tbuckley/cabot-search huggingface dataset:
Abstract 2870: The inhibitory effects of propolin C and propolin G on human lung adenocarcinoma A549 cells through autophagy and apoptosis pathway
Authors: Hui-Chen Hsu, Feng-Chuan Ku, Yu-Fen Chen, Hsiao-Feng Wang, Zhong-Zhe Lin, Yue-Wen Chen, Meng-Geng Tsai
Journal: Cancer Research (2011)

Abstract Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. Propolis has over 150 constituents such as polyphenols (flavonoids, phenolic acids and their esters), terpenoids, steroids, and amino acids, but its composition varies qualitatively and quantitatively with the geographical and botanical origins. In Tawiwan, there are ten propolins (A-J) were isolated and characterized from the local propolins. Propolins, prenylflavanones are isolated and characterized from Taiwanese propolis have been shown inhibits certain cancer cell lines growth and induced apoptosis. In this study, human lung adenocarcinoma cell (A549) was used to investigate the anticancer activity of Proploins. Propolin C and propolin G could inhibit A549 cell growth by dose-dependent manner. The combination of propolin C with propolin G was more predominantly inhibited the cell viability. Propolin C or propolin G treatment alone could suppress Akt and p70S6K activation by blocking the PI3K/Akt/mTOR pathway. Moreover, the pro-apoptotic protein Bax and Bad expression were increased. The procaspase 9, procaspase 3, and PARP activated in cascade to lead to mitochondria-mediated apoptosis pathway of apoptosis. Flow cytometry assay showed that sub-G1 phase increased significantly in propolin G treatment but not in propolin C group. Both propolin C and G could promote LC3B increased within 6 hours treatment, moreover, and AVOs (acidic vesicular organelles) significantly increased by AO (Acridine orange) staining. Combination treatment had synergies effect to induce significantly apoptosis and autophagy in A549 cells. 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 2870. doi:10.1158/1538-7445.AM2011-2870
The Overutilization of X-Rays
Authors: Herbert L. Abrams
Journal: New England Journal of Medicine (1979)

When the term "overutilization" is applied to x-rays, its meaning should be defined. The definition that I shall employ is straightforward: "over-utilization" means excessive irradiation per unit of diagnostic information, therapeutic impact or health outcome. In the broadest sense, it comprises excessive radiation per film, excessive films per examination or excessive examinations per patient.Excessive Radiation per FilmThe patient receives more radiation than is justified when the shutters of an x-ray unit are more widely opened and encompass a larger area than the region of interest. It has been estimated that, if exposure were consistently limited to the size . . .
Abstract 1286: Endothelin-1-induced angiogenesis is regulated by PHD2 in a HIF-1α-dependent manner
Authors: Francesca Spinella, Laura Rosanò, Valentina Caprara, Valeriana DiCastro, Maria Rita Nicotra, Pier Giorgio Natali, Anna Bagnato
Journal: Cancer Research (2010)

Abstract The endothelin B receptor (ETBR) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF)-1α is essential for melanomagenesis and progression. In melanoma cells cultured in normoxic conditions, ET-1, ET-2, and ET-3 through ETBR enhance HIF-1α and HIF-2α expression, and activity and both transcriptional factors regulate the expression of target genes, such as vascular endothelial growth factor (VEGF) and ET-1 in response to ETs or hypoxia. In turn, ETs control HIF-1α stability by inhibiting its degradation. In particular, ETs through ETBR markedly decrease prolyl hydroxylase domain (PHD)2 mRNA and protein levels and promoter activity. In addition, we found that activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT-mammalian target of rapamycin (mTOR) pathway is required for ETBR-mediated PHD2 inhibition, HIF-1α, HIF-2α, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced angiogenesis and melanoma cell invasiveness demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanomas, that express high level of HIF-1α, ETBR expression is associated with low PHD2 levels. In melanoma xenografts, ETBR blockade by ETBR antagonist results in a concomitant reduction of angiogenesis, HIF-1α, HIF-2α and VEGF expression, and an increase in PHD2 levels. In conclusion, we identified the underlying mechanism by which ET-1 controls HIF-1α stability and thereby regulates angiogenesis and tumor invasion through the regulation of PHD2. These results further indicate that targeting ETBR may represent a potential therapeutic treatment of melanoma by impairing HIF-1α stability. Supported by AIRC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1286.
Abstract P6-15-01: A Phase 1b Study To Assess the Safety and Tolerability of the PARP Inhibitor Iniparib (BSI-201) in Combination with Irinotecan for the Treatment of Patients with Metastatic Breast Cancer (MBC)
Authors: S Moulder, M Mita, C Bradley, C Rocha, L. Harris
Journal: Cancer Research (2010)

Abstract Background: Inhibition of poly (ADP-ribose) polymerase-1 (PARP1), a key regulator of DNA repair and cell proliferation, potentiates the anti-tumor activity of DNA-damaging chemotherapy agents, including irinotecan, a topoisomerase inhibitor (Ossovskaya et al. AACR 2009). Combination of gemcitabine and carboplatin with the PARP inhibitor iniparib has demonstrated promising efficacy and safety in patients with triple-negative MBC (O'Shaughnessy et al. SABCS 2009). Single agent irinotecan is active in heavily pre-treated metastatic breast cancer (MBC), with response rates (RR) up to 23% (Perez et al. JCO 2004;22:2849). A Phase 1 dose-escalation study of iniparib in advanced solid tumors showed no dose-limiting toxicities (DLTs) at iniparib doses of 0.5 to 8.0 mg/kg (Kopetz et al. ASCO 2008). That study was expanded here to determine the maximum-tolerated dose (MTD) of irinotecan that can be used in combination with fixed dose iniparib in patients with locally advanced or MBC. Methods: Patients were treated with a 3+3 study design to determine safety of iniparib (8 mg/kg IV twice-weekly on Days 1, 4, 8, and 11 every 21 days) in combination with escalating doses of irinotecan (80 — 125 mg/m2 IV on Days 1 and 8 every 21 days). RRs were measured per modified RECIST criteria. Serial pharmacokinetic (PK) assessments were performed during Cycle 1, and archived paraffin-embedded tumor samples were collected to correlate markers of hypoxia (CAIX) with PARP1 expression (as measured by immunohistochemistry [IHC]) and response. Results: The median age of 34 patients who received therapy was 50 years (range, 32-84), and the median number of prior therapies was 2 (range, 0-6). Preliminary analysis show that tumors from 22 (65%) patients were ER-/PR-/HER2- (triple-negative), 10 (29%) were ER+/HER2-, and 1 (3%) was HER2+. One DLT of Grade 3 diarrhea with lower GI bleed was observed, thus establishing the optimal regimen from this study at 8 mg/kg iniparib + 125 mg/m2 irinotecan. Other toxicities included neutropenia, anemia and diarrhea. Of 26 patients evaluable for response, 5 (19%) had partial response (PR), 10 (38%) had stable disease (SD) for &amp;gt;4 cycles of therapy, and 9 (35%) developed progressive disease (PD) as best response. Of 10 patients who had reached 6 cycles at time of analysis, 5 (50%) had SD. Median follow-up time was 11 weeks. PK and IHC evaluations are ongoing and will be presented, along with mature response data. Conclusions: An MTD of 8 mg/kg iniparib and 125 mg/m2 irinotecan was identified in patients with MBC. Iniparib in combination with irinotecan was well tolerated and showed promising efficacy, with evidence of clinical benefit (RR + SD ≥6 cycles) in 50% in patients with treatment-refractory MBC. (ClinicalTrials.gov number, NCT00298675) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-01.
Phase I Clinical Trial of Recombinant Human Interleukin-3 Combined With Carboplatin in the Treatment of Patients With Recurrent Ovarian Carcinoma
Authors: J J Rusthoven, E Eisenhauer, J Mazurka, H Hirte, G O'Connell, A Muldal, H X Lu, N Onetto, K Swenerton, J Jeffrey
Journal: JNCI Journal of the National Cancer Institute (1993)
Abstract 1143: Translational control analysis by translationally active RNA capture/microarray analysis (TrIP-Chip)
Authors: Kenji Kudo, Yaguang Xi, Yuan Wang, Bo Song, Edward Chu, Jingyue Ju, James J. Russo, Jingfang Ju
Journal: Cancer Research (2010)

Abstract We have developed a new approach to systematically study post-transcriptional regulation in a small number of cells. Actively translating mRNAs are associated with polysomes and the newly synthesized peptide chains are closely associated with molecular chaperones such as hsp70s, which assist in the proper folding of nascent polypeptides into higher ordered structures. These chaperones provide an anchor with which to separate actively translating mRNAs associated with polysomes from free mRNAs. Affinity capture beads were developed to capture hsp70 chaperones associated with the polysome complexes. The isolated actively translating mRNAs were used for high throughput expression profiling analysis. Feasibility was demonstrated using an in vitro translation system with known translationally regulated mRNA transcript thymidylate synthase (TS). We further developed the approach using HCT-116 colon cancer cells with both TS and p53 as positive controls. The steady state levels of TS and p53 mRNAs were unaltered after 5-fluorouracil (5-FU) treatment as assessed by real time qRT-PCR analysis. In contrast, the protein expression and polysome-associated mRNA levels of both genes were increased. These differences in translational rate were revealed with our new approach from 500 cells. This technology has the potential to make investigation of translational control feasible with limited quantities of clinical specimens. 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 1143.
Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects
Authors: D T George, C Benkelfat, R R Rawlings, M J Eckardt, M J Phillips, D J Nutt, D Wynne, D L Murphy, M Linnoila
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in healthy comparison subjects.The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or type II alcoholics (early onset with antisocial traits) (N = 24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion.m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype.Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects.
A5.1 Culture OF human chondrocytes in high glucose induces inflammatory markers and impairs autophagy
Authors: A T Rufino, M Ribeiro, F Judas, M C Lopes, A F Mendes
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Accumulating evidence indicates that Diabetes Mellitus is an independent risk factor for severe osteoarthritis (OA). Understanding the mechanisms involved is essential for designing preventive strategies and targeted therapies that can halt OA progression. Our previous studiesshowed that culture of human chondrocytes under excess glucose favours catabolic responses and oxidative stress. This study aims at elucidating whether exposure of chondrocytes to high glucose favours inflammatory responses and impairs autophagy, a crucial mechanism for the elimination of damaged molecules and organelles. <h3>Materials and Methods</h3> Human chondrocytes isolated from knee cartilage obtained from multi-organ donors at the Orthopaedics Department of the University and Hospital Center of Coimbra and the human chondrocytic cell line, C28/I2, were cultured in medium containing regular (10 mM) or excess (30 mM) glucose for various periods. The expression of pro-inflammatory and pro-catabolic markers (iNOS, IL-1β and TNF-α) was evaluated by qRT-PCR. iNOS protein levels and the nuclear translocation of p65, a marker of NF-κB activation, were evaluated by western blot. NO production was assessed by the Griess reaction. Autophagy was assessed by determining the protein levels of LC3-I and II in the presence and absence of the lysosome inhibitor, chloroquine. To rule out possible osmotic effects, parallel experiments were performed in the presence of the cell-impermeable polyol, mannitol. <h3>Results</h3> Culture of human chondrocytes in high glucose (30 mM) for 24h significantly increased iNOS mRNA and protein levels, as well as NO production relative to cells maintained in regular glucose. IL-1β and TNF-α mRNA levels were also significantly increased, while nuclear levels of NF-κB p65 increased in a time-dependent manner, peaking after 1h treatment. On the other hand, LC3-II levels were significantly reduced by culture of C28/I2 cells in high glucose for 24h, either in the presence or absence of chloroquine, indicating that its synthesis was decreased relative to cells maintained in regular glucose medium. <h3>Conclusions</h3> Hyperglycemia-like glucose concentrations are sufficient to induce the inflammatory process and to impair autophagy in human chondrocytes which can contribute to the development and progression of OA. Work supported by grants PEst-C/SAU/LA0001/2011 and PTDC/EME-TME/113039/2009 from FEDER through COMPETE and FCT.
A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss
Authors: Simon Stritt, Paquita Nurden, Ernest Turro, Daniel Greene, Sjoert B. Jansen, Sarah K. Westbury, Romina Petersen, William J. Astle, Sandrine Marlin, Tadbir K. Bariana, Myrto Kostadima, Claire Lentaigne, Stephanie Maiwald, Sofia Papadia, Anne M. Kelly, Jonathan C. Stephens, Christopher J. Penkett, Sofie Ashford, Salih Tuna, Steve Austin, Tamam Bakchoul, Peter Collins, Rémi Favier, Michele P. Lambert, Mary Mathias, Carolyn M. Millar, Rutendo Mapeta, David J. Perry, Sol Schulman, Ilenia Simeoni, Chantal Thys, Keith Gomez, Wendy N. Erber, Kathleen Stirrups, Augusto Rendon, John R. Bradley, Chris van Geet, F. Lucy Raymond, Michael A. Laffan, Alan T. Nurden, Bernhard Nieswandt, Sylvia Richardson, Kathleen Freson, Willem H. Ouwehand, Andrew D. Mumford
Journal: Blood (2016)
Diagnosis of Pericardial Effusion and Its Effects on Ventricular Function Using Gated Tc-99m Sestamibi Perfusion SPECT
Authors: EYAL HERZOG, NORMAN KRASNOW, GORDON DePUEY
Journal: Clinical Nuclear Medicine (1998)

Pericardial effusion is a common disorder associated with a variety of medical disorders. Diagnostic methods of choice include echocardiography, CT, and MRI. However, diagnosing pericardial effusion with radionuclides is uncommon. A pericardial effusion under pressure may result in tamponade and hemodynamic compromise, which constitutes a cardiac emergency, necessitating emergency intervention with pericardiocentesis or pericardiotomy. Presented is an unusual case of a patient who was referred to the nuclear cardiology laboratory for evaluation of atypical chest pain using stress and rest Tc-99m sestamibi perfusion SPECT. The patient had a large pericardial effusion evident on planar projection images and tomograms. From the gated perfusion study, the authors were able to evaluate left and right ventricular function and to exclude cardiac tamponade because there was no evidence of diastolic collapse of the right ventricle.
ESTUDIO COMPARATIVO DE LA REPERCUSIÓN HEMODINÁMICA Y RESPIRATORIA DE LA PERITONEOSCOPIA POR NOTES VERSUS LAPAROSCOPIA EN UN MODELO PORCINO
Authors: R Navarro-Ripoll, G Martínez-Pallí, H Córdova, A Rodríguez D'Jesús, C Guarner-Argente, C Rodríguez de Miguel, M Beltrán, J Comas, MA Martínez, S Delgado, A Lacy, CC Thompson, À Ginès, M Pellisé, B González-Suárez, O Sendino, JM Bordas, J Llach, G Fernández-Esparrach
Journal: Endoscopy (2010)

Objetivo: evaluar los cambios hemodinámicos y respiratorios durante la peritoneoscopia por NOTES y compararlos con la laparoscopia
AB0093 Study of B-cell activation factor (BAFF) and proliferation-inducing ligand (april) in rheumatoid arthritis patients:
Authors: M.Y. Tayel, E. abdel Hamid, Z.E. Morad, E.A.K. Rashad
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The TNF superfamily member B lymphocyte stimulator (BLyS), referred to as BAFF, is known to be an effective modulator of peripheral B cell homeostasis that promotes B cell survival and differentiation. BLyS is expressed by a few stromal cells, T cells, and most myeloid cell. BLyS transgenic mice show an expansion of the peripheral mature B cell compartment, hyperglobulinemia, anti-single-stranded DNA and anti-double-stranded DNA antibodies, and circulating immune complexes. A proliferation-inducing ligand (APRIL) is a homolog to BLyS that is expressed by monocytes, macrophages, DCs, T cells, and others. APRIL is virtually undetectable in normal tissues but is strongly expressed in adenocarcinomas and can accelerate the growth of malignant cells in vitro and in vivo. APRIL/BLyS heterotrimers are present in the serum of patients with systemic autoimmune diseases like rheumatoid arthritis (RA), SLE, and SS. APRIL over expression promotes a strong survival signal for both CD4+ and CD8+ T cells in vivo. T cell dependent humoral responses revealed an increase in serum IgM, while serum IgG levels remained unaffected. T cell independent type II humoral responses were also enhanced, manifested by elevated IgM and IgG serum levels. These two related members of the tumor necrosis factor family, BAFF and APRIL, are already known for their crucial role in normal B-cell survival, differentiation and apoptosis. <h3>Objectives</h3> is to investigate the relation between levels of BAFF and APRIL in serum of patients with RA and their correlation to clinical disease and some laboratory parameters <h3>Methods</h3> 60 patients divided into 2 groups. Group 1, 40 patients having RA and fulfilling the (ACR) criteria for diagnosis of the disease. Group 2, 20 healthy age and sex matched individuals as controls for the serum level of BAFF and APRIL. Patients positive for hepatitis C and/or B virus infection were excluded. Patients were subjected to clinical assessment of disease activity by DAS 28 score. Health assessment questionnaire for disability index (HAQ-DI) and x- ray of both hands and feet. Routine laboratory investigations, rheumtoid factor titre by Rose Waaler technique, Anti- cyclic citrullinated peptide Abs titre. Detection of serum and synovial fluid levels of BAFFand APRIL by ELISA <b>Results:</b> <h3>Conclusions</h3> the elevation of BAFF and APRIL in RA patients supports that B cell activation has a role in the pathogenesis of rheumatoid arthritis. BAFF and APRIL correlates with inflammatory, autoantibody markers and activity markers which confirm that targeting these cells might be a useful strategy in treatment of rheumatoid arthritis. <h3>Disclosure of Interest</h3> None Declared
99mTc HYNIC-TOC Imaging and 177Lu DOTA-Octreotate Treatment in Non–Iodine-Concentrating Dedifferentiated Thyroid Carcinoma Metastases
Authors: Sandip Basu, Amit Joshi
Journal: Clinical Nuclear Medicine (2014)

The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.
Complete obstructive esophageal cancer with esophagopleural fistula successfully treated by combined antegrade and retrograde rendezvous technique
Authors: V. Prachayakul, P. Aswakul, U. Kachintorn
Journal: Endoscopy (2011)

A 56-year-old man with advanced esophageal cancer who had undergone percutaneous endoscopic gastrostomy (PEG) 4 months previously presented to our unit with refractory coughing and chest discomfort for 3 months. He had refused chemotherapy. Computed tomography (CT) scan showed a large esophagopleural fistula ([Fig. 1]) and the insertion of an esophageal stent was planned.