBM cultures and IFP levels rapidly increased during the exponential growth phase in GBM xenografts. In contrast to Avastin that targets the vasculature, SPC diet induced AF expression only in tumor cells. In addition to reducing IFP levels, AF-induction also inhibited proliferation, induced apoptosis, and increased survival in mice xenografted with human GBM cells. SPC diet and intranasal injection of AF increased uptake of doxorubicin in GBM xenografts. In vitro, AF augmented TMZ-induced apoptosis and reduced proliferation at both baseline and increased hydrostatic compression. CONCLUSIONS: In contrast to IFP-reducing therapies targeting the vasculature, treatments that reduced osmotic pressure in GBM cells effectively reduced tumor growth and invasion in vivo. AF and bumetanide increased uptake and cytotoxic response from chemotherapies by inhibiting NKCC1 activity in GBM cells. Our studies suggest that elevated IFP promotes tumor growth, reduces drug uptake, and limits therapy-response in GBM. AF-induction represents an attractive strategy to reduce invasion, inhibit tumor growth, increase drug uptake, and ultimately improve the survival of GBM patients. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
P212 The DECAF score: predicting in-hospital mortality in acute exacerbations of COPD
Authors: J. Steer, G. J. Gibson, S. C. Bourke
Journal: Thorax (2011)

<h3>Background</h3> Despite the often poor outcome of patients hospitalised with acute exacerbations of COPD (AECOPD), it is difficult accurately to identify those at high risk of mortality. To aid prognostication in AECOPD, we have developed a simple, easily memorable and effective tool, based on clinical data available shortly after admission. <h3>Methods</h3> Consecutive patients hospitalised with AECOPD were recruited, with clinical and demographic data collected at admission. In-hospital mortality data were collected from hospital records. Variables were dichotomised and the strongest independent predictors of mortality were identified by logistic regression analysis. Tool performance was assessed using ROC curve analysis. <h3>Results</h3> 920 patients were recruited: mean (SD) age was 73.1 (10.0) years, with 53.9% female; most had severe airflow obstruction (FEV<sub>1</sub> 43.6 (17.2) % predicted) and were of normal weight (BMI 24.6 (6.3) kg/m<sup>2</sup>). 32.5% of patients had coexistent consolidation and 199 (21.6%) received assisted ventilation during their hospital stay. 96 (10.4%) patients died in-hospital. In descending order of strength, the factors independently predicting mortality were: the extended MRC Dyspnoea Scale (eMRCD)1; coexistent radiographic consolidation; eosinopenia (&lt;0.05×10<sup>9</sup>/l); pH &lt;7.3; atrial fibrillation; cough effectiveness; albumin &lt;36 g/dl; age=80 years; cerebrovascular disease; and BMI &lt;18.5 kg/m<sup>2</sup>. The strongest five variables were selected to form the DECAF (Dyspnoea, Eosinopenia, Consolidation, Acidaemia, atrial Fibrillation) score (Abstract P212 table 1). Each predictor was assigned a score of 1 (present) or 0 (absent), except for eMRCD score which could be 0, 1 or 2, giving a maximum DECAF score of 6. The DECAF score showed good performance for the prediction of in-hospital mortality (area under ROC curve=0.858, 95% CI 0.82 to 0.89), and was a stronger predictor (p&lt;0.0001) than either the APACHE (AUROC=0.727) or CAPS (AUROC=0.710) prognostic scores. In patients with coexistent consolidation (n=299), DECAF was a stronger predictor of mortality than CURB-65 (AUROC=0.77 vs 0.66, p=0.0064). <h3>Conclusion</h3> The DECAF score is a strong predictor of in-hospital mortality and may improve the prognostication of patients hospitalised with AECOPD. External validation is required before recommending widespread application.
Chromosomal Aberrations in Spontaneous Human Abortions
Authors: A. E. Szulman
Journal: New England Journal of Medicine (1965)

THIS study was stimulated by the classic discoveries of the association of chromosomal aberrations with several syndromes of multiple congenital anomalies1 2 3 4 5 followed by a rapid expansion of research activities in the field of human cytogenetics.6 It seemed reasonable to believe that since the syndromes already described were characterized by multiple anatomic anomalies and often by a "failure to thrive,"5 there were many more cases with similar or even more advanced chromosomal aberrations waiting to be discovered among the embryos and fetuses too severely handicapped to survive beyond the first trimester in utero. Such high hopes were only partially realized since . . .
P3-02-02: Novel Ranpirnase-Based ImmunoRNases Display Potent Cytotoxicity in Diverse Human Breast Cancer Cell Lines.
Authors: DM Goldenberg, D Liu, Y Wang, EA Rossi, C-H Chang
Journal: Cancer Research (2011)

Abstract Ranpirnase (Rap) is an amphibian ribonuclease originally isolated from the oocytes of Rana pipiens. Rap shows anti-tumor activity in diverse cancers and its potency can be enhanced by chemically linking or recombinantly fusing Rap to a tumor-targeting antibody, as demonstrated for CD22- or CD74-expresing hematological malignancies, as well as a variety of Trop-2-expressing cell lines derived from breast, cervical, lung, pancreatic, and prostate cancers. The Dock-and-Lock (DNL) platform enables the design and generation of targetable therapeutics that are multivalent, multispecific, and multifunctional. Here, we report the successful application of the DNL method to generate a novel class of Rap-based immunoRNases, each of which features a pair of dimeric Rap molecules covalently tethered to a select monoclonal antibody at the carboxyl termini of the heavy chains. Two such constructs, designated E1-Rap and 22-Rap, were developed with hRS7 (humanized anti-Trop-2) and epratuzumab (humanized anti-CD22), respectively, purified to near homogeneity, and evaluated in a panel of human breast cancer lines, including the basal-like, triple-negative subtype (MDA-MB-468, MDA-MB-231, BT20, HCC1806, and HCC1395), the luminal B, HER2−negative subtype (MCF-7), and the HER2−positive subtype (SKBR3), all except HCC1395 expressing high to moderate levels of Trop-2, and none expressing CD22. As demonstrated by flow cytometry, E1-Rap and hRS7 bound equivalently to MDA-MB-468, indicating the affinity of E1-Rap for Trop-2 is not compromised. Surprisingly, 22-Rap, but not epratuzumab, also bound substantially to MDA-MB-468, albeit to a lesser extent than E1-Rap. We thus postulate that the four highly basic Rap molecules in the DNL conjugate may confer a spatial configuration to largely enhance their interaction with negatively-charged cell surface proteins, such as heparan sulfate proteoglycans. Whereas the individual DNL component (IgG or Rap) alone or in combination showed negligible in vitro cytotoxicity in all seven breast cancer cell lines examined, E1-Rap exhibited EC50 values of 1 nM or less in MDA-MB-468 (0.03 nM), MCF-7 (0.1 nM), BT20 (0.18 nM), HCC1806 (0.19 nM), and SKBR3 (1.29 nM). In comparison, the potency of 22-Rap was at least 10-fold lower than E1-Rap in MDA-MB-468, BT20 and HCC1806, with an EC50 of ∼2 nM. Neither E1-Rap nor 22-Rap was very effective in inhibiting the proliferation of the more aggressive MDA-MB-231, with an EC50 above 50 nM. In the Trop-2-negative HCC1395, the dose-response curves obtained for E1-Rap and 22-Rap were nearly identical (EC50 ∼100 nM), as they should be if the cytotoxicity was mediated mainly through the Rap component. The results of Immunofluorescence microscopy showed E1-Rap was effectively internalized and localized in the cytosol. Thus, these ImmunoRNases are potentially new cancer therapeutics for breast and other solid tumors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-02-02.
Respiratory syncytial virus and rhinovirus severe bronchiolitis are associated with distinct nasopharyngeal microbiota
Authors: Jonathan M. Mansbach, Kohei Hasegawa, David M. Henke, Nadim J. Ajami, Joseph F. Petrosino, Chad A. Shaw, Pedro A. Piedra, Ashley F. Sullivan, Janice A. Espinola, Carlos A. Camargo
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract LB-16: Inhibition of RalA as a novel strategy for targeting ovarian cancer
Authors: Faris Farassati
Journal: Cancer Research (2011)

Abstract Abstract: The Ral (Ras like) GTPase guanyl nucleotide-binding proteins, RalA and RalB are direct effectors of pro-oncogene Ras. RalA and RalB are implicated in tumorigenesis and play distinct roles in mediating carcinogenesis. The critical role of RalA in the initiation and progression of ovarian cancer is entirely unclear. Here, we report that RalA is overactivated in human ovarian cancer cells and human ovarian cancer tissues. The RalA downstream effectors (RalBP-1 and CDC42) and the regulators (GalGDS, PP2A Aα and β, as well as Aurora Kinase) that modulate RalA activation during the post-translational process were found to be de-regulated in ovarian cancer cells. ShRNA-mediated knockdown of RalA inhibited ovarian cancer cell proliferation and invasion. Geranyl-Geranyl transferase inhibitors (GGTI-2147) or Aurora Kinase Inhibitor (AKI) that inhibit RalA activation at post-translational levels suppressed ovarian cancer cell growth and invasion in-vitro. Additionally, subcutaneous (SC) mouse model with these two inhibitors also showed effective inhibition of tumor growth in-vivo. Therefore, RalA is a key player in the biology and dispersal of ovarian cancer cells and is a promising target for the development of novel therapeutics. To the best of our knowledge, the role of RalA in ovarian cancer tumorigenesis has not been documented before, therefore our strategy in targeting RalA for treatment of ovarian cancer merits highly in terms of novelty. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-16. doi:10.1158/1538-7445.AM2011-LB-16
DISECIÓN SUBMUCOSA ENDOSCÓPICA EN MODELO PORCINO IN VIVO. EDICIÓN 2.0
Authors: E Albéniz, A Pueyo, J Eguaras, M Montes, J Jiménez, J Vila, I Fernández-Urién, JM Urman, M Ostiz, A Ciáurriz
Journal: Endoscopy (2011)

Introducción: La Disección Submucosa Endoscópica (DSE) en una técnica compleja y laboriosa que requiere de un prolongado aprendizaje. Hace un año, presentamos nuestros resultados iniciales en un modelo porcino “in vivo”, pudiendo ser calificados como esperanzadores. A continuación mostramos los resultados de la segunda edición de entrenamiento en esta técnica.
Case 20-2004
Authors: Lori R. Berkowitz
Journal: New England Journal of Medicine (2004)

A woman told her physician that she had pelvic pressure and a vaginal bulge shortly after her second vaginal delivery. Examination showed uterine prolapse, cystocele, and rectocele. Despite conservative management with a pessary and exercises, the prolapse worsened and urinary symptoms developed. Is there a link among pregnancy, vaginal delivery, uterine prolapse, and incontinence? How should this condition be managed?