tbuckley/cabot-search huggingface dataset:
Effect of megestrol acetate, cyproheptadine, and their combination on appetite, body weight and quality of life (QOL) in cancer patients: A double-blind placebo-controlled clinical trial
Authors: S. Z. Latifzadeh, V. Entezari
Journal: Journal of Clinical Oncology (2004)

8141 Background: This study aimed to evaluate effect of progestinal agent and cyproheptadine on Anorexia-cachexia syndrome and QOL in cancer patients. Methods:This study is a double-blind placebo-controlled clinical trial. Eligible cases were non-hormone dependent cancer patients with history of appetite loss or significant weight loss (> 5%) between ages 18–75 years who completed informed consent. Patients stratified according to: 1) >5%below IBW / IBW ± 5% or >5% above IBW 2) Complete or Partial response / stable or progressive disease 3) Cisplatin / Non-Cisplatin based chemotherapy and assigned (by minimization method) to four treatment arms: Megestrol Acetate (320mg/d, BID) + Placebo (MP), Cyproheptadine (8mg/d, BID) + Placebo (CP), Megestrol Acetate + Cyproheptadine (MC) and Placebo + Placebo (PP) for a period of one month. QOL evaluated by EORTC-QLQ-C30 for cancer studies. Results: During 1999 to 2003, 161 cancer patients included and 98 cases (60.9%) completed treatment period (85.4 % in stages III - IV). During study, 75.6 % of cases received chemotherapy and 6 % undergone radiation. Stratified parameters were balanced between treatment arms. Appetite, body weight and QOL changes evaluated at entrance and after one month that their results are summarized in the table below. Conclusions: Appetite and body weight improvements occurred at most in megestrol acetate treatment group (MP) but its difference with other groups was not significant. QOL parameters were not different between treatment arms (P values > 0.05). Considering the short treatment period and difficulties in follow-up of end-stage cancer patients, qualified large-scale clinical trials is needed for defining therapeutic role of these medications. No significant financial relationships to disclose.
AB0353 More corticosteroids and less biotherapy in elderly RA patients: Results on a survey on 454 RA
Authors: A. Fradin, F. Girard, C. Lormeau, A. Deplas, E. Solau-Gervais
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In front of ageing of the population, rheumatologists are more and more confronted with the coverage of elderly, particularly regarding rheumatoid arthritis (RA). The objective of the study was to evaluate the coverage in two populations of RA, one age of more than 65 years old and one of age less than 65 years old. <h3>Methods</h3> This descriptive, transversal and retrospective study concerned patients followed in one university hospital and one hospital during the year 2008 for RA. Clinical, biological, radiological characteristics and treatments have been compared between the younger-onset RA and elderly-onset RA (begun after 65 years old), and on the other hand RA of younger patients and elderly patients (of 65 and more years old). Age, duration of the disease, disease activity score including a 28-joint count (DAS28), presence or not of anti-citrullinated protein antibodies (ACPA) and of rheumatoid factor, presence of X-Rays erosions, prescription of corticosteroids, disease modifying anti rheumatoid drugs (DMARD) or biotherapy. <h3>Results</h3> 454 patients were included in the study. There was no statistically significant difference regarding either age of diagnosis or age. There was an higher DAS 28 among elderly patients (3.72 vs. 3.14, p≤0.05) compared to younger. Corticosteroids were significantly more prescribed in elderly patients (60.5% vs. 50.8%, p=0.05) than in younger patients and in elderly-onset RA (68% vs. 52%, p=0.005) compared to younger-onset RA. As regards to DMARDs, there was no difference in the prescription of DMARD in the 2 groups (p=0,326) but biotherapy was significantly less prescribed in elderly patients than in younger patients (21% vs. 35%, p=0,001) and in elderly-onset RA compared to younger-onset RA (10% vs. 32%, p=0.001). <h3>Conclusions</h3> Even in elderly RA and elderly onset RA, corticosteroids are significantly more prescribed although biotherapy are less prescribed than in younger RA and younger onset RA. <h3>Disclosure of Interest</h3> None Declared
Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer
Authors: Lynn C. Hartmann, Daniel J. Schaid, John E. Woods, Thomas P. Crotty, Jeffrey L. Myers, P.G. Arnold, Paul M. Petty, Thomas A. Sellers, Joanne L. Johnson, Shannon K. McDonnell, Marlene H. Frost, Clive S. Grant, Virginia V. Michels, Robert B. Jenkins
Journal: New England Journal of Medicine (1999)

Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete.
GMC dismisses case against top NHS boss
Authors: C. Dyer
Journal: BMJ (2013)

The General Medical Council has thrown out a complaint of bullying, dishonesty, and unprofessional conduct against Barbara Hakin, NHS England’s interim deputy chief executive and chief operating officer.

After a year long investigation into 17 allegations, GMC case examiners have concluded that there was “no reasonable prospect” of proving that Hakin’s fitness to practise was impaired in relation …
RT-24 * EXTENT OF CEREBRAL RADIONECROSIS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM) TREATED ON A CLINICAL TRIAL WITH HYPOFRACTIONATED INTENSITY-MODULATED RADIATION THERAPY (HYPO-IMRT) COMBINED WITH TEMOZOLOMIDE (TMZ) AND BEVACIZUMAB (BEV)
Authors: D. Ney, B. K. Kleinschmidt-DeMasters, J. Carlson, D. Damek, L. Gaspar, B. Kavanagh, A. Waziri, K. Lillehei, K. Reddy, C. Chen
Journal: Neuro-Oncology (2014)

BACKGROUND: Hypofractionated RT schemes may result in increased occurrence of clinically-significant radionecrosis (CSRN), but this potentially might be mitigated by bevacizumab (BEV). METHODS: 30 patients received hypo-IMRT to the surgical cavity and residual tumor with a 1cm margin (PTV1) to a total dose of 60 Gy in 10 daily fractions and to the T2 abnormality with a 1cm margin (PTV2) to 30 Gy. Concurrent TMZ (75mg/m2 daily) and BEV (10mg/kg every 2 weeks) was administered followed by adjuvant TMZ and BEV for 6 months. CSRN was defined as progressive MRI changes not attributable to tumor progression resulting in neurological deficits. Differentiation from tumor progression was based on perfusion weighted imaging showing hypoperfusion in areas of MRI change. RESULTS: 16/30 developed CSRN at a median of 12.5 months. The median PTV1 volume in these patients was 131.0 cm3(range: 37.9-241.7), and the median PTV2 volume was 337.3 cm3 (range: 130.6-519.2.0). PTV1 and PTV2 volumes were not statistically different between those patients who developed CSRN and those who did not (p = .88, p = .40). Median OS of patients with CSRN was 18.4 months versus 16.9 months in those without (p = 0.05). Development of CSRN was not associated with MGMT methylation status (p = 0.66). Four patients underwent re-operation (showing 60-100% necrosis), 13 patients died, and 2/13 underwent autopsy. One patient (survival 10.1 months), showed predominantly RN with scant residual tumor cells, whereas the second (survival 17.5 months) manifested focal RN with extensive, residual, bulky leptomeningeal tumor at surrounding base of brain, brainstem, and spinal cord. CONCLUSIONS: CSRN was extensive in this cohort and not mitigated by BEV. Development of RN not only failed to prolong survival, but in at least one patient allowed development of known late complications of GBM, ie., distant spread beyond original tumor bed.
549Monocytes activate the non-canonical Wnt5a pathway in microvascular endothelial cells and induce tissue factor expression and tube formation
Authors: S Espinosa, G Arderiu, R Aledo, E Pena, L Badimon
Journal: Cardiovascular Research (2014)

Purpose: Atherosclerosis is characterized by lipid accumulation, inflammation and neovascularization. Advanced atherosclerotic plaques can be destabilized and become vulnerable to rupture by microcapillary formation and inflammatory cell infiltration; and can lead to thrombosis and acute coronary syndromes. We have demonstrated in previous studies that increased tissue factor (TF) expression, that it is induced in microvascular endothelial cells (mECs), triggers angiogenesis; however, the signals that induce TF expression in mECs are barely understood. Here, we hypothesize that monocytes, that are strongly involved in atherosclerotic plaque inflammation, can interact with mECs and induce TF expression and, consequently, neovessel formation.
MECHANICAL FUNCTION OF LEFT ATRIUM IS IMPROVED WITH EPICARDIAL LIGATION OF LEFT ATRIAL APPENDAGE: INSIGHTS FROM LAFIT-LARIAT REGISTRY
Authors: Muhammad Rizwan Afzal, Shelby Kutty, Quanliang Shang, Sampath Gunda, Sandia Iskandar, Anweshan Samanta, Arun Kanmanthareddy, Madhu Reddy, Donita Atkins, Sudharani Bommana, Buddhadeb Dawn, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2016)
Abstract P2-11-11: Patient Reported Outcomes after Breast Cancer Surgery and Adjuvant Therapy from a German Breast Cancer Centre
Authors: S Feiten, J Dünnebacke, J Heymanns, H Köppler, J Thomalla, C van Roye, D Wey, R Weide
Journal: Cancer Research (2012)

Abstract Objectives: Evaluation of the subjectively experienced physical, psychological, social and job-related consequences of breast cancer. Methods: Standardized paper pencil interview of patients with the initial diagnosis of breast cancer who had their primary surgery between 01/2006 and 12/2010 at an accredited breast cancer centre followed by systemic adjuvant treatment. The data collection was conducted with the help of a self-developed scanner-readable questionnaire which had been evaluated in a pretest. Results: 1260 patients were contacted, 871 completed questionnaires (return rate 72%) were analyzed. Median age of the patients (99.5% women) at the time of the interview was 65 years (30–91). 6% relapsed during the observation period. 91% were “satisfied” or “very satisfied” with the surgical result. 67% indicated a complete freedom of pain. 23% received lymphatic drainage at the time of the questioning (11/2011), 33% complained about limitations of arm and/or shoulder function. 76% received anti-hormonal therapy, 13% stopped the anti-hormonal medication prematurely. Patients received a mean of 1.3 different anti-hormonal therapies, 54% took Tamoxifen. Psychological distress, cognitive limitations and physical consequences were rated on a scale from 1 – “not at all” to 4 – “very much”. The highest average values were found for the items sleep disturbances (2.3) and exhaustion (2.3), the lowest for depression (1.7) and word-finding difficulties (1.8). After therapy only 39% described a complete recovery of their physical capacity, 62% regained their previous mental capacity. 44% were in employment before their disease. 67% returned to their workplace but only 65% of them with their previous number of hours. 15% indicated disadvantages in their workplace due to the breast cancer disease. For 75% their partnership did not change, 12% experienced a deterioration, 13% an improvement. Before the illness 9% consulted a psychiatrist/psychotherapist, after the illness 18%. Before the diagnosis of breast cancer 13% received antipsychotic drugs, after the disease 25%. Conclusions: Breast cancer diagnosis and therapy leads to long lasting impairment of physical, psychological, social and job-related functioning in a significant number of patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-11.
In vivo molecular imaging of gastric cancer by targeting MG7 antigen with confocal laser endomicroscopy
Authors: Z. Li, X. Zuo, C. Li, C. Zhou, J. Liu, M. Goetz, R. Kiesslich, K. Wu, D. Fan, Y. Li
Journal: Endoscopy (2013)

<b>Background and study aims:</b> In vivo molecular imaging represents a powerful tool for the immediate diagnosis of gastric cancer. In this study, the monoclonal antibody MG7, which is a specific molecular marker against gastric cancer, was labeled with fluorescent agents to enable in vivo real-time imaging by confocal laser endomicroscopy (CLE). <b>Patients and methods:</b> In vivo molecular imaging was performed in tumor-bearing mice from two kinds of human gastric cancer cell lines. Xenograft tumors were visualized in vivo first with a whole-body fluorescent imaging device and then by CLE using fluorescently labeled MG7 antibody. Gastric cancerous tissue and noncancerous mucosa from human biopsies or surgical specimens were also examined ex vivo by CLE. <b>Results:</b> Intravital imaging of xenograft tumors revealed a specific cellular signal, whereas no specific signal was observed in control tissue or in mice injected with irrelevant antibodies. An ex vivo experiment on human specimens using a rigid confocal probe showed positive fluorescent staining in 22 /23 samples diagnosed as gastric cancer and weak signals in 5 /23 noncancerous tissue samples. CLE evaluation correlated well with immunohistochemical findings. <b>Conclusions:</b> Screening tumors in vivo by CLE may help to detect MG7-Ag-positive tissues, decrease the sampling error by screening the large tumor surface not routinely screened by biopsy or conventional immunohistochemistry, and facilitate early detection of gastric carcinoma.
Abstract SY29-01: mTOR, metabolism, and cell growth control
Authors: John Blenis, Alfredo Csibi, Sang Gyun Kim, Andrew Choo, Gwen Buel, Young Jin Jang, Gregory Hoffman
Journal: Cancer Research (2012)

Abstract The mTOR complex 1 (mTORC1) is a ser/thr protein kinase complex and critical regulator of cellular metabolism, protein synthesis, autophagy and cell growth. This signaling system is normally carefully controlled by the integration of inputs from growth factors, nutrients, cellular energy status, oxygen availability and stress. A variety of loss-of-function or gain-of-function alterations in key mTORC1 regulatory proteins, very often results in inappropriate regulation of this signaling system. Uncontrolled mTORC1 activation contributes on its own or in combination with other pathways to metabolic diseases ranging from diabetes and obesity, cardiac hypertrophy, neurodegeneration, aging, benign tumor syndromes to highly malignant cancers. Mechanistically, uncontrolled mTORC1 activation leads to a constant positive input into anabolic processes and suppression of many catabolic processes. As a result, these cells require increased energy and carbon sources to meet their high metabolic needs for cell growth. To meet this demand, we have found in cells that are PTEN or TSC1/2 null, that activated mTORC1 uses distinct mechanisms to increase glutamine consumption (glutaminolysis) by elevating the expression of glutaminase and the activity of glutamate dehydrogenase. Furthermore, under nutrient-rich conditions, these tumor cells sense the increased energy production and in a positive feedback loop, promote more mTORC1 assembly via an AMP kinase (AMPK)-dependent, and a novel AMPK-independent mechanism. This acquired addiction to glutamine provides a novel therapeutic strategy for treating patients with activated mTORC1. Indeed, by acutely blocking the ability of energetically stressed cells with hyperactive mTORC1 to metabolize glutamine, we can selectively kill some tumor cells without damaging normal cells. We anticipate that these studies will lead to the development of “synthetic-lethal” drugs useful in the treatment of patients with diseases linked to inappropriate activation of mTORC1. Research supported by NIH RO1-GM51405 and the LAM Foundation. 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 SY29-01. doi:1538-7445.AM2012-SY29-01
Abstract 232: Targeting HER3 mRNA by a locked nucleic antisense molecule enhances the antitumor activity of gefitinib in vivo
Authors: Yaming Wu, Maoliang Wang, Patricia Kraft, Zhengxing Qu, Yixian Zhang, Victoria Shi, Lee M. Greenberger, Ivan D. Horak
Journal: Cancer Research (2011)

Abstract Background: The HER family consists of four tyrosine kinase receptors designated as EGFR, HER2, HER3 and HER4. HER3 is a unique member that plays a critical role in tumor growth since it 1) can heterodimerize with EGFR or HER2 and is the main link to the downstream PI3K/Akt signaling axis, 2) can mediate resistance to HER1/2-targeted therapeutics, and 3) unlike EGFR or HER2, is not typically overexpressed but still hyperphosphorylated in a variety of tumors. Resistance to the EGFR-tyrosine kinase inhibitors, such as gefitinib, can be associated with EGFR mutations and/or activation of HER3 ultimately leading to activation of the PI3K/AKT axis. We have used an RNA antagonist of HER3, designated EZN-3920, to explore the ability of this compound to inhibit tumor growth and overcome resistance to HER1/2 therapeutics. Methods: Tissue culture cells were treated with EZN-3920, a locked nucleic acid (LNA)-based oligonucleotide complementary to HER3. Compound was either added to tissue culture media (i.e. no transfection) in vitro or prepared in saline and given IV in vivo. Endpoints were measured by qRT-PCR, MTT, Western Blot analysis, Immunohistochemistry, and tumor size. Results: EZN-3920 down modulated HER3 mRNA, protein expression, PI3K/AKT signaling, and inhibited tumor cell proliferation. In vivo, systemic administration of EZN-3920, prepared in saline, resulted in specific down- modulation of HER3 mRNA and protein expression, as well as blockade in PI3K/AKT signaling pathways in NSCLC HCC827 associated with tumor growth inhibition. Similar results were also shown in tumor derived from BT-474-M1 breast carcinoma xenograft models. Interestingly, in the HCC827 tumor model, EZN-3920 at 30 mg/kg (biweekly for 4 weeks, i.v.) and gefitinib at 15 mg/kg (5 times a week for two weeks) completely shrank established tumors while either treatment alone only delayed tumor growth by 40-60%. Conclusions: The studies suggest that down regulation of HER3 by antisense molecule EZN-3920 inhibits human tumor growth in mice. Beyond this, antitumor effects of gefitinib can be enhanced by HER3 down modulation in gefitinib-sensitive tumors. On-going studies will determine if tumors that are resistant to HER1/2 therapeutics will either have enhanced sensitivity to EZN-3920 and/or the compound can restore sensitivity to such agents. 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 232. doi:10.1158/1538-7445.AM2011-232
Treatment of Insulin-Resistant Diabetic Ketoacidosis with Insulin-like Growth Factor I in an Adolescent with Insulin-Dependent Diabetes
Authors: Anton-Lewis Usala, Timothy Madigan, Bartolome Burguera, Madhur K. Sinha, Jose F. Caro, Paul Cunningham, John G. Powell, Peter C. Butler
Journal: New England Journal of Medicine (1992)

INSULIN plays a central part in the regulation of carbohydrate, fat, and protein metabolism. Severe insulin resistance, in which treatment with large doses of insulin does not result in adequate metabolic control, is uncommon. Such resistance occurs in the presence of circulating insulin or insulin-receptor antibodies,1 , 2 insulin-receptor abnormalities,3 and episodically in patients with previously typical insulin-dependent diabetes mellitus (IDDM).4 The therapeutic options in patients with severe insulin resistance have been limited, since insulin has been the only available hormone with insulin-like metabolic effects. Recombinant human insulin-like growth factor I (IGF-I), which shares considerable sequence homology as well as biologic properties . . .
OC-039 Eps8: A Master Regulator of Integrin-Dependent Pancreatic Cancer Invasion
Authors: J Tod, V Jenei, M Chrzan, C Johnson, D Fine, G J Thomas
Journal: Gut (2013)

<h3>Introduction</h3> EGFR pathway substrate 8 (Eps8) is an adapter protein that sits at the heart of a complex system regulating re-organisation of the actin cytoskeleton. Eps8 has been shown to be involved in cell motility and EGFR internalisation, via interactions with multiple intracellular proteins, including integrins. αvβ6 is an epithelial specific integrin, not present in healthy tissue but over-expressed in many carcinomas. αvβ6 promotes tumour invasion and is a key activator of TGFβ, which modulates tumour cell EMT and the desmoplastic response characteristically present in PC. The aim of this study was to investigate whether there is a link between Eps8 and αvβ6 in pancreatic cancer invasion. <h3>Methods</h3> We used immunochemistry to examine the expression of Eps8 and αvβ6 in normal pancreas and PC in vivo using tissue microarrays. PC cell motility was investigated using Transwell® assays. siRNA interference was used to down-regulate genes of interest. The ability of PC cells to activate TGFβ was measured using TGFβ-responsive mink lung epithelial cells. Cell surface αvβ6 levels were assessed with FACS analysis. Endocytosis of αvβ6 was suppressed using Clathrin siRNA to examine the role of endocytosis in αvβ6 functions. Pancreatic stellate cells (PSCs) were isolated from primary pancreatic resection tissue and used to optimise 3D pancreatic organotypic cultures. <h3>Results</h3> Eps8 and αvβ6 were up-regulated in &gt; 70% PC in vivo but were not generally detected in normal pancreas. An organotypic model of pancreatic cancer was developed using primary PSCs to study αvβ6 functions. αvβ6 promoted PC cell invasion and TGFβ activation. Interestingly, Eps8 knockdown suppressed αvβ6-dependent motility but conversely, promoted αvβ6-dependent TGFβ activation. Although inhibition of αvβ6 endocytosis also increased TGFβ activation, this was not Eps8 dependent, nor did Eps8 knockdown affect total cell surface levels of the integrin. <h3>Conclusion</h3> αvβ6 and Eps8 are over-expressed in PC. αvβ6 promotes both invasion and TGFβ activation, and Eps8 appears to act as a molecular switch between these functions. How this relates to disease progression is unclear; in late stage disease, where canonical TGFβ signalling is dysregulated (e.g. SMAD4 mutations which are seen in &gt; 50% of PCs) both αvβ6 functions are likely to be tumour promoting. However, in premalignancy when canonical TGFβ signalling acts as a tumour suppressor, we speculate that up-regulation of Eps8 may result in a pro-invasive phenotype and facilitate tumour development. Eps8 may therefore act as a master regulator of PC invasion by switching the cell function between motility and TGFβ activation at critical time points in PC progression. <h3>Disclosure of Interest</h3> None Declared
Asymptomatic Bacteriuria in Diabetes Mellitus
Authors: D. Pometta, S. B. Rees, D. Younger, E. H. Kass
Journal: New England Journal of Medicine (1967)

PYELONEPHRITIS is a common and often severe complication of diabetes mellitus. It is generally believed that pyelonephritis occurs more frequently among diabetic than among nondiabetic persons.1 2 3 Unfortunately, most of the analyses of the relation of diabetes to susceptibility to infection of the urinary tract are obtained from hospital and autopsy experiences. From these studies, it cannot be determined whether diabetic patients are intrinsically more susceptible to infection, or whether they have more infections of the urinary tract because they are more likely to have been catheterized, or in other ways to have undergone instrumentation, or whether coincident bladder dysfunction or . . .