tbuckley/cabot-search huggingface dataset:
Clinical usefulness of KRAS gene mutation analysis, in EUS-FNA specimens from pancreatic mass lesions
Authors: Ogura Takeshi
Journal: Endoscopy (2011)

It is difficult to differentiate pancreatic ductal adenocarcinoma (PDAC), from non-ductal carcinomas and benign masses. KRAS mutation is present in 75%–95% of PDAC. We studied the clinical usefulness of KRAS gene mutation analysis in EUS-FNA specimens for diagnosis of PDAC.
Response Rates in Non-Anthracycline Versus Anthracycline Exposed Patients with Metastatic Breast Cancer Treated with Lapatinib.
Authors: H. Rugo, S. Johnston, A. Preston, A. Kemner, S. Stein, H. Gomez
Journal: Cancer Research (2009)

Abstract Introduction: Anthracycline free regimens are increasingly used as adjuvant therapy for HER2 positive breast cancer due to concerns related to cardiac toxicity. Lapatinib plus capecitabine is approved for the treatment of patients with prior exposure to anthracyclines, taxanes and trastuzumab. With this recent shift in treatment practice, an exploratory analysis was performed to evaluate whether prior anthracycline exposure had an effect on clinical benefit in patients treated with lapatinib.Methods: The activity of lapatinib was examined in 7 completed studies (2 Phase III, 5 Phase II) in which lapatinib was administered as monotherapy or in combination with paclitaxel, bevacizumab, or letrozole for the treatment of HER2 positive metastatic breast cancer. In each study, patients were grouped by prior anthracycline exposure to evaluate the clinical activity of lapatinib containing regimens, as measured by overall response rate (RR).Results: In 7 studies, 192 of 593 patients were exposed to prior anthracycline. 401 patients were not. Lapatinib was administered as monotherapy in 3 studies and in combination in 4 studies. Within in each study, RR were similar in both groups (no prior anthracycline and prior anthracycline). In the combination of lapatinib plus letrozole, overall RR was higher in patients not exposed to prior anthracyclines (36.1% versus 18%). Cardiac data to be presented. Recognizing the limitations of patient numbers and cross study comparisons, as a whole, the results of this analysis indicate that patients had similar overall response rates to lapatinib regardless of exposure to prior anthracycline.Summary of Response Rate Response Rate by Prior Exposure to Prior AnthracyclineStudyTreatment ArmsNo Prior Anthracycline, % (n/N)Prior Anthracycline, % (n/N)Total, % (n/N)EGF30001 (HER2+)lapatinib+paclitaxel56.7 (17/30)63.6 (14/22)59.6 (31/52)EGF30008 (HER2+)lapatinib+letrozole36.1 (22/61)18.0 (9/50)27.9 (31/111)EGF20009lapatinib QD22.4 (11/49)30.0 (6/20)24.6 (17/69) lapatinib BID30.2 (13/43)34.6 (9/26)31.9 (22/69)EGF102580lapatinib42.9 (18/42)N/A42.9 (18/42)EGF103009lapatinib10.6 (15/141)N/A10.6 (15/141)EGF103890lapatinib+bevacizumab16.7 (3/18)8.8 (3/34)11.5 (6/52)EGF105764lapatinib+paclitaxel76.5 (13/17)77.5 (31/40)77.2 (44/57) Conclusions: With the increasing availability of agents to treat breast cancer, it is common that many patients do not receive prior anthracycline treatment for their disease. In this exploratory analysis, it appears the clinical activity of lapatinib is maintained in patients with no prior anthracycline exposure; and as observed in the lapatinib plus letrozole combination study, may even increase the overall response rate. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5105.
Polycythemia vera megakaryocytes but not megakaryocytes from normal controls and patients with smokers polyglobuly spontaneously express IL-6 and IL-6R and secrete IL-6
Authors: C Wickenhauser, J Thiele, J Lorenzen, B Schmitz, S Frimpong, K Schramm, I Neumann, R Zankovich, R Fischer
Journal: Leukemia (1999)
Abstract 3084: Chfr in breast cancer development
Authors: Saheli Jha, Snigdha Banerjee, Smita Mehta, Suman Kambhampati, Inamul Haque, Sushanta K. Banerjee
Journal: Cancer Research (2010)

Abstract Breast cancer is a common malignancy and is the most frequently diagnosed cancer in USA. It can be developed when genes that control the cell cycle and genomic stability are aberrantly expressed or non-functional. Where CHFR encodes an ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazoles and taxanes). CHFR (Checkpoint with FHA and Ring Finger) is hypothesized to mediate a delay in cell cycle progression, early in mitosis, in response to microtubule stress, independent of the spindle assembly checkpoint. As a potential regulator of cell cycle progression, CHFR naturally becomes an interesting target for understanding cancer cells. Low or moderate CHFR mRNA expression has been already reported in many cancers including breast cancer with some relevance to tumor suppressor activities. In this study we analyzed the expression profiles of CHFR in different breast cancer cell lines at mRNA and protein levels using real-time PCR and immuno-Western blot analysis. We also analyzed its expression in various breast tissue samples using immunohistochemistry. We found CHFR mRNA was significantly higher in BT474 and MCF-7 cells as compared to MDA-MB-231 cells. Two isoforms (i.e.,) of CHFR protein were detected in these cells. High molecular weight (∼89kD) isoform was markedly elevated in MDA-MB-231 cells as compared to MCF-7 cells while low molecular weight (∼52kD) isoform markedly reduced in MDA-MB-231 cells. Moreover, in normal breast sample CHFR expression is nuclear while in adenocarcinoma samples CHFR was prominent expression in cytoplasmic. Finally, we found that high molecular weight CHFR isoform expression can be regulated negatively by CCN5/WISP-2, an anti-invasive gene. Collectively, these studies suggest that CHFR may play dual roles in the genesis of breast cancer and possibly, the high molecular weight isoform may play critical role in progression of breast cancer. 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 3084.
OP0052 Prospective Evaluation of 18F-FDG and 18F-Naf Pet/Ct: Imaging Analysis of Inflammation and Bone Metabolism in Rheumatoid Arthritis
Authors: T. Watanabe, K. Minegishi, A. Ihata, M. Hama, R. Yoshimi, Y. Kirino, S. Ohno, U. Tateishi, A. Ueda, M. Takeno, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Synovitis causes joint destruction in rheumatoid arthritis (RA). While FDG-PET illustrates synovitis sensitively, NaF-PET detects accelerated bone metabolism in osteoplastic lesions of osteoarthrists (OA) as well as osteolytic lesions. <h3>Objectives</h3> This study examined the relationship between inflammation and bone damages in joint lesions of RA by using 18F-FDG and 18F-NaF PET/CT of the hands. <h3>Methods</h3> Twelve RA patients who started to receive a new biologic agent (naïve 9, switch 3; Etanercept 4, Infliximab 2, Golimumab 2, Tocilizumab 3, Abatacept 1) were enrolled. The bilateral hands were examined by FDG-, NaF-PET/CT and MRI at the entry. Intensity of PET signals was determined by standardized uptake value max (SUVmax) in MCPs, PIPs, and ulnar, medial, and radial regions of the wrist. All joints were also evaluated by power doppler (PD) and gray scale (GS) scores (0-3) in ultrasonography (US). Total score of each parameter was determined by summing up of individual parameters in all joints. Hand X-rays were evaluated according to Genant-modified Sharp score at the baseline and 6 months later. Findings of these imaging modalities and clinical assessments were comparatively analyzed in individual joints. <h3>Results</h3> The SUVmax of FDG correlated with that of NaF in individual joints (r=0.62), though detail anatomical localizations were different between them (Figure 1). While NaF signals located on the bone, those of FDG were mainly found in the synovial brusa and tendons On the other hand, NaF accumulation was not accompanied by FDG signals in osteoplastic lesions which were diagnosed as complicated OA in X-ray. Both total FDG and total NaF scores correlated with total PD and total GS of US and DAS 28. Moreover, NaF scores also correlated with HAQ. Both FDG and NaF SUVmax were significant higher in 44 joints having progression of erosion score than the other 268 joints (FDG; p=0.004, NaF p&lt;0.001). Moreover, total NaF, but not FDG, score was correlated with deterioration of total Sharp score (r=0.66). <h3>Conclusions</h3> FDG-PET detects synovistis sensitively, whereas NaF accumulation is more closely associated with bone destructive and plastic lesions. Simultaneous accumulation of the both molecules suggest coupling of inflammation and accelerated bone metabolism in RA joints. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2231
Abstract 3466: Reduced expression of CYLD is an independent prognostic factor in breast cancer and confers treatment resistance and migratory activity <i>in vitro</i>.
Authors: Mitsuhiro Hayashi, Satoru Shinriki, Hirofumi Jono, Takuya Nakamura, Jianying Guo, Yutaka Yamamoto, Hirotaka Iwase, Yukio Ando
Journal: Cancer Research (2013)

Abstract Background: CYLD was originally identified as a tumor suppressor that is mutated in familial cylindromatosis. CYLD has deubiquitinase activity and can negatively regulate NF-κB pathways. Recent study has revealed that CYLD plays important roles in tumor progression as well as immune response and osteoclastogenesis. CYLD loss of function has been associated with several tumors. Despite the broad relevance of CYLD to various tumors, its clinical and biological significances in breast cancer are still largely unknown. Materials and Methods: We assessed CYLD expression in 171 primary breast cancer tissues by immunohistochemistry and examined the correlations with CYLD expression and clinicopathological factors as well as patients’ prognosis. In addition, we investigated effects of CYLD knockdown by using siRNA on malignant state in breast cancer cell lines. Results: Our immunohistochemical analysis revealed a significant correlation between loss of CYLD expression and poor patients’ disease free survival (log-rank, p = 0.004), particularly in luminal and triple negative breast cancer patients. Multivariate analysis revealed that loss of CYLD expression was an independent poor prognosis factor (Hazard ratio 2.95, 95% CI 1.20 - 7.98, p = 0.02) in addition to hormone receptor expression status. Loss of CYLD expression correlated with high nuclear grade but not hormone and HER2 status. Consistent with our clinical data, repression of CYLD increased CD44 high/ CD24 low cancer stem-like cell population with acquisition of resistance to apoptosis induced by conventional therapy in MDA-MB-231 cells. Moreover, CYLD knockdown promoted migration through downregulation of Maspin which is a potent suppressor of breast cancer metastasis. Conclusions: CYLD expression was an independent prognostic factor in primary breast cancer. Reduced CYLD function may promote breast cancer progression and treatment resistance. Citation Format: Mitsuhiro Hayashi, Satoru Shinriki, Hirofumi Jono, Takuya Nakamura, Jianying Guo, Yutaka Yamamoto, Hirotaka Iwase, Yukio Ando. Reduced expression of CYLD is an independent prognostic factor in breast cancer and confers treatment resistance and migratory activity in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3466. doi:10.1158/1538-7445.AM2013-3466
Long-Term Parenteral Nutrition through an External Arteriovenous Shunt
Authors: Maurice E. Shils, William L. Wright, Alan Turnbull, Frank Brescia
Journal: New England Journal of Medicine (1970)

An arteriovenous shunt with a side arm was used for the intravenous feeding of a patient who had bowel resected from the third part of the duodenum to the ascending colon and who could no longer be maintained by indwelling venous catheters. The nutrient solution is prepared in plastic bags by a procedure that minimizes contamination and permits preparation and administration at home. Infusion is given in a period of nine hours or less, a special pump, filter and valve being employed. The patient has been maintained in good nutritional status by this means for a period of many months.
Does Adrenocortical Hyperplasia Result in Adrenocortical Carcinoma?
Authors: George J. Hamwi, Richard A. Serbin, Fred A. Kruger
Journal: New England Journal of Medicine (1957)

ONLY 72 cases of masculinizing tumors of the adrenal cortex were reported in a recent twenty-year survey.1 In the case reported below, symptoms of masculinization were present for thirty years before the removal of an adrenocortical carcinoma. There was responsiveness both to stimulation by ACTH and to inhibition by adrenal corticoids. Both the duration of illness and behavior are exceedingly unusual for such a lesion, although they are not without precedent.Case ReportA 39-year-old colored woman was transferred to Ohio State University Hospital from another hospital on January 18, 1957, for evaluation of the possibility of an adrenal tumor . . .
AB0429 The association between psychosocial factors and physical activity measured by actigraphy in patient with rheumatoid arthritis:
Authors: S. van Dartel, H. Repping-Wuts, H. Knoop, D. van Hoogmoed, G. Bleijenberg, P. van Riel, J. Fransen
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Previous studies showed that fatigue in RA is related to pain and disability, and to several psychosocial factors including coping and cognitions. Physical activity patterns, especially a pervasively passive pattern,are related to RA fatigue. Psychosocial factors and specific coping styles may be associated with activity patterns in patients with RA. <h3>Objectives</h3> The objective of this study was to investigate whether there is an association between self-efficacy with respect to fatigue, coping style, beliefs about fatigue, and activity patterns in RA patients. <h3>Methods</h3> Consecutive RA patients of the rheumatology clinic of the Radboud University Nijmegen Medical Centre (N=152) were enrolled for this study. Patients physical activity during 12 consecutive days was measured with the actometer. A general physical activity score (DOM) reflected the average physical activity over the total 12-day time period and was expressed in the average number of accelerations per 5-min period. The individuals' activity patterns were based on 12 individual daily physical activity scores. Patients with at least 90% of the daily activity scores below the DOM were classified as pervasively passive while the remaining patients were labeled as (pervasively or fluctuating) active. Beliefs regarding the somatic and non-somatic causes of fatigue were assessed using the Causal Attribution List (CAL), consisting of a somatic and non-somatic factor. Self-efficacy concerning fatigue was assessed using the Self-Efficacy Scale 28 (SES28). Coping strategies were assessed using the Modified Fatigue Coping Inventory (MPC-I-F). Catastrophizing of fatigue was assessed with the Fatigue Catastrophizing Scale. The association between these psychosocial factors and active/passive daily activity patterns was analyzed using an independent t-test or Mann-Whitney U test, as appropriate. <b>Results:</b> There were no differences found between causal attributions, self-efficacy, several coping styles and the level of daily activity. Passive patients had resting more frequently as coping style. <h3>Conclusions</h3> In RA patients, having a pervasively passive or active activity level was unrelated to beliefs, self-efficacy, and coping style. Therefore, activity level and coping style may be independent factors to target in RA. <h3>Disclosure of Interest</h3> None Declared
Cannabis, heroin, and cocaine dominate Europe’s €24bn illegal drugs market
Authors: Rory Watson
Journal: BMJ (2016)

The illegal drugs trade in the 28 member European Union is worth at least €24bn (£19.4bn; $27.4bn) a year, says a report released ahead of the United Nations General Assembly’s special session on drugs later this month.

The estimate was made in the EU Drug Markets Report 2016 ,1 produced jointly by the Portugal based European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and Europol, the EU’s law enforcement agency located in The Hague, Netherlands.

The joint report—the second in three years—combined the drugs agency’s analytical skills …
LONG-TERM OUTCOMES OF VASOSPASTIC ANGINA PATIENTS WITH DIABETES MELLITUS
Authors: Choong-Sil Seong, Hyunsung Joh, Kyung Hee Lim, Taek Kyu Park, Jeong Hoon Yang, Seoung-Hyuk Choi, Young Bin Song, Joo-Yong Hahn, Jin-Ho Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2016)
P02.03 * INCREASED COUNTS OF NK AND NKT CELLS ARE ASSOCIATED WITH PROLONGED SURVIVAL IN PRIMARY GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY IN COMBINATION WITH RADIO- AND CHEMO-THERAPY
Authors: S. Pellegatta, M. Eoli, G. Cantini, E. Anghileri, C. Antozzi, S. Frigerio, M. Bruzzone, B. Pollo, E. Parati, G. Finocchiaro
Journal: Neuro-Oncology (2014)

Two clinical studies, DENDR1 and DENDR2 including, respectively, the treatment of first diagnosis and recurrent glioblastoma (GB) patients with dendritic cells (DCs) loaded with autologous tumor lysate are currently active at Istituto Neurologico Besta, Milan. Our first results obtained on a group of recurrent GB patients demonstrated that the response of NK cells correlates with significantly prolonged survival. Here we provide results of the interim analysis on 22 patients affected by primary GB. Patients with post-surgery volume ≤10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC were done before adjuvant chemotherapy. The subsequent 4 injections were performed 17 ± 3 days after adjuvant TMZ. MRI, clinical and immunological follow-up were performed every 2 months. The median age at surgery was 54.5 years (28-69). RT-TMZ induced significant lymphopenia ( 1000 lymphocytes/microl (5/22) before first vaccination had shorter PFS than others (p < 0.005). Peripheral Blood Lymphocytes (PBLs) were analyzed by flow cytometry to identify CD8+ T cells, NK and NKT cells before and after DC vaccines. The ratio of vaccination/baseline frequencies and counts (V/B ratio) of all of the immunological parameters for each patient was calculated, and the median of all of the observations used as the cut off value to separate patients. V/B ratio was correlated with the progression free survival (PFS) of each patient. Increased V/B ratio for NK cells and in particular NKT cells, but not for CD8 T lymphocytes, was significantly associated with prolonged PFS (median PFS 14 vs 8.0 mo, p = 0.01; 15.0 vs 8.0 mo, respectively). Interferon (IFN)-γ in PBLs was significantly higher in patients with PFS12 (p < 0.02), increasing immediately after the second vaccination as evaluated by real time-PCR. No changes in the expression levels of IFN-γ were observed in the other patients. After a median follow up of 14 months (6-27), the median progression-free survival (PFS) was 9 mo, with PFS6 90% (C. I. 0.78-1.029%) and PFS12 42% (C. I: 0.20-0.64) at Kaplan Meier analysis. Median overall survival (OS) was 22 mo with OS 12 70%. (C. I. 0.50-0.9). 2/4 patients with MGMT methylation were in the group of high V/B ratio. Our results show a positive association between increased peripheral NK and NKT cells response and prolonged survival. Further investigations are required on possible interference of radio-chemotherapy on activation of CD8+ T cells.
Macrophage damage in relation to the pathogenesis of lung diseases.
Authors: J D Brain
Journal: Environmental Health Perspectives (1980)

Pulmonary macrophages are important since their migratory patterns and behavior are often pivotal events in the pathogenesis of pulmonary disease. Alveolar macrophages act to decrease the probability of particle penetration through epithelial barriers, and their phagocytic and lytic potentials provide most of the known bactericadal properties of the lung. Macrophages are also involved in immune responses and in defense against neoplasms. Increased inert or infectious particles stimulate the recruitment of additional macrophages. Most free cells containing particles eventually reach the airways and are quickly carried to the pharynx and swallowed. In addition, evidence has now accumulated that macrophages play a part in the pathogenesis of pulmonary diseases. For example, the ingestion of some particles by macrophages causes a release of lysosomal enzymes into the macrophage cytoplasm. These enzymes may kill the macrophage, and dead or dying macrophages release a substance with attracts fibroblasts that elicit fibrogenic responses. Other toxic particles, such as cigarette smoke, my lead to a release of proteases and other toxic enzymes. All particles are capable of competitive inhibition of phagocytosis in macrophages and many may be cytotoxic and further depress phagocytosis. In addition, connective tissue macrophages may contribute to lung disease by concentrating and storing potent carcinogens or other toxic particles close to a reactive bronchial epithelium for long periods. Thus, even through macrophages serve as a first line of defense for the alveolar surface, they may also be capable of injuring the host while exercising their defensive role.