tbuckley/cabot-search huggingface dataset:
PTU-149 Malnutrition And Gastrointestinal (gi) Symptoms In Patients With Upper-gi Cancer
Authors: E Grace, K Mohammed, C Shaw, K Whelan, J Andreyev
Journal: Gut (2014)

<h3>Introduction</h3> Persistent GI symptoms and malnutrition have been associated with poorer quality of life in upper-GI cancer patients. This study aims to assess GI symptoms and nutritional status in patients undergoing modern treatment. <h3>Methods</h3> Patients with newly diagnosed upper-GI cancer were prospectively reviewed at the time of diagnosis and at 3- and 12-months following radical treatment. Nutritional assessment was performed using the patient-generated subjective global assessment (PG-SGA), which is considered the ‘gold-standard’ for nutritional assessment and has been validated in the oncology setting (score ≥ 4 intervention needed; score ≥ 9 critical intervention needed). The gastrointestinal symptom rating scale (GSRS) was used to evaluate the presence/absence and severity of 22 GI symptoms using a 4-point response scale. Total scores range from 0–66, where 0 = all symptoms absent and 66 = all symptoms severe. <h3>Results</h3> 61 males and 19 females, median age 66 (range 46–89) years were recruited (61% oesophageal, 33% gastric, 6% gastro-oesophageal junction tumours). Of these, 68 were reviewed at 3-months and 25 at 12-months. Mean (SD) body weight and body mass index (BMI) were 76.7 kg (17.4) and 26.7 kg/m<sup>2</sup> (4.7) at baseline, 74.4 kg (14.8) and 25.9 kg/m<sup>2</sup> (4.4) at 3-months and 72.1 kg (16.3) and 24.7 kg/m<sup>2</sup> (4.4) at 12-months. There was a significant mean difference in weight (-2.0 kg, p = 0.002) and BMI (-0.56 kg/m<sup>2</sup>, p = 0.006) at 3-months compared to baseline. These reduced further by 12-months. Mean (SD) PG-SGA score at baseline 9.0 (6.3), 3-months 7.8 (5.6), and 12-months 7.4 (5.0) indicated that intervention was required. At baseline, 3- and 12-months 61%, 52% and 68% of patients respectively were considered moderately or severely malnourished. Mean (SD) total GSRS scores were 14.2 (10.8), 12.0 (9.4) and 15.5 (11.5) at baseline, 3- and 12-months respectively. The symptoms with the greatest increase in prevalence (% more patients) from baseline to 3-months (n = 68) were nausea (+24%), loose stool (+16%), urgency (+6%), flatulence (+6%) and early satiety (+6%). Those with the greatest decrease in prevalence (% less patients) during this time were difficulty swallowing (-24%), painful swallowing (-24%), regurgitation (-21%), belching (-15%) and acid reflux (-12%). Of the n = 25 followed up at 12-months, the most common symptoms reported were flatulence (76%), belching (72%), abdominal pain (68%), abdominal grumbling (56%) and early satiety (52%). <h3>Conclusion</h3> After treatment commences there is progressive weight loss over time. Troublesome GI symptoms persist at 12-months and may be contributing to this weight loss. Optimising nutritional status and controlling GI symptoms is required throughout the treatment pathway. <h3>Disclosure of Interest</h3> None Declared.
Treatment of early breast cancer in women over 65: what is important? Retrospective trial.
Authors: K Kim, Y Jung, L Hur, S Kim
Journal: Cancer Research (2009)

Abstract Abstract #1125 Introduction-Background-Objective&amp;#x2028; There are some demonstrations for the under-treatment of elderly (age 65 or older) women with early breast cancer. However, a few reports are available for overall survival as well as treatment patterns. To characterize treatment patterns and to determine the impact of under-treatment of early breast cancer in the elderly population compared to younger population.&amp;#x2028; Methods&amp;#x2028; We analyzed data of 4,990 early (stage I, II) breast cancer patients aged ≥ 50 years old postmenopausal women, registered in the Korean Breast Cancer Society Registration Program (KBCSRP) between 1992 and 2001 retrospectively. We compared elderly group (age 65 or older) with younger group (age 50 or older, and under age 65) in cancer stage, hormonal receptor status, p53 status, HER-2 status, breast conservation rate, radiation therapy omission rate after breast conservation surgery, chemotherapy rate, hormonal therapy rate and overall survival.&amp;#x2028; Results&amp;#x2028; 942(19%) patients were in the elderly group and 4,048(81%) patients were in the younger group. We followed up to 2004 and median follow up period were 5.7 years. There were no differences in cancer stage, HER-2 status, and hormonal therapy rate.&amp;#x2028; In elderly group, tumor had two better prognostic factors: more hormonal receptor positivity (63.3% vs. 59.3%; p=0.001) and less p53 positivity (37.3% vs. 49.5%: p&amp;lt;0.001). Overall survival, however, was lower than younger group: 83% vs. 91% in 5 year survival rate, 68% vs. 81% in 10 year survival rate, respectively. Elderly group had less breast conservation rate (16.4% vs. 20.4%; p&amp;lt;0.001), more radiation omission rate after breast conservation surgery (59.8% vs. 15.3%; p&amp;lt;0.001) and less chemotherapy rate (43% vs. 70.6%; p&amp;lt;0.001). Using log-rank analysis, overall survival was affected by under-treatment of disease: women who underwent breast conservation surgery without radiation therapy experienced a significant decreased survival compared to women with radiation therapy (68% vs. 84% in 10 year survival rate; p&amp;lt;0.001). Total mastectomy was not superior to breast conservation surgery plus radiation therapy (p=0.2856). Women who underwent chemotherapy, however, revealed no survival gains, but women with hormonal therapy showed superior survival rate (p=0.0019).&amp;#x2028; Conclusions&amp;#x2028; Our data revealed that elderly patients had better prognostic tumor characteristics, but lower survival rate. Deviated under-treatment patterns in elderly early breast cancer patient could be dangerous choice to patients, therefore, radiation therapy after breast conservation surgery should not be omitted and hormonal therapy should be recommended especially. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1125.
AIDS Epidemic Cuts Cancer Survival in Younger Men
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article AIDS Epidemic Cuts Cancer Survival in Younger Men Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Pages 87–88, https://doi.org/10.1093/jnci/86.2.87 Published: 19 January 1994
Passive Smoking and the Risk of Coronary Heart Disease — A Meta-Analysis of Epidemiologic Studies
Authors: Jiang He, Suma Vupputuri, Krista Allen, Monica R. Prerost, Janet Hughes, Paul K. Whelton
Journal: New England Journal of Medicine (1999)

The effect of passive smoking on the risk of coronary heart disease is controversial. We conducted a meta-analysis of the risk of coronary heart disease associated with passive smoking among nonsmokers.
Abstract LB-397: Deep sequencing of Xenografts and case-matched blood and primary tumors reveals a 20 folds enrichment of loss of heterozygosity versus somatic mutations suggesting LOH plays an ever important role in tumorigenesis
Authors: Qiang Xu, Guan Wang, Douglas D. Fang, Yibo Gao, Yundi Chen, lele Sun, Xuelan Yan, Ou Li, Quanyu Yang, Maoxiang Qian, Bin Zhang, Zhaoli Chen, Chi-Chung Chan, Hongye Sun, Jie He
Journal: Cancer Research (2012)

Abstract The double hits theory suggests a major mechanism of tumorigenesis. However, compared to the somatic mutations, the loss of heterozygosity (LOH) was not frequently identified in many sequencing projects. Unlike the somatic mutations that were detected by the evidence of novel alleles in tumor tissue, the alleles involving in the LOH are present in normal tissues as well. Given the high level of tissue heterogeneity of primary tumors, including both tumorous cells and normal stroma cells, at whole tissue or million cells level LOH can only be detected as a quantitative change between tumor and normal samples, which are not easily distinguished from potential sequencing errors or other artifacts especially with low depth sequencing. By applying whole exome capture deep sequencing on case-matched primary tumor, blood and xenograft samples, we found that xenografts represent a much purer human tumor cell population than primary tumor tissues. These tumor cells growing in mice not only contain the majority of somatic mutations in the primary tumors (&amp;gt;95%), but also reveal a &amp;gt;20 folds enrichment of somatic LOH events, which were not categorized as LOH in primary tumors, versus somatic mutations. All these findings were detected after removing mouse sequence contaminations, which if included will induce about half of the total variations observed in the xenograft samples. We found that these LOH events affect both tumor suppressor genes and oncogenes. Given that driver mutations or other variations that are implicated in oncogenesis are most likely preserved in xenografted tumor cells in immunedeficient mice, we hypothesize that the bigger range of somatic LOH events that we observed in xenograft samples play a potential ever important role in tumorigenesis than what we thought previously. Our finding also sheds a new light on a novel approach for the discovery of potential drug targets by sequencing xenograft samples. 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 LB-397. doi:1538-7445.AM2012-LB-397
Association of Hormone-Replacement Therapy with Various Cardiovascular Risk Factors in Postmenopausal Women
Authors: Azmi A. Nabulsi, Aaron R. Folsom, Alice White, Wolfgang Patsch, Gerardo Heiss, Kenneth K. Wu, Moyses Szklo
Journal: New England Journal of Medicine (1993)

Most epidemiologic studies of cardiovascular disease in postmenopausal women suggest that estrogen-replacement therapy has a protective effect. The effects of the use of estrogen combined with progestin are less well studied.
Abstract 2583: Green tea polyphenols cause stabilization and increased transcriptional activity of p53 by increasing its acetylation through inhibition of class I histone deacetylases
Authors: Vijay S. Thakur, Karishma Gupta, Sanjay Gupta
Journal: Cancer Research (2012)

Abstract p53, a major tumor suppressor and transcription factor protects the cells from both internal and external stress by modulating cell cycle and apoptotic pathways. p53 is mutated in more than 50% of human cancer and in most others, its pathway is defective. p53 undergoes a number of posttranslational modifications including acetylation of lysine (Lys) residues on its C-terminal. Acetylation of p53 at Lys373 and Lys382 has been reported to decrease its degradation and increased binding to DNA, leading to increased transcription of its downstream targets such as p21/waf1 and Bax. The process of acetylation is regulated by a group of opposing enzymes histone acetyltransferase (HATs) and histone deacetylases (HDACs). Class I HDACs (HDAC 1, 2, 3 and 8) are shown to be upregulated in a variety of human cancers including prostate cancer and their inhibition by HDAC inhibitors leads to cell cycle arrest and apoptosis in cancer cells. In pursuit of safe and effective HDAC inhibitors, we earlier demonstrated that green tea polyphenols (GTP) and its major constituent, (-) epigallocatechin-3-gallate (EGCG) has ability to inhibit class I HDACs in human prostate cancer cells. Here we demonstrate that GTP and EGCG activates p53 through acetylation at the Lys373 and Lys382 residues by inhibiting class I HDACs in human prostate cancer LNCaP cells. Treatment of cells with GTP (2.5-10μg/ml) and EGCG (5-20μM) resulted in dose and time dependent inhibition of class I HDACs, albeit at varying levels. Discontinuation of treatment with GTP/EGCG resulted in the loss of p53 acetylation at both the sites in these cells. GTP/EGCG treatment also resulted in increased expression of p21/waf1 and Bax at the protein and message levels. The increased GTP/EGCG-mediated p53 acetylation enhanced its binding on the promoters of p21/waf1 and Bax, which was associated with the increase accumulation of cells in the G0/G1 phase of the cell cycle and induction of apoptosis. Taken together, our findings indicate that GTP/EGCG causes acetylation of p53 by inhibiting class I HDACs which is likely to be part of the mechanism that control the physiological activity of p53. 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 2583. doi:1538-7445.AM2012-2583
Abstract 5311: Transducer of Cdc42-dependent actin assembly-1 (Toca-1) promotes breast cancer invasion and metastasis
Authors: Harish Chander, Jalna A. M Meens, Peter F. Truesdell, Colin D. Brien, Stephanie L. Everingham, Andrew W.B Craig
Journal: Cancer Research (2012)

Abstract Metastatic breast adenocarcinomas display activation signatures for signaling pathways like Epidermal Growth Factor Receptor (EGFR) that trigger cell motility and tissue invasion. Transducer of Cdc42-dependent actin assembly-1 (Toca-1) is an adaptor protein that promotes recruitment of actin nucleation promoting factors to cellular membranes. Although these actin regulatory proteins have been linked to breast cancer invasion, the role of Toca-1 in this process has not been reported. In this study, breast cancer cell lines with a range of invasive and metastatic properties were used, including human MDA-MB-231 cells, rat MTLn3 cells, and MTLn3-B1 cells expressing human EGFR. To test the role of Toca-1 in these cell lines, we established stable Toca-1 knock-down (KD) using lentiviral delivery of shRNAs specific for human or rat Toca-1. Here, we report that Toca-1 is expressed in highly invasive breast cancers cell lines, and that Toca-1 co-localizes with components of invadopodia. Toca-1 localizes to the filamentous actin-rich core of invadopodial protrusions in breast cancer cells that are actively degrading the extracellular matrix (ECM). In MDA-MB-231 cells, Toca-1 KD led to a significant defect in EGF-induced cell migration and invasion compared to control cells. This correlated with a significant defect in EGF- and Src-induced ECM digestion in Toca-1 KD compared to control MDA-MB-231 cells. Next, control and Toca-1 KD cells were compared in orthotopic mammary tumors that were xenografted in Rag2−/−:[[Unsupported Character - Symbol Font &amp;#61543;]]c−/− mice. Although Toca-1 KD remained effective in primary tumors, no defects in tumor growth were observed. However, mice bearing Toca-1 KD cell tumors displayed a significant reduction in spontaneous metastases to the lung. Similar results were obtained for weakly metastatic MDA-MB-231 cells and highly metastatic MTLn3-B1 cells. In contrast, Toca-1 was not required for efficient lung seeding following tail vein injection of MTLn3-B1 cells, suggesting that Toca-1 functions at an early step in the dissemination of metastatic breast tumor cells. Taken together, this investigation identifies Toca-1 as a pro-invasive protein in breast cancer, and a potential therapeutic target to limit tumor metastasis. 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 5311. doi:1538-7445.AM2012-5311
THU0328 Changes in health-related quality of life in systemic juvenile idiopathic arthritis patients after single dose of canakinumab
Authors: N. Wulffraat, T. Kallinich, L. McCann, R. Brik, L. Rutkowska-Sak, M. Ferrandiz, K. Lheritier, D. Kim, A. Gnanasakthy, H. Ozdogan
Journal: Annals of the Rheumatic Diseases (2013)

Background Patient's quality of life is markedly affected by the persistent and disabling disease features of systemic juvenile idiopathic arthritis (SJIA). We evaluated the direct impact of the disease on patients' well being and the improvements observed following treatment with a single dose of canakinumab (CAN) using a variety of patient reported outcomes (PROs). Objectives To assess improvement in Health-Related Quality of Life (HRQoL) with CAN vs placebo for the treatment of SJIA patients. Methods In a 4-week, randomized, double blind, single-dose study (β-SPECIFIC 1), 84 patients with active systemic features at enrollment were randomized 1:1 to receive a single dose of CAN (4mg/kg) or placebo sc on Day 1. The primary endpoint was proportion of patients achieving an adapted ACRpedi 30 criteria (plus absence of fever) at Day 15. Secondary endpoints included change in HRQoL and disability over time, pain intensity (0-100 mm VAS) and safety. Both concepts were measured by CHQ-PF50 and CHAQ© respectively. Results 84 patients (2-18 yrs) were randomized to CAN (n=43) or placebo (n=41). High discontinuation rate in the placebo group (90.2%) was due to unsatisfactory therapeutic response vs CAN group (14%). At baseline (BL), the median CHQ-PF50 physical and psychosocial scores for all patients (5-18 yrs, n=28) were 19.2 and 40.0 for CAN and 18.1 and 44.9 for placebo. Median baseline CHAQ score was 1.6 for CAN and 1.5 for placebo. At BL, mean pain intensity was 69.7mm for CAN and 60.9mm for placebo. CAN provided statistically significant higher improvement in CHQ-PF50 physical and psychosocial scores compared to placebo (Table). The median improvement in the CHAQ disability score achieved with CAN both at Days 15 and 29 exceeded a previously established minimal clinical important difference (MCID) cited to be -0.19 by at least a factor of 5. Least square means in overall pain intensity were significantly lower in the CAN vs placebo group at Days 15 and 29 (both, p<0.0001). 55.8% patients in the CAN vs 39.0% placebo group had AEs with the most frequently reported AEs being upper respiratory tract infections. 4 patients had serious AEs, 2 in each treatment group. ![Figure][1]</img> Conclusions A single dose of canakinumab demonstrated significant and rapid improvement in HRQoL and baseline disability of SJIA patients. Such benefits will be of high importance to patients and payers. Disclosure of Interest N. Wulffraat: None Declared, T. Kallinich: None Declared, L. McCann: None Declared, R. Brik: None Declared, L. Rutkowska-Sak: None Declared, M. Ferrandiz: None Declared, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, D. Kim Shareholder of: Novartis, Employee of: Novartis, A. Gnanasakthy Employee of: Novartis, H. Ozdogan Speakers Bureau: Novartis [1]: pending:yes
Cost Effectiveness of Prophylactic Intravenous Immune Globulin in Chronic Lymphocytic Leukemia
Authors: Jane C. Weeks, Maureen R. Tierney, Milton C. Weinstein
Journal: New England Journal of Medicine (1991)

A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness.
Abstract 189: miRNAs regulating members of SLC transporter family genes in penile carcinomas
Authors: Juan J. Muñoz, Sandra A. Linde, Mateus C. Barros, Ariane F. Busso, Fábio Marchi, Fernando A. Soares, Silvia R. Rogatto
Journal: Cancer Research (2012)

Abstract Background: Penile cancer (PeCa) is a rare disease in developed countries, but with high incidence in South America and Africa. Surgery is frequently used for local control of the disease and it can lead to partial or complete amputation of the organ, with subsequent psychosexual morbidity. Integrating data previously obtained using CGH-array and large-scale gene expression in PeCa, we found deregulation of members of solute carriage (SLCs) gene family that was not associated with genomic alterations. These findings suggested that other regulatory mechanisms could be involved, such as miRNAs. Aim: The purpose of this study was to confirm the gene expression pattern of six SLC genes (SLC1A3, SLC8A1, SLC25A4, SLC25A16, SLC25A25 and SLC27A4) and their putative regulatory miRNAs (miR-22, miR223, miR-23b, miR-26b, miR-27b and, miR-133b, respectively) in PeCa and associate the findings with clinical and pathological data. Patients and Methods: RNA was obtained from fresh PeCa (27 training and 13 validation set samples) and 4 normal penile tissues. SLC genes and miRNAs expression were evaluated by RT-qPCR. HPV genotyping was assessed using Linear Array HPV Test Genotyping (Roche). Results: Positive correlation between SLC1A3, SLC8A1, SLC25A4 and SLC27A4 expression levels detected by microarray and RT-qPCR was observed in the training set samples. Downexpression of SLC8A1 (P=0.009) and SLC25A25 (P=0.002) and overexpression of SLC27A4 (P=0.006) were detected in tumors (training and validation set) compared with normal controls, thus validating the previous findings of global gene expression. Significant downexpression of miR-23b, miR-26b, miR-27b and miR-133b and overexpression of miR-223 were detected in tumors compared with normal controls. Interestingly, lower levels of miR-133b were observed in 96% of the tumors (P=0.0007). Significant negative correlation was detected between SLC8A1 transcript levels and its putative regulatory miRNA (miR-223, P=0.015, r = −0.482) and between SLC27A4 e miR-133b (P=0.023, r = –0.454), suggesting that these genes are regulated by these miRNAs. Higher levels of SLC25A16 were found in HPV positive tumors (P=0.012). A significant association was found between lower levels of miR-23b and miR-27b and perineural invasion (P=0,032 and P=0,032; respectively). Conclusions: This study showed the deregulation of members of SLC gene family in PeCa and the involvement of putative regulatory miRNAs. miR-23b and miR-27b were found as putative prognostic markers in PeCa patients and with potential as therapeutic targets. 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 189. doi:1538-7445.AM2012-189